Serum adipokine profile in Indian men with nonalcoholic steatohepatitis: Serum adiponectin is paradoxically decreased in lean vs. obese patients

BackgroundAsian Indians are known to be more insulin resistant for the same degree of weight gain. It is therefore likely that the adipokine profile in nonalcoholic fatty liver disease (NAFLD) in Asian Indian population could be different from the Western subjects.AimsTo study the serum adiponectin, resistin, leptin and TNF-α profile in NAFLD and cryptogenic cirrhosis patients.Subjects and methodsBody mass indices, insulin resistance and serum adipokine levels were studied in 56 patients; 10 with fatty liver, 30 with nonalcoholic steatohepatitis (NASH) and 16 with cryptogenic cirrhosis. Eighteen healthy controls were also included.ResultsPatients in general were obese compared to controls (mean BMI 26.9 ± 4.5 vs. 22.6 ± 2.5, respectively, p < 0.0001). In patients with NASH, adiponectin levels were lower than controls (5.4 ± 3 μg/ml vs.7.2 ± 2.9 μg/ml, p = 0.037). Insulin Resistance as assessed by homeostasis model assessment (HOMA) was higher in obese than lean, NAFLD patients (HOMA IR obese, median = 2.8, range = 0.8–16.3 and lean: median = 1.05, range = 0.51–2.75, p = 0.003). Lean NAFLD patients had adiponectin levels lower than obese patients (3 ± 1 μg/ml vs.6.7 ± 3.8 μg/ml respectively, p = 0.003). Serum resistin levels were higher in NAFLD patients (3.7 ± 3 ng/ml) than controls (2.1 ± 1.7 ng/ml, p = 0.007). This difference was significant even when cirrhotic patients were excluded (3.4 ± 2.7 ng/ml, p = 0.036). Serum leptin levels were raised in cryptogentic cirrhosis compared to NASH (p = 0.03). All adipokines tested were raised in cirrhotic patients compared to NAFLD and controls.ConclusionsA significant reduction in serum adiponectin and increase in serum resistin levels were observed in NAFLD patients, more so in lean than obese NAFLD. This paradoxical decrease of serum adiponectin as well as low frequency of insulin resistance in lean NAFLD suggests a possible different etiology for this subset of patients.     

Development and evaluation of a competitive ELISA for estimation of rabies neutralizing antibodies after post-exposure rabies vaccination in humans.

OBJECTIVES: Currently three tests are approved for the estimation of neutralizing antibodies after rabies vaccination: the mouse neutralization test (MNT), the rapid fluorescent focus inhibition test (RFFIT), and the fluorescent antibody virus neutralization (FAVN) test. Performance of these tests requires a lot of expertise and is generally carried out in reference laboratories and, hence, they are not available to many people. The aim of the present study was to develop and evaluate a competitive ELISA (C-ELISA) for estimation of neutralizing antibodies in order to make this testing more widely available. METHODS: The C-ELISA was designed based on competition between a murine neutralizing monoclonal antibody (Mab) and the antibodies in serum of vaccinated people. The test was initially standardized using known negative and known positive serum samples for determining the optimal dilution of the Mab as well as the cut-off value (%) for ascertaining the level of inhibition. Nine hundred and ninety serum samples were tested from 250 people who had been administered purified chick embryo cell vaccine (PCECV). Serum samples were collected on days 0, 14, 30 and 90 post-vaccination, and were tested by C-ELISA. RESULTS: All the serum samples that were positive by RFFIT were also positive by C-ELISA. The titers obtained with C-ELISA were marginally higher than the RFFIT titers, but a significant correlation was noted between the two tests (r=0.897). None of the negative controls were detected to be positive for rabies antibodies by either of these tests. Therefore the C-ELISA was found to be 100% specific and sensitive in comparison to RFFIT. Further, the initial rise and fall of antibody titers on different days post-vaccination was comparable for both tests. CONCLUSIONS: The C-ELISA described herein can be used to quantify rabies neutralizing antibody levels after vaccination. This test is simple and can be conveniently used under field conditions for monitoring seroconversion after post-exposure rabies vaccination. Moreover it does not require handling of infectious virus by the end user.     

Prevalence and Correlates of Non-Disclosure of HIV Serostatus to Sex partners among HIV-Infected Female Sex Workers and HIV-infected Male Clients of Female Sex Workers in India

This study examines non-disclosure of HIV serostatus to sex partners among HIV-infected adults involved with transactional sex in Mumbai, India. Surveys were conducted with HIV-infected female sex workers (n = 211) and infected male clients (n = 205) regarding HIV knowledge, awareness of sex partners’ HIV serostatus, alcohol use, transactional sex involvement post-HIV diagnosis and non-disclosure of HIV serostatus. Gender-stratified multiple logistic regression models were used for analysis. Non-disclosure of one’s serostatus to all sex partners was reported by almost three-fifths of females and two-fifths of males. Predictors of non-disclosure included lack of correct knowledge about HIV and no knowledge of sex partners’ HIV serostatus. Among females, recent alcohol consumption also predicted non-disclosure. Among males, 10 + paid sexual partners in the year following HIV diagnosis predicted non-disclosure. Secondary HIV prevention efforts in India require greater focus on HIV disclosure communication and integrated alcohol and sexual risk reduction.     

Synthesis of some novel orsellinates and lecanoric acid related depsides as α-glucosidase inhibitors

Abstract

Sixteen novel orsellinic esters (6a-l, 7a-d) along with four lecanoric acid related depsides (3a-c, 4) were synthesized and confirmed their structures by spectroscopic data (¹H, ¹³C & HRMS). The synthesized compounds were evaluated for their in vitro α-glucosidase (Saccharomyces cerevisiae) inhibitory potential. Among the tested compounds, 3c (IC₅₀: 140.9 μM) and 6c (IC₅₀: 203.9 μM) displayed potent α-glucosidase inhibitory activity and found more active than the standard drug acarbose (IC₅₀: 686.6 μM). Both the test compounds were subjected to in vivo antihyperglycemic activity using sucrose loaded model in Wistar rats and found compound 3c exhibited significant reduction in glucose levels.     

A new prenylated isoflavone from Derris scandens Benth

The phytochemical study of the whole plant of Derris scandens (Leguminosae) has resulted in the isolation of a new isoflavone derivative, scandinone A (11), together with 11 known compounds (1–10, 12). Structural elucidations of these compounds were performed using spectroscopic methods especially 1D, 2D NMR, and mass spectral analyses. The α-glucosidase-inhibitory activity of the isolates was also evaluated.     

Biomarkers in nonalcoholic fatty liver disease-the emperor has no clothes?

Fatty liver is present in over ten percentage of the world population and it is a growing public health problem.Nonalcoholic fatty liver disease(NAFLD) is not a single disease,but encompasses a spectrum of diseases of different etiologies.It is difficult to find highly specific and sensitive diagnostic biomarkers when a disease is very complex.Therefore,we should aim to find relevant prognostic markers rather than accurate diagnostic markers which will help to minimize the frequency of liver biopsies to evaluate disease progression.There are several biomarker panels commercially available,however,there is no clear evidence that more sophisticated panels are better compared to simple criteria such as,presence of diabetes over five years,metabolic syndrome,obesity,obstructive sleep apnea,aspartate transaminase/alanine transaminase(ALT) ratio > 0.8 or ferritin levels > 1.5 times normal in patients with over six month history of raised ALT and/or ultrasonological evidence of fat in the liver.Currently the biomarker panels are not a replacement for a liver biopsy.However the need and benefit of liver biopsy in NAFLD is questionable because there is no convincing evidence that biopsy and detailed staging of NAFLD improves the management of NAFLD and benefits the patient.After all there is no evidence based treatment for NAFLD other than management of lifestyle and components of "metabolic syndrome".     

A comparative study on the safety and immunogenicity of purified duck embryo cell vaccine (PDEV,Vaxirab) with purified chick embryo cell vaccine (PCEC,Rabipur) and purifed vero cell rabies vaccine (PVRV,Verorab)

Rabies is a fatal but preventable disease. Cell culture vaccines (CCV) and purified duck embryo vaccines (PDEV) are currently recommended by WHO for post-exposure prophylaxis. In India, a PDEV (Vaxirab) is being manufactured and is in use since 2003. In the present study, we have evaluated the safety, immunogenicity and tolerance of this vaccine with two other WHO approved CCVs, viz., purified chick embryo cell vaccine (PCEC, Rabipur) and purified vero cell rabies vaccine (PVRV, Veroroab). This study was an open label, randomized phase IV comparative clinical trial. A total of 152 people bitten by dogs and other animals were recruited from 4 different centres from India. They were randomly assigned to receive one of the vaccines by Essen intramuscular regimen (52 subjects received Vaxirab and 50 each Rabipur and Verorab) and rabies immunoglobulin was also administered in all category III exposures. Their blood samples were collected on day 0 (prior to vaccination), 14, 28, 90 and 180. Side effects if any were monitored. The rabies neutralizing antibody titers in their blood samples were estimated by the rapid fluorescent focus inhibition test (RFFIT). Subjects in all three groups had neutralizing antibody titers by day 14 (>0.5 IU/mL) and geometric mean titers (GMT) observed for different vaccines on all days tested did not vary significantly (p > 0.5). Side effects observed were minimal and did not vary significantly among the groups. The results of the present study indicate that PDEV (Vaxirab) is as safe, tolerable and immunogenic as both PCEC (Rabipur) and PVRV (Verorab). Thus this vaccine can be a good alternative to WHO approved CCVs for rabies post-exposure prophylaxis.     

Cricopharyngeal dysfunction—An often missed cause of dysphagia

Two cases of dysphagia, due to cricopharyngeal dysfunction are presented. Dysphagia, cough on swallowing, salivation and need for repeated acts of swallowing to force the food down, are the typical symptoms. Both patients improved following a cricopharyngeal myotomy. The clinical and radiological features and the steps of the operation are described in detail.     

HPLC method for the determination of rosiglitazone in human plasma and its application in a clinical pharmacokinetic study

Rosiglitazone (CAS 155141-29-0, Avandia) is a novel insulin sensitizer used in the treatment of type 2 diabetes. A sensitive high performance liquid chromatography (HPLC) method for its determination in human plasma using fluorescence detection (excitation: 247 nm, emission: 367 nm) with a suitable internal standard (I. S.) is described. Ethyl acetate was used as extraction solvent. A mobile phase consisting of phosphate buffer, acetonitrile and methanol was used at a flow rate of 1.0 ml/min on a C18 column. The absolute recovery was > 90% and the lower limit of quantitation was 5 ng/ml. The intra- and inter-day relative standard deviations ranged from 0.58-6.69% and 0.82-6.63%, respectively. The method described is simple, economical, precise and accurate and has been successfully applied in a pharmacokinetic study conducted in healthy human volunteers.