Scielo RSS <![CDATA[Brazilian Journal of Medical and Biological Research]]> vol. 51 num. 9 lang. en <![CDATA[SciELO Logo]]> <![CDATA[Mycotic aneurysm due to <em>Salmonella</em> species: clinical experiences and review of the literature]]> The mortality of patients with mycotic aneurysms is high, especially in East Asia, and infection by Salmonella species is the most common. Our study aimed to improve prognosis of adult mycotic aneurysms with early diagnosis and accurate treatment. Four adult patients with mycotic aneurysm caused by Salmonella were included and analyzed by single-center retrospective analysis. Cases reported in the literature during the past 10 years were also summarized. The average age of the 4 male patients was 61.25 years, while that of the 53 cases reported in the literature was 65.13 years. Hypertension, diabetes, and atherosclerosis were common complications. Most patients presented fever and experienced pain at the corresponding position of the aneurysm. Laboratory examination found an increased number of white blood cells accompanied by an increase in inflammatory markers. Most aneurysms were found in the abdominal aorta, while the rupture of an aneurysm was the most common complication. The mortality rates were 21.43 and 7.14% after open surgery or endovascular aneurysm repair (EVAR) intervention, respectively. The recurrence rates of infection were 0 and 17.85% for both treatments, respectively. The mortality rate of mycotic aneurysm caused by Salmonella infection was high in middle-aged males with hypertension, diabetes, and atherosclerosis. The possibility of a Salmonella-infected aneurysm should be considered in these high-risk groups presenting chills, fever, chest, and back pain. Open surgery was superior to EVAR treatment in the clearance of infected foci and the reduction of postoperative recurrence. The recurrence of postoperative infection can be prevented by intravenous antibiotic therapy for 6 weeks post-surgery. <![CDATA[Study of major genetic factors involved in pituitary tumorigenesis and their impact on clinical and biological characteristics of sporadic somatotropinomas and non-functioning pituitary adenomas]]> Genetic and functional aberrations of guanine nucleotide-binding protein, alpha stimulating (GNAS), aryl hydrocarbon receptor interacting protein (AIP), and pituitary tumor transforming gene (PTTG) are among the most prominent events in pituitary tumorigenesis. A cohort of Brazilian patients with somatotropinomas (n=41) and non-functioning pituitary adenomas (NFPA, n=21) from a single tertiary-referral center were evaluated for GNAS and AIP mutations and gene expression of AIP and PTTG. Results were compared to the clinical and biological (Ki67 and p53 expression) characteristics of tumors and their response to therapy, if applicable. Genetic analysis revealed that 27% of somatotropinomas and 4.8% of NFPA harbored GNAS mutations (P=0.05). However, no differences were observed in clinical characteristics, tumor extension, response to somatostatin analog therapy, hormonal/surgical remission rates, Ki67 index, and p53 expression between mutated and non-mutated somatotropinomas patients. PTTG overexpression (RQ mean=10.6, min=4.39, max=11.9) and AIP underexpression (RQ mean=0.56, min=0.46-max=0.92) were found in virtually all cases without a statistically significant relationship with clinical and biological tumor features. No patients exhibited somatic or germline pathogenic AIP mutations. In conclusion, mutations in GNAS and abnormal PTTG and AIP expression had no impact on tumor features and treatment outcomes in this cohort. Our data support some previous studies and point to the need for further investigations, probably involving epigenetic and transcriptome analysis, to improve our understanding of pituitary tumor behavior. <![CDATA[Mechanisms involved in anti-aging effects of guarana (<em>Paullinia cupana</em>) in <em>Caenorhabditis elegans</em>]]> Guarana (Paullinia cupana) is habitually ingested by people in the Amazon region and is a key ingredient in various energy drinks consumed worldwide. Extension in longevity and low prevalence of chronic age-related diseases have been associated to habitual intake of guarana. Anti-aging potential of guarana was also demonstrated in Caenorhabditis elegans; however, the mechanisms involved in its effects are not clear. Herein, we investigated the putative pathways that regulate the effects of guarana ethanolic extract (GEE) on lifespan using C. elegans. The major known longevity pathways were analyzed through mutant worms and RT-qPCR assay (DAF-2, DAF-16, SKN-1, SIR-2.1, HSF-1). The possible involvement of purinergic signaling was also investigated. This study demonstrated that GEE acts through antioxidant activity, DAF-16, HSF-1, and SKN-1 pathways, and human adenosine receptor ortholog (ADOR-1) to extend lifespan. GEE also downregulated skn-1, daf-16, sir-2.1 and hsp-16.2 in 9-day-old C. elegans, which might reflect less need to activate these protective genes due to direct antioxidant effects. Our results contribute to the comprehension of guarana effects in vivo, which might be helpful to prevent or treat aging-associated disorders, and also suggest purinergic signaling as a plausible therapeutic target for longevity studies. <![CDATA[Establishment of a rat model for uterine leiomyomas based on Western and traditional Chinese medicine theories]]> Uterine leiomyomas (ULs) are benign monoclonal tumors that arise from the underlying myometrial tissue in the uterus. Effective therapies are still lacking because of poor understanding of the pathophysiology and epidemiology. Hence, it is urgent to establish efficient animal models to screen novel anti-UL therapies. In this study, for the first time, traditional Chinese medicine and Western medicine were combined to establish an animal model of ULs in rats. In order to evaluate the function and value of the novel model, it was compared with other models. The long-term and short-term rat models for ULs were established using progesterone and diethylstilbestrol. Rats in Qi stagnation and blood stasis group were injected with epinephrine hydrochloride and received chronic unpredictable stress for two weeks. Rats in combining disease with syndrome group (CDWSG) received not only epinephrine hydrochloride injection and chronic unpredictable stress but also progesterone and diethylstilbestrol treatment. We analyzed differences in organ coefficient, uterus size, uterine pathology, concentrations of progesterone, estradiol, progesterone receptor, estrogen receptor, expression of desmin, α-smooth muscle actin, and vimentin among the five groups. The animal model of ULs was successfully constructed by loading the rats with estrogen and progesterone. The rat model of CDWSG was more stable than other groups and the method was the most efficient. <![CDATA[Imbalance of γδT17/γδTreg cells in the pathogenesis of allergic asthma induced by ovalbumin]]> We aimed to explore the imbalance between the T helper 17 γδT cells (γδT17) and the regulatory γδT cells (γδTreg) in asthmatic mice. Male Balb/c mice were randomly divided into the normal control group and the asthmatic model group. The asthmatic model group mice were intraperitoneally injected with the mixture of ovalbumin (OVA)/Al(OH)3 and then activated by exposure of the animals to OVA atomization. Airway hyperresponsiveness (AHR) was determined by a non-invasive lung function machine. Hematoxylin and eosin and Alcian blue-periodic acid Schiff staining were done for histopathological analysis. Interleukin (IL)-17 and IL-35 levels in bronchoalveolar lavage fluid were detected by ELISA. The percentage of IL-17+ γδT cells and Foxp3+ γδT cells in spleen cells suspension were detected and the transcription levels of RORγt and Foxp3 in the lung tissue were determined. Compared with the normal control, the severity of airway inflammation and AHR were higher in the asthmatic mice. Furthermore, mice in the asthmatic group displayed significant increases of IL-17+ γδT cells, expression of IL-17A, and RORγt, whereas control mice displayed marked decreases of Foxp3+ γδT cells, expression of IL-35, and transcription factor Foxp3. In addition, the mRNA expression of RORγt was positively correlated with the percentage of IL-17+γδT cells, and the mRNA level of Foxp3 was positively correlated with the percentage of Foxp3+ γδT cells. The imbalance of γδT17/γδTreg in the asthmatic mice may contribute to the pathogenesis of OVA-induced asthma. <![CDATA[Strontium ranelate inhibits wear particle-induced aseptic loosening in mice]]> The imbalance between bone formation and osteolysis plays a key role in the pathogenesis of aseptic loosening. Strontium ranelate (SR) can promote bone formation and inhibit osteolysis. The aim of this study was to explore the role and mechanism of SR in aseptic loosening induced by wear particles. Twenty wild-type (WT) female C57BL/6j mice and 20 sclerostin-/- female C57BL/6j mice were used in this study. Mice were randomly divided into four groups: WT control group, WT SR group, knockout (KO) control group, and KO SR group. We found that SR enhanced the secretion of osteocalcin (0.72±0.007 in WT control group, 0.98±0.010 in WT SR group, P=0.000), Runx2 (0.34±0.005 in WT control group, 0.47±0.010 in WT SR group, P=0.000), β-catenin (1.04±0.05 in WT control group, 1.22±0.02 in WT SR group, P=0.000), and osteoprotegerin (OPG) (0.59±0.03 in WT control group, 0.90±0.02 in WT SR group, P=0.000). SR significantly decreased the level of receptor activator for nuclear factor-κB ligand (RANKL) (1.78±0.08 in WT control group, 1.37±0.06 in WT SR group, P=0.000) and improved the protein ratio of OPG/RANKL, but these effects were not observed in sclerostin-/- mice. Our findings demonstrated that SR enhanced bone formation and inhibited bone resorption in a wear particle-mediated osteolysis model in wild-type mice, and this effect relied mainly on the down-regulation of sclerostin levels to ameliorate the inhibition of the canonical Wnt pathway. <![CDATA[Analysis of radioprotection and antimutagenic effects of <em>Ilex paraguariensis</em> infusion and its component rutin]]> DNA repair pathways, cell cycle checkpoints, and redox protection systems are essential factors for securing genomic stability. The aim of the present study was to analyze the effect of Ilex paraguariensis (Ip) infusion and one of its polyphenolic components rutin on cellular and molecular damage induced by ionizing radiation. Ip is a beverage drank by most inhabitants of Argentina, Paraguay, Southern Brazil, and Uruguay. The yeast Saccharomyces cerevisiae (SC7Klys 2-3) was used as the eukaryotic model. Exponentially growing cells were exposed to gamma rays (γ) in the presence or absence of Ip or rutin. The concentrations used simulated those found in the habitual infusion. Surviving fractions, mutation frequency, and DNA double-strand breaks (DSB) were determined after treatments. A significant increase in surviving fractions after gamma irradiation was observed following combined exposure to γ+R, or γ+Ip. Upon these concomitant treatments, mutation and DSB frequency decreased significantly. In the mutant strain deficient in MEC1, a significant increase in γ sensitivity and a low effect of rutin on γ-induced chromosomal fragmentation was observed. Results were interpreted in the framework of a model of interaction between radiation-induced free radicals, DNA repair pathways, and checkpoint controls, where the DNA damage that induced activation of MEC1 nodal point of the network could be modulated by Ip components including rutin. Furthermore, ionizing radiation-induced redox cascades can be interrupted by rutin potential and other protectors contained in Ip. <![CDATA[NLRP3 inflammasome signaling as an early molecular response is negatively controlled by miR-186 in CFA-induced prosopalgia mice]]> The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is the most frequently studied in the central nervous system and has been linked to neuropathic pain. In this study, a post-translational mechanism of microRNA (miR)-186 via regulating the expression of NLRP3 in the complete Freund's adjuvant (CFA)-treated mice was investigated. The injection of CFA was used to induce trigeminal neuropathic pain in mice. miRs microarray chip assay was performed in trigeminal ganglions (TGs). CFA treatment significantly increased the mRNA expression of NLRP3, interleukin (IL)-1β, and IL-18 in TGs compared to the control group. Moreover, 26 miRs were differentially expressed in TGs from trigeminal neuropathic pain mice, and the expression of miR-186 showed the lowest level of all the miRs. Further examination revealed that NLRP3 was a candidate target gene of miR-186. We delivered miR-186 mimics to CFA-treated mice. The head withdrawal thresholds of the CFA-treated mice were significantly increased by miR-186 mimics injection compared with CFA single treatment. The mRNA and protein expression of NLRP3, IL-1β, and IL-18 in TGs from trigeminal neuropathic pain mice were significantly inhibited by miR-186 mimics treatment compared to the CFA group. miR-186 was able to suppress the neuropathic pain via regulating the NLRP3 inflammasome signaling.