Biliary,fecal and plasma deoxycholic acid in rabbit,hamster, guinea pig,and rat: comparative study and implication in colon cancer

Bile acids are believed to play a role in the etiology of colorectal cancer, and high fecal excretion of secondary bile acids was correlated with increased incidence of colon cancer. Recently, it was also reported that there is an increase in plasma of the secondary bile acid, deoxycholic acid in men with colorectal adenomas. Since deoxycholic acid is formed in the colon and absorbed into the portal systemic circulation, it was suggested that the blood concentration of this bile acid reflects the level of exposure of colonic cells to deoxycholic acid. The objective of this study was to investigate whether plasma deoxycholic acid level represents the fecal content of this bile acid in several animal species with different bile acid composition and deoxycholic acid contribution to the bile acid pool. Eight rabbits, hamsters, guinea pigs, and rats were used in this study. Blood samples and feces were collected on days 1, 3, 5 and 7. Bile samples were obtained only on day 7. The plasma, fecal and biliary bile acids were analyzed by gas chromatography-mass spectrometry. Bile acid composition and deoxycholic acid content varied greatly between the animal species studied. There was a variation in the concentration of total bile acids in the plasma and feces obtained at different times during the experiments, however, the bile acids profile remained constant throughout the study. The data obtained shows that although plasma bile acid profile was not similar to fecal bile acids profile, however, there was a significant correlation between the level of plasma and fecal deoxycholic acid. Plasma deoxycholic acid concentration might be a reliable biomarker for the degree of exposure of colon cells to this bile acid, and may be useful in further studies on the role of secondary bile acids in colon carcinogenesis.     

Short- and intermediate-term follow-up results of percutaneous transluminal balloon valvuloplasty in adolescents and young adults with congenital pulmonary valve stenosis

Percutaneous pulmonary balloon valvuloplasty (PBV) is a well-established treatment alternative to surgery in many cardiology centers. We described our experience with PBV in 25 adolescent and young adult patients with isolated pulmonary valve stenosis (PVS). Among 20 successful PBVs, there was a significant immediate decrease in right ventricular systolic pressure from 116.9 32.4 mmHg to 60.5 18.7 mmHg (p < 0.0001) and a decrease in transpulmonary valve pressure gradient from 93.5 32.8 mmHg to 33.5 9.7 mmHg (p < 0.0001) was noted. The follow-up period was 1-5 years (mean = 3.2 1.2 years), during which patients were periodically assessed by Doppler echocardiogram. During follow-up, the transpulmonary valve pressure gradient further decreased from 33.5 9.7 mmHg to 18.6 3.4 mmHg (p < 0.0001) mainly due to regression of infundibular hypertrophy. Thus, the study showed excellent short-term and intermediate-term results of PBV.     

Aetiology and prognostic factors in acute liver failure in India

The early prognostic indicators for acute liver failure in endemic zones for hepatitis E virus have not been determined. All consecutive patients with acute liver failure from a geographically defined region endemic for hepatitis E virus were studied over the period April 1989-April 1996. Demographic, clinical and biochemical parameters were recorded at presentation and serum samples were analysed for known viral hepatitis (A-E) markers. Multiple parameters were compared in survivors and non-survivors in a univariate analysis. All significant factors on univariate analysis were entered into a stepwise logistic regression analysis to identify independent variables of prognosis. The sensitivity and specificity of significant prognostic factors was then assessed. A total of 180 [69 males and 111 females: age (mean +/- SD) 31.1 +/- 14.7 years] with acute liver failure were studied. Of these, 131 (72.8%) patients died. Hepatitis E virus was the aetiological cause in 79 (43.9%) patients, while hepatitis A virus, hepatitis B virus, hepatitis C virus and non-A, non-E agent/'s could be incriminated in four (2.1%), 25 (13.9%), 13 (7.2%) and 56 (31.1%) patients respectively. Of 83 women in childbearing age, 49 (59.0%) were pregnant, 33 (67.3%) of these were in the third trimester. Forty-seven (95.8%) pregnant women had HEV infection. Nine variables differed significantly between survivors and non-survivors on univariate analysis. Of these, four variables which predicted the adverse outcome on multivariate analysis were non-hepatitis-E aetiology, prothrombin time >30 s, grade of coma >2 and age >40 years in that order of significance. Pregnancy per se or duration of gestation did not adversely affect the prognosis. In endemic areas, hepatitis E virus is the commonest cause of acute liver failure. Acute liver failure occurs in a high proportion of pregnant women, mostly in third trimester. Early predictors of a poor outcome are non-E aetiology, prothrombin time >30 s, grade of coma >2 and age >40 years.     

Perceptions of Pakistani medical students about drugs and alcohol: a questionnaire-based survey

Background  

Drug abuse is hazardous and known to be prevalent among young adults, warranting efforts to increase awareness about harmful effects and to change attitudes. This study was conducted to assess the perceptions of a group of medical students from Pakistan, a predominantly Muslim country, regarding four drugs namely heroin, charas, benzodiazepines and alcohol.     

A novel biomarker for staging human prostate adenocarcinoma: overexpression of matriptase with concomitant loss of its inhibitor, hepatocyte growth factor activator inhibitor-1.

BACKGROUND: Matriptase, a type II transmembrane serine protease is involved in angiogenesis, degradation of extracellular matrix, and in the progression of some epithelial cancers. Here, we establish the clinical significance of matriptase and its inhibitor, hepatocyte growth factor activator inhibitor-1 (HAI-1), during the progression of human prostate cancer (CaP). METHODS: The expression patterns of matriptase and HAI-1 were determined in primary cultures of normal human prostate epithelial (NHPE) cells, human CaP cells LNCaP, DU-145, CWR22Rnu1, and PC-3, and in tissue samples of 172 patients with normal prostate, benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN), and adenocarcinoma of different tumor grades. RESULTS: The protein and mRNA levels of matriptase were significantly higher in all carcinoma cells as compared with NHPE cells. Conversely, all CaP cells exhibited a reduced expression of HAI-1 as compared with NHPE cells. A progressive increase in the protein levels of matriptase was observed with increasing tumor grade in CaP specimens as compared with normal and BPH tissue specimens. Tissue samples of normal prostate exhibited a high constitutive protein level of HAI-1 compared with BPH and low-grade cancer with a progressive loss with increasing tumor grade. CONCLUSION: The increased expression of matriptase and loss of HAI-1 may be an important event during the progression of CaP in humans. We suggest that the ratio of these two gene products may serve as a promising biomarker for CaP progression and a potential marker for establishing the efficacy of therapeutic and chemopreventive interventions.     

A clinical study of patients with genetically confirmed Huntington's disease from India

Background: Clinical data across the globe especially in genetic diseases like Huntington's disease (HD) is most helpful when collected using standardized formats. This helps in proper comparison of clinical and genetic data. Methods: Herein, we report clinical data on 26 genetically confirmed HD patients from 19 Indian families predominantly from South India. Clinical data and evaluation was performed using standardized formats used by the Huntington Disease Study Group. Results: Adult onset HD was commonest while Juvenile HD (onset <20 years) was observed in 15% of patients. Chorea was the commonest presenting symptom (n=23, 88.5%) while remaining presented with psychiatric symptoms (n=3, 11.5%). Impairment of saccades was observed in 75% of patients. Mean (SD) CAG repeats in the abnormal allele was 48.4 (8.7). Total motor score but not the total behavioral score worsens with duration of symptoms. The functional checklist score correlates with total motor score rather than with duration of symptoms. Conclusions: We detail clinical characteristics in genetically confirmed HD patients from a predominantly South Indian cohort. We observed a slightly higher occurrence of Juvenile HD. Functional disabilities in our patients correlate with worsening of motor rather than behavioral symptoms.     

Evaluation of the efficacy of Lawsonia alba in the alleviation of carbon tetrachloride-induced oxidative stress

The hepatoprotective activity of the 50% ethanol extract of the bark of Lawsonia alba syn. L. inermis was investigated against the carbon tetrachloride-induced oxidative stress. Pretreatment of rats with doses of 250 and 500 mg/kg of the plant extract significantly (P < 0.001) lowered serum transaminases (GOT and GPT) and LDH levels, respectively, in a dose dependent manner against the significant (P < 0.001) rise of these damage marker enzymes when challenged with CCl4 (1 ml/kg, orally). Parallel to these changes, the plant extract prevented CCl4-induced oxidative stress by significantly maintaining the levels of reduced glutathione (GSH), its metabolizing enzymes and simultaneously inhibiting the production of free radicals. Pretreatment of rats with the extract also inhibited the peroxidation of microsomal lipids in a dose-dependent manner.