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Brazilian Journal of Pharmaceutical Sciences, Volume: 55, Published: 2019
  • Design and evaluation of rhubarb total free anthraquinones oral colon-specific drug delivery granules to improve the purgative effect Original Article

    Wei, Hongwei; Chang, Jinhua; Liu, Pei; Li, Zhongsi; Miao, Guangxin; Liu, Xigang; Liu, Cuizhe; Zhang, Xiangrong

    Abstract in English:

    Rhubarb is commonly used as a cathartic in Asian countries. However, researchers have devotedextensive concerns to the quality control and safety of rhubarb and traditional Chinese preparations composed of rhubarb due to the instable purgative effect and potential nephrotoxicity of anthraquinones. In this study, we aimed to prepare rhubarb total free anthraquinones (RTFA) oral colon-specific drug delivery granules (RTFA-OCDD-GN) to delivery anthraquinones to colon to produce purgative effect. RTFA-OCDD-GN were prepared using chitosan and Eudragit S100 through a double-layer coating process and the formulation was optimized. Continuous release studies were performed in a simulated gastric fluid (pH 1.2), followed by a small-intestinal fluid (pH 6.8) and a colonic fluid (pH 7.4, containing rat cecal contents). The purgative effect test was performed in rats. The dissolution profile of RTFA-OCDD-GN showed that the accumulative dissolution rate of RTFA was about 83.0% in the simulated colonic fluid containing rat cecal contents and only about 9.0% in the simulated gastrointestinal fluids. And the RTFA-OCDD-GN could produce the comparative purgative activity as rhubarb, suggesting it could deliver the free AQs to the colon. The RTFA-OCDD-GN was a useful media to enhance the purgative activity of free anthraquinones after administered orally.
  • Pharmaceutical ethnobotany in the Mahabad (West Azerbaijan) biosphere reserve: ethno-pharmaceutical formulations, nutraceutical uses and quantitative aspects Original Article

    Jafarirad, Saeed; Rasoulpour, Ibrahim

    Abstract in English:

    This study endeavors to overcome the limits of an orally transmitted pharmacopoeia, and tries to utilize the large ethnobotany patrimony of the area to investigate the biological diversity. Thirty-five traditional practitioners from dissimilar ethnic groups including traditional health practitioners (THPs) and indigenous people were interviewed. A total of 35 species of plants, belonging to 20 families were recognized for the treatment of more than 26 types of ailments. Informant consensus factor (FIC) values of this study reflected the high agreement in the use of plants in the treatment of gastro-intestinal complaints, infectious, parasitic diseases and constipation among the informants. Constipation had the highest use-reports and 8 species of plants had the highest fidelity level (FL) of 100%. In addition one of the species showed the highest relative importance (RI) value of 2.00. Priority should be given to phytochemical investigation of plants that scored the highest FL, FIC, RI values; as such values could be considered as a good indicator of potential plants for discovering new drugs. In addition, traditional knowledge of THPs should be taken into consideration in order to smooth continuation and extension of the nutraceutical aspects and biological diversity of the region.
  • Risk assessment of the occurrence of aflatoxin and fungi in peanuts and cashew nuts Original Article

    Kujbida, Paula; Maia, Patrícia Penido; Araújo, Ariadne Naama de; Mendes, Leonardo Daniel; Oliveira, Mariana Lepri de; Silva-Rocha, Walicyranison Plinio; Brito, George Queiroz de; Chaves, Guilherme Maranhão; Martins, Isarita

    Abstract in English:

    In the present study, the occurrence of fungi and aflatoxins (AFs) in peanut and cashew nut samples was investigated. Mycological analysis revealed the presence of fungi in 58.8% of samples, and assessment of AFs by chromatographic methods revealed that 52.9% were contaminated by AFs. AFB1 was the principal component in all AF-contaminated samples, with a mean level of 14.0, and 1.08 µg/kg in peanut and cashew nut, respectively. Eleven samples (32.4%) exceeded the total AF maximum level (4 μg/kg) and 8 samples (23.5%) exceeded the AFB1 (2 μg/kg) established by the European Commission. Our findings suggest that the incidence of AFs emphasizes the need for regular monitoring and a more stringent food safety system to control AFs at the lowest possible levels in peanuts and cashew nuts. The hypothetical dietary exposure suggests that the food products evaluated may significantly contribute to the overall human exposure.
  • Association of hypertension and dyslipidaemia with increasing obesity in patients with Type 2 Diabetes Mellitus Original Article

    Saleem, Zikria; Saeed, Hamid; Khan, Zohaib Abbas; Khan, Muhammad Imran Hassan; Hashmi, Furqan Khurshid; Islam, Muhammad; Bashir, Afzaal; Sadeeqa, Saleha

    Abstract in English:

    The study was performed to estimate the association of hypertension and dyslipidaemia with increasing body weight and obesity in Type II diabetics of Lahore, Pakistan. An observational study was conducted by enrolling 2708 obese diabetics from four diabetes care centres of Lahore, Pakistan. Data was collected for a period of 7 months. Associations were estimated using chi-square, binary and multinomial logistic regression. Data suggested that blood pressure, systolic and diastolic, exhibited continual increase with increasing body weight and obesity class in diabetes patients with 41.8% increase in the prevalence of hypertension in obesity class III subjects (OR; 1.91, p=0.02). Likewise, triglycerides and total cholesterol exhibited continual increase in their mean values with increasing obesity, i-e., an overall increase in the prevalence of dyslipidaemia of 27.2% in obesity class 3 subjects (OR; 1.94, p=0.29). Taken together, this data suggested that hypertension is potentially associated with increasing obesity in diabetics, while dyslipidaemia demonstrated plausible association only with obesity class 3.
  • Antidiabetic activity evaluation of Onobrychis species on alloxan-induced diabetic mice Original Article

    Ozbek, Hanefi; Acikara, Ozlem Bahadir; Oz, Burcin Ergene; Ozbilgin, Serkan; Kirmizi, Neriman Ipek; Ozrenk, Bade Cevriye; Tekin, Mehmet; Saltan, Gulcin

    Abstract in English:

    In the current study, four Onobrychis species, O. albiflora Hub.-Mor., O. argyrea Boiss. subsp. argyrea Boiss., O. galegifolia Boiss., and O. tournefortii (Willd.) Desv. were collected from Anatolia to be evaluated for their antidiabetic activities. Methanol water extracts of the aerial parts were used for experiments. An alloxan-induced diabetic mice test model was used. Phytochemical analysis of the tested extracts was investigated using the HPLC method. The highest activity was observed with treatment of O. albiflora aerial part extract. Significant decrements were detected in the blood glucose levels as follows: 180.83±47.48 and 252.83±50.47mg/dL at 100 mg/kg and 200 mg/kg doses of O. albiflora, respectively, when compared to the isotonic saline solution control group, eliciting a blood glucose level of 494.20±27.32. Among the tested standard compounds, rutin and isoquercetin were detected in the examined species. The highest amount of rutin (1.1981±0.0017%) and isoquercetin (0.7318±0.0197%) were found in O. albiflora and O. argyrea subsp. argyrea, respectively. Antidiabetic activities of the tested Onobrychis species seem to indicate a possible correlation with their rutin and isoquercetin contents. Therefore, rutin and isoquercetin may be the antidiabetic compounds that contribute to the antidiabetic activity of the tested Onobrychis species.
  • Evaluation of oxidative stability of mayonnaise containing poly ε- caprolactone nanoparticles loaded with thyme essential oil Original Article

    Passos, Rhaysa Beatriz dos; Bazzo, Giovana Carolina; Almeida, Aline da Rosa; Noronha, Carolina Montanheiro; Barreto, Pedro Luiz Manique

    Abstract in English:

    Suspensions of poly ε-caprolactone (PCL) nanoparticles loaded with thyme essential oil were prepared as a natural antioxidant in mayonnaise. Mean particle size was 204.9 ± 2.7 and 240.0 ± 5.5 nm respectively for nanoparticles prepared with PCL alone (NP-C) and for those loaded with thyme essential oil (NP-T). The polydispersity index indicated a homogeneous distribution of all particles, with no significant difference between NP-C and NP-T samples. The nanoparticles showed a large negative charge evidenced by zeta potential rates, indicating high physical stability. The use of PCL as a polymer provided high encapsulation efficiency for thyme essential oil (91.15 ± 2.12 %). DPPH (2,2-diphenyl-1-picrylhydrazyl) method determined IC50 rates were 476.4 ± 33.6 and 483.5 ± 20.4 µg mL-1respectively for unencapsulated oil and for NP-T, evidencing pronounced antioxidant activity. NP-C, NP-T and synthetic antioxidant butylhydroxytoluene (BHT) were applied to samples of mayonnaise and their oxidative stability evaluated for eight days in an oven at 63 ± 3ºC. Results of hydroperoxide value (HP) and thiobarbituric acid reactive substances (TBARS) showed that NP-T had a similar performance as synthetic antioxidant BHT in the prevention of mayonnaise lipid oxidation.
  • Effect of MDR C3435T polymorphism on Varenicline treatment in quit smoking Original Article

    Bozkurt, Nurgul; Altıntas, Fatih; Bozkurt, Ali Ihsan; Turgut, Gunfer; Turgut, Sebahat

    Abstract in English:

    Despite so many global efforts, smoking still remains to be one of the most common addictions worldwide. Even though most smokers wish to quit smoking, many of them fail. In this respect, genetic variants are thought to be remarkable factors in nicotine dependence and in treatment of smoking cessation. This is a paper investigating a single variant p-glycoprotein (P-gp) polymorphisms and its effect on Varenicline efficacy in the smoking cessation. 158 smokers and 52 non-smoker healthy volunteers were included. We determined the P-gp C3435T gene polymorphisms in all subjects. Face to face interviews with smokers were performed for smoking cessation and Varenicline was given for smoking cessation. Cessation success was evaluated in the 6th month and success rates were compared according to the P-gp genotype distributions. In our study, smoking cessation rate by Varenicline was 57.0%. This rate was 55.0% in females, and 57.2% in males (p=0.85). The P-gp C3435T gene distribution was similar in control, quitters and not-quitter groups. Cessation rate was at highest point in genotype CT (62.2%) and at the lowest in TT (47.6%). It was 53.8% in genotype CC and there was no statistically significant difference (p=0.27). Our results suggest that genetic variants of P-gp C3435T did not significantly affect Varenicline treatment for smoking cessation.
  • Biomarker responses (serum biochemistry) in pregnant female wistar rats and histopathology of their neonates exposed prenatally to pesticides Original Article

    Upadhyay, Jyoti; Rana, Mahendra; Bisht, Satpal Singh; Rana, Amita; Durgapal, Sumit; Juyal, Vijay

    Abstract in English:

    Experiments were conducted to investigate the effects on health of pregnant female rats exposed to pesticides glyphosate and carbendazim. Glyphosate is used as herbicide and carbendazim as a fungicide; all are commercially available readily for various agricultural and domestic purposes. The hypothesis tested in this investigation is that pesticide exposure during pregnancy causes changes in biomarker responses like serum glucose level, total protein, total cholesterol, triglycerides, SGOT, SGPT, and billirubin level. Significant changes were observed in all above biomarker responses, when compared with the reference. Histopathology of skin and kidney of rat neonates showed marked damage. Degenerative changes and vacuolization with eroded capsule were observed in kidney sample and thinning of epidermis in skin sample was seen in pesticides exposed neonates of rats. The serum biochemistry and histopathological findings are valuable markers for observing the changes caused by pesticide exposure.
  • Modulatory effect of baicalein on gene expression and activity of antioxidant enzymes in streptozotocin-nicotinamide induced diabetic rats Original Article

    Sarkar, Purabi; Nath, Kaberi; Banu, Sofia

    Abstract in English:

    Oxidative stress plays the central role in the pathogenesis and progression of diabetic complications. The present study aims to investigate the beneficial effect of oral administration of flavone baicalein in streptozotocin-nicotinamide (STZ-NA) induced diabetic rats by measuring oxidative stress markers, antioxidant enzyme activities and expression analysis of antioxidant genes. Experimental diabetes was induced by a single intraperitoneal (i.p.) injection of STZ (55 mg /kg b.wt), 15 min after the i.p. administration of NA. At the end of the experimental period, thiobarbituric acid reactive substances (TBARS), activities of antioxidant enzymes and expression levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx) were measured in diabetic rats along with serum biochemical parameters namely total cholesterol (TC), total triglyceride (TG), aspartate transaminase (AST) alanine transaminase (ALT) and glycosylated hemoglobin (HbA1c). Oral administration of baicalein (40 mg/kg b.wt/day) demonstrated a significant ameliorative effect on all studied biochemical and oxidative stress parameters. Biochemical findings were corroborated by qPCR expression analysis which showed significant upregulation of antioxidant genes in diabetic rats. These results suggest that baicalein supplementation may reduce diabetes and its complications by suppressing oxidative stress and enhancing gene expression and antioxidant enzyme activities in diabetic rats.
  • Assessment of anti-diabetic activity of a novel hydrazine-thiazole derivative: in vitro and in vivo method Original Article

    Resende, Marina Ferrara de; Lino, Cleudiomar Inácio; Souza-Fagundes, Elaine Maria de; Rettore, João Vitor Paes; Oliveira, Renata Barbosa de; Labanca, Renata Adriana

    Abstract in English:

    Diabetes mellitus is a chronic disease resulting in oxidative stress that promotes tissue damage. The appearance of this disease is highly related to lifestyle and food of the population, being of great interest to search for a dietary supplement that can also act by reducing oxidative alterations. Based on the broad range of biological activity of thiazole derivatives, this work aimed to evaluate the in vitro antioxidant activity of a novel hydrazine-thiazole derivative and studies in vivo. In in vivo experiments, the liver extracts of healthy and diabetic Wistar rats were used, with analysis to determine the enzymatic activity of SOD, CAT, GPx, and GR, and determination of lipid peroxidation. Finally, in the blood of these animals, biochemical parameters were evaluated. Statistical evidence of changes caused in liver enzymes and liquid peroxidation was not detected; however, these parameters were also not changed between control groups with and without diabetes. On the other hand, concerning biochemical parameters, significant differences were detected in uric acid, alkaline phosphatase, ALT, and urea, indicating a possible antioxidant protective role of such substances in the liver and kidney of diabetic animals that could be acting by means other than that commonly reported in the literature.
  • To be or not to be a carcinogen; delving into the glyphosate classification controversy Original Article

    Paumgartten, Francisco José Roma

    Abstract in English:

    The International Agency for Research on Cancer (IARC) placed the most widely used herbicide glyphosate (GLY) into the category 2A (probably carcinogenic to humans), a classification questioned by experts from academia and industry. This article critically appraised the epidemiological and experimental data that led the IARC working group (WG) to consider GLY a probable human carcinogen and the ensuing controversy. An association of GLY with non-Hodgkin lymphoma was suggested by some observational studies. A non-causal explanation for this weak association, however, cannot be excluded. Contrary to WG’s view, long-term rodent assays yielded no convincing evidence that GLY is carcinogenic. The mechanistic evidence remains elusive as well. Bacterial reverse mutation tests (including tester strains sensitive to oxidative mutagens) were clearly negative, and so were rodent genotoxicity assays by oral route. Tests with mammalian cells in vitro yielded conflicting results at high (cytotoxic) concentrations of GLY-based formulations. Conflicting results were also obtained when high doses of GLY-based herbicides were administered to rodents by the intraperitoneal route. Such high doses are unlikely to be attained in realistic scenarios of exposure. Finally, the IARC classification is based on a conjectural hazard, and rational public health interventions must be based on estimated risks.
  • Toxicity assessment of the alcoholic leaves extract of Reinwardtia indica Original Article

    Upadhyay, Prabhat; Shukla, Rashmi; Tiwari, Kavindra Nath; Dubey, G P; Mishra, Sunil Kumar

    Abstract in English:

    The present study aimed to evaluate the safety of the alcoholic leaves extract of Reinwardtia indica in Charles foster rats through an acute and sub-acute oral administration.For assessment of acute oral toxicity test, ratswere orally treated with single dose of the alcoholic leaves extract of Reinwardtia indica at the doses of 50, 250, 500, 1000 2000 and 5000 mg/kg. In sub-acute toxicity study, using the OECD guidelines no. 407, the extract was administered at the doses of 50, 250, 500, 1000, 2000 mg/kg/day for 28 consecutive days and at the dose of 2000 mg/kg satellite group also used for 6 weeks.In acute toxicity above mentioned doses neither showed mortality nor exterior signs of toxicity. In sub-acute, study no significant changes found in haematological and biochemical level ofthe treated rat after 14 days and 28 days in comparison to control. The histopathology of rat brain, kidney, liver, and heart also showed the no cellular changes after extract treated rat.The alcoholic leaves extract of Reinwardtia indica was found non-toxic in single drug dose administration up to 5000 mg/kg (acute study) and in sub-acute administration up to 2000 mg/kg.
  • Curcumin combining with si-MALAT1 inhibits the invasion and migration of colon cancer SW480 cells Original Article

    Wei, Dai; Yun, LI Shi; Dejun, Xiao; Cong, Liu; He, Jin-Hua; Yan, Lin

    Abstract in English:

    To study the effect of small interfering RNA targeting metastasis-associated lung adenocarcinoma transcript1 (si-MALAT1) combining with curcumin on the invasion and migration abilities of human colon cancer SW480 cells, and to explore the involved molecular mechanism. The recombinant lentiviral vector expressing si-MALAT1 was constructed, and its titer was determined by gradient dilution method. The colon cancer SW480 cells with stable expression of si-MALAT1 was established, followed by treatment with curcumin at different concentrations. The effect of curcumin or si-MALAT1 alone and the combination of the two on the cell activity was detected by MTT assay. The cell invasion and migration abilities were detected by transwell and scratch-wound assay. The relative expression level of MALAT1 was detected by RT-qPCR. The protein expression was determined by Western blot analysis. The IC50 of curcumin alone was 77.69 mmol/L, which was 51.17 mol/L when combined with curcumin and random sequence. The IC50 of curcumin was 30.02 mmol/L when combined with si-MALAT1. The increased susceptibility multiples was 2.58. The wound healing rates were 30.9% and 67.5% after treatment with si-MALAT1 combined with curcumin for 24 hrs and 48 hrs, respectively. The numbers of invasion cells were 200±12, 162±13, 66±8, 53±4 and 16±3 after treatment with si-MALAT1 combined with curcumin for 48 hrs. The relative expression level of lncRNA-MALAT1 in the curcumin group was 68%, and the relative expression level of lncRNA-MALAT1 in si-MALAT1group was 56%, and that for the combination treatment group was about 21%. The protein expression levels of β- catenin, c-myc and cyclinD1 were significantly down-regulated upon treatment with certain concentration of si-MALAT1 alone or combined with curcumin.si-MALAT1 could significantly inhibit the invasion and migration of SW480 cells by enhancing the sensitivity of SW480 cells to curcumin. The mechanism involved mignt be related to the down-regulation of β-catenin, c-myc and cyclinD1 proteins.
  • Ocotea nutans (Nees) Mez (Lauraceae): chemical composition, antioxidant capacity and biological properties of essential oil Original Article

    Betim, Fernando Cesar Martins; Oliveira, Camila Freitas de; Souza, Angela Maria de; Szabo, Ellis Marina; Zanin, Sandra Maria Warumby; Miguel, Obdulio Gomes; Miguel, Marilis Dallarmi; Dias, Josiane de Fátima Gaspari

    Abstract in English:

    The present study was undertaken to assess the potential uses of the essential oil obtained from Ocotea nutans (Nees) Mez. The hydrodistilled essential oil from O. nutans leaves was analyzed by gas chromatography-mass spectrometry. Fifty-eight compounds representing 87,29% of the total leaf essential oil components were identified, of which biciclogermacrene(11.41%), germacrene-D (4.89%), bisabolol-11-ol(3.73%) and spathulenol (3.71%) were the major compounds. The essential oil from O. nutans were tested for antibacterial activity using the minimum inhibitory concentracion (MIC) method, Artemia salina method, larvicidal activity in Aedes aegypti, and antioxidant capacity.The antioxidant activity measured by the phosphomolybdenum complex and Prussian blue method had positive results. The minimum inhibitory concentration for the microorganisms tested allowed moderate inhibitionfor Enterococcus faecalis (MIC=500 µg/mL). Artemia salina were toxic to the organisms in the study (LC50= 71,70 μg /mL). The essential oil showed remarkable larvicidal activity potencial (LC50= 250 µg/mL). The present results showed thatO. nutans essential oil has potential biological uses.
  • Design and characterization of nanocarriers loaded with Levofloxacin for enhanced antimicrobial activity; physicochemical properties, in vitro release and oral acute toxicity Original Article

    Siafaka, Panoraia; Okur, Mehmet Evren; Ayla, Şule; Er, Sevda; Cağlar, Emre Şefik; Okur, Neslihan Üstündağ

    Abstract in English:

    Inorganic and carbon based nanomaterials are widely used against several diseases, such as cancer, autoimmune diseases as well as fungi and bacteria colonization. In this work, Santa Barbara Amorphous mesoporous silica (SBA), Halloysite Nanotubes (HNTs) and Multiwalled Carbon Nanotubes (CNTs) were loaded with fluoroquinolone Levofloxacin (LVF) to be applied as antimicrobial agents. The prepared via adsorption nanocarriers were characterized by Fourier-Transformed Spectroscopy, Scanning Electron Microscopy as well as High Pressure liquid Chromatography. In vitro release studies were carried out using Simulated Body Fluid at 37oC and data analyzed by various kinetic models showing slow dissolution over 12-24 hours. Antimicrobial studies showed improved antibacterial activity against Escherichia coli, Enterococcus faecalis, Listeria monocytogenes, Staphylococcus aureus, and Staphylococcus epidermidis compared to neat nanomaterials. CNTs were found to be the most promising candidates for LVF delivery and they were chosen to be further studied for their acute oral toxicity and histopathological examination using C57/Black mice. Histological examination depicted that drug loading did not affect mice organs morphology as well as hepatocyte degeneration, central vein degeneration and parenchymal necrosis scores. To conclude, the prepared nanomaterials present significant characteristics and can act as antimicrobial drug carriers; CNTs found to be safe candidates when orally fed to mice.
  • Study on influence of polymer and surfactant on in vitro performance of biodegradable aqueous-core nanocapsules of tenofovirdisoproxil fumarate by response surface methodology Original Article

    Srikar, Grandhi; Rani, Avula Prameela

    Abstract in English:

    The major objective of this study was to investigate the effect of biodegradable polymer type and surfactant concentration on various characteristics viz. particle size, entrapment efficiency and drug release rate constant of aqueous core nanocapsules (ACNs) containing tenofovirdisoproxil fumarate. In this study, the nanocapsules were prepared by modified multiple emulsion technique with biodegradable polymers viz. poly(lactide-co-glycolide) of two different grades (PLGA RG502H and PLGA RG503H) and poly lactic acid (PLA R203H); and the surfactant employed was span 80. The experiments were designed under response surface methodology by employing the Design Expert software. Entrapment efficiency, particle size and drug release rate constant were taken as response variables. The prepared nanocapsules were subjected to characterization studies and the obtained results were statistically analyzed by Analysis of Variance (ANOVA) for response surface 2-Factorial Interaction model. ANOVA studies showed that the influence of both factors on all the response variables were significant at p<0.05. The optimized formulation was found to have the entrapment efficiency of 71.58%, particle size of 252.41 nm and the drug release rate constant of 0.045 h-1; thus, indicating that the ACNs were obtained with finest characteristics. SEM studies showed that the particles were spherical.
  • Anticonvulsant evaluation of 2-pyrazolines carrying naphthyl moiety: An insight into synthesis and molecular docking study Original Article

    Nusrat, Birjees; Siddiqui, Nadeem; Sahu, Meeta; Naim, Mohd. Javed; Shahar Yar, Mohammad; Ali, Ruhi; Ozair, Alam

    Abstract in English:

    A series of N-substituted-3-(napthalen-2-yl)-5-substituted phenyl-4,5-dihydropyrazole-1-carbothioamide derivatives (4a-n) were synthesized with the view of structural requirements of pharmacophore for potential anticonvulsant agents. The synthesized compounds were assayed intraperitoneally (i.p.) and subcutaneously (s.c.) in mice against seizures induced by MES and scPTZ methods, respectively.Neurologic deficit was evaluated by rotarod method. Among the tested compounds, 4g, 4i, 4j and 4n emerged as the most active molecule in the MES model at a dose of 30 mg/kg at 0.5h comparable to standardscarbamazepine and phenytoin. In the scPTZ test,4e and 4l were found to be most active compounds at the lowest dose of 30 mg/kg at 0.5h, in the management of the convulsive disorder. Molecular docking studies of the titled compounds were also donewith 3D crystal structure of human cytosolic branched chain amino transferase (hBCATc) enzyme and compound 4e was found to have five hydrogen bond interactions with the most important active site residues.In neurotoxicity studies, except compounds 4b, 4c, 4h and 4k, rest of the compounds showed no sign of toxicity.
  • Protective effects of salidroside on chronic heart failure in rats and the underlying mechanisms Original Article

    Zhang, Chengxi; Pan, Sinian; Tang, Leile; Ling, Yesheng; Zhou, Xiaojing; Feng, Wei

    Abstract in English:

    The present study aimed to investigate the protective effects of salidroside on chronic heart failure (CHF) in rats and to explore the underlying mechanisms. One hundred SD rats were randomly divided into sham-operated, model, and low-, medium- and high-dose salidroside groups. The CHF model was established in later 4 groups. The later 3 groups were intragastrically administrated with 6, 12 and 24 mg/kg salidroside, respectively, once a day, for continuous 4 weeks. Finally, the serum levels of brain natriuretic peptide (BNP) and interleukin 6 (IL-6), cardiac function indexes, and expression levels of myocardial cysteinyl aspartate-specific proteinase (Caspase)-3, Caspase-9, matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) protein were determined. Results showed that, after treatment, compared with model group, in high-dose salidroside group the heart function indexes were significantly improved (P < 0.05), the serum levels of BNP and IL-6 were significantly decreased (P < 0.05), the expression levels of myocardial Caspase-3, Caspase-9 and MMP-1 protein were significantly decreased (P < 0.05), and the expression level of TIMP-1 protein was significantly increased (P < 0.05). In conclusion, salidroside has obvious protective effects on CHF in rats. The mechanisms may be related to its regulation of cardiomyocyte apoptosis and ventricular remodelingregulation related protein expressions.
  • Synthesis of new 2-{2,3-dihydro-1,4-benzodioxin-6-yl[(4-methylphenyl) sulfonyl]amino}-N-(un/substituted-phenyl)acetamides as α-glucosidase and acetylcholinesterase inhibitors and their in silico study Original Article

    Abbasi, Muhammad Athar; Riaz, Sajid; Rehman, Aziz-ur-; Siddiqui, Sabahat Zahra; Shah, Syed Adnan Ali; Ashraf, Muhammad; Lodhi, Muhammad Arif; Khan, Farman Ali

    Abstract in English:

    The aim of the present research work was to investigate the enzyme inhibitory potential of some new sulfonamides having benzodioxane and acetamide moieties. The synthesis was started by the reaction of N-2,3-dihydrobenzo[1,4]-dioxin-6-amine (1) with 4-methylbenzenesulfonyl chloride (2) in the presence of 10% aqueous Na2CO3 to yield N-(2,3-dihydrobenzo[1,4]-dioxin-6-yl)-4-methylbenzenesulfonamide (3), which was then reacted with 2-bromo-N-(un/substituted-phenyl)acetamides (6a-l) in DMF and lithium hydride as a base to afford various 2-{2,3-dihydro-1,4-benzodioxin-6-yl[(4-methylphenyl)sulfonyl]amino}-N-(un/substituted-phenyl)acetamides (7a-l). All the synthesized compounds were characterized by their IR and 1H-NMR spectral data along with CHN analysis data. The enzyme inhibitory activities of these compounds were tested against a-glucosidase and acetylcholinesterase (AChE). Most of the compounds exhibited substantial inhibitory activity against yeast a-glucosidase and weak against AChE. The in silico molecular docking results were also consistent with in vitro enzyme inhibition data.
  • Preparation and characterization of novel, mucoadhesive ofloxacin nanoparticles for ocular drug delivery Original Article

    Taghe, Shiva; Mirzaeei, Shahla

    Abstract in English:

    The efficacy of conventional ocular formulations is limited by poor corneal retention and permeation, resulting in low ocular bioavailability. Mucoadhesive chitosan (CS)/ tripolyphosphatesodium (TPP) and chitosan (CS)/ tripolyphosphatesodium (TPP)-alginate (ALG) nanoparticles were investigated for the prolonged topical ophthalmic delivery of ofloxacin. A modified ionotropic gelation method was used to produce ofloxacin-loaded nanoreservoir systems. The ofloxacin-loaded CS/TPP and CS/TPP-ALG nanoparticles were characterized for particle size, morphology, zeta potential, encapsulation efficiency, subsequent release and corneal penetration study. The designed nanoparticles have a particle size from 113.8 nm to 509 nm and zeta potential from 16.2 mV to 40.3 mV and encapsulation efficiency values ranging from 19.7% to 33.1%. Nanoparticles revealed a release during the first hours, followed by a more gradual drug release. The ofloxacin-loading CS/TPP or CS/TPP-ALG NPs developed are pronounced penetration enhancing effect as compared to OFX solution (5-6.5 times). Thus, these nanoparticles have a strong potential for ocular drug delivery.
  • Amphotericin-B and vancomycin-loaded chitosan nanofiber for antifungal and antibacterial application Original Article

    Karimi, Soroush; Moradipour, Pouran; Azandaryani, Abbas Hemati; Arkan, Elham

    Abstract in English:

    In the present study, a mucoadhesive non-woven fiber mat (d= 116 nm) was fabricated by the electrospinning method using chitosan (80% Wt), polyethylene oxide (10% Wt), cysteine (4% Wt) and drugs (6% Wt), respectively. In addition, a comparative study was conducted to define effect of drugs and mucoadhesive agent on the nanofiber formation. FTIR, SEM, DSC and DMA were used to investigate the chemical and physical properties of the nanofibers. In vitro release of the drugs was assessed over a 48-hour period by the total immersion method. Release data were fitted to kinetic models, including the zero-order, first-order, Higuchi matrix, and Hixson-Crowell. Zone inhibition investigations were used to describe the inhibition content of vancomycin and amphotericin B loaded in the mats. The SEM images displayed a slight decrease in the fiber diameter with adding drugs and mucoadhesive agents. FTIR spectra confirmed that any undesirable reaction between VAN-AMB and CS-PEO was not observed. DSC test recognized the uniform distribution of drugs in the polymeric bead of the fiber without any crystal form. The elasticity modulus of the nanofiber was in an acceptable range for oral mucosa (approximately 5 Mpa). The results indicated that biodegradable mucoadhesive nanofibrous membranes released high concentrations of VAN in the first 24 hours, but the AMB release was affected in more controlled phenomena.
  • How much to invest in glycemic control of a patient with diabetes mellitus type 2? A constant dilemma for the Brazilian Public Health System (SUS) Original Article

    Gonçalves, Ana Carolina de Oliveira; Cazarim, Maurilio de Souza; Sanches, Cristina; Pereira, Leonardo Régis Leira; Baldoni, André de Oliveira

    Abstract in English:

    Diabetes mellitus type 2 (DM2) affects millions of people worldwide and causes several complications for the patient, consuming large sums of financial resources from the health services. This study aims to estimate the financial investment of DM2 treatment for glycemic control of the patient, from the point of view of the municipal Public Health System (SUS). The Delphi technique was used to validate the opinion of a team of judges, specialists in DM2, and health service managers, on the investment necessary for glycemic control of patients with DM2 through the application of questionnaires. In order for the patient to achieve glycated hemoglobin (A1c) < 7%, an investment of US$ 2,419.06 (value/patient/year) is necessary. As the value of A1c increases, investment is reduced. This result reveals the intention to allocate resources for the prevention of DM2 and its complications.
  • Effect of iguratimod on diclofenac metabolism by CYP2C9 in rats and human recombinant CYP2C9 yeast cells Original Article

    Usman, Muhammad; Zhen-Han, Zhu; Ze-Na, Chang; Jun-Ping, Han; Wen, Qian; Chang-Qing, Yang; Miyu, Nishikawa; Toshiyuki, Sakaki

    Abstract in English:

    Iguratimod (IGU, also known as T-614), a novel disease modifying antirheumatic drug intended to cure patients with rheumatoid arthritis (RA). The purpose of this study is to evaluate the effect of IGU on the pharmacokinetics of CYP2C9 probe drug diclofenac and its metabolite 4′-hydroxy diclofenac in vivo and in vitro. In in vivo experiments, 24 rats were randomly assigned to three groups consisting of the control group (Normal saline), low dose IGU group (10 mg/kg) and high dose IGU group (30 mg/kg). Blood samples were collected from orbital sinuses vein before 1 hour and serial times of giving diclofenac (15 mg/kg) to all the rats. Plasma concentration of diclofenac and its metabolite 4´-hydroxy diclofenac were assayed by high performance liquid chromatography. Pharmacokinetic parameters were assessed by Winnonlin 6.4 pharmacokinetic software. Moreover, in vitro studies were performed in recombinant human CYP2C9 yeast cell system. IGU at low dose showed no significant differences in the pharmacokinetic parameters of diclofenac and 4-hydroxy diclofenac in vivo when compared with control group (p>0.005). However, at the high dose of IGU, the pharmacokinetic parameters of 4´-hydroxy metabolite of diclofenac increase in half-life (T1/2) and mean area under the curve (AUC0→24), while a decrease in mean clearance (CL, mL/h/kg) and volume of distribution Vz (mL/kg). In addition, in in vitro study, high doses of IGU reduces the metabolism rate of diclofenac. IGU at high dose significantly increase the pharmacokinetics parameters of 4´-hydroxy diclofenac in rats. Additionally, it also showed the potent inhibitory effect on diclofenac metabolism in recombinant human CYP2C9 yeast cells.
  • Midazolam and haloperidol for palliative sedation: physicochemical stability and compatibility of parenteral admixtures Original Article

    Estan-Cerezo, Gabriel; Rodríguez-Lucena, Francisco José; Chirivella, Carmen Matoses; Jiménez-Pulido, Inmaculada; García-Monsalve, Ana; Navarro-Ruiz, Andrés

    Abstract in English:

    This study was done to determine the time while the binary admixtures with midazolam and haloperidol drugs are administered by perfusion to the patients in the clinical routine. Samples with different concentrations of both drugs were prepared following the usual clinical practice. Solvents used were 0.9 % sodium chloride solution and 5% dextrose, and viaflo plastic bags were used as the containers of the admixtures. Samples were not protected from light and were stored at 20 ºC or at 4 ºC. Compatibility and physicochemical stability were studied by visual inspection, turbidity measurement, pH determination and ultraviolet detection high performance liquid chromatography (UV-HPLC) was used to determine midazolam and haloperidol concentrations. The assay was validated following the FDA and EMA guidelines. Darunavir was used as internal standard (IS). For the studied admixtures, turbidity measurements and pH determinations showed little changes in function of the time. Haloperidol and midazolam concentrations determined by HPLC are within the acceptable range of drug concentrations, which are considered stable for four days in case of admixtures stored at 20 ºC and for seven days for refrigerated admixtures. Taking into account the microbiological risk matrix, the compatibility and the chemical and microbiological stability of the midazolam and haloperidol in the co-administered admixtures in viaflo plastic bags with 0.9 % sodium chloride solution and 5% dextrose can be set as 48 hours when samples are stored at 20 ºC and one week if they are refrigerated.
  • Identifying probiotic characteristics of Lactobacillus crispatus isolated from the vagina Original Article

    Er, Sevda; Erim, Ümit Can; Koç, Fatma; Kıvanç, Merih

    Abstract in English:

    Lactobacilli prevent overproduction of pathogenic microorganisms and contribute protecting vaginal microbiota. Many probiotic microorganisms are categorized as Lactic Acid Bacteria. In this study, it was aimed identifying probiotic characteristics of Lactobacillus crispatus isolated from the vagina of a healthy woman. For this purpose, lactic acid, hydrogen peroxide and proteolytic activity quantities and auto-aggregation, co-aggregation and hydrophobicity abilities of Lactobacillus crispatus, which has been isolated and identified by 16s rRNA sequence analysis, were determined. Additionally, bile salt and acid resistance, along with antibiotic susceptibility of Lactobacillus crispatus were analyzed by the end of 3 hours. Lactic acid, hydrogen peroxide and proteolytic activity quantities of Lactobacillus crispatus were measured 2.275%, 0.334±0.075 µg/mL and 2.131±0,000 mg/mL respectively. The findings include existence of co-aggregation and auto-aggregation ability, but not hydrophobicity. By the end of 3 hours, the viability was preserved in 0.1% and 0.3% bile salt medium and, at pH 3. L. crispatus exhibited resistance to methicillin, metronidazole, oxacillin, and sulfamethoxazole + trimethoprim, but the bacteria exhibited susceptibility to tested the other antibiotics. This study will make an important contribution to the literature about probiotic characteristics of L. crispatus and our strain isolated from the vagina might be considered as a candidate probiotic.
  • Development and in vitro/in vivo evaluation of thermo-sensitive in situ gelling systems for ocular allergy Original Article

    Güven, Umay Merve; Berkman, Murat Sami; Şenel, Behiye; Yazan, Yasemin

    Abstract in English:

    Ocular allergy is one of the most common disorders of the eye surface. Following diagnosis this condition is typically treated with preparations containing antihistamines. However, anatomy of the eye and its natural protective mechanisms create challenges for ocular drug delivery. Rapid elimination of antihistamine substances due to short residency times following application can lead to insufficient treatment of ocular allergies. With this in mind, the aim of this study was to prepare a controlled ocular delivery system to extend the retention time of olopatadine hydrochloride (OLO) and in doing so to reduce the need for frequent application. We developed extended-release ocular in situ gelling systems for which in vivo retention times were determined in sheep following in vitro characterization and cytotoxicity studies. In vivo results were then compared to commercially available Patanol eye drops. the transparent gels formulated using appropriate amounts of polymers and having longer ocular retention times appear to be a viable alternative to commercially available eye drops.
  • Evaluating the discriminatory power of a dissolution assay for rosuvastatin calcium capsules: Solid-state properties and dissolution media Original Article

    Ângelo, Marilene Lopes; Ruela, André Luís Morais; Ferreira, Anna Clara Marques; Ramos, Marcus Vinicus de Faria; Montanari, Cristina Martiniano; Silva, Lucélia Magalhães da; Araújo, Magali Benjamim de

    Abstract in English:

    We propose to evaluate the dissolution properties of rosuvastatin calcium (ROSC) capsules in different media to characterize the discriminatory power of the assay method. Dissolution assays were performed in media with different pH, and including the surfactant sodium dodecyl sulfate (SDS). Several immediate-release formulations were manufactured using the commercial raw material characterized as amorphous solid. The hydrophobic adjutant magnesium stearate was employed in some formulations due to its negative effect in the wettability and dissolution efficacy of solid dosages. These formulations showed the lower dissolution efficacy values in media without surfactant; however, when SDS was added to the medium, the dissolution efficacy increased, and the discriminatory power was lost. In spite of micellar solubilization does not increase the ROSC solubility, it modifies the discriminatory power of the assay method, increasing the wettability of the powder mixtures. The crystalline form M of ROSC was recrystallized in our laboratory, and it showed lower solubility in water than amorphous solid. However, its dissolution properties were not influenced by SDS. These results are important to develop dissolution assays for other hydrophilic drugs with increased water solubility, once that dissolution media with surfactants increase the wettability of the formulations, leading to an overrated dissolution rate.
  • Access and use of medicines by elderly individuals with dementia Original Article

    Barros, Débora Santos Lula; Silva, Dayde Lane Mendonça da; Leite, Silvana Nair

    Abstract in English:

    The objective is to reveal the difficulties concerning the access and use of medicines by elderly individuals with dementia, reported by their caregivers. This qualitative study applied the participant observation method during pharmaceutical appointments performed in a specialized geriatrics service of the University Hospital of Brasília. Caregivers reported facing difficulties regarding the itinerary for medicines access in public pharmacies, as well as the high cost of these technologies in private establishments. Psychiatric symptoms, cognitive deficits, behavioral changes, apraxia, dysphagia, among other clinical manifestations of dementia syndromes, incapacitates the elderly for self-responsibility concerningthe use of drugs, which accentuates the complexity of medicines administration within the care process. In conclusion, it is fundamental to recognize caregivers’ role in promoting the rational use of medicines, and so this theme should be highlighted within the pharmaceutical services context.
  • Influence of preparation procedures on the phenolic content, antioxidant and antidiabetic activities of green and black teas Original Article

    Almeida, Tânia Santos de; Araújo, Maria Eduarda Machado; Rodríguez, Lucía González; Júlio, Ana; Mendes, Beatriz Garcia; Santos, Rui Miguel Borges dos; Simões, José Artur Martinho

    Abstract in English:

    The influence of common tea preparation procedures (temperature, infusion time, consumption time interval and tea bag/loose-leaf) and the type of water used, on the total phenolic content (TPC), the radical scavenging activity and the α-glucosidase inhibitory activity were assessed. Higher TPC and antioxidant activity were obtained when using lower mineralized waters. Tea bags also evidenced higher antioxidant activity than loose-leaf samples. Under the same conditions (90 ºC and five minutes of infusion time) green tea contains almost twice the quantity of polyphenols and the free radical scavenging ability of black tea. In the α-glucosidase assay all infusions were active (97-100 %). Furthermore, HPLC allowed to identify some of the polyphenols present in both teas and to monitor their composition change with time. After twenty-four hours, the antioxidant activity was maintained without significant changes, but a small decrease in enzyme inhibition was observed, although this activity was still very high.
  • Antifungal effect of sesame medicinal herb on Candida Species: original study and mini-review Original Article

    Lavaee, Fatemeh; Moshaverinia, Maryam; MalekHosseini, Seyed Ali; Jamshidzade, Akram; Zarei, Maryam; Jafarian, Hadis; Haddadi, Pardis; Badiee, Parisa

    Abstract in English:

    The aim of this study was to evaluate the antifungal susceptibility patterns of three antifungals, methanolic extracts and N-hexane oil of sesame seeds on C. albicans and C. glabrata, isolated from oral cavity of liver transplant recipients. The results were compared with other reports to develop a mini review as well. Candida species were isolated from liver transplant recipients. To evaluate the antifungal activity of sesame seed oil and methanolic extract, fluconazole, caspofungin and nystatin, the corresponding minimum inhibitory concentrations were determined by CLSI M27-A3 standard method. Minimum fungicidal concentration was also evaluated. The most prevalent species was C. albicans, followed by C. glabrata. Findings indicated sensitivity to antifungal agents and resistance to methanolic extract and N-hexane oil for all C. albicans and C. glabrata isolates. The rate of Candida colonization in the oral cavity of liver transplant recipients was high. Our results revealed that the methanolic and N-hexan extracts of sesame seeds are not effective on C. albicans and C. glabrata species, isolated from the patients. The sesame seed oil pulling and mouthwash cannot effectively cleanse and remove the Candida species in the mouth. Investigation of other medicinal plants or other parts of sesame like leaves and roots are suggested.
  • Assessing the overall medication use by elderly people in a Brazilian hospital using the start/stopp criteria version 2 Original Article

    Pereira, Thayná Ferreira Furtado; Soares, Alessandra de Sá; Trevisol, Daisson José; Schuelter-Trevisol, Fabiana

    Abstract in English:

    To estimate the frequency of the use of medicines listed in the Screening Tool to Alert Doctors to the Right Treatment (START) and Screening Tool of Older Person’s Prescriptions (STOPP) criteria version 2 among the elderly. A cross-sectional study was conducted on elderly who were attended in medical clinic and cardiology sectors in a hospital in southern Brazil attended at a hospital from February through September 2016. A data-collection tool was used to obtain information on variables, such as demographic and clinical data, and medications used before and during the hospitalization period. The adequacy of the medicines taken was examined with regard to omission (START) or inappropriate use (STOPP). This study was approved by the Research Ethics Committee of the University of Southern Santa Catarina. A total of 307 subjects were included in the final sample. The mean age was 75.2 years (SD = 8; range 65-102). Of the total, 93.5% had had at least one potential prescribing omission (PPO) listed in the START criteria, whereas 95.4% used at least one medicine of the STOPP criteria. PPO was significantly associated with lower mean age (74.9 years, SD = 7.9 versus 79.0 years, SD = 8.8) among the elderly who did not have PPOs detected by the START criteria (p-value=0.03). Furthermore, PPO was associated with longer hospital stay (18 versus 9 days; p-value=0.03). This study revealed inadequate prescription affecting 99.3% of the participating patients. To the best of our knowledge, this was the first to use the START and STOPP criteria, version 2, in Brazil.
  • Essential oil of the leaves of Eugenia sulcata preserve myocardial contractility and does not present immunotoxicity Original Article

    Santos, Karolina Torres; Silva, Fabricio Ocampo da Luz e; Schneider, Leandro Alves; Santos, Carlos Eduardo Rangel dos; Silva, Sue Elle Berro da; Fernandes, Maquelen Blanco; Rocha, Leandro; Oliveira, Luís Flávio Souza de; Machado, Michel Mansur; Moreira, Cleci Menezes

    Abstract in English:

    The essential oil of the leaves of Eugenia sulcata, in the Myrtaceae family, has a demonstrated antihypertensive effect, but its effects on heart muscle and its toxicity have not yet been elucidated. Little chemical or biological data are available for E. sulcata, whether emphasizing the beneficial effects or the pharmacological security of this species. This study aims to evaluate myocardial contractility and to analyze angiotensin converting enzyme (ACE) and myosin ATPase activities associated with use of this essential oil. In addition, we evaluated the immunotoxicity of E. sulcata essential oil. Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) were treated daily for 30 days (10 mg/kg of oil) to evaluate the isometric force of the papillary muscle, ACE measured by fluorimetry, and myosin ATPase activities by inorganic phosphate. Lymphocyte cultures were used to evaluate cytotoxicity, DNA damage, and mutagenicity of the essential oil. The results demonstrate that the treatment did not change the cardiac contraction force and did not alter the functioning of the sarcoplasmic reticulum, extrusion of the membrane calcium, or modify the membrane calcium channels or β-adrenergic receptor activity. Tetanic contractions were potentiated in the SHR animals. Myosin ATPase activity was also increased in the SHR animals. Cardiac ACE activity was reduced in both animal strains, and the serum ACE was reduced only in the SHR animals. The essential oil did not cause cytotoxicity or mutagenicity and presented low DNA damage. Our results demonstrated that the essential oil does not change myocardial contractility and does not present relevant immunotoxicity.
  • Vasorelaxant activity and acute toxicity of the ethanolic extract of Zanthoxylum rhoifolium Lam leaves Original Article

    Silva, Joliane Carvalho; Azevedo, Pedro Simão da Silva; Souza, Fabiana de Moura; Aragão, Kalynca Kayla Viana; Sabino, Carla Kelly Barroso; Carvalho, Gabriela Dantas; Morais, Ilmara Cecília Pinheiro; Mendes, Marcelo Bezerra; Chaves, Mariana Helena; Oliveira, Aldeídia Pereira de

    Abstract in English:

    The study evaluated the vasorelaxant effect induced by the ethanolic extract of the leaves of Zanthoxylum rhoifolium Lam (EEtOH-Zr/leaves). Wistar rats were treated with the leaf extract containing a single dose of 2,000 mg / kg, v.o. After 14 days, the animals were anesthetized for blood collection and subsequent analysis of the biochemical parameters; they were then euthanized (sodium pentobarbital-100 mg/kg, i.p.) for the removal and morphological analysis of the heart, lung, liver and kidney. The vasorelaxation activity the and vascular reactivity of EEtOH-Zr/leaves were evaluated on artery mesenteric rings isolated from rats. The extract showed no signs of toxicity and no significant difference in the values of the biochemical parameters between the control group and the group of treated animals. In the evaluation of pharmacological activity in the smooth muscle, the EEtOH-Zr/leaves caused vasorelaxant effect on the tonic contraction induced by phenylephrine in mesenteric artery preparations in the presence (pD2=2.17±0.05 µg/mL; Emax=99.8±5.2%) and absence (pD2=2.14±0.05 µg/mL; Emax=95.3±6.4%) of the vascular endothelium. Oral administration of EEtOH-Zr/leaves reduced the contraction induced by the cumulative addition of PHE. It is concluded that the EEtOH-Zr/leaves promote vasorelaxation and reduce vascular reactivity of adrenergic alpha-1 agonist in the mesenteric artery. The results did not show toxic effects of the extract.
  • Development of a generic method for the determination of proton-pump inhibitors by capillary zoneelectrophoresis Original Article

    Papp, Lajos Attila; Gyéresi, Árpád; Hancu, Gabriel; Mircia, Eleonora; Kelemen, Hajnal

    Abstract in English:

    A generic capillary zone electrophoresis method was developed for the analysis of four proton pump inhibitors: omeprazole, pantoprazole, lansoprazole and rabeprazole. During preliminary analysis screening of phosphate buffers at different pH levels was performed, in order to determine the optimum pH domain suitable for the simultaneous determination of all studied compounds. A face centered central composite design was employed for the optimization of separation conditions. The effect of buffer concentration, pH and applied voltage was studied; resolution between peaks and migration time of the last compound were considered as responses. Other factors as system temperature, injection parameters, capillary length, were held constant during the optimization process. The optimized conditions consisted of 40mM phosphate background electrolyte at pH 5.0, +25 kV applied voltage and 20 °C temperature. The migration order of the analytes was as follows: rabeprazole, omeprazole, lansoprazole and pantoprazole. Full resolution of all analytes was achieved within 9 minutes. The method was validated and proved to be suitable in terms of repeatability, sensitivity, linearity, accuracy and robustness. Determinations from commercially available pharmaceutical formulation were performed for omeprazole; good reproducibility and recovery were obtained.
  • Metabolic dysregulation in early onset psychiatric disorder before and after exposure to antipsychotic drugs Original Article

    Shah, Rehmat; Subhan, Fazal; Sultan, Syed Muhammad; Haq, Matiul; Ahmad, Hussain; Khan, Qasim Riaz; Ali, Gowhar; Ullah, Sami; Ullah, Ihsan

    Abstract in English:

    Antipsychotic Drugs (APDs) are being widely prescribed to treat various disorders, including schizophrenia and bipolar disorder; however, abnormal glucose metabolism and weight gain have been reported with Atypical Anti-Psychotic drugs (AAPDs) that can lead to insulin-resistance and type 2 diabetes mellitus. The study was designed to assess various biochemical parameters including insulin and blood sugar before and after exposure to APDs in order to exclude the involvement of psychiatric disorders and certain other factors in metabolic dysregulations. Fifty seven APDs-naïve patients with first episode psychosis were divided into six groups who received olanzapine, quetiapine, risperidone, aripiprazole, haloperidol or combination of olanzapine with escitalopram and haloperidol. The serum samples were taken before the intake of the first dose and then on follow-up. Decrease in the level of elevated insulin and glucose was observed post-treatment in some patients, while others were observed whose insulin and glucose levels increased post-treatment, yet some patients did not show any disturbance in the insulin and glucose levels. It is concluded that psychiatric disorders by itself, narcotics, cigarette smoking and use of oral snuff may be also be implicated in metabolic dysregulations. The effects of APDs on insulin and glucose in healthy volunteers might be different than in patients with psychiatric disorders.
  • Antinociceptive local activity of 4-allyl-1-hydroxy-2-methoxybenzene (eugenol) by the formalin test: an anti-inflammatory effect Original Article

    Lugo-Lugo, Daniela Elizabeth; Pozos-Guillén, Amaury de Jesús; Zapata-Morales, Juan Ramón; Rodríguez-Chong, Antonio; Rangel-López, Azahel de Jesús; Saavedra-Leos, María Zenaida; Vértiz-Hernández, Angel Antonio

    Abstract in English:

    Eugenol has been employed for decades as a condiment, an antimycotic, an antibacterial, an antiviral, and an antioxidant, and it is one of the natural analgesics most frequently utilized for pain and inflammation. Our objective was to determine the analgesic/anti-inflammatory effect of eugenol compared with diclofenac, naproxen, and tramadol using the formalin test. The formalin method was used in 6- to 10-week-old Wistar rats (weighing 250 g each) divided into six groups: saline (0.9%); formalin (5%); diclofenac (250 µg/kg); naproxen (400 µg/kg); tramadol (500 µg/kg), and eugenol (1,400 µg/kg), in the intraplantar part of the hind-end trunk of the rats, with n = 5 per group. Eugenol diminished 44.4% of nociceptive behavior in phase 1 and 48% in phase 2 (p ≤0.05 vs formalin). Eugenol was shown to be 1.14 times more effective than diclofenac, but 1.62 and 1.75 times less effective than naproxen and tramadol, respectively, in phase 1 and 1.45 times less effective than diclofenac and naproxen and 1.66 less effective than tramadol in phase 2 (p ≤0.05). These data suggest that eugenol possesses moderate activity in the acute pain phase and greater activity in inflammatory-type pain, and both effects are comparable to those produced by diclofenac and are less than the effects produced by naproxen and tramadol in the formalin test.
  • Study of erythrocytes as a novel drug carrier for the delivery of artemether Original Article

    Riaz, Muhammad Ijaz; Sarwar, Hafiz Shoaib; Rehman, Mubashir; Gohar, Umar Farooq; Raza, Syed Atif; Siddique, Muhammad Irfan; Shahnaz, Gul; Sohail, Muhammad Farhan

    Abstract in English:

    Resealed erythrocytes have been explored in various dimensions of drug delivery, owing to their high biocompatibility and inability to initiate immune response. The present research was designed to evaluate the drug delivery potential of erythrocytes by loading a hydrophobic anti-malarial drug, Artemether. Three different loading techniques were applied to achieve maximum optimized drug loading. A HPLC method was validated for drug quantification in erythrocytes. The relatively high loading was achieved using hypotonic treatment was 31.39% as compared to other two methods. These, drug loaded erythrocytes were characterized for membrane integrity via ESR showing higher ESR values for drug loaded cells as compared to normal cells. Moreover, microscopic evaluation was done to observe morphological changes in erythrocytes after successful loading which showed swollen cells with slight rough surface as compared to smooth surface of normal cells. Drug release was studied for 8 h which showed more than 80% release within 3-7 h from erythrocytes treated with different hypotonic methods. Overall, the study revealed a potential application of erythrocytes in delivery of hydrophobic drugs using hypotonic treatment as compared to other methods.
  • LC-UV method to assay raloxifene hydrochloride in rat plasma and its application to a pharmacokinetic study Original Article

    Fontana, Márcia Camponogara; Laureano, João Víctor; Forgearini, Betielli; Chaves, Paula dos Santos; Araujo, Bibiana Verlindo de; Beck, Ruy Carlos Ruver

    Abstract in English:

    A specific, precise, and accurate LC-UV method was developed and validated to assay raloxifene hydrochloride in rat plasma. Raloxifene was analyzed after liquid-liquid extraction and quantified by reversed phase liquid chromatography (C18 column) using acetonitrile and ammonium acetate buffer 0.05 M (pH 4.0) as mobile phase at a flow rate of 1 mL.min-1 and UV detection at 287 nm. Retention times of raloxifene and internal standard (dexamethasone) were approximately 11 min and 14 min, respectively. Linearity was checked for a concentration range between 25 ng.mL-1 and 1000 ng.mL-1. Intra- and inter-day precision had relative standard deviation lower than 10% and 15%, respectively. Recovery from plasma was higher than 90%. Accuracy values were 98.21%, 99.70%, and 102.70% for lower, medium, and upper limits of quantification, respectively. Limit of quantification was 25 ng.mL-1. Drug stability was analyzed at room temperature using plasma kept in a freezer at -80 °C for 45 days after processing for 6 h and three freeze-thaw cycles. The advantages of the method developed include stability under different conditions and low limit of quantification. Its applicability was confirmed by the analysis of raloxifene levels in plasma samples in a designed pharmacokinetic study in rats after intravenous administration (5 mg.kg-1).
  • Cytotoxicity and antiviral activity evaluation of Cymbopogon spp hydroethanolic extracts Original Article

    Chiamenti, Lisandra; Silva, Francini Pereira da; Schallemberger, Karoline; Demoliner, Meriane; Rigotto, Caroline; Fleck, Juliane Deise

    Abstract in English:

    Cymbopogon citratus and C. nardus are noteworthy among the several existing plant species displaying medicinal properties, due to the potential pharmacological activity of these species, including antiviral, antibacterial, antifungal and anti-trypanosomal activities. The objective of this study was to carry out in vitro toxicity tests of plant extracts from both species and analyze potential antiviral activity against Human mastadenovirus serotype 5 (HAdV-5). Two cell lines (A549 and VERO) were used and mitochondrial and lysosomal viability were determined by the MTT and neutral red assay, respectively, after two exposure times (24 hours and six days). The aim of these assays was to counteract the behavior of the extracts against the different cell lines and determine their non-toxic concentration range, in order to evaluate possible antiviral activity against HAdV-5. Plaque reduction and inhibition index of viral titer assays were performed using the maximum non-cytotoxic concentrations (MNCC) of each extract. The results indicate MNCC at 625 μg/mL for all extracts, except for Cymbopogon nardus obtained with 80% ethanol (CN80), which showed toxicity at concentrations higher than 312.5 μg/mL. CN80 was the only extract that displayed potential activity against HAdV-5, at a concentration of 75 μg/mL, becoming a candidate for extract fraction purification and/or the isolation of substances related to the observed antiviral activity.
  • Validated analytical study of the effect of Lycopene on the pharmacokinetics of Paracetamol and Chlorzoxazone in rats Original Article

    Youssef, Reem Baha-Aldeen; Fouad, Marwa Ahmed; El-Zaher, Asmaa Ahmed

    Abstract in English:

    Lycopene was reported to influence some cytochrome P450 enzymes activity. The present study investigates the effect of lycopene on the pharmacokinetics of paracetamol and chlorzoxazone. Lycopene (20 mg/kg) was intra-peritoneally administered to two groups of rats for eight consecutive days and two other groups were given vehicle. On the eighth day, chlorzoxazone and paracetamol were separately intravenously administered to a lycopene group and a control group. Blood samples were collected at different time intervals, treated and analyzed using HPLC. The HPLC method used for paracetamol analysis was based on isocratic elution using a mobile phase consisting of water: methanol, (77:23 v/v) at a flow rate 1 mL min−1, Kromasil C18 column, and UV detection at 254 nm using caffeine as internal standard. About chlorzoxazone, separation was carried out using water: acetonitrile (60: 40, v/v) as the mobile phase at a flow rate 1 mL min−1, Inertsil ODS-3 C18 column, UV detection at 283 nm and esomeprazole as internal standard. Statistical analysis of the pharmacokinetic data using student t test showed a significant increase in AUC 0-t , AUC 0-Inf and t1/2 of paracetamol (P<0.05) and of chlorzoxazone (P<0.05) in the groups pretreated with lycopene (20 mg/kg), significant increase in the volume of distribution of paracetamol (P < 0.05), but no significant difference in that of chlorzoxazone. In other words, paracetamol and chlorzoxazone showed significant decrease (P < 0.05), respectively. These results demonstrate that treatment of rats with Lycopene (20mg/kg, ip) has a significant effect on the metabolic clearance and the pharmacokinetics of both drugs.
  • Sub-chronic toxicity evaluation of Dryopteris filix-mas (L.) schott, leaf extract in albino rats Original Article

    Erhirhie, Earnest Oghenesuvwe; Ilodigwe, Emmanuel Emeka

    Abstract in English:

    This study evaluated the acute and sub-chronic toxicities of ethanol leaf extract of Dryopteris filix-mas. Acute toxicity and phytochemical tests on ethanol leaf extract were determined. In sub-chronic toxicity test, animals were treated with 62.5, 125, 250 and 500 mg/kg of extract every day for 90 days. Blood samples were collected via retro-orbital puncture for baseline studies and at 31, 61 and 91st days for determination of hematological, kidney and liver function parameters. Liver and kidneys were harvested for histopathology analyses on 91st day. Also, a 28 day recovery study was carried out to determine reversibility in toxicological effects. Phytochemical screening revealed the presence of tannins, phenols, flavonoids, saponins, steroids, alkaloids, terpenoids, reducing sugar and cardiac glycosides. Acute toxicity test did not show toxicity or death at 5000 mg/kg. There was significant (p<0.005) reduction in white blood cell and lymphocyte counts, significant (p<0.05) increase in some liver and kidney biomarkers as well as alterations in liver and kidney histo-architecture on 91st days in animals that were treated with 250 and 500 mg/kg extract. However, toxicities observed on 91st day were reversible in recovery studies. The leaf extract of Dryopteris filix-mas may be hepatotoxic and nephrotoxic when used for long periods.
  • Preparation and evaluation of 2-methoxyestradiol-loaded pH-sensitive liposomes Original Article

    He, Suna; Wang, Bowen; Zhang, Runfang; Zhou, Huanhuan; Yang, Qian

    Abstract in English:

    The development and clinical application of 2-methoxyestradiol (2-ME) as a new type of antitumor drug are limited due to its poor solubility, rapid metabolism in vivo, and large oral dosage. 2-ME-loaded pH-sensitive liposomes (2-ME-PSLs) was prepared containing the lipids, Lipoid E-80 (E-80), cholesteryl hemisuccinate (CHEMS), and cholesterol (CHOL) via thin-film ultrasonic dispersion. First, preparation conditions of 2-ME-PSLs were optimized by orthogonal test. Then 2-ME-PSL was characterized, and the release behavior and stability of 2-ME-PSL in vitro were evaluated. The optimal preparation conditions for 2-ME-PSLs were as follows: 2-ME : E-80+CHEMS 1:15; CHOL : E-80+CHEMS 1:5; ultrasonication time 20 minutes. The mean particle size, PDI, zeta potential, and entrapment efficiency (EE) of 2-ME-PSLs were 116 ± 9 nm, 0.161 ± 0.025, −22.4 ± 1.7 mV, and 98.6 ± 0.5%, respectively. As viewed under a transmission electron microscope, 2-ME-PSLs were well dispersed and almost spherical. They exhibited significant pH-sensitive properties and were fairly stable when diluted with a physiological solution. In conclusion, 2-ME-PSLs were successfully prepared and possessed a favorable pH sensitivity and good dissolution stability with a normal solution.
  • Evaluation of the pharmaceutical assistance structure in Maranhão State, Brazil Original Article

    Maximino, Flávio Donalwan Sá; Brito, Maria Helena Seabra Soares de; Castilho, Selma Rodrigues de; Cordeiro, Benedito Carlos

    Abstract in English:

    Assessment instruments can measure the effectiveness of health policy organizations. This research is a descriptive diagnostic study the Pharmaceutical Assistance structure in Maranhão State, Brazil. The methodology consisted of obtaining secondary data from institutions related to the Pharmaceutical Assistance in the State. Structure indicators were calculated using methodology adapted from the World Health Organization (WHO), and pharmacists perception about the structure of the Pharmaceutical Assistance was analysed through questionnaires. There are 3,003 pharmacists and 3,410 healthcare establishments registered in the Regional Pharmacy Council CRF-MA, particularly in the capital area. Two main problems were identified by pharmacists: the “ineffective management of the public health system” and the “amount of available medicine is insufficient to meet the rising demands of the population” (23.08%; 18 each). We concluded that the Pharmaceutical Assistance organization in Maranhão State is in a precarious situation that requires an investment of resources to improve the physical structures, expand the amount and improve the qualifications of human resources, and procure medicines in sufficient quantities to meet the population’s needs.
  • Antifungal activity of some Sternbergia taxa: effects on germ tube and biofilm formation Original Article

    Kaskatepe, Banu; Yilmaz, Betul Sever; Acikara, Ozlem Bahadir; Iscan, Gulcin Saltan; Vlainic, Josipa; Kosalec, Ivan

    Abstract in English:

    Natural products are rapidly becoming the primary sources of novel antimicrobial agents, as resistance to existing antimicrobial agents is increasing. Apart from determining the antimicrobial activity of natural products, it is also important to understand their effects on the virulence factors of microorganisms. This study aimed to determine the antimicrobial activity of Sternbergia species prevalent in Turkey and investigate their role in the inhibition of germination tube and biofilm formation, both of which are known to be important virulence factors of Candida albicans. The antimicrobial activities of the plant extracts were evaluated using bore-plate and broth microdilution method. The extracts’ capacity to inhibit the formation of the germ-tube was also evaluated. The findings of our study revealed that Sternbergia lutea, Sternbergia vernalis possessed antimicrobial activities, with MIC values ranging between 0.048 mg/mL and 0.39 mg/mL. The highest antimicrobial activity was observed against Candida dubliniensis (0.048 mg/mL). While evaluating the inhibition of fungal germination activities, S. vernalis extract (at a concentration of 0.09 mg/mL) was found to be the most effective against C. albicans ATCC 90028 strain. The results also indicated that S. vernalis extracts at sub-MIC levels inhibited germ tube formation and modulated the tail-length of germinated cells, both of which are important virulence factors of C. albicans. Furthermore, the inhibition of biofilm-formation was also investigated, and it was found that two Sternbergia spp. extracts at or below MIC levels inhibited biofilm formation.
  • Pharmacobotanical study of Manilkara zapota (L.) P.Royen (Sapotaceae) Original Article

    Moura, Bruna Izabela de Vasconcelos; Araújo, Bárbara Priscylla Lira de; Sá, Rafaela Damasceno; Randau, Karina Perrelli

    Abstract in English:

    Manilkara zapota (L.) P. Royen, popularly known as sapoti or sapota (sapodilla), is a tree bearing an important fruit, in addition to different parts of the plant being widely used in folk medicine in the management of inflammation, pain, fevers, coughs, diarrhea, dysentery, among other ailments. This study aimed to conduct a pharmacobotany standardization study of M. zapota. Semi-permanent slides, containing transversal sections of stem, petiole, leaf blade and fruit; and paradermic sections of leaf blade were prepared, and analyzed by light microscopy. Histochemical tests were also performed in cross-sections of the leaf blade. Microscopic analysis allowed the identification of important elements in the diagnosis of the species; while the use of histochemical techniques on the leaf blade showed evidence of the presence of phenolic compounds, tannins, triterpenes and steroids, lipophilic compounds, starch, lignin and calcium oxalate crystals. The results presented contributed to characterization of the species.
  • Short-term high-fat diet affects macrophages inflammatory response, early signs of a long-term problem Original Article

    Santos, Ed Wilson; Oliveira, Dalila Cunha; Hastreiter, Araceli; Silva, Graziela Batista; Beltran, Jackeline Soares de Oliveira; Rogero, Marcelo Macedo; Fock, Ricardo Ambrósio; Borelli, Primavera

    Abstract in English:

    Obesity is a chronic inflammatory disease that affects millions of people worldwide. Most studies observe the effects of a high-fat diet (HFD) in 10-12 weeks. This work investigated the effects induced by a HFD administered for 6 weeks on the nutritional status of mice and some aspects of the inflammatory response in mouse peritoneal macrophages. Male Swiss Webster mice, 2-3 months of age, were fed a control diet or HFD for 6 weeks. After this period, the mice were euthanized, and peritoneal macrophages were collected for immunoassays and assessment of biochemical parameters. A HFD was associated with increased cholesterol, insulin resistance, C-reactive protein (CRP), leptin, and serum resistin levels. Lipopolysaccharide (LPS)- stimulated adipocyte cultures of animals subjected to a HFD showed increased production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). However, peritoneal macrophages of the HFD group showed no changes in the levels of these cytokines. LPS-stimulated peritoneal macrophages from HFD-treated animals showed a reduction in mRNA expression of TNF-α and IL-6, as well as a decrease in expression of the transcription factor nuclear factor-kappa B (NF-kB). In conclusion, HFD treatment for 6 weeks induces similar signs to metabolic syndrome and decreases the capacity of peritoneal macrophages to develop an appropriate inflammatory response to a bacterial component.
  • Evolution of potential biomarkers of acute muscle injury after physical exercise Original Article

    Chielle, Eduardo Ottobelle; Granella, Lucilene Wildner; Maziero, Jorlana Stacke; Vidigal, Tiago Mateus Andrade; Mallmann, Bárbara Lidiane Kummer; Karal, Jaison

    Abstract in English:

    Skeletal muscle injury is a frequent event and diagnosis using the classical blood markers sometimes produces unsatisfactory results. Therefore, objective of the study was to detect new biomarkers in plasma, saliva and urine in response to acute muscle damage induced by physical exercise. A cross-sectional study was conducted with 27 American football players. Before the physical exercises (T0), 60 minutes (T1) and 24 hours (T2) after physical exercise, was determined the clinical, biochemical and molecular parameters, including ADA, TBARS, leukocytes, lymphocytes and comet assay. The serum ADA was significantly higher in T1 and T2, in the urine there was a significant increase in T1, in the saliva there was no significant differences. There was an increase in serum TBARS in T2, saliva and urine in T1. The leukocytes increased in T1 and decreased in T2. Through the comet assay was observed significant DNA damage in T1 and T2. Serum and urinary ADA activity, serum, urinary and salivary TBARS are robust and promising biomarkers of acute muscle injury and that the comet assay allows a quick and effective evaluation of DNA lesions induced by physical exercise and could be used to monitor athletes avoiding injuries that are more serious.
  • Do Brazilian hospital pharmacists record, document, archive and disseminate their clinical practice? Original Article

    Néri, Eugenie Desirèe Rabelo; Vasconcelos, Hemerson Bruno da Silva; Romeu, Geysa Aguiar; Fonteles, Marta Maria de França

    Abstract in English:

    An exploratory study was conducted to present the approach of Brazilian hospital pharmacists to registering, documenting, archiving and disseminating clinical practice. The data were collected using an electronic questionnaire (n=348). In fact, 97.41% of pharmacists record their clinical practice, out of which 64.01% (n=217) do in electronic form, mainly in private hospitals (p<0.000), in the central, southern and southeastern regions (p=0.040), and by professionals with 1-5 years of experience (p=0.001). The main software used is non-specific to clinical practice: an electronic spreadsheet (47.93%; n=104) and text editor (13.37%; n=29). The archiving of records is performed by 87.61% (n=297) of professionals, where 80.13% (n=238) do so in physical form; however, 77.31% (n=184) of these files are kept for less than the standard recommended time. Documentation in medical records is carried out by 55.17% (n=192) of pharmacists, increasing among those with 1-5 years of clinical practice (p=0.001), and dissemination is performed by 74.71% (n=260) of hospital pharmacists, with a lower frequency in public hospitals (p=0.012) and among professionals with fewer hours dedicated exclusively to clinical pharmacy (p=0.012). These results can undergird the revision of competency-based training programs of Brazilian clinical pharmacists to remain pharmacists as a valuable health team member.
  • Inclusion complexes and self-assembled cyclodextrin aggregates for increasing the solubility of benzimidazoles Original Article

    Rodrigues, Leticia Norma Carpentieri; Tavares, Anna Carollina Moraes; Ferreira, Beatriz Tavares; Reis, Adriana Karla Cardoso Amorim; Katiki, Luciana Morita

    Abstract in English:

    Albendazole and fenbendazole are imidazole derivatives that exhibit broad spectrum activity against parasites, but the low solubility of these drugs considerably reduces their effectiveness. Complexation of albendazole and fenbendazole with cyclodextrins (β-cyclodextrin and hydroxypropyl-β-cyclodextrin) in both water and an aqueous solution of polyvinylpyrrolidone (PVP-k30) was studied to determine if it could increase the solubility and dissolution rate of the drugs. In an aqueous solution, β-cyclodextrin increased the solubility of albendazole from 0.4188 to ~93.47 µg mL-1 (223×), and of fenbendazole from 0.1054 to 45.56 µg mL-1 (432×); hydroxypropyl-β-cyclodextrin, on the other hand, increased solubility to ~443.06 µg mL-1 (1058×) for albendazole and ~159.36 μg mL-1 (1512×) for fenbendazole. The combination of hydroxypropyl-β-cyclodextrin and polyvinylpyrrolidone enabled a solubility increase of 1412× (~591.22 µg mL-1) for albendazole and 1373× (~144.66 µg mL-1) for fenbendazole. The dissolution rate of the drugs was significantly increased in binary and ternary systems, with hydroxypropyl-β-cyclodextrin proving to be more effective. The presence of the water-soluble PVP-k30 increased the dissolution rate and amorphization of the complexes. Analysis of the changes in displacement and the profile of the cyclodextrin bands in the 1H NMR spectra revealed a molecular interaction and pointed to an effective complexation in the drug/cyclodextrin systems. Monomeric forms and nanoclusters of cyclodextrins were observed in the drug/cyclodextrin systems, suggesting that the increase in solubility of the drugs in the presence of cyclodextrins should not be attributed only to the formation of inclusion complexes, but also to the formation of cyclodextrin aggregates.
  • Schizophrenia: effects of aripiprazole in metabolic syndrome Original Article

    Silva, Deborah Galvão Coelho da; Kanazawa, Luiz Kae Sales; Vecchia, Débora Dalla

    Abstract in English:

    Schizophrenia, in general, is characterized by severe and disabling mental alterations, characterized by the impairment of one’s mental, behavioral and social activities, developing certain clinical symptoms, relevant to the diagnosis. The drugs used for the reversion of the symptoms cause several adverse effects that affect the patient’s health and well-being, such as motor, endocrine and cardiovascular damages. For a long time, little was known about the origin and the treatment of schizophrenia, which has become a curiosity for science, originating countless researches and theories that are background for several treatments. It is known that alterations in dopaminergic pathways are related to the development of the symptoms of the disease, and evaluating these symptoms, the diagnosis is made and the treatment is initiated. The insertion of new drugs with different characteristics and mechanisms tends to be an advance in the treatment of schizophrenia, as well as reducing the occurence of adverse effects or not worsening already existing cases. Aripiprazole is an innovative atypical antipsychotic employed in the pharmacotherapy of schizophrenia, which tends to attenuate the symptoms, inducing few adverse effects compared to other drugs that are already used, and promotes better quality of life to patients.
  • In vitro characterization and in vivo performance of mefenamic acid-sodium diethyldithiocarbamate based liposomes Original Article

    Jarrar, Qais Bashir; Hakim, Muhammad Nazrul; Cheema, Manraj Singh; Zakaria, Zainul Amiruddin

    Abstract in English:

    Mefenamic acid (MFA) is a hydrophobic drug with low dissolution rate. This study aimed to develop stable and reproducible aqueous formulations of MFA using liposomes as drug carriers. The drug entrapment, particles size and drug release profiles, and stability and reproducibility of the liposomes were determined. In addition, the maximum tolerated dose (MTD) was determined in rats via the oral and intraperitoneal routes of administration. Also, the anti-inflammatory efficacy of these liposomes was evaluated using carrageenan-induced paw edema model in rats. MFA-DDC based liposomes demonstrated a drug entrapment efficacy of 93.6%, particles size of 170.9 nm, and polydispersity index of 0.24 which were not statistically affected when stored in room and refrigerated temperatures for at least 4 weeks. The MTD of the intraperitoneally administrated MFA-loaded liposomes was 20 mg MFA/kg, whereas for those of oral administrations, it was up to 80 mg MFA/kg. Intraperitoneal dose (80 mg MFA/kg) of MFA-DDC liposomes induced extrapyramidal symptoms associated with significant elevation in serum potassium and muscle enzymes. Moreover, significant inhibition of paw edema was demonstrated by the oral and intraperitoneal routes. These findings suggest that MFA-DDC based liposomes are an effective formulation of MFA and recommend the use of bioequivalence assessments with commercial formulations.
  • Effect of ethanol Adiantum capillus-veneris extract in experimental models of anxiety and depression Original Article

    Rabiei, Zahra; Setorki, Mahbubeh

    Abstract in English:

    Depression is one of the most common psychiatric disorders with a prevalence of 15%-25%. Monoamine aminotransferases, in particular, norepinephrine, serotonin, and dopamine, change in the brain of depressed people. Adiantum capillus-veneris is one of the species of the maidenhair fern genus that have traditionally been used to treat cough, cold symptoms, and local hair loss.In this experimental study, white male rats weighing 250-300 g were assigned to 5 groups of 10 each; group 1: Receiving normal saline; groups 2-4: Receiving A.capillus-veneris extract at 50, 100, and 200 mg/kg, respectively; and group 5: Receiving fluoxetine at 10 mg/kg. Chronic unpredictable stress (CUS) was induced by 3-week exposure to chronic stress. The forced swim test and plus maze were used to assess depression and anxiety, respectively. Malondialdehyde (MDA) levels and antioxidant capacity in the serum and brain were measured. Treatment with A.capillus-veneris extract at 200 mg/kg significantly reduced the duration of immobility. In the group given extract at 200 mg/kg, a significant increase in the number of open arm entries was observed when compared to the control group. A.capillus-veneris extract at 50, 100, and 200 mg/kg resulted in a significant increase in the time spent in the open arm. A.capillus-veneris extract reduced MDA levels and increased antioxidant levels of serum and brain in rat. A.capillus-veneris has significant antidepressant and anti-anxiety effects in rat, probably due to its antioxidant and anti-inflammatory activities.
  • Enhancing immune effects of a DNA vaccine against kidney cancer using CD40L as an adjuvant Original Article

    Jiang, Guohong; Song, Rixin; Ma, Peilong

    Abstract in English:

    The use of specific combinations of antigens and adjuvant represents a promising approach for increasing the immunogenicity of DNA vaccines. In the present study, we evaluated the immunity and antitumor effects of DNA vaccines with G250 as the target antigen in a mouse model of renal cell carcinoma. We constructed two recombinant plasmids, pVAX1-G250 and pVAX1-CD40L. The recombinant plasmids were injected into mice by intramuscular injection and electrical pulse stimulation. ELISA and ELISPOT experiments were performed to evaluate the corresponding humoral and cellular immune responses following immunization. To further investigate the antitumor potential of the DNA vaccines, we established a tumor-bearing mouse model expressing G250 target antigen. Our results showed that immunization with the combination of the two plasmids exerted the strongest anti-tumor effects. Therefore, our findings demonstrated the effectiveness of CD40L as an adjuvant for DNA vaccines and highlighted the promising use of these vaccines for the treatment of tumors.
  • Safety and efficacy of ketamine xylazine along with atropine anesthesia in BALB/c mice Original Article

    Jamal, Muhammad Ameen; Ahmed, Arslan Mahmood; Tahir, Muhammad; Ashraf, Muhammad; Sattar, Abdul; Ghafoor, Aamir; Munir, Shahzad; Ahmed, Irfan; Hussain, Mubashir; Riaz, Amjad

    Abstract in English:

    Anesthetics are an indispensable prerequisite for surgical intervention and pharmacological animal studies. The objective of present study was to optimize the dose of ketamine (K) and xylazine (X) along with atropine sulfate (A) in order to achieve surgical tolerance in BALB/c mice. Several doses of ketamine (100, 150, 200 mg/kg) and xylazine (10, 15, 20 mg/kg) were mixed and combination of nine doses (K/X: 100/10, 100/15, 100/20, 150/10, 150/15, 150/20, 200/10,200/15,200/20) were evaluated (n=9 per combination). A constant dose of atropine (0.05 mg/kg) was also used to counter side effect. Time-related parameters were evaluated on the basis of reflexes. KX at dose 200/20 mg/kg produced surgical tolerance in all nine mice with duration 55.00±6.87 minutes. The induction time 0.97±0.09 minutes, sleeping time 90.67±5.81 minutes and immobilization time (102.23±6.83 minutes) were significantly higher than all combination. However, this combination was considered unsafe due to 11 % mortality. While, KX at dose 200/15 mg/kg results in none of the mortality, so was considered as safe. Moreover, this combination produces surgical tolerance in 89 % mice with duration (30.00±7.45 minutes). It was concluded that KX at dose 200/15 mg/kg along with atropine 0.05 mg/kg is safe for performing surgical interventions in BALB/c mice.
  • Solid dispersion-based pellet for colon delivery of tacrolimus through time- and pH-dependent layer coating: preparation, in vitro and in vivo studies Original Article

    Guo, Jian; Fang, Huihui; Gui, Shuangying; Huang, Yuzhe

    Abstract in English:

    The intent of the present investigation is to develop and evaluate colon-specific coated tacrolimus solid dispersion pellet (SDP) that retards drug release in the stomach and small intestine but progressively releases in the colon. Tacrolimus-SDP was prepared by extrusion-spheronization technology and optimized by the micromeritic properties including flowability, friability, yields and dissolution rate. Subsequently, the pH-dependent layer (Eudragit L30D55) and time-dependent layer (Eudragit NE30D and L30D55) were coated on the SDP to form tacrolimus colon-specific pellets (CSP) using a fluidized bed coater. Under in vitro gradient pH environment, tacrolimus only released from CSP after changing pH to 6.8 and then quickly released in the phosphate buffer solution of pH 7.2. The Cmax of CSP was 195.68 ± 3.14 ng/mL at Tmax 4.5 ± 0.24 h where as in case of SDP, the Cmax was 646.16 ± 8.15 ng/mL at Tmax 0.5 ± 0.03 h, indicating the ability of CSP targeted to colon. The highest area under the curve was achieved 2479.58 ± 183.33 ng·h/mL for SDP, which was 2.27-fold higher than tacrolimus suspension. However, the best biodistribution performance was achieved from CSP. In conclusion, SDP combining of pH- and time-dependent approaches was suitable for targeted delivery of tacrolimus to colon.
  • Antileishmanial in vitro activity of essential oil from Myrciaria plinioides, a native species from Southern Brazil Original Article

    Kauffmann, Carla; Giacomin, Ana Caroline; Arossi, Kelen; Pacheco, Leandra Andressa; Hoehne, Lucélia; Freitas, Elisete Maria de; Machado, Gérzia Maria de Carvalho; Cavalheiro, Marilene Marcuzzo do Canto; Gnoatto, Simone Cristina Baggio; Ethur, Eduardo Miranda

    Abstract in English:

    In South American folk medicine members of the genus Myrciaria are used for the treatment of malaria, diarrhoea, asthma, inflammation and post-partum uterine cleansing. The aim of this work was to evaluate its antileishmanial properties (in vitro) of essential oil derived from leaves of Myrciaria plinioides D. Legrand, a plant species that is native in South of Brazil. The essential oil was obtained by hydro-distillation using fresh leaves of M. plinioides. The chemical composition of this essential oil (MPEO, M. plinioides essential oil) was determined by gas chromatography coupled to mass spectrometry (GC-MS). MPEO was assayed in vitro for antileishmanial properties against promastigotes of Leishmania amazonensis and Leishmania infantum, and for cytotoxicity against murine peritoneal macrophages. The MPEO comprised 66 components and was rich in oxygenated sesquiterpenes (82.66%) containing spathulenol (21.12%) as its major constituent. The MPEO was effective against L. amazonensis with IC50 value of 14.16 ± 7.40 µg/mL, while against L. infantum the IC50 value was higher with 101.50 ± 5.78 µg/mL. The MPEO showed significant activity against L. amazonensis, and presented a selectivity index (SI) of 6.60. The results suggest that the essential oil from leaves of M. plinioides is a promising source for new antileishmanial agents against L. amazonensis.
  • Goitrogenic/antithyroidal potential of moringa leaves (Moringa oleifera) and spinach (Spinacia oleracea) of Indian origin on thyroid status in male albino rats Original Article

    Mondal, Chiranjit; Chandra, Amar Kumar

    Abstract in English:

    Moringa leaves and spinach used as vegetables containing cyanogens and polyphenols having suspected antithyroidal activity; however, detailed studies in this aspect found unavailable. Goitrogenic/antithyroid potentiality of those plant foods of Indian origin was evaluated. To explore the goitrogenic/antithyroid effect of those plant foods cyanogenic glucosides, glucosinolates, thiocyanate and polyphenol content were measured. These plant foods were fed with diet regularly to adult male albino rats for 30 and 60 days respectively, followed by evaluation of morphological and functional status of thyroid,as thyroid gland weight, the activity status of thyroid hormone synthesizing enzymes viz. TPO, Na+-K+-ATPase, deiodinase I, thyroid hormone profiles, thyroid histoarchitecture as well as urinary iodine and thiocyanate. In moringa leaves and spinach fed diet, there was a significant increase in urinary excretion of thiocyanate and iodine, enlargement of thyroid gland along with hypertrophy of thyroid follicles and altered in the activities of thyroid hormone synthesizing enzymes with concomitant changes of thyroid hormone profiles. Effects were more severe in moringa leaves treated group than that of spinach. Biochemical analysis moringa leaves and spinach reveal that those are rich sources of goitrogens and their prolonged consumption gradually developed a relative state of biochemical and morphological hypothyroidism.
  • The effect of single-bulb garlic oil extract toward the hematology and histopathology of the liver and kidney in mice Original Article

    Lestari, Sri Rahayu; Rifai, Muhaimin

    Abstract in English:

    Single garlic has been used as a traditional medicine for hypercholesterolemia and increasing stamina. The aim of this research was to analyze the effect of single-bulb garlic oil (SGO) extract toward hematology and histopathology liver and kidney in mice. Male mice (strain Balb-C, 12 weeks old, weight of 28±3 g) was treated by SGO for 28 days (once per days) with various doses K- (Normal); K+ (SGO 0.0 mg/kg BW); T1 (SGO 6.25 mg/kg BW); T2 (SGO 12.5 mg/kg BW); T3 (SGO 25.0 mg/kg BW); T4 (SGO 50.0 mg/kg BW). The end of the treated mice was sacrificed. Blood was collected to analyze hematology. Liver and kidney were collected then made microanatomy slide with Hematoxylin-Eosin staining. Parameters of hematology are the levels of hemoglobin, hematocrit, number of erythrocytes, and number of leukocytes. Histopathology of liver and kidney determine by cell necrosis. The result of the research showed that SGO increased the number of erythrocytes and leucocytes but there is no effect on the levels of hemoglobin and hematocrit. Histopathology on liver and kidney showed there is no effect in necrosis. The conclusion is the single-bulb garlic oil extract safe if consumed continuously
  • Late cardiac perconditioning by phenylephrine in an isolated rat heart model is mediated by mitochondrial potassium channels Original Article

    Nazari, Afshin; Sedighi, Mehrnoosh; Dalvand, Parvin; Azizi, Yaser; Moghimian, Maryam; Boroujeni, Shakiba Nasiri

    Abstract in English:

    The present study was designed to investigate the effect of early and late administration of phenylephrine during ischemia against regional ischemia-reperfusion injuries in an isolated rat heart model. All animals were randomly divided into experimental groups: (I) IR (Ischemic/ reperfusion): the hearts underwent 35 min of regional ischemia followed by 60 min of reperfusion; (II) 5HD-IR-0: the hearts were perfused for 5 min with 5HD (5-hydroxydecanoate, specific mKATP channel blocker, 100 µM) at the onset of regional ischemia; (III) 5HD-IR-20: the hearts were perfused for 5 min with 5HD 20 min after regional ischemia; (IV) PE-IR-10: the hearts were perfused for 5 min with phenylephrine 10 min after regional ischemia; (V) PE-IR-30: the hearts were perfused for 5 min with phenylephrine (100 µM) 30 min after regional ischemia; (VI) PE-5HD-IR-10 group: the hearts were perfused for 5 min with 5HD at the onset of regional ischemia after which phenylephrine was administrated as in group IV; and (VII) PE-5HD-IR-30: the hearts were perfused for 5 min with 5HD 20 min after the ischemia and then phenylephrine was administrated as in group V. The hemodynamic parameters were recorded throughout the experiment. Ischemia-induced arrhythmias, myocardial infarct size (IS), creatin kinase-MB isoenzyme (CK-MB), plasma lactate dehydrogenase (LDH) activities, and coronary blood flow (CBF) were measured in all animals. Perfusion of phenylephrine 30 min after the regional ischemia curtailed the myocardial infarct size, reduced CK-MB, and improved cardiac function and CBF. Administration of 5HD 30 min after the ischemia abolished cardioprotective effects of phenylephrine in the late phase. These results suggest the involvement of mKATP in the mechanism of phenylephrine-induced late preconditioning.
  • N-Myristoyltransferases as antileishmanial targets: a piggyback approach with benzoheterocyclic analogues Original Article

    Junqueira, Luis Otávio; Costa, Marcela Oliveira Legramanti da; Rando, Daniela Gonçales Galasse

    Abstract in English:

    Leishmaniasis is one of the neglected diseases that remain in need for pharmacological alternatives. In this context, N-Myristoyltransferases (NMT) arise as interesting targets to explore since they are involved in the co/post-translational processing of peptides which are responsible for host cell invasion. Studies that consider these enzymes as targets point out the potential of benzoheterocyclic compounds as inhibitors of Candida albicans’s N-myristoyltransferase. Here we applied a combination of comparative binding site analysis and molecular docking studies based on a Piggyback approach in the search for new Leishmania major NMT ligands. Our results revealed that NMT enzymes from both pathogens present enough structural similarity to allow extrapolation of the knowledge available from C. albicans studies to develop new L. major NMT inhibitors. Molecular docking studies with benzoheterocyclic analogues indicate the potential of benzothiazole derivatives as L. major NMT ligands, giving rise to a completely new class of chemical compounds to be explored in the development of antileishmanial drugs.
  • Antimicrobial and antibiofilm activities of phenolic compounds extracted from Populus nigra and Populus alba buds (Algeria) Original Article

    Nassima, Boumghar; Nassima, Behidj; Riadh, Ksouri

    Abstract in English:

    The interest of this work is the discovery of new antimicrobial agents of plant origin to inhibit the formation of microbial biofilms. The present research was conducted to identify and quantify the phenolic compounds extracted from Populus nigra and Populus alba buds harvested in the area of Tizi-Ouzou (Algeria), and to evaluate their antimicrobial and antibiofilm activity. High performance liquid chromatography (HPLC) was performed to identify the phenolic compounds in the ethyl acetate fraction of P. nigra and the methanolic extracts of P. nigra and P. alba. The antimicrobial activity of the crude extracts and the fractions of these two species was tested against 11 microorganisms, using the disk diffusion method, while the antibiofilm effect of certain extracts was carried out in a 96-well microplate and on a biomaterial (catheter). HPLC analysis revealed the presence of 10 bioactive compounds. The main phenolic compounds identified in the three extracts were p-coumaric acid, ellagic acid, and Kaempferol. This study was able to demonstrate that the extracts of P. nigra and P. alba buds have interesting antimicrobial properties, with diameters ranging from 6.6 to 21.3 mm. In addition, extracts of P. nigra exhibited antibiofilm effects greater than 70%. Our results provide evidence for the antimicrobial and antibiofilm potential of bud extracts from both poplar species. Thus, these results will pave the way for further research on these two plants.
  • Application of quality by design approach in RP-HPLC method development for simultaneous estimation of saxagliptin and dapagliflozin in tablet dosage form Original Article

    Gundala, Aruna; Prasad, KVSRG; Koganti, Bharathi

    Abstract in English:

    A simple, sensitive, precise, accurate and robust high performance liquid chromatographic method has been developed for simultaneous estimation of saxagliptin (SAXA) and dapagliflozin (DAPA) in pharmaceutical formulation. Design of experiments (DoE) was applied for multivariate optimization of the experimental conditions of RP-HPLC method. Risk assessment was performed to identify the critical method parameters. Three independent factors; mobile phase composition, flow rate and column temperature were used to design mathematical models. Central composite design (CCD) was used to study the response surface methodology and to study in depth the effects of these independent factors. Desirability function was used to simultaneously optimize the retention time and resolution of SAXA and DAPA. The optimized and predicted data from contour diagram consisted of acetonitrile and ortho phosphoric acid (0.1%) in the ratio of 50:50 respectively, at a flow rate of 0.98 ml/min and column temperature 31.4 °C. Using these optimum conditions baseline separation of both drugs with good resolution and run time of less than 6 min were achieved. The optimized assay conditions were validated according to ICH guidelines. Hence, the results clearly showed that Quality by design approach could be successfully applied to optimize RP-HPLC method for simultaneous estimation of SAXA and DAPA.
  • The importance of corrosion resistance test of cannulas in the quality control of hypodermic needles Original Article

    Feitoza-Silva, Michele; Carvalho, Carolina Mesquita de; Bittencourt, Lívia Bretas; Leandro, Katia Christina; Gemal, André Luis

    Abstract in English:

    According to Anvisa risk rating, hypodermic needles offer medium risk to the user’s health. This study discussed the importance of the corrosion resistance test in tubes of hypodermic needles, in the product quality control. A review of cannulas of hypodermic needles was carried out according to ISO 9626:2003 and 9259:1997 ABNT NBR. For the results evaluation, a scale which classifies the extent of corrosion was adjusted. 174 samples of PNI needles from 17 States and 9 different record holders were analyzed. According to the methodology of ISO 9626:2003, 100% of the samples were considered satisfactory. However, in accordance with the methodology of ISO 9259:1997, 97.1% of the samples were rejected. Irregularities can lead to impairment of product quality, resulting in risks to the consumer’s health. Since 2011 the product has undergone certification, so it is necessary to reflect on the importance of corrosion resistance testing and mandatory certification for health monitoring.
  • Hesperidin inhibits the epithelial to mesenchymal transition induced by transforming growth factor-β1 in A549 cells through Smad signaling in the cytoplasm Original Article

    Ren, Zhouxin; Shen, Junling; Mei, Xiaofeng; Dong, Haoran; Li, Jiansheng; Yu, Haibin

    Abstract in English:

    Hesperidin, a natural compound, suppresses the epithelial-to-mesenchymal transition through the TGF-β1/Smad signaling pathway. However, studies on the detailed effects and mechanisms of hesperidin are rare. The present study showed that, for A549 alveolar epithelial cells, the anti-proliferative effects of hesperidin occurred in a dose-dependent manner, with an IC50= 216.8 µM at 48 h. TGF-β1 was used to activate the Smad signaling pathway and induce the epithelial to mesenchymal transition in cells. Treatment with hesperidin or SB431542 was used for antagonism of Smad pathway activation. Hesperidin inhibited the increase in ɑ-SMA and Col1ɑ-1 and the decrease in E-cadherin in a dose-dependent manner from concentration of 20 µM to 60 µM, as assessed by both ELISA and Western blotting assays; however, there was no significant effect on cellular morphological alterations. Moreover, the Western blotting assay showed that, in the cytoplasm, hesperidin and SB431542 had no significant effect on the protein expression of Smad 2, 3, 4, or 7 as well as 2/3. However, 60 µM hesperidin and SB431542 significantly decreased p-Smad2/3 protein expression. From the above results, it is concluded that hesperidin can partly inhibit the epithelial to mesenchymal transition in human alveolar epithelial cells; the effect accounts for the blockage of the phosphorylation of Smad2/3 in the cytoplasm rather than a change in Smad protein production in the cytoplasm.
  • Nanoemulsion containing caffeine for cellulite treatment: characterization and in vitro evaluation Original Article

    Freire, Thamires Batello; Dario, Michelli Ferrera; Mendes, Otávio Gil; Oliveira, Andressa Costa de; Vetore, Alberto; Faria, Dalva Lucia Araújo de; Silva, Vânia Rodrigues Leite e; Baby, André Rolim; Velasco, Maria Valéria Robles

    Abstract in English:

    The Ginoide Hydrolipodystrophy (GHLD), commonly known as cellulite, occurs in 80-90% of the female population after the puberty period and comes from a metabolic modification in the cutaneous adipose tissue. Caffeine has been used in topical formulations due to its lipolytic action. We studied a nanoemulsion (F3) containing caffeine with two surfactants (oleth-3 and oleth-20) by emulsification method by phase inversion temperature inversion (PIT). The polydispersion indices (PDI) showed the reduced deviation of 0.1. The mean droplet size was ~ 40 nm. The evaluated constant of Ostwald, in the refrigerator condition was the most favorable during the stability test. In the In Raman spectroscopy assay, the caffeine bands found in F3 were compatible with those found in the caffeine solution (1337, 652.5 and 558.2 cm-1). There was no interaction of caffeine anhydrous with other ingredients in nanoemulsion. In the in vitro safety assay the result of 1.4 ranked the F3 as slightly irritating. In the natural membrane, cutaneous permeation test (human skin) permeate concentrations did not exceed the saturation concentration of the PBS buffer (48.96 µg/3 mL). The caffeine solution and F3 permeated statistically equal, but the nanoemulsion visually and sensorially improved the caffeine precipitation.
  • Effects of gallic acid and physical exercise on passive avoidance memory in male rat Original Article

    Salehi, Azadeh; Rabiei, Zahra; Setorki, Mahbubeh

    Abstract in English:

    Learning and memory play main roles in daily life of human, and memory represents the basis of all trainings and learning. The aim of the current study is to investigate the effects of gallic acid and physical exercise on the levels of passive avoidance memory in rat. In this experimental study, 46 rats weighing 200-300 g were randomLy divided to six groups of eight each: including control group, groups treated with 10 and 20 mg/kg gallic acid, group undergoing physical exercise alone, and groups both undergoing physical exercise and treated with 10 and 20 mg/kg gallic acid. The interventions continued for 10 days. After the intervention, passive avoidance memory was measured by shuttle box, blood samples were taken, and serum and brain antioxidant capacity and malondialdehyde (MDA) levels were measured. Secondary latency in shuttle box significantly increased in groups undergoing treadmill exercise and undergoing treadmill exercise + treating 10 and 20 mg/kg gallic acid. In groups treated with 10 and 20 mg/kg gallic acid alone, secondary latency increased significantly. Results confirmed the effects of gallic acid and physical exercise, either alone or combined, in improving memory.
  • Antioxidant and cytotoxic properties of protein hydrolysates obtained from enzymatic hydrolysis of Klunzinger’s mullet (Liza klunzingeri) muscle Original Article

    Rabiei, Sana; Rezaei, Masoud; Asgharzade, Samira; Nikoo, Mehdi; Rafieia-kopai, Mahmoud

    Abstract in English:

    Today, consumers are looking for functional foods that promote health and prevent certain diseases in addition to provide nutritional requirements. This study aimed to evaluate the antioxidant and cytotoxic properties of Liza klunzingeri protein hydrolysates. Fish protein hydrolysates (FPHs) were prepared from L. klunzingeri muscle using enzymatic hydrolysis with papain at enzyme/substrate ratios of 1:25 and 1:50 for 45, 90 and 180 min. The antioxidant activities of the FPHs were investigated through five antioxidant assays. The cytotoxic effects on 4T1 carcinoma cell line were also evaluated. The amino acid composition and molecular weight distribution of the hydrolysate with the highest antioxidant activity were determined by HPLC. All six FPHs exhibited good scavenging activity on ABTS (IC50=0.60-0.12 mg/mL), DPPH (IC50= 3.18-2.08 mg/mL), and hydroxyl (IC50=4.13-2.07 mg/mL) radicals. They also showed moderate Fe+2 chelating capacity (IC50=2.12-12.60 mg/mL) and relatively poor ferric reducing activity (absorbance at 70 nm= 0.01-0.15, 5 mg/mL). In addition, all hydrolysates showed cytotoxic activities against the 4T1 cells (IC50=1.62-2.61 mg/mL). 94.6% of peptide in hydrolysate with the highest antioxidant activity had molecular weight less than 1,000 Da. L. klunzingeri protein hydrolysates show significant antioxidant and anticancer activities in vitro and are suggested to be used in animal studies.
  • Beta-glucan attenuates cerebral ischemia/reperfusion-induced neuronal injury in a C57BL/J6 mouse model Original Article

    Kaya, Kürşat; Çiftçi, Osman; Öztanır, Mustafa Namık; Taşlıdere, Elif; Türkmen, Neşe Başak

    Abstract in English:

    Beta-glucans (βg), that have many useful effects on human health, are natural polysaccharides. Our aim in this study was to determine useful effect of βg against oxidative and neuronal damage caused by global cerebral ischemia/reperfusion (IR) in stroke imitated mice via surgical operation. A total of 40 mice divided into four equal groups randomly. The group 1 (sham operated) was kept as control. Bilateral carotid arteries of subjects in group 2 (I/R) and group 4 (I/ R + βg) were clipped for 15 min, and the mice in group 4 (I/R + βg) were treated with βg (50 mg/kg/day), while the mice in group 2 (I/R) were treated with only vehicle for 10 days. The mice of group 3 (βg) were treated with βg for 10 days without carotid occlusion. Global cerebral I/R significantly increased oxidative stress and decreased members of anti-oxidant defense system. In addition, I/R caused histopathological damage in the brain tissue. However, βg treatment ameliorated both oxidative and histopathological effects of I/R. Our present study showed that βg treatment significantly ameliorated oxidative and histological damage in the brain tissue caused by cerebral I/R. Therefore, βg treatment can be used as supportive care for ischemic stroke patients.
  • Evaluation of recombinant human interferon beta 1b by liquid chromatography methods and bioassay Original Article

    Silva, Francielle Santos da; Walter, Maurício Elesbão; Xavier, Bruna; Perobelli, Rafaela Ferreira; Calegari, Guilherme Zanini; Cardoso, Douglas Franco; Perlin, Valquiria Guedes; Dalmora, Sérgio Luiz

    Abstract in English:

    Recombinant human interferon beta 1b (rhIFNβ-1b) is clinically used to treat multiple sclerosis. A reversed-phase liquid chromatography (RP-LC) method was carried out on a Jupiter C4 column (250 mm × 4.6 mm i.d.). The mobile phase A consisted of 0.1% trifluoroacetic acid (TFA) in water, and the mobile phase B was acetonitrile with 0.1% TFA run at a flow rate of 1.0 mL/min. A size exclusion liquid chromatography (SE-LC) method was carried out on a BioSep-SEC-S 2000 column (300 mm × 7.8 mm i.d.). The mobile phase consisted of 1 mM monobasic potassium phosphate, 8 mM sodium phosphate dibasic and 200 mM sodium chloride buffer pH 7.4, run isocratically at a flow rate of 0.8 mL/min. Retention times were 31.87 and 17.78 min, and calibration curves were linear over the concentration range of 1-200 µg/mL (r2 = 0.9998) and 0.50-200 µg/mL (r2 = 0.9999), respectively, for RP-LC and SE-LC, with detection at 214 nm. Liquid chromatography (LC) methods were validated and employed in conjunction with the in vitro bioassay to assess the content/potency of rhIFNβ-1b, contributing to improve the quality control and to ensure the efficacy of the biotherapeutic.
  • Evaluation of adherence to pharmacological treatment Original Article

    Silva, William Henrique da; Dantas, Débora Santos; Nóbrega, Baldoíno Sonildo da; Queiroz, Maria do Socorro Ramos de; Alves, Harley da Silva

    Abstract in English:

    The adherence to therapy associated with the socio-demographic variables and the habits of patients with hypertension and/or diabetes mellitus were investigated in this study. The registration forms of 105 patients in the Hiperdia program in the municipality of Campina Grande-PB were used as a data collection instrument, applying the Morisky-Green test (MGT) and Batalla test (BT) to assess compliance treatment. For the MGT, there was a prevalence of non-adherent individuals (76.2%) and the type of predominant behavior was unintentional. The internal consistency of the responses obtained through the MGT presented good reliability, according to the value of 0.69 obtained by Cronbach’s alpha. For the BT, there was a predominance of adherence (68.6%) and the alpha value was 0.80, showing a high reliability level. It was found that a diet lacking in salt is a strong impact variable for determining the adherence to the BT. Given the representativity of the tests, there is a need to amend the interferences that facilitate the low adherence to drug treatment. The results of this study can be used to construct strategies that will address these difficulties and optimize the adherence level and quality of life of patients.
  • Topical ophthalmic antimicrobials: unfulfilled demands and possibility of new investments in Brazil and in the United States Original Article

    Kollross, Bianca; Gelfuso, Guilherme Martins; Cunha-Filho, Marcilio; Gratieri, Tais

    Abstract in English:

    In general, topical ophthalmic drug products, especially those used for treating infections, present low effectiveness because of various reasons, from unfavorable drug physicochemical properties to physiological protective mechanisms of the eye. The fact is such group of products holds room for improvement, which could mean the development of better drugs or dosage forms. To achieve this, the knowledge of market composition is essential. The present work studied and compared the antimicrobial ophthalmic markets of Brazil and of the United States (US). Official databank of Brazilian Health Regulatory Agency and of US Food and Drug Administration were assessed for registered antimicrobial topical ophthalmic drug products. Brazilian market has registered greater number of drug products (119) than the US (94), but the latter involves more variety of substances and dosage forms. In both countries, non-innovative products registered as solutions of antibacterials, especially fluoroquinolones and aminoglycosides lead the market. Despite the clinical demand, the US has only one group of antimycotics (polyenes) registered, while in Brazil, there is not any ophthalmic antimycotic product marketed. This study evidences there is not only space for development of newer drugs and formulations but also a demand for already existing technologies and products in both countries.
  • Does Lycium europaeum leaf have antihyperglycemic, antihyperlipidemic and antioxidant effects Original Article

    Tej, Rabeb; Hamdi, Amel; Serairi Beji, Raja; Aidi Wannes, Wissem; Bettaieb Rebey, Iness; Oueslati, Samia; Ksouri, Riadh; Saidani Tounsi, Moufida; Lachaal, Mokhtar; Karray Bouraoui, Najoua

    Abstract in English:

    The purpose of the present investigation is to assess, for the first time, the antidiabetic, antihyperlipidemic and antioxidant activities of Lycium europaeum extract in alloxan-induced diabetic rats. Diabetes was induced in adult male Wistar rats via a single subcutaneous alloxan injection (120 mg/kg). Lycium europaeum aqueous extract was orally administered at a dose of 20 mg/kg for 28 consecutive days. Serum concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were assayed at the end of the experimental period in all investigated groups. Antioxidant enzymes such as glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) were sought in the serum and pancreas. Lycium europaeum extract significantly increased HDL-C and reduced blood glucose, TC, LDL-C and TG as compared to the alloxan-control group. Lycium europaeum extract was also efficient in reducing oxidative stress in diabetic rats by increasing SOD, CAT and GPx activities both in the pancreas and the plasma of the animals. Moreover, Lycium europaeum extract contained considerable levels of polyphenols and flavonoids. It also exhibited an important antioxidant capacity and a remarkable ability to quench DPPH radicals and reduce irons. The obtained results highlight potentially relevant health beneficial effects of Lycium europaeum extract, reversing hyperglycemic, hyperlipidemic and oxidative stress effects in rats with alloxan-induced diabetes. Therefore, it may be considered as a promising alternative or complementary agent to diabetes treatment.
  • Acetylcholinesterase inhibition, antioxidant and identification of some chemical constituents of Phyllanthus atropurpureus cultivated in Egypt Original Article

    Abdallah, Walid Elsayed; Elsayed, Wael Mohamady; Hassan, Rasmia Ali; Nazif, Naglaa Mohammed; Ali, Mohammed Ibrahim; Abdelshafeek, Khaled Abdelhady

    Abstract in English:

    Investigation of the lipid constituents of the aerial parts of Phyllanthus atropurpureus resulted in isolation and identification of the fatty acid mixture which consists of eight acids with linolenic acid as major and the unsaponifiable fraction that contain a series of hydrocabons, sterols, in addition to one triterpene (α-amyrin). The acetone insoluble fraction was found to contain two fatty alcohols and three n-hydrocabons in which the n-eicosane is the most abundant (44.16%). The flavonoidal constituents were isolated from ethyl acetate and butanol fractions which were identified as: luteolin-7-O-glucoside, kaempferol 3-O-(p-coumaroylglucoside), kaempferitrin, luteolin and kaempferol. Evaluation of different extracts as acetylcholinesterase inhibitors (AChI), established the chloroform fraction as a promising inhibitor of the enzyme. The antioxidant testing with DPPH radical revealed the potential of precipitate from MeOH extract as a radical scavenger.
  • E-learning in Pharmacy Education: what do we know about it? Original Article

    Lorenzoni, Andrigo Antonio; Manzini, Fernanda; Soares, Luciano; Leite, Silvana Nair

    Abstract in English:

    The increase and flexibilization of e-learning in Brazil has generated concern about the low capacity to ensure the quality of institutions and courses. The objective is to identify the literature on experiences of pharmaceutical e-learning. A scope review was carried out, mapping key concepts and evidence. The selected articles, without period restriction, from the Scielo, Pubmed and Scopus databases provided data on the educational level of experience, modality, workload, content delivery method, instruments used, types of topics, evaluation information and purpose of the study. There were 87 articles on preparation for subsequent classes; feedback or continuation of previous classes; to specific training; the comparison between face-to-face and distance education modalities; and distance learning. Among the subjects treated, 51.8% involved pharmaceutical clinic and 42.5% basic science. Positive student assessment was found in more than 92% of cases. Isolation, and deficits in social and analytical skills were negative points. Technology infrastructure can impact learning. In Brazil, the health area has manifested opposition to the use of distance education in undergraduate studies. There is no evidence on the organization of undergraduate distance courses, but there are elements indicating risks to the results of training and development of professional skills in this modality.
  • In vitro biological activities of silver nanoparticles synthesized from Scedosporium sp. isolated from soil Article

    Panchangam, Rajeeva Lochana; Upputuri, Ravi Theaj Prakash

    Abstract in English:

    One of the important fields in nanotechnology is the development of an environment friendly method for the synthesis of nanoparticles. Many approaches show that microorganisms are the most reliable tools for biosynthesis of nanoparticles compared to physical and chemical methods. In our study, fungi have been exploited for extracellular production of metal nanoparticles. It was observed that in Scedosporium, silver ions are reduced to silver nanoparticles, which was confirmed by UV-visible spectrophotometry and AFM. Optimization studies showed that as the concentration of AgNO3 used for synthesis increased, particles’ size also increased. Size of the particles at different concentrations of AgNO3 was observed to be 79-107 nm with particles being ellipsoidal to spherical in shape. Silver nanoparticles synthesized from 2.0 mM silver nitrate, showed maximum antimicrobial activity compared to all antibiotics tested including synergistic effects. In vitro cytotoxicity of silver nanoparticles against MCF 7 and PC 3 showed that as the concentration of silver nanoparticles increased, a decrease in the percentage cell viability was observed with IC50 values being 60.09 and 57.43 µg/ml respectively. Therefore, through this study, it could be said that extracellular synthesis of silver nanoparticles from Scedosporium was simple, ecofriendly, proving excellent antimicrobial and anticancer agents.
  • Encapsulation of flaxseed oil extract in alginate-salep system by ionic gelation Article

    Wissam, Zam; Samer, Housheh

    Abstract in English:

    The objective of the current study was to encapsulate flaxseed oil extracted from finely grounded flaxseed powder and determined for its fatty acids content by GC/FID. Ionotropic gelation method was used to form beads containing 40% flaxseed oil with vitamin E being used as an antioxidant agent. The study employed calcium chloride solution as crosslinking agent with a combination of sodium alginate and salep. The effect of polymer concentrations and calcium chloride concentration on the morphology, entrapment efficiency and oil release was studied. The encapsulation efficiency reached 93.46 ± 0.064% using 0.6% of salep and 2% sodium alginate with 0.3M calcium chloride gelling solution. In SGF medium, the matrix released only about 28.56% of the entrapped flaxseed oil after 2 hours. The rest of the oil then released in the SIF medium, continuing for up to 5 h to release 99.32% of the oil.
  • Analgesic and antiinflammatory activities of the essential oil from Artemisia sieberi Besser Article

    Pishgahzadeh, Elahe; Shafaroodi, Hamed; Asgarpanah, Jinous

    Abstract in English:

    The analgesic activity of Artemisia sieberi oil was assessed by acetic acid-induced writhing test and Eddy’s hot plate method; while the acute anti-inflammatory effect was investigated by inflammatory paw edema test in rats. The administration rout of the essential oil, standard drugs and the vehicle used in all assays was intraperitoneal injection. The 1 and 2.5 mg/kg doses of the studied oil significantly decreased the number of acetic acid-induced writhes in mice. The dose of 1 mg/kg of the oil also exhibited a central analgesic effect as evidenced by a significant increase in reaction time at several time points after 15 min treatment in the hot plate method. In addition, the 1 mg/kg dose of the oil significantly reduced carrageenan induced paw edema in rats at the first hour of the test by 72.7% inhibition and lasted to the third hour of the test by 74.3% inhibition found to be very close to that of the standard drug, diclofenac sodium (50 mg/kg). The major components of the oil were characterized as camphor (31.2%) and 1,8-cineole (20.0%). The results suggest that A. sieberi essential oil has a significant effect against acute inflammation and has central and peripheral anti-nociceptive effects.
  • Characterization and optimization of oil microcapsules from Attalea phalerata Mart. for the preservation of bioactive compounds Article

    Lima, Fernando Freitas de; Lescano, Caroline Honaiser; Oliveira, Elaine Florinda Rodrigues de; Fakhouri, Farayde Matta; Moraes, Izabel Cristina Freitas; Kassuya, Cândida Aparecida Leite; Sanjinez-Argandoña, Eliana Janet

    Abstract in English:

    This study aimed microencapsulating Attalea phalerata Mart. oil, containing high carotenoid and phenolic compounds content, with Arabic gum and gelatin, using the complex coacervation method. The yield, efficiency, morphology of microcapsules and content of phenolic compounds, carotenoids and antioxidant activity in different processes conditions (concentration of the filling, temperature and agitation speed) were evaluated. The results showed 88% of yield, efficiency up to 70% and a characteristic size of microcapsules. The amount of carotenoids was high in crude oil (394.84 µg of carotenoids/g oil) and the microencapsulation tests showed amounts of 19.19 to 166.40 µg of carotenoids/g oil. The phenolic compounds in the crude oil were 20.73 mg GAE/g sample and the microencapsulation tests showed amounts of 3.17 to 15.16 mg GAE/g oil. The values of bioactive compounds influenced in the antioxidant activity though ABTS•+ method with values of 161.70 µM trolox/g oil to crude oil and 7.70 and 159.54 µM trolox/g oil for microcapsules tests.
  • Retrospective cost-utility and budget impact assessments of Hypericum perforatum in contrast with Fluoxetine treatment for depression in Karachi, Pakistan Article

    Ahmad, Syed Muzzammil; Masroor, Darakhshan; Azhar, Iqbal; Ahmed, Nadia

    Abstract in English:

    In this study we have compared two different types of therapies i.e. herbal and allopathic system of therapies for Depression and studied them from the social perspectives. The Hypericum perforatum is compared with Fluoxetine [HCL] in terms of cost-utility and financial savings thereby evaluating its influence on annual expenditure of depressive patients that were randomly selected from 178 union councils of the city of Karachi, Pakistan. For both system of therapies a total of 356 patients were selected by stratified random sampling. Taking frequency of depression as ‘1’ annually with discount rate at 3% for calculating the burden-of-illness in terms of disability-adjusted-life-years. The cost-utility and the budget-impact assessments were carried out to assess incremental-cost-effectiveness-ratio, and the budget-impact-per-onset as well as budget-impact-per-year values. In comparison with the Fluoxetine therapy, the Hypericum perforatum was found to relieve symptoms in 21.47% less cost; owing 29.23% less disability-adjusted-life-years and 21.45% less budget-impact-per-onset as well as budget-impact-per-year. The annual mean incremental-cost-effectiveness-ratio was found to be at 36.95±270.74 (less than GDP per capita threshold of Rs. 38,173.02). Hypericum perforatum provide the optimal utility with less impact on budget of a patient in comparison with the treatment of symptoms of depression with Fluoxetine.
  • Simultaneous determination of anti-diabetic drugs Article

    Sher, Nawab; Fatima, Nasreen; Perveen, Shahnaz; Siddiqui, Farhan Ahmed

    Abstract in English:

    A novel reverse phase, isocratic HPLC method is described to separate five anti-diabetic drugs i.e., glimepiride, metformin, sitagliptin, rosiglitazone and pioglitazone. Nucleosil C18 analytical column was used as stationary phase, while mobile phase consisted of acetonitrile:phosphate buffer: methanol (40/40/20, v/v) pH 2.0. Effluent was monitored at a flow rate 1 mL/min and detected at wavelength of 240 nm. This research produced excellent chromatography over a wide concentration range of 25-10000 ng/mL. Sepprated and well resolved quantifiable peaks were obtained and test results were linear in this range. Correlation coefficient of more than 0.9990 was witnessed as well as Low %RSD values i.e., maximum 2.0% documented excellent precision of the method. Good recoveries from pharmaecutical (99-101%), urine and plasma samples (>96%) in a range of concentrtion granted very good linearity, accuracy and precision. The projected method has satisfactory applications in quality control of these molecules as well as quantification of these molecules in urine and plasma samples.
  • Development and optimization of erythromycin-loaded lipid-based gel by Taguchi design: In vitro characterization and antimicrobial evaluation Article

    Dhillon, Pallavi; Mirza, Mohd. Aamir; Anwer, Md. Khalid; Alshetaili, Abdullah Saud; Alshahrani, Saad Maria; Iqbal, Zeenat

    Abstract in English:

    The foremost aim of the current research was to prolong and sustain the release of erythromycin (ERY) by preparing a solid lipid nanoparticles (SLNs)-based gel formulation for the safe and effective treatment of acne. ERY-loaded SLNs were developed, and various process variables were optimized with respect to particle size, zeta potential, and entrapment efficiency using the Taguchi model. The average particle size, PDI, zeta potential, drug entrapment efficiency, and drug loading of optimized SLN (F4) were found to be 176.2±1.82 nm, 0.275±0.011, -34.0±0.84, 73.56%, and 69.74% respectively. The optimized SLN (F4) was successfully incorporated into the carbopol-based hydrogel. The in vitro release of ERY from the SLN gel and plain gel were compared and found to be 90.94% and 87.94% respectively. In vitro study of ERY-loaded SLN gel showed sustained delivery of drug from formulation thus enhancing the antimicrobial activity after 30 hours when compared to ERY plain gel.
  • Assessment of an anti-ageing structured cosmetic formulation containing goji berry Article

    Leite, Fernanda de Godoy; Oshiro, João Augusto; Chiavacci, Leila Aparecida; Chiari-Andréo, Bruna Galdorfini

    Abstract in English:

    Based on previous studies, it has been found that goji berry (GB), popularly known as a ‘miracle fruit’, has excellent antioxidant potential and can be used in the treatment of skin disorders associated with ageing. This study aimed to incorporate GB into a structured cosmetic in order to optimise its penetration. Stability studies of the formulation, determination of the antioxidant activity of the extract and of the formulation, rheological measurements, SAXS, polarised light microscopy and bioadhesion analyses were performed. The results indicated the antioxidant activity of the extract, which can be incorporated into an emulsified cosmetic formulation. The emulsified formulation containing the extract remained stable, even after being submitted to thermal and luminous stresses for 30 days. In addition, rheological tests revealed that the addition of the GB soft extract reduced the viscosity of the formulation, increasing thixotropy and deformation. These systems were characterised by SAXS as a lamellar phase, which was confirmed by polarised light microscopy. These highly organised structures indicate their excellent stability. In vitro bioadhesion experiments revealed that these formulations exhibited skin adhesion strength statistically similar to commercial anti-ageing formulation. These results suggest that this formulation has excellent potential to be used as a topical treatment for ageing.
  • Strategic situational planning and management of pharmaceutical services and supply: The experience of a municipality in the State of São Paulo with regard to optimizing spending on medicinal lawsuits Article

    Portella, Amanda Patrícia Favaron; Mendes, Samara Jamile; Araújo, Raquel Queiroz de; Gastaldo, Brunno Carvalho; Leite, Silvana Nair; Storpirtis, Silvia

    Abstract in English:

    One of the actions taken was to offer training on pharmaceuticals via the distance education model (EAD) with the course titled Pharmaceutical Services and Supply Management Course (PSSMC). PSSMC, which was based on the idea of expanded management, is guided by Strategic Situational Planning (PES) concepts, and structured around an Operational Plan (OP) that serves as a practical didactic tool. The aim of this study is to report and analyze a case study based on the implementation of the Operational Plan in a municipality in the State of São Paulo, while focusing on the judicialization of access to medicines and health products. Since judicialization is an important topic, the problem chosen for resolution with the PES was attendance at the issuance of court orders by the municipality for items of medium and high complexity. The PES allows researchers to analyze reality through different points of view, of which participation is a key aspect. With the OP, it was possible to disseminate a proposal for expanded planning, to advance resolution of the problem, achieve positive results, and reduce expenses associated with the municipality’s legal actions.
  • Influence of sonication and in vitro evaluation of nifedipine self-nanoemulsifying drug delivery system Article

    Eid, Ahmad M; Elmarzugi, Nagib A; Jaradat, Nidal A

    Abstract in English:

    In order to develop a self-nanoemulsifying system, three components, olive oil, Tween 80, and Capmul, were used to construct a ternary phase diagram that helped to find the optimum formulation, which was loaded with nifedipine. The effect of sonication on drug loading was also evaluated. After that, measurement of the droplet size, size distribution, zeta potential, and scanning electron microscopy were conducted for evaluation and characterisation of the formulations. The phase diagram of four formulations showed nanosizes below 200 nm; however, only one was selected to be loaded with nifedipine. The selected formulation had the lowest droplet size of 98 nm and size distribution 0.192, and was composed of 48% Tween 80, 32% Capmul, and 20% olive oil. The nifedipine self-nanoemulsifying drug delivery system (SNEDDS) showed a significant change in the particle size (97 nm) and size distribution (0.257) after sonication. Its zeta potential was -32.3 mV indicating good stability. The SEM photographs of nifedipine showed particles with spherical shape and smooth surface. Finally, a self-nanoemulsifying formulation containing nifedipine, loaded in olive oil, was successfully prepared by mixing the oil with various types of surfactants and co-surfactants. A significant nifedipine self-nanoemulsifying system was developed and significantly improved accordingly.
  • Tadalafil-loaded PLGA microspheres for pulmonary administration: preparation and evaluation Article

    Yang, Zhenlei; Wang, Longmei; Tian, Liu; Zhang, Xiuping; Huang, Guihua

    Abstract in English:

    Tadalafil, a long-acting PED-5 inhibitor, is commonly used for the treatment of pulmonary arterial hypertension (PAH). However, its efficacy and clinical application are severely limited by the poor water solubility, low bioavailability and a series adverse effects (e.g. headaches, indigestion). In this study, tadalafil was prepared and loaded into biodegradable PLGA (poly(lactic-co-glycolic acid)) microspheres (TDF-PLGA-MS) via emulsification-solvent evaporation. The resulting microspheres were processed into pulmonary inhalant by freeze drying. The TDF-PLGA-MS was spherical and uniform, with an average particle diameter ~10.29 µm. The encapsulation efficiency and drug loading yield of TDF-PLGA-MS were 81.68% and 8.52%, respectively. The investigation of micromeritics showed that the TDF-PLGA-MS had low moisture content. The fluidity of powders was relatively good. The aerodynamic diameter and emptying rate of microspheres powders were 3.92 µm and 95.41%, respectively. Therefore, the microspheres powders were easy to be atomized, and can meet the requirements of pulmonary administration. In vitro release results showed that the microspheres group released slowly. The cumulative release in 24 h and 10 d was 46.87% and 84.06%, respectively. The in vitro release profile of TDF-PLGA-MS was in accordance with the Weibull model. The results of Pharmacokinetics showed that tadalafil from microspheres slowly released into the blood after intratracheal instillation. The pulmonary drug residue in 0.5 h was 3.5 times compared with solution group. The residual concentration in lung after 10d was still higher than that of solution group in 48 h. The t1/2β and MRT0-∞ were 3.10 times and 3.96 times that of solution group, respectively. Moreover, the Cmax and AUC of drug residues in lung ​​were 3.48 times and 16.36 times that of solution group, respectively. The results of tissue distribution showed that the Re in lung was 16.358, which indicated the lung targeting. In conclusion, the TDF-PLGA-MS for pulmonary administration in this study can significantly improve the pulmonary targeting, increase efficacy of tadalafil and reduce other non-target organs toxicity. This study will have an important clinical significance for PAH patients who need long-term drug therapy.
  • Toxicological effects of ciprofloxacin and chlorhexidine on growth and chlorophyll a synthesis of freshwater cyanobacteria Article

    Azevedo, Fernanda Cristina Rezende; Vaz, Izabela Cristina Dias; Barbosa, Francisco Antônio Rodrigues; Magalhães, Sérgia Maria Starling

    Abstract in English:

    Cyanobacteria are phytoplanktonic microorganisms that are susceptible to the deleterious effects of pharmaceutical residues in the aquatic environment, which poses a challenge to the environment exposed to diverse pharmaceutical products and their potential effects. The objective of this study was to evaluate the effects of the antibiotic substances ciprofloxacin and chlorhexidine in pharmaceutical preparations on the growth and production of chlorophyll of two cyanobacterial strains, Microcystis aeruginosa and Microcystis panniformis, isolated from a lake in a Brazilian environmental protection area. The EC50 and EC10 of chlorhexidine for M. aeruginosa were 206.4 µg/L and 108.5 µg/L, respectively, and for M. panniformis were 171.4 µg/L and 116.6 µg/L, respectively. The EC50 and EC10 of ciprofloxacin for M. aeruginosa were 17.24 µg/L and 3.21 µg/L, respectively, and for M. panniformis were 13.56 µg/L and 1.50 µg/L, respectively. The toxicity of the antibiotic ciprofloxacin (drug) and chlorhexidine (standard solution) to the Microcystis species was demonstrated, and these species were both very sensitive to ciprofloxacin. Our results suggest that the strains of M. aeruginosa and M. panniformis may be affected by exposure to residues of ciprofloxacin (>1.5 µg/L), which may represent a risk to the survival of aquatic species.
  • Effect of prodigiosin on the alleviation of the intestinal inflammation of weaned rats based on 1H-NMR spectroscopy study and biochemistry indexes Article

    Yang, Peizhou; Wu, Yun; Qian, Jing; Cai, Kezhou; Cao, Lili; Zheng, Zhi; Luo, Shuizhong; Jiang, Shaotong; Zhu, Xingxing

    Abstract in English:

    Weaning results in intestinal dysfunction, mucosal atrophy, transient anorexia, and intestinal barrier defects. In this study, the effect of prodigiosin (PG) on the intestinal inflammation of weaned rats was investigated by using 1H-NMR spectroscopy and biochemistry indexes to regulate the intestinal metabolism. After administration for 14 days, the body mass of the PG group was increased by 1.29- and 1.26-fold compared with those of the control and alcohol groups, respectively, using a dose of 200 µg PG·kg-1 body weight per day. PG increased organic acid content and decreased moisture, pH values, and free ammonia in feces. In addition, PG alleviated the intestinal inflammation of weaned rats. The analysis of 1H-NMR signal peak attribution and the model validation of metabolic data of feces contents showed that PG significantly affected the metabolism of small molecular compounds in the intestinal tract of weaned rats. This study presents the promising alternative of using PG to alleviate intestinal inflammation effectively in the intestinal tract of weaned rats.
  • Evaluation of in vitro and in vivo therapeutic efficacy of Ribes alpestre Decne in Rheumatoid arthritis Article

    Hasan, Alamgeer Umme Habiba

    Abstract in English:

    Rheumatoid arthritis is an autoimmune inflammatory disorder, despite the discovery of numerous drugs there is still need to introduce newer, safer and more effective sources of drugs such as medicinal herbs. Present research work was an attempt to appraise the antiarthritic potential of Ribes alpestre Decne in rheumatoid arthritis. In vitro inhibition of protein (bovine serum albumin and egg albumin) denaturation, Human red blood cell membrane stabilization assays along with formaldehyde induced arthritis in rats were commenced in this study. Findings of present investigation demonstrated significant and dose dependent antiarthritic effect of Ribes alpestre. Aqueous ethanolic extract, butanol and aqueous fraction illustrated 95%, 69.233% and 92.840% protection at 6400 ug/mL against bovine serum albumin denaturation respectively. Similarly, plant extract together with butanol and aqueous fractions showed 3653.47%, 1484.03% and 3563.19% inhibition of pathological alteration of egg albumin in that order. Moreover, hydroethanolic extract with butanol and aqueous fraction exhibited 91.29%, 65.73% and 89.62% stabilization against erythrocyte hemolysis at 6400 ug/mL correspondingly. Furthermore, hydroethanolic extract, butanol and aqueous fraction notably 73.49%, 66.42% and 68.87% decreased paw edema at highest dose (200 mg/kg). Similarly aqueous ethanolic extract, butanol and aqueous fraction illustrated 72.38%, 54.90% and 66.33% decrease in paw thickness at 200 mg/kg. Hence results suggested that Ribes alpestre possess antiarthritic potential thus supporting its use as natural remedy in rheumatic conditions.
  • Delay of neuropathic pain sensitization after application of dexamethasone-loaded implant in sciatic nerve-injured rats Article

    Bastos, Leandro Francisco Silva; Vago, Juliana Priscila; Caux, Thaís Rolla; Costa, Bruna Lopes; Godin, Adriana Martins; Menezes, Raquel Rezende; Pena, Roberta Ribas; Silva-Cunha, Armando; Sousa, Lirlândia Pires; Machado, Renes Resende; Moraes, Márcio Flávio Dutra; Fialho, Sílvia Ligório; Coelho, Márcio Matos

    Abstract in English:

    Neuroimmune interactions underlying the development of pain sensitization in models of neuropathic pain have been widely studied. In this study, we evaluated the development of allodynia and its reduction associated with peripheral antineuroinflammatory effects induced by a dexamethasone-loaded biodegradable implant. Chronic constriction injury (CCI) of the sciatic nerve was performed in Wistar rats. The electronic von Frey test was applied to assess mechanical allodynia. The dexamethasone-loaded implant was placed perineurally at the moment of CCI or 12 days after surgery. Dorsal root ganglia (DRG; L4-L5) were harvested and nuclear extracts were assayed by Western blot for detection of nuclear factor (NF)-κB p65/RelA translocation. Dexamethasone delivered from the implant delayed the development of allodynia for approximately three weeks in CCI rats when the implantation was performed at day 0, but allodynia was not reversed when the implantation was performed at day 12. NF-κB was activated in CCI rat DRG compared with naïve or sham animals (day 15), and dexamethasone implant inhibited p65/RelA translocation in CCI rats compared with control. This study demonstrated that the dexamethasone-loaded implant suppresses allodynia development and peripheral neuroinflammation. This device can reduce the potential side effects associated with oral anti-inflammatory drugs.
  • Icariin stimulates differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) through activation of cAMP/PKA/CREB Article

    Lou, Dan; Ye, Jifeng; Yang, Lianhua; Wu, Zheng; Zheng, Wei; Zhang, Hui

    Abstract in English:

    Icariin, a prenylated flavonol glycoside isolated from Epimedium, has been considered as a potential alternative therapy for osteoporosis. The present study aimed to clarify the detailed molecular mechanisms of action of icariin on osteoblast function, using bone marrow-derived mesenchymal stem cells (BM-MSCs). BM-MSCs were first stimulated by icariin. Then, gene and protein expression of cAMP/PKA/CREB signaling molecules were analyzed by RT-PCR and western blotting (WB), and alkaline phosphatase (ALP) was analyzed in cell lysates by ELISA. MTT assays indicated that icariin did not have significant effects on cell viability up to 1 µM. Icariin showed a dose-dependent effect on the alkaline phosphatase activity of BM-MSCs. WB analysis showed that icariin treatment of BM-MSCs significantly enhanced the protein expression of protein kinase A (PKA) and cAMP-responsive element binding protein (CREB), while RT-PCR results showed that icariin dose-dependently increased the mRNA levels of PKA and CREB. Icariin induced BM-MSC differentiation by BMP2, Smad1, and Runx2. RT-PCR and WB results indicated that icariin significantly increased the expression of BMP2, Smad1, and Runx2 in BM-MSCs. These results suggest that icariin is an agonist of the cAMP/PKA/CREB pathway in BM-MSC differentiation, raising the possibility that it could be used in the treatment of osteoporosis.
  • Composition, antioxidant properties, and biological activities of the essential oil extracted from Ocotea diospyrifolia (Meisn.) Mez. Article

    Fabri, Natasha Tiemi; Gatto, Larissa Junqueira; Furusho, Alethéia Santos; Garcia, Meira Janette Ballestros; Marques, Francisco de Assis; Miguel, Marilis Dallarmi; Montrucchio, Deise Prehs; Zanin, Sandra Maria Warumby; Miguel, Obdulio Gomes; Dias, Josiane de Fátima Gaspari

    Abstract in English:

    The article has aimed to characterize the essential oil extracted from Ocotea diospyrifolia (Meisn.) Mez. leaves, in terms of its chemical composition and antioxidant, hemolytic, and phytotoxic potentials, as well as its toxicity against Artemia salina. The major constituents identified by CG-MS were d-elemene, spathulenol, and b-atlantol. When screened for potential biological activities, the essential oil presented low toxicity against Artemia salina, and a capacity of lysing red blood cells. Also, the evaluation of its in vitro antioxidant activity, using the phosphomolybdenum method, showed better results when compared to butylhydroxytoluene (BHT) and rutin. In conclusion, the results obtained showed certain in vitro toxicity, leading to an interesting target for cytotoxicity evaluations of carcinoma cells.
  • Antimicrobial activity of actinomycetes and characterization of actinomycin-producing strain KRG-1 isolated from Karoo, South Africa Articles

    Charousová, Ivana; Medo, Juraj; Hleba, Lukáš; Císarová, Miroslava; Javoreková, Soňa

    Abstract in English:

    In the present study we reported the antimicrobial activity of actinomycetes isolated from aridic soil sample collected in Karoo, South Africa. Eighty-six actinomycete strains were isolated and purified, out of them thirty-four morphologically different strains were tested for antimicrobial activity. Among 35 isolates, 10 (28.57%) showed both antibacterial and antifungal activity. The ethyl acetate extract of strain KRG-1 showed the strongest antimicrobial activity and therefore was selected for further investigation. The almost complete nucleotide sequence of the 16S rRNA gene as well as distinctive matrix-assisted laser desorption/ionization-time-of-flight/mass spectrometry (MALDI-TOF/MS) profile of whole-cell proteins acquired for strain KRG-1 led to the identification of Streptomyces antibioticus KRG-1 (GenBank accession number: KX827270). The ethyl acetate extract of KRG-1 was fractionated by HPLC method against the most suppressed bacterium Staphylococcus aureus (Newman). LC//MS analysis led to the identification of the active peak that exhibited UV-VIS maxima at 442 nm and the ESI-HRMS spectrum showing the prominent ion clusters for [M-H2O+H]+ at m/z 635.3109 and for [M+Na]+ at m/z 1269.6148. This information could be assigned to chromopeptide lactone antibiotic - actinomycin. Our results suggest that unexplored soils could be an interesting source for exploring antibacterial secondary metabolites.
  • Toxicological evaluation of Lafoensia pacari A. St.-Hil. (Lythraceae) stem bark extract: Acute and subchronic studies in mice Articles

    Ávila, Renato Ivan de; Ferreira, Camila Carvalho; Alvarenga, Cátia Belo Mattos; Vieira, Marcelo de Sousa; Cortez, Alane Pereira; Batista, Aline Carvalho; Costa, Elson Alves; Valadares, Marize Campos

    Abstract in English:

    This study evaluated the safety of Lafoensia pacari A. St.-Hil. (Lythraceae) stem bark hydroalcoholic extract (LPE) through acute and subchronic toxicological assessments in mice. In the acute toxicity evaluation, a single 2000 mg/kg oral dose of LPE was administered to mice and clinical observations were conducted for 14 days. For subchronic toxicity, LPE doses (6.25-1000 mg/kg) were administered orally for 28 days and biochemical, hematological, histopathological analyses and renal and liver expression of Ki-67 were carried out. The acute oral toxicity evaluation of LPE showed no toxicity in mice and it was was classified as category 5 (LD50>2000-5000 mg/kg). In a repeated dose 28-day toxicity study, LPE (100-1000 mg/kg) led to an increase in reticulocytes, which suggests a possible proliferative effect on blood cells. In addition, LPE (400-1000 mg/kg) of produced alterations in biochemical parameters, although no microscopic changes were found in the organs analyzed. A normal expression of the Ki-67 cell proliferation indicator was observed in the kidney and liver tissues, which suggests that LPE does not bring about changes in the proliferative activity of these organs. In conclusion, LPE should be used with caution, particularly in larger doses over longer periods and also in combination with other medication.
  • Evaluation of triterpenes derivatives in the viability of Leishmania amazonensis and Trichomonas vaginalis Articles

    Cargnin, Simone Tasca; Staudt, Andressa Finkler; Menezes, Camila; Azevedo, Ana Paula de; Fialho, Saara Neri; Tasca, Tiana; Teles, Carolina Bioni Garcia; Gnoatto, Simone Baggio

    Abstract in English:

    Trichomonas vaginalis and Leishmania spp. are protozoal species responsible for millions of cases of parasitic diseases worldwide. Considering the potential of natural products and the need for more effective and less toxic alternatives to treat trichomoniasis and leishmaniasis, this study aimed to evaluate the effect of two series of triterpenes derivatives with different modifications at C-3 and C-28 positions of the ursolic acid (UA) and betulinic acid (BA) against trophozoites of Trichomonas vaginalis and promastigotes forms of Leishmania (L.) amazonensis. The compounds modified just at C-3 were the most active. The 3β-acetyl betulinic acid (1b) reduced the trophozoites viability of T. vaginalis at 74%, followed by the 3-oxo ursolic acid and 3-oxo betulinic acid (3a and 3b) compounds (55% of reduction). The compound 3β-isobutyl ursolic acid (7a) inhibited the viability of L. amazonensis promastigotes by 55%. Therefore, analyzing the structure-activity relationship and the data of literature, it is possible to suppose that the inclusion of polar groups in the skeletons could improve the antiprotozoal activity. Overall, further studies are necessary to develop triterpenic derivatives with more powerful trichomonicidal and leishmanicidal properties.
  • Development and characterization of photoprotective formulations containing keratin particles Articles

    Teixeira, Jessica; Freitas, Zaida Maria Farias de; Monteiro, Mariana Sato de Souza Bustamante; Vermelho, Alane Beatriz; Ricci, Eduardo; Santos, Elisabete Pereira dos

    Abstract in English:

    This work deals with development and evaluation of MFQ protective formulation, which contains two organic filters, namely: octyl-p-methoxycinnamate (OMC) and benzophenone-3 (BP-3); a photostabilizing agent called ethylhexylmethoxycrylene (EHMCR) and keratin particles. The MFQ formulation was evaluated in order to measure its pH, spin-spin lattice relaxation time (T2H), occlusivity factor, formulation efficacy, photostability and skin permeation, as well as keratin particle properties. Keratin particle size increased when incorporated to formulation, however, it did not affect pH. The MFQ formulation was found to be photostable and photoprotective, as evidenced by sunlight photostability test, sun protection factor (SPF), UVA/UVB ratio and critical wavelength. Interaction between keratin particles and active substances (OMC, BP-3 and EHMCR) was evidenced by T2H measurements. Evidences suggest that keratin reduces the permeation of both UV filters employed along this study, therefore, it can be stated that keratin has a promising potential for use in sunscreen formulations.
  • Effect of lesimarin against thioacetamide-induced liver cirrhosis in rat Articles

    Ra, Sang-Ho; Shin, Ri-Hwa; Ri, Hak-Chol; Ri, Jong-Hui; Ri, Hui-Chol; Ri, Ae-Jong

    Abstract in English:

    Liver cirrhosis is one of chronic liver diseases with high disability and mortality accompanying fibrosis, hepatocyte damage, and liver dysfunction. In this study, the hepatoprotective and the antifibrotic properties of lesimarin(lecithin - silymarin - Artemisia messerschmitiana Besser(AMB) extract complex at 11:3:6 ratio) on rat hepatic fibrosis induced by thioacetamide (TAA) was investigated. Rats were divided into seven groups: control, lesimarin, TAA, TAA+lesimarin, TAA+lecithin, TAA+silymarin, TAA+AMB. Rats were administered with TAA at a dose of 200 mg/kg body weight intraperitoneally twice a week for three months. Lesimarin, lecithin, silymarin and AMB were administered at a dose of 1.0, 1.0, 0.5, 1.0g/kg body weight orally daily for three months, respectively. TAA administration resulted in hepatic fibrosis, significant decrease in body weight, albumin level and A/G ratio and increase in plasma transaminase, GGT(γ-glutamyltransferase) and ALP(alkaline phosphatase) activities as well as hepatic hydroxyproline content, which were attenuated by lesimarin administration. Lesimarin was found to decrease AST, ALT and GGT, ALP and bilirubin, hydroxyproline levels and increase albumin level and A/G ratio and its effect is more prominent than those of individual constituents. These results suggest this new drug, lesimarin, might be a promising drug to be used for chronic liver diseases.
  • The production of biopharmaceuticals in Brazil: current issues Articles

    Pimenta, Marcela Valente; Monteiro, Gisele

    Abstract in English:

    Biopharmaceuticals are gaining a growing share of the pharmaceuticals market. In recent years, the Brazilian Health Surveillance Agency (ANVISA) has approved the registration of biological drugs with domestic production. Although Brazil is in the early stages of biopharmaceutical production, governmental incentives and the investment in private companies in the technological domain in this country have created expectations of an increase in the capacity of biopharmaceutical production. Private initiatives, once rare, have now started to blossom in this field, such as collagenase from Cristalia and filgrastim from Eurofarm. The expiry of the patents for certain biopharmaceuticals (e.g. infliximab, filgrastim and rituximab) has generated the possibility of savings to the Brazilian National Health System (SUS) in terms of biosimilars and incentives for national production. National production could also avoid dependence on external imports and a lack of essential supplies. In the next few years, Brazil is expected to bring nationally produced biopharmaceuticals to the market. Although there is some way to go before Brazil will be able to sustain the national demand for biopharmaceuticals and supply international markets with new products, the country is starting to take its first steps towards these objectives.
  • Chemical composition and bioactivity of methanolic extract obtained from Lepista sordida Articles

    Acharya, Krishnendu; Ghosh, Sandipta; Biswas, Rhituparna

    Abstract in English:

    The present study aimed at the evaluation of chemical composition and bioactive potential of methanolic extract obtained from Lepista sordida in terms of antioxidative and antimicrobial efficacy. The macrofungus is recognized for its high nutritional value and medicinal properties. However, to the best of our knowledge bioactivity of its methanolic extract is yet to be explored. In this investigation, quantitative analysis of mycochemicals revealed the extract contained significant amount of phenolic compounds such as phenols and flavonoids. Ascorbic acid was found in higher amount than β carotene and lycopene which were present in vestigial amounts. A phenolic profile was also determined using high performance liquid chromatography that further confirmed the presence of 10 phenolic constituents in the extract. Furthermore, the extract was subjected for determining antioxidant potential in different in-vitro assays. The findings showed remarkable 2, 2-Diphenyl-1-picrylhydrazyl and ABTS radical scavenging ability which was evident by low EC50 values, 330 µg/mL and 30 µg/mL respectively. The extract also demonstrated good chelating and reducing ability, an important marker of antioxidant compounds. Antimicrobial screening displayed positive results against Staphylococcus aureus and Escherichia coli. Altogether, the observations recommend therapeutic application of this mycotaxon on a commercial basis.
  • Evaluation of polyelectrolyte and emulsion covalent crosslink of chitosan for producing mesalasine loaded submicron particles Articles

    Lacerda, Gabriel José Silveira; Piantino, Beatriz Lemos; Gonzaga, Edeilson Vitor; Naves, Valéria de Moura Leite; Pedreiro, Liliane Neves; Gremião, Maria Palmira Daflon; Pereira, Gislaine Ribeiro; Carvalho, Flávia Chiva

    Abstract in English:

    This study evaluates various techniques for producing mesalamine (5ASA)-loaded particles employing chitosan as a biopolymer: (1) the polyelectrolyte complexation of chitosan with phthalate hypromelose (HP), (2) the chemical crosslinking of chitosan with genipin and (3) the water-in-oil emulsion method associated with chemical crosslinking with genipin. Systems were characterized by dynamic light scattering, zeta potential (ζ), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR) and a drug release profile. Method (1) was efficiently produced unloaded nanoparticles (491 nm, PdI=0.26 and ζ = 23.2), but the conditions for chitosan and HP cross-linking enhanced the precipitation of 5ASA. Method (2) caused the degradation of the drug. Method 3 produced sub-micron and microparticles, thereby varying the agitation method; 3 h magnetic agitation resulted in 2692 nm, Pdi = 0.6 and ζ = 46, while Ultra-Turrax, 5 min produced submicron particles (537 nm, PdI = 0.6). The percentage yield was approximately 50%, which is very satisfactory considering the impossibility of encapsulating 5ASA using other methods. FTIR showed the covalent interaction of chitosan and genipin. The drug release was rapid in acidic fluid, but in neutral pH a slower release was obtained in the initial stage, followed by rapid release, which may ensure the controlled release of 5ASA in the colon.
  • Preformulation of a liquid dosage formulation of captopril for pediatric use: drug-excipient compatibility and stability studies Articles

    Goes, Janaina da Silva; Freire, Fátima Duarte; Moura, Túlio Flávio Accioly de Lima e; Aragão, Cícero Flávio Soares; Raffin, Fernanda Nervo

    Abstract in English:

    Currently, medications used in children are typically modified from pharmaceutical dosage forms designed for adults. Captopril is widely adapted to liquid formulations for use in hospitals. Its stability in the aqueous medium is reduced since it undergoes oxidation producing captopril disulfide (its main metabolite). The aim of this formulation study was to suggest favorable conditions for the development of a stable captopril formulation. The compatibility between the drug and excipients was evaluated by differential scanning calorimetry analysis (DSC). For studies in solution, different formulations were prepared according to a factorial design varying EDTA concentration, water purity and pH. The resultant formulations were stored at 60°C and analyzed over a twelve-day period using HPLC. The DSC curves obtained suggested, although not conclusive to elucidation, interactions of captopril with citric acid and sucralose. The stability study of these solutions revealed that the variables significantly influenced captopril content, which degraded at zero order kinetics and rates differing by a factor of up to 7 times, where pH proved the most influential factor. Interactions between variables were observed. Therefore, development of a stable captopril formulation is feasible provided EDTA and a buffering agent is used at suitable concentrations (0.08% and pH 3.85).
  • Multidrug-resistant Candida glabrata strains obtained by induction of anidulafungin resistance in planktonic and biofilm cells Articles

    Hatwig, Camila; Balbueno, Eduardo A.; Bergamo, Vanessa Z.; Pippi, Bruna; Fuentefria, Alexandre M.; Silveira, Gustavo P.

    Abstract in English:

    Candida glabrata has emerged as a common cause of serious life-threatening fungal infections, largely owing to their low susceptibility to azole antifungals. Recent guidance indicates the use of echinocandins as the first-choice drug for the treatment of systemic infections of C. glabrata; however, C. glabrata resistance to echinocandins is reportedly increasing. Herein, we present the induction of anidulafungin resistance in planktonic and sessile cells of C. glabrata and the development of fluconazole cross-resistance. MICs of 21 clinical C. glabrata strains were determined by a broth microdilution method using anidulafungin and fluconazole. Biofilm formation on a tracheal catheter was determined using 1- × 1-cm2 polyvinyl polychloride catheter fragments. Induction of anidulafungin resistance in planktonic and sessile cells and evaluation of its stability were performed by exposing the strains to successively higher concentrations of the antifungal. The induction resulted in strains strongly resistant to anidulafungin (MICs: 1-2 µg/mL) and fluconazole (≥64 µg/mL). Most of the sessile cells of C. glabrata presented slightly reduced susceptibility compared with the planktonic cells. Clinically, this cross-resistance could lead to therapeutic failure while using fluconazole in patients previously exposed to subinhibitory concentrations of anidulafungin for extended periods.
  • The traditional Chinese medicine formulation Ruanjian Sanjie Decoction regulates the tumor matrix and improves the anti-tumor efficacy of TP-PEG-LPs Articles

    Cai, Xin-jun; Wang, Zeng; Xu, Ying-ying; Ye, Lihong; Cao, Jia-wei; Ni, Jian-jun; Wu, Ting-ting

    Abstract in English:

    The Ruanjian Sanjie Decoction (RSD) is a traditional Chinese medicine (TCM) formulation consisting of Spica Prunellae, Pseudobulbus Cremastrae Seu Pleiones, Concha Ostreae and Semen Coicis, and widely used as an adjuvant in anti-cancer therapy. The aim of this study was to determine the effects of RSD on the extracellular matrix (ECM) of tumors, and on the efficacy of anti-cancer nano-formulations in a tumor-bearing mouse model. The mice were treated with triptolide encapsulated in PEG-modified liposomes (TP-PEG-LPs), either alone or in combination with RSD. The combination treatment significantly retarded tumor growth relative to the untreated controls, indicating the potent adjuvant effect of RSD in targeted anti-cancer therapy. In addition, RSD also reduced the amount of total collagen and collagen I and increased that of collagen III in the tumor ECM, along with decreasing the expression of the pro-angiogenic VEGF. Finally, even high doses of RSD did not significantly affect the liver and kidney function or body weight, indicating low toxicity.
  • Protective effect of citrus lemon on inflammation and adipokine levels in acrylamide-induced oxidative stress in rats Articles

    Haidari, Fatemeh; Mohammadshahi, Majid; Zarei, Mehdi; Fathi, Mojdeh

    Abstract in English:

    The high exposure to acrylamide (AA) due to smoking and increased consumption of processed and fast foods in recent years, has become one of the health threatening problems. This study examined the effect of lemon juice on inflammation and adipokines in acrylamide-induced oxidative stress in rats. Forty animals were divided into five groups. Toxicity was induced by AA (35mg/kg) for two weeks in all groups except normal control group. After that, lemon juice in three doses was administrated to treatment groups for 4 weeks. Serum levels of adipokines and inflammatory parameters and both serum and liver levels of oxidative stress parameters were measured. The results showed groups were received AA had significant higher levels of malondialdehyde, tumor necrosis factor alpha, leptin and C-reactive protein and lower levels of total antioxidant capacity compared to the negative control group. Lemon juice in all three doses significantly improved serum levels of TAC, MDA, TNFα and hs-CRP in treated groups. Also, 7.5 ml/kg lemon juice significantly decreased leptin levels. However, lemon juice had no significant effect on adiponectin levels. This study suggests lemon juice as a potential dietary alternative could attenuate leptin levels and manage oxidative and inflammatory damages in acrylamide- induced toxicity in rats.
  • Antidiabetic activity of aqueous extract of Sigesbeckia orientalis (St. Paul’s Wort) in alloxan-induced diabetes model Articles

    Asif, Muhammad; Saleem, Mohammad; Yousaf, Sobia; Saadullah, Malik; Zafar, Memoona; Khan, Rizwan Ullah; Yuchi, Alamgeer

    Abstract in English:

    The current study evaluated antidiabetic and antihyperlipidemic activities of aqueous extract of Sigesbeckia orientalis L. (St. Paul’s Wort) (AESO) in an alloxan-induced diabetic rat model. Following OECD guidelines safe doses of AESO were assessed in rats for the main study. Serum/bood glucose, α-amylase, and lipids levels and histopathological evaluations were conducted to assess antidiabetic and associated antihyperlipidemic efficacies of AESO. AESO was found to be safe up to the dose of 2000 mg/kg. Significant (p < 0.05) reduction in glucose and lipids (total cholesterol, triglycerides, low-density lipoproteins) levels was observed in AESO treatment groups. Serum α-amylase, high-density lipoproteins, and total body weight was increased significantly (p < 0.05) in diabetic rats treated with AESO. Histopathological data showed improvement in hepatocyte and pancreatic β-cells islets architecture. HPLC analysis identified quercetin, gallic acid, vanillic acid, p-coumaric acid, m-coumaric acid and cinnamic acid in AESO which are suggested to be responsible for observed antihyperglycemic and antihyperlipidemic attributes. Further studies to standardise the extract and evaluation of safety profile in long-term toxicity studies are recommended for safe and effective antidiabetic nutraceuticals development.
  • The anti-obesity potential of Ilex paraguariensis: results from a meta-analysis Review

    Luís, Ângelo Filipe Santos; Domingues, Fernanda da Conceição; Amaral, Luísa Maria Jota Pereira

    Abstract in English:

    The dried leaves of Ilex paraguariensis, also known as yerba mate or chimarrão, are used to produce infusions consumed by over 1 million people worldwide, being a traditional drink in several South American countries, particularly, Argentina, Brazil, Uruguay, and Paraguay. The positive effects of I. paraguariensis in obesity have been described and observed in some clinical trials both in animals and in humans. The main goal of this work was to perform a systematic review, complying with the PRISMA (Preferred Reported Items for Systematic Reviews and Meta-Analysis) recommendations, followed by a meta-analysis and Trial Sequential Analysis (TSA), to summarize the results of the recent clinical trials, clarifying the anti-obesity potential of I. paraguariensis. The search for this systematic review was performed on several electronic databases (Pubmed, Web of Science, Scopus, SciELO and Cochrane Library) in July 2017. A total of 22 clinical trials were considered for the quantitative synthesis of the data, totalizing 726 patients enrolled. In conclusion, this systematic review demonstrated the positive effects of I. paraguariensis consumption on the reduction of body weight, body mass index (BMI), and waist circumference of patients, showing its anti-obesity potential.
  • A review on medicinal plants used for treating ototoxicity and acoustic trauma induced hearing loss Review

    Mahmoudian-sani, Mohammad-Reza; Sheikhshabani, SomayehHashemi; Mirfakhar, Farzaneh Sadat; Asgharzade, Samira

    Abstract in English:

    Hearing loss induced by chemotherapy and acoustic trauma is mainly associated with two factors, free radical formation and apoptosis pathway activation. Despite numerous efforts on reducing the effects of these factors, no definite strategy is still determined to interfere with and control these processes. In recent studies, various protective agents, including antioxidants have been used on animal models, to inhibit the formation of free radicals thus improving hearing loss.In this review article we will discuss the role of traditional herbal medicine in treatment of noise/drug induced hearing loss, focusing on medicinal plants’ active substances,as well as their mechanisms of action in reducing or preventing the formation of free radicals thus increasing the rate of survival of cochlea cells. Data have been gathered since year 2000, from scientific publications including the following keywords: deafness, drug toxicity, acute trauma, medicinal herbs and oxidative stress. The study includes all herbs and medicinal plants that have been experimentally used in studies on animal models and clinical trials. The results from these studies indicate the effectiveness of most of these herbs and their active substances through their antioxidative properties. Medicinal plants reported in this review can thus be considered as effective remedies intreating noise/drug induced hearing loss,yet further studies need to be done.
Universidade de São Paulo, Faculdade de Ciências Farmacêuticas Av. Prof. Lineu Prestes, n. 580, 05508-000 S. Paulo/SP Brasil, Tel.: (55 11) 3091-3824 - São Paulo - SP - Brazil
E-mail: bjps@usp.br