Abstract: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. We have previously shown that hepatic reticuloendothelial system (RES) iron deposition is associated with an advanced degree of nonalcoholic steatohepatitis (NASH) in humans. In this study, we aimed to determine differentially expressed genes related to iron overload, inflammation and oxidative stress pathways, with the goal of identifying factors associated with NASH progression. Seventy five patients with NAFLD were evaluated for their biochemical parameters and their liver tissue analyzed for NASH histological characteristics. Gene expression analysis of pathways related to iron homeostasis, inflammation and oxidative stress was performed using real-time PCR. Gene expression was compared between subjects based on disease status and presence of hepatic iron staining. We observed increased gene expression of hepcidin (HAMP) (2.3 fold, p = 0.027), transmembrane serine proteinase 6 (TMPRSS6) (8.4 fold, p = 0.003), signal transducer and activator of transcription 3 (STAT3) (5.5 fold, p = 0.004), proinflammatory cytokines; IL-1β (2.7 fold, p = 0.046) and TNF-α (3.8 fold, p = 0.001) in patients with NASH. TMPRSS6, a negative regulator of HAMP, is overexpressed in patients with NASH and HIF1α (hypoxia inducible factor-1) is downregulated. NAFLD patients with hepatic iron deposition exhibited higher hepcidin expression (3.1 fold, p = 0.04) but lower expression of cytokines. In conclusion, we observed elevated hepatic HAMP expression in patients with NASH and in NAFLD patients who had hepatic iron deposition, while proinflammatory cytokines displayed elevated expression only in patients with NASH, suggesting a regulatory role for hepcidin in NAFL to NASH transition and in mitigating inflammatory responses.

ABSTRACT Biologically active proteins isolated from plant species can be used in traditional medicine as prolific resources for new drugs Morinda pubescens Sm., Rubiaceae, is a promising medicinal plant which is widely used in folk medicine to treat fever due to primary complex, ulcer and glandular swellings. In this study, proteins were extracted from the leaves of M. pubescens, and precipitated with ammonium sulphate at various saturation concentrations ranging from 20 to 80%. The precipitated protein sample obtained with 80% saturation was further purified using ultrafiltration membrane (<10 kDa). SDS-PAGE analysis identified the presence of crude and ultrafiltered protein bands. FTIR spectrum of the ultrafiltered protein fractions depicted the presence of hydroxyl and carbonyl groups of proteins. The ultrafiltered proteins exhibited increased cytotoxic activity on A549 cells at the concentrations ranging from 15 to 100 µg/ml. About 98% cell viability was also observed in Vero cells treated with the maximum concentration of 100 µg/ml of ultrafiltered protein extract. DNA fragmentation was observed in A549 cells treated with 10 µg/ml of ultrafiltered proteins, indicating the onset of apoptosis.

ABSTRACT Valeriana wallichii DC., Caprifoliaceae, is used to have anti-ulcer, anti-spasmodic, anti-epileptic, memory enhancer, anti-anxiety, anti-rheumatic, sedative, anti-asthmatic and diuretic activities. V. wallichii is reported to contain valpotriates, valeric acid, valerenic acid, valechlorine, valerianine, resins and alkaloids. Valeric acid, found in V. wallichii appears similar in structure to the neurotransmitter GABA. Valeric acid also acts as an NMDA-receptor antagonist. The aim of present study was to investigate the neuroprotective effect of V. wallichii containing valeric acid and its possible mechanism of action in amelioration of intracerebroventricular streptozotocin induced neurodegeneration in Wistar rats. The rhizomes of V. wallichii were powdered coarsely and extracted by percolation method using dichloromethane. Wistar rats (220–250 g) of either sex were divided into 5 groups, comprising 6 animals each. Valeric acid was isolated from plant extract and characterized using FT-IR. Picrotoxin (2 mg/kg) was used as GABA-A antagonist. Intracerebroventricular streptozotocin administration caused significant (p < 0.05) increase in escape latency, retention transfer latency on morris water maze on 17th, 18th, 19th and 20th day and elevated plus maze on 19th and 20th day respectively, as compared to normal untreated rats. Treatment with V. wallichii extract 100 and 200 mg/kg and valeric acid 20 and 40 mg/kg significantly decreased the escape latency and retention transfer latency, as compared to intracerebroventricular-streptozotocin group. Plant extract and valeric acid also decreased the level of lipid peroxidation and restored glutathione level in rat brains. Administration of picrotoxin significantly reversed the effects produced by plant extract and valeric acid in intracerebroventricular-streptozotocin treated rats. The findings may conclude that valeric acid present in V. wallichii has significant GABAergic effect in amelioration of experimental dementia.

ABSTRACTThe decoctions of the Butea monosperma (Lam.) Taub., Fabaceae, Bauhinia variegata L., Fabaceae, and Ocimum gratissimum L., Lamiaceae, are traditionally used for the treatment of various types of hepatic disorder. Phytochemical studies have shown that total flavonoids from these plants were the major constituents of the picked out part of each plant. The present study was planned to investigate the hepatoprotective effect of flavonoid rich fractions of the B. monosperma, B. variegata and O. gratissimum against paracetamol induced liver damage. Flavonoid rich fractions were isolated by solvent fractionation from each plant. Each fraction was subjected to various qualitative chemical tests to findout the metabolites. Flavonoid fractions of each plant were subjected for pharmacological screening. The rats were monitored for change in liver morphology, biochemical parameters like serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase and total bilirubin for the groups receiving the flavonoid-rich fractions. All flavonoid rich fractions showed significant hepatoprotective activity. The histological studies supported the biochemical parameters. From the results of biochemical analysis and histopathological studies, it can be accomplished that in the ethyl acetate fraction of O. gratissimum showed highest hepatoprotective activity as compared to other fractions. The present study was the first evidence of flavonoid-rich fractions of each plant have a remarkable hepatoprotective effect. All fractions contain a potent hepatoprotective agent suggested to be a flavone, which may find clinical application in amelioration of paracetamol-induced liver damage.

A full-length cDNA clone encoding cyclophilin gene of 848 bp, including a 519 bp open reading frame, has been isolated from the cDNA library constructed from etiolated seedlings of Vigna mungo (GenBank FN668732). The cDNA sequence showed 97% identity with Vigna radiata cyclophilin mRNA. The sequence was GC rich and lacked introns. The open reading frame encoded 172 amino acid polypeptide with molecular weight 18.3 kDa and theoretical pI 8.61. BlastP analysis indicated that its putative amino acid sequence shared 100% identity with several plant cyclophilins particularly legumes. The conserved seven amino acid residues region in V. mungo cyclophilin was RSGKPLH (present in legumes) instead of KSGKPLH, indicating its similarity to the cyclophilins of other legumes. This novel V. mungo cyclophilin gene will broaden the pool of plant cyclophilin genes for further studies.

PURPOSE: Re-procedure in patients with history of open stone surgery is usually challenging due to the alteration in the retroperitoneal anatomy. The aim of this study was to determine the possible impact of open renal surgery on the efficacy and morbidity of subsequent percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: From March 2009 until September 2010, 120 patients underwent PCNL. Of these, 20 patients were excluded (tubeless or bilateral simultaneous PCNL). Of the remaining 100, 55 primary patients were categorized as Group 1 and the remaining (previous open nephrolithotomy) as Group 2. Standard preoperative evaluation was carried out prior to intervention, Statistical analysis was performed using SPSS v. 11 with the chi-square test, independent samples t-test, and Mann-Whitney U test. A p-value < 0.05 was taken as statistically significant. RESULTS: Both groups were similar in demographic profile and stone burden. Attempts to access the PCS was less in Group 1 compared to Group 2 (1.2 + 1 2 vs 3 + 1.3 respectively) and this was statistically significant (p < 0.04). However, the mean operative time between the two groups was not statistically significant (p = 0.44). Blood transfusion rate was comparable in the two groups (p = 0.24). One patient in Group 2 developed hemothorax following a supra-11th puncture. Remaining complications were comparable in both groups. CONCLUSION: Patients with past history of renal stone surgery may need more attempts to access the pelvicaliceal system and have difficulty in tract dilation secondary to retroperitoneal scarring. But overall morbidity and efficacy is same in both groups.

We examine quark flavour mixing matrices for three and four generations using the recursive parametrization of U(n) and SU(n) matrices developed earlier. After a brief summary of the recursive parametrization, we obtain expressions for the independent rephasing invariants and also the constraints on them that arise from the requirement of mod symmetry of the flavour mixing matrix.

Las matrices de mezcla de sabor de quarks para tres y cuatro generaciones son examinadas usando la parametrización recursiva de las matrices U(n) y SU(n) desarrolladas con anterioridad. Después de un breve resumen de la parametrización recursiva, se obtienen las expresiónes para los invariantes independientes de un cambio de fase y las restricciónes sobre estos que se producen del requerimiento de que la matriz de mezcla de sabor sea modulo simétrica.

Um método espectrofotométrico novo e altamente sensível foi desenvolvido para a determinação do inseticida cipermetrina em níveis de partes por milhão. O método é baseado na hidrólise alcalina de cipermetrina ao íon cianeto, o qual reage posteriormente com iodeto de potássio e leuco cristal violeta. A absorção máxima do corante cristal violeta formado é medida em 595 nm em meio ácido. A lei de Beer é obedecida no intervalo de concentração de 3,0 a 17 µg, em um volume final da solução de 25 mL (0,12-0,68 ppm). A absortividade molar e sensibilidade de Sandell encontradas foram 3,3<FONT FACE=Symbol>´</FONT>10(5) L mol-1 cm-1 e 0,054 µg cm-2, respectivamente. O desvio padrão e desvio padrão relativo foram ± 0,001 e 0,22%, respectivamente. O método é simples, sensível e livre de interferências de outros pesticidas e íons. Outros inseticidas piretróides não interferem no método proposto. O método tem sido aplicado satisfatoriamente para a determinação de cipermetrina em amostras ambientais e biológicas.

A new and highly sensitive spectrophotometric method was developed for the determination of parts per million levels of widely used cypermethrin insecticide. The method is based on alkaline hydrolysis of cypermethrin to cyanide ion, which further reacts with potassium iodide and leuco crystal violet. The absorption maxima of the crystal violet dye formed was measured at 595 nm in acidic medium. Beer's law obeys over the concentration range of 3.0 to 17 µg in a final solution volume of 25 mL (0.12-0.68 ppm). The molar absorptivity and Sandell's sensitivity were found to be 3.3<FONT FACE=Symbol>´</FONT>10(5) L mol-1 cm-1 and 0.054 µg cm-2, respectively. The standard deviation and relative standard deviation were found to be ± 0.001 and 0.22%, respectively. The method is simple, sensitive and free from interferences of other pesticides and diverse ions. Other pyrethroid insecticides do not interfere in the proposed method. The method has been satisfactorily applied to the determination of cypermethrin in environmental and biological samples.

A phenomenological model which has had some success in explaining polarization phenomena and left-right asymmetry in inclusive proton-proton scattering is considered for reactions involving photons. In particular, the reactions (a) gamma + p -> H + X; (b) gamma + p(<IMG SRC="/img/revistas/bjp/v34n3a/a46img01.gif">) <FONT FACE=Symbol>® p</FONT>± + X and (c) p(<IMG SRC="/img/revistas/bjp/v34n3a/a46img01.gif">) -> + p <FONT FACE=Symbol>® g</FONT> + X are considered where gamma = resolved photon and hyperon H = lambda, sigma, xi etc. Predictions for hyperon polarization in (a) and the asymmetry (in (b) and (c)) provide further tests of this particular model. Feasibility of observing (b) at HERA and the effect of the polarization of the sea in the proton in p(<IMG SRC="/img/revistas/bjp/v34n3a/a46img01.gif">) + p <FONT FACE=Symbol>® p</FONT>± + X is briefly discussed.

For accurate determination of the three-dimensional structure of atmospheric circulation, it is very important to assimilate every observation from all available sources, especially over the data sparse oceanic regions. During the Indian Ocean Experiment Intensive Field Phase -1999 (INDOEX-IFP 99) several special observations were taken over the Indian Ocean region, which gave an opportunity to study this region more thoroughly. In this study these special observations, along with atmospheric motion vectors that form METEOSAT-5(63ºE), have been assimilated along with other conventional as well as non-conventional observations received at the National Centre for Medium Range Weather Forecasting (NCMRWF) through the Global Telecommunication System (GTS) in its global analyses-forecast system. The aim of this study is to assess the impact of the additional data on the Global Data Assimilation system of NCMRWF as well as to create better initial conditions for its future use in modeling studies. Impact of INDOEX data sets on analyses and subsequent 5-day forecast has been studied on the monthly mean fields. Mean wind field shows the strengthening of trade winds in the lower levels and the strengthening of the wind around sub-tropical anticyclone in the higher levels. It is found that the impact is stronger over the data sparse oceanic region and in the higher levels compared to the lower levels. The impact of these data sets is studied on different initial conditions as well as forecast as part of case studies. Significant positive impacts, specially on analysis, are noticed over those oceanic regions where some well-defined synoptic system persisted.

Para la determinación precisa de la estructura tridimensional de la circulación atmosférica es muy importante asimilar cada observación de todas las fuentes de variables, especialmente sobre las regiones oceánicas escasas de datos. Durante la fase intensiva de campo de 1999 del experimento del Océano índico (INDOEX-IFP 99), se hicieron varias observaciones particulares sobre el Océano Indico que dieron la oportunidad de estudiarlo más exhaustivamente. En este estudio, estas observaciones particulares se han asimilado, junto con otras observaciones convencionales y no convencionales recibidas en el Centro Nacional para el Pronóstico Meteorológico de Rango Medio (NCMRWF), a través del Sistema Global de Telecomunicaciones en su sistema de análisis global de pronóstico. El propósito de este estudio es determinar el impacto de los datos adicionales sobre el Sistema Global de Asimilación de Datos del NCMRWF, así como generar mejores condiciones iniciales para su uso futuro en estudios de modelado. Se ha estudiado el impacto de los grupos de datos en análisis y pronósticos subsecuentes de 5 días en los campos medios mensuales. El campo medio de viento muestra el fortalecimiento de las tendencias de los vientos en los niveles bajos y el fortalecimiento del viento alrededor del anticiclón subtropical en los niveles altos. Se ha encontrado que el impacto es mayor sobre las regiones oceánicas escasas de datos y en los niveles altos en comparación con los niveles bajos. Se ha estudiado el impacto de estos grupos de datos sobre diferentes condiciones iniciales así como sobre el pronóstico. Se han observado impactos significativos sobre aquellas regiones oceánicas donde persisten sistemas sinópticos bien definidos.

We report on an illuminated, low-cost (Rs 1500 (US$ 36)) magnifying device (Magnivisualizer) for detecting precancerous lesions of the uterine cervix. A total of 403 women attending a maternal and child health care clinic who had abnormal vaginal discharge and related symptoms were referred for detailed pelvic examination and visual inspection by means of the device after the application of 5% (v/v) acetic acid. Pap smears were obtained at the same time. The results were compared with those obtained using colposcopy and/or histology. The Magnivisualizer improved the detection rate of early cancerous lesions from 60%, for unaided visual inspection, to 95%. It also permitted detection of 58% of cases of low-grade dysplasia and 83% of cases of high-grade dysplasia; none of these cases were detectable by unaided visual inspection. For low-grade dysplasia the sensitivity of detection by means of the Magnivisualizer was 57.5%, in contrast with 75.3% for cytological examination. However, the two methodologies had similar sensitivities for higher grades of lesions. The specificity of screening with the Magnivisualizer was 94.3%, while that of cytology was 99%. The cost per screening was approximately US$ 0.55 for the Magnivisualizer and US$ 1.10 for cytology.

El cáncer cervicouterino es el tumor maligno más frecuente entre las mujeres de la India. En los países en desarrollo no es posible emprender programas de cribado citológico de ámbito nacional debido a la escasez de personal adiestrado y a la falta de la infraestructura necesaria. La simple inspección visual del cuello uterino detecta los cánceres tempranos con una menor sensibilidad y especificidad que los estudios citológicos. En nuestros estudios anteriores hallamos una tasa de detección relativamente baja de las lesiones cervicouterinas precancerosas. A raíz de ello desarrollamos el Magnivisualizador, un dispositivo de iluminación y aumento cuyo precio es de Rs 1500 (US$ 36). Pretendíamos así mejorar la sensibilidad de la inspección visual simple en la detección de lesiones precancerosas o indicativas de cáncer temprano.De fácil manejo, este instrumento portátil funciona con una pila recargable de 12 V. Consiste en una cámara de luz con un reflector en un lado y un condensador en el otro, equipada con una bombilla halógena de 12 V y 50 W. La cámara tiene en la parte superior, en el extremo del condensador, un cristal de aumento de 2,5 dioptrías y 100 mm de diámetro. Los resultados de la inspección visual simple realizada mediante el Magnivisualizador fueron comparados con los de la colposcopia y/o los informes histológicos en una muestra de 402 mujeres. En total se diagnosticaron histológicamente 73 displasias leves, 76 displasias avanzadas y 59 carcinomas in situ o cánceres invasivos en sus primeras fases. En el caso de las displasias leves, la sensibilidad del análisis citológico fue del 75,3%, y la del Magnivisualizador, del 57,5%. En lo que atañe a las displasias graves y los carcinomas in situ o los cánceres invasivos tempranos, en cambio, la sensibilidad fue del 94,9% con los dos métodos. La tasa de falsos positivos fue del 1,0% en los estudios citológicos, frente al 5,7% con el Magnivisualizador. La especificidad del cribado alcanzó el 94,3% con este último, y el 99% en el análisis citológico.El Magnivisualizador aumentó considerablemente la sensibilidad conseguida mediante la inspección visual simple, no sólo en la detección de carcinomas in situ o de cánceres invasivos tempranos, sino también en el caso de las lesiones precancerosas. Su sensibilidad en la detección de las displasias avanzadas y las lesiones más graves precitadas fue comparable a la del análisis citológico, y disminuyó la tasa de falsos positivos. Además, el costo del examen con Magnivisualizador fue de US$ 0,55, mientras que el del análisis citológico fue de US$ 1,10. La sencilla inspección visual que permite el dispositivo puede realizarse incluso en un centro de atención primaria, sin más requisito que una mesa de exploración

Le cancer du col utérin est la principale tumeur maligne rencontrée chez les femmes indiennes. Dans les pays en développement, il n’est pas possible de lancer des programmes nationaux de dépistage cytologique du fait de la rareté du personnel qualifié et de l’absence des infrastructures nécessaires. La simple inspection visuelle du col est moins sensible et moins spécifique que l’examen cytologique pour détecter des cancers précoces. Le taux de détection des lésions cervicales précancéreuses était plutôt faible dans nos études antérieures. Nous avons mis au point le « Magnivisualizer », un dispositif de grossissement muni d’une source lumineuse, qui coûte 1500 roupies (US $36), afin d’améliorer la sensibilité de l’inspection visuelle simple pour détecter des lésions précancéreuses ou des lésions cancéreuses précoces.Cet instrument portatif est facile à utiliser et fonctionne au moyen d’une pile rechargeable de 12 V. Il consiste en une chambre lumineuse avec d’un côté un réflecteur et de l’autre un condenseur, et elle est munie d’une ampoule à halogène de 50 W (12 V). Une loupe de 2,5 dioptries et de 100 mm de diamètre est fixée au sommet de la chambre lumineuse sur le bord de la lentille du condenseur. On a comparé l’inspection visuelle à l’aide du Magnivisualizer avec les résultats de la colposcopie et/ou de l’examen histologique sur un échantillon d’étude de 402 femmes. Au total, l’examen histologique a permis de diagnostiquer 73 dysplasies discrètes, 76 dysplasies graves et 59 carcinomes in situ ou cancers invasifs précoces. Pour les dysplasies discrètes, la sensibilité de l’examen cytologique a été de 75,3 %, alors que celle du Magnivisualizer a été de 57,5 %. En revanche, pour les dysplasies graves et les carcinomes in situ ou les cancers invasifs précoces, la sensibilité a été de 94,9% pour les deux méthodes. Le taux de faux positifs a été de 1% pour l’examen cytologique contre 5,7% pour le Magnivisualizer. La spécificité du dépistage a été de 94,3% avec le Magnivisualizer et de 99% à l’examen cytologique.L’emploi du Magnivisualizer a sensiblement augmenté la sensibilité de l’inspection visuelle du col, non seulement pour la détection des carcinomes in situ ou des cancers invasifs précoces, mais également pour les lésions précancéreuses. Il a montré une sensibilité analogue à celle de l’examen cytologique pour la détection des dysplasies graves et des lésions plus graves, et a permis de réduire le nombre de faux positifs. En outre, le coût d’un dépistage au moyen du Magnivisualizer est de US $0,55 contre US $1,10 pour l’examen cytologique. Cette technique simple d’inspection visuelle à l’aide du Magnivisualizer peut même être utilisée dans un centre de santé primaire, le seul élément supplémentaire nécessaire étant une table d’examen.