Aim. To compare two strengths of a fi xed drug combination (FDC) containing metoprolol XL and amlodipine (metoprolol/amlodipine 50/5; and metoprolol/amlodipine 25/2.5) with its components in hypertension. Methods . We conducted this multicentre, randomized, open-label, trial in Indian patients with hypertension (140 -180 mmHg/90 -114 mmHg) in 11 centres from nine cities. Eligible patients ( n ϭ 402) were randomized into one of fi ve treatment groups (metoprolol XL 50 mg ϩ amlodipine 5 mg, metoprolol XL 25 mg ϩ amlodipine 2.5 mg, metoprolol XL 50 mg, metoprolol XL 25 mg or amlodipine 5 mg) and treated for 8 weeks with fi ve follow-up visits to record blood pressure (BP) and clinical status. Results. At baseline, treatment groups were well balanced; mean Ϯ SD BP was 154.87 Ϯ 11.91/96.63 Ϯ 6.97 mmHg. The greatest reduction in BP from baseline to 8 weeks was seen in the high-dose FDC group (23.61/14.91 mmHg; p Ͻ 0.001). The remaining 4 groups too demonstrated a signifi cant reduction ( p Ͻ 0.001): low-dose FDC Ϫ 22.29/ Ϫ 14.66; metoprolol 50, Ϫ 23.17/ Ϫ 13.37; metoprolol 25, Ϫ 18.41/ Ϫ 12.50 and amlodipine 5, Ϫ 23.01/ Ϫ 13.08. BP reductions by FDCs, however, were not statistically superior to monotherapies. Responder rates (sitting diastolic BP Ͻ 90 mmHg or reduction Ն 10 mmHg) were 93% in the high-dose FDC group and 97% in the low-dose FDC group, and control rates (sitting BP Ͻ 140/90 mmHg) were 66% and 58%, respectively. These rates were higher than that seen in individual components. There were no reports of serious adverse events related to study medications. One each from the low-dose FDC and metoprolol 25 mg group discontinued because of adverse events. Conclusions. FDCs of metoprolol and amlodipine are effective and safe in mild to moderate hypertension.

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Burden of rotavirus gastroenteritis (RVGE) in outpatient setting in India is not fully understood. A prospective study was undertaken to describe RVGE among Indian children less than 5 years of age presenting in outpatient departments with acute gastroenteritis (AGE). This study was conducted at 11 outpatient departments (OPDs) of private pediatric clinics in urban areas of India. A total of 605 eligible children were enrolled at OPDs. Stool samples of the subjects were collected and tested for presence of rotavirus antigen by enzyme immune assay (EIA) and were typed by reverse-transcriptase polymerase chain reaction (RT-PCR). Physician examined the children and documented the disease particulars. In addition, parents/guardians were interviewed for AGE related symptoms, health care utilization and cost incurred due to AGE, and parental stress associated with AGE. After OPD, parents/guardians completed diary cards and questionnaires to capture the information for 14 days following the enrollment. Complete data for analysis including stool sample results was available from 552 subjects. 23% (127/552; [CI 19.5, 26.5]) of stool samples were rotavirus (RV) positive. RT-PCR was done for 85.8% (109/127) of RV positive samples. G1, G2, G9, and G12 types were identified in 34.9% (38/109), 37.6% (41/109), 8.3% (9/109), and 6.4% (7/109) stool samples, respectively. P[4] and P[8] were identified in 36.7% (40/109) stool samples each, followed by P[6] identified in 15.6% (17/109) stool samples. At the time of enrollment, all three symptoms (vomiting, diarrhea, and fever) were observed concurrently in higher proportion of RV positive subjects compared to RV negative subjects (60.6% [77/127] vs. 42.8% [182/425], p=0.0004). Healthcare resource utilization, costs incurred due to disease, and parental stress were higher for RV positive subjects compared to RV negative subjects. In conclusion, RVGE was found to be a definite burden in AGE cases attending pediatric outpatient clinics in urban areas and it was associated with substantial economic and psychological burden. Introduction of rotavirus vaccine in India may help in reducing this disease burden.

BackgroundHIV-specific Antibody Dependent Cell Cytotoxicity (ADCC) has shown to be important in HIV control and resistance. The ADCC is mediated primarily by natural killer cell activated through the binding of FcγRIIIa receptor to the Fc portion of antibody bound to the antigen expressed on the infected cells. However, no data is available on the influence of the polymorphism in FcγRIIIa receptor on HIV-specific ADCC response.MethodsThe Sanger’s method of sequencing was used to sequence the exon of FcγRIIIa receptor while the ADCC activity was determined using NK cell activation assay. The polymorphism in FcγRIIIa receptor was assessed in HIV-infected Indian individuals with or without HIV-specific ADCC antibodies and its influence on the magnitude of HIV-specific ADCC responses was analyzed.ResultsTwo polymorphisms: V176F (rs396991) and Y158H (rs396716) were observed. The Y158H polymorphism is reported for the first time in Indian population. Both, V176F (V/V genotype) (p = 0.004) and Y158H (Y/H genotype) (p = 0.032) were found to be significantly associated with higher magnitude of HIV-specific ADCC response.ConclusionThe study underscores the role of polymorphism in the FcγRIIIa receptor on HIV-specific ADCC response and suggests that the screening of the individuals for FcγRIIIa-V176F and Y158H polymorphisms could be useful for prediction of efficient treatment in monoclonal antibody-based therapies aimed at ADCC in HIV infection.

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Although HIV-1 epidemic in India is mainly driven by subtype C, subtype A has been reported for over two decades. This is the first comprehensive analysis of sequences of HIV-1 subtype A from India, based on the near full-length genome sequences of six different HIV-1 subtype A Indian isolates along with available partial gene sequences from India and global sequences. The phylogenetic analyses revealed the convergence of all Indian whole-genome sequences and majority of the partial gene sequences to a single node with the sequences most closely related to African sub-subtype A1. The presence of the signature motifs consistent with those observed in subtype A and CTL epitopes characterized specifically for subtype A1 were observed among the study sequences. Deletion of LY amino acid of LYPXnL motif of p6gag and one amino acid in V3 loop have been observed among the study isolates, which have also been observed in a few sequences from East Africa. Overall, the results are indicative of a monophyletic lineage or founder effect of the Indian epidemic due to sub-subtype A1 and supportive of a possible migration of subtype A1 into India from East Africa.

Background High-fat diet (HFD) possesses a major cause of cardiovascular disease, and hepatosteatosis. Unfortunately, long-term use of statins has a theoretical possibility of worsening of hepatic histology in the patients with non-alcoholic fatty liver disease (NAFLD). The objective of the study was to explore hepatoprotective potential of policosanol as an alternative to statins in experimental NAFLD. For the same, young male Wistar rats were fed with HFD for 8 weeks to induce NAFLD. 48 adult Wistar rats were distributed into six investigational groups: normal control, HFD control, and four treatment groups, receiving policosanol (50 and 100 mg/kg/day), atorvastatin (30 mg/kg/day), and silymarin (100 mg/kg/day) for 8 weeks along with HFD. Result HFD consumption caused profound hepatotoxicity evident by hepatic oxidative stress, increased Serum glutamic oxaloacetic transaminase (SGOT), Serum glutamic pyruvic transaminase (SGPT), Alkaline phosphatase (ALP), and bilirubin content. Treatment with policosanol (100 mg/kg) markedly reduced the elevated SGOT, SGPT, and ALP levels in HFD-fed rats. Moreover, policosanol significantly reduced hepatic oxidative stress manifest by reduced malondialdehyde (MDA) and increased glutathione (GSH) level. The treatment with policosanol (100 mg/kg) was found to be more active in attenuating the HFD-induced hepatotoxicity as compared to policosanol (50 mg/kg) and atorvastatin (30 mg/kg). Moreover, we observed that the hepatoprotective potential of policosanol was comparable to the silymarin. Conclusions The results of the study clearly indicated that the policosanol could be considered an intriguing approach for the treatment of NAFLD.