Duration of seroprotection of the live attenuated SA-14-14-2 Japanese encephalitis vaccine in children in India.

BACKGROUND: Acute encephalitis syndrome (AES) is a major public health concern in India, and the Japanese Encephalitis (JE) virus is the most common cause of viral encephalitis in Asia affecting children under the age of 15 years. In India, despite the introduction of the JE vaccine (SA-14-14-2) in the immunization programme, JE continues to account for 15-20% of AES cases to date. This study evaluates the immunogenicity of live attenuated SA-14-14-2 JE vaccine in terms of persistence of the humoral response after two doses. METHODS: A cross-sectional study was conducted among 266 children belonging to one of the JE endemic regions of Uttar Pradesh, India. Blood samples were taken from children (2-10 years) and grouped according to the duration (in years) after two doses of the vaccine (5 groups with a class interval of 2 years). Informed written consent was obtained from the parents/guardians. All the samples collected were tested for the presence of anti-JEV-specific IgG antibodies by enzyme-linked immunosorbent assay (ELISA) and further confirmed by micro neutralization test (MNT) and immunofluorescence assays. RESULTS: Of the 266 samples tested by ELISA for anti-JEV-specific IgG antibodies, 260 (97.74%) were negative and 6 (2.26%) were equivocal. The geometric mean immune status ratio across the five groups, 0-2 years (n = 59), 2-4 years (n = 73), 4-6 years (n = 65), 6-8 years (n = 48) and 8-10 years (n = 21) post-two doses of SA-14-14-2 JE vaccine was 1.143, 1.059, 1.138, 1.075 and 1.130, respectively, and the geometric mean titre obtained from MNT across the five groups was 10.77, 8.400, 8.453, 9.517 and 9.674, respectively. CONCLUSION: The study showed a decreasing trend of anti-JEV specific IgG antibody titres across the five groups based on the duration following two doses of SA-14-14-2 vaccine. The results emphasize the significance of booster doses of vaccine for children living in endemic areas.

In-silico comparison of cytochrome P450 inhibitory and dopaminergic activity of Piperine, Curcumin and Capsaicin.

Psychiatric disorders are a heterogeneous group of mental disorders that manifest as abnormal mental or behavioral habits that cause the individual discomfort or disability. Dopamine imbalance plays a major role in many psychiatric disorders. Piperine, Curcumin and Capsaicin are CYP P450 3A4 & 2D6 inhibitors. The objective of this study is to determine the dopaminergic activity of Piperine, Curcumin and Capsaicin and also to compare cytochrome P450 3A4 and 2D6 inhibition activity by in-silico methods. In this in-silico study, we utilised compounds such as Piperine, Curcumin and Capsaicin were subjected to Lipinski's rule of five, and ligands were also evaluated for toxicity profile and ADMET properties. Furthermore, the ligands were performed in docking studies. All three compounds were docked with three different targeted proteins (PDB IDs: 4D7D, 4WNW and 6LUQ). According to the docking result, Piperine has higher binding energy(-8.55 kcal/mol)(-8.1 kcal/mol)(-8.57 kcal/mol) when compared with Curcumin(-7.39 kcal/mol)(-5.61 kcal/mol)(-6.57 kcal/mol) and Capsaicin (-6.86 kcal/mol)(-6.57 kcal/mol)(-5.42 kcal/mol) and also with standard drug (-8.61 kcal/mol)(-7.65 kcal/mol)(-6.16 kcal/mol). The present study concluded that the bioactive compound Piperine has a better inhibitory activity of CYP 3A4, 2D6 enzymes and dopamine D2 receptor among the three compounds and also with the standard drug thioridazine.

Safety and Efficacy of Saroglitazar in Nonalcoholic Fatty Liver Patients With Diabetic Dyslipidemia-A Prospective, Interventional, Pilot Study.

BACKGROUND: Saroglitazar-a unique dual peroxisome proliferator-activated receptor agonist was approved marketing authorization in India in 2013 for diabetic dyslipidemia. Postmarketing studies have additionally shown improvement in liver parameters in diabetic dyslipidemia patients with nonalcoholic fatty liver disease (NAFLD) who received saroglitazar. AIM: The aim of this study was to evaluate the effect of saroglitazar on liver function test, liver fibrosis score by FibroScan, lipid profiles, HbA1c in NAFLD patients with diabetic dyslipidemia in southern India. METHODOLOGY: A prospective, interventional, pilot study was performed to study the safety and efficacy of saroglitazar in NAFLD patients having type 2 diabetes mellitus. About 97 patients were screened, of which 85 patients were involved in the study based on the inclusion criteria. The clinical parameters and liver stiffness were measured at the baseline and also after 12 weeks of treatment with administration of saroglitazar 4 mg once daily. The change in the parameters at the baseline and after the end of the treatment was measured and was subjected to statistical analysis using SPSS software. RESULTS: The recruited patients received saroglitazar and were followed up for a period of 12 weeks. The clinical parameters such as fasting blood sugar, postprandial blood sugar, HbA1c, total cholesterol, triglycerides, SGPT, and liver stiffness showed significant difference after 12 weeks of treatment when compared with the baseline values. No adverse drug reaction was reported in patients receiving saroglitazar during the study. CONCLUSION: Saroglitazar was found to show significant improvement in liver parameters in NAFLD patients with a significant reduction in liver fibrosis and triglycerides level.

Safety and efficacy of newer biologics DMARDs in the management of rheumatoid arthritis: A systematic review.

Objective: To analyze the safety and efficacy of certain biologics DMARDs (Adalimumab, Baricitinib, Pefacitinib and Sirukumab) either used alone or as a combination with MTX for management of rheumatoid arthritis. Method: We conducted a systematic literature review on various phase 3 Randomized controlled trails, double blind, placebo controlled, parallel group clinical trials for 52 weeks from 2017 to 2019 conforming to the Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. The primary efficacy endpoints were American College of Rheumatology 20 response rate improvement criteria, other secondary endpoints were American College of Rheumatology 50/70 response rates, Health Assessment Questionnaire Disability Index, Disease Activity Score-28 for rheumatoid arthritis with Erythrocyte Sedimentation Rate/C Reactive Protein and Radiographic outcomes. Results: Finally, four studies were included for qualitative synthesis in which we observed improvement in ACR 20 response rate was found in the newer agents study group. SB5 (72.4%) at week 24, Baricitinib (70%) at week 12, Pefacitinib 100 mg and 150 mg (57.7% & 74.5%) at week 12 and Sirukumab 50 mg and 100 mg (55% & 54%) at week 16 respectively. ACR 50 and ACR 70 response rate at different point in time was also found to be higher in the study group which indicates their efficacy. Conclusion: In this systematic review, we observed an improvement in ACR 20 response rate and other secondary efficacy outcomes with an acceptable safety margin. From the evidence of RCTs, we have identified that newer therapeutic agents has beneficial effects when compared to existing therapy.

Cefotaxime induced generalized bullous fixed drug eruption - A case report.

Fixed drug eruption (FDE) is the most common cutaneous adverse drug reaction. Cefotaxime, a broad-spectrum third-generation cephalosporin, appeared to be a safe and effective therapy in greater than 90% of infections including cellulitis, abscesses and necrotizing ulcers of the skin and subcutaneous tissues but here we report a rare case of 36 years old female patient developed generalized bullous FDE after intravenous administration of Cefotaxime.