Potentiation of anticonvulsant activity of phenytoin by calcium channel blockers (verapamil and amlodipine) against maximal electroshock seizures in rats

Background: The objective of this work was to study the anticonvulsant activity of calcium channel blockers verapamil and amlodipine and their interaction with an established antiepileptic drug diphenylhydantoin (DPH) in experimental model of epilepsy in albino rats.Methods: Maximal electroshock (MES) convulsions were induced by electroconvulsiometer and different phases of MES were noted in control and drug treated groups. Effect of different doses of verapamil (dose-5, 10 and 15 mg/kg), amlodipine (dose-2.5, 3 and 3.5 mg/kg) and DPH (dose-0.5 and 1 mg/100 g) on MES was studied. Finally, effect of combined treatment consisting of non-protective dose of DPH with different doses of verapamil and amlodipine were also studied on MES induced seizures.Results: Combination of non-protective dose (0.5 mg/100 g) of DPH with all the three doses of verapamil and amlodipine offered significant protection against MES induced seizures.Conclusions: From the present investigation, it may be concluded that the dose of DPH may be reduced in an antiepileptic individual who is on verapamil and amlodipine therapy

Diagnosis of Ectopic Pregnancy

Ectopic pregnancy is defined as the implantation of a fertilised egg outside the uterine cavity. The site of ectopic pregnancy are Fallopian tube. Cervix, ovary, peritoneal cavity, or uterine scars. Other two site of implantation are cornual pregnancy and interstitial pregnancy. Diagnostic tests for ectopic pregnancy include a urine pregnancy tests, Serum beta hcG and ultrasound. The instant result of a urine pregnancy test is a useful pointer for the clinician to suspect an ectopic pregnancy. The test is a useful triage tool for clinicians to rule out a pregnancy when the clinical situation is not clear such as a patient who is not sure of dates, does not remember or is in a state of shock and the history cannot be elicited. Ultrasound remains the mainstay of the diagnosis and high index of suspicion and a detailed history are pre-requisite of scanning. Different ultrasonography feature are diagnostic of different site of implantation. For uterine scar pregnancy ultrasonologic criteria are not validated still now

Quantitative and Qualitative Analysis of Micronuclei in the Buccal Mucosal Cells of Individuals Associated with Tobacco

Introduction: Micronucleus/micronuclei) have the potential to serve as an important biomarker in exfoliated cell. Exfoliated buccal mucosal cells can be evaluated using MN assay which can be applied to individuals practicing tobacco habits and are at risk of developing oral cancer. Material and Methods: 80 tobacco users and 20 non tobacco users as control were included in the study. Smears were taken and stained with H&E, feulgen, acridine orange. MN was counted using criteria given by Tolbert et al. Data was analyzed using SPSS software. Results: MN higher in tobacco users. The values obtained for the MN count in tobacco chewers using these stains were statistically significant (P<0.05). The values obtained for the MN count in tobacco smokers using these stains were statistically significant (P<0.05). Qualitatively a good score for staining intensity; MN outline and nuclear outline was obtained for acridine orange, followed by H&E and feulgen stain. Discussion: In our study quantitatively, MN was counted in maximum number using H&E stain, followed by acridine orange and feulgen. Qualitatively, MN count was best viewed using acridine orange stain under a fluorescence microscope, followed by H&E and feulgen under a light microscope. Conclusion: Assessment of MN in exfoliated cells is a promising tool to study epithelial carcinogens in the oral cavity

A comprehensive insight on the challenges for COVID-19 vaccine: A lesson learnt from other viral vaccines

The aim of this study is to comprehensively analyze previous viral vaccine programs and identify potential challenges and effective measures for the COVID-19 vaccine program. Previous viral vaccine programs, such as those for HIV, Zika, Influenza, Ebola, Dengue, SARS, and MERS, were evaluated. Paramount challenges were identified, including quasi-species, cross-reactivity, duration of immunity, revaccination, mutation, immunosenescence, and adverse events related to viral vaccines. Although a large population has been vaccinated, mutations in SARS-CoV-2 and adverse events related to vaccines pose significant challenges. Previous vaccine programs have taught us that predicting the final outcome of the current vaccine program for COVID-19 cannot be determined at a given state. Long-term follow-up studies are essential. Validated preclinical studies, long-term follow-up studies, alternative therapeutic approaches, and alternative vaccines are necessary

Short- and long-term safety and efficacy of corneal collagen cross-linking in progressive keratoconus: A systematic review and m eta-analysis of randomized controlled trials

PURPOSE: The purpose of the study is to evaluate the safety and outcomes of corneal collagen cross-linking (CXL) and different CXL protocols in progressive keratoconus (PK) population at short and long-term. MATERIALS AND METHODS: A systematic review and meta-analysis was conducted. A total of eight literature databases were searched (up to February 15, 2022). Randomized controlled trials (RCTs) comparing CXL versus placebo/control or comparing different CXL protocols in the PK population were included. The primary objective was assessment of outcomes of CXL versus placebo and comparison of different CXL protocols in terms of maximum keratometry (Kmax) or Kmax change from baseline (Δ), spherical equivalent, best corrected visual acuity (BCVA), and central corneal thickness (CCT) in both at short term (6 months) and long term (1st, 2nd, and 3rd year or more). The secondary objective was comparative evaluation of safety. For the meta-analysis, the RevMan5.3 software was used. RESULTS: A total of 48 RCTs were included. Compared to control, CXL was associated with improvement in Δ Kmax at 1 year (4 RCTs, mean difference [MD], −1.78 [−2.71, −0.86], P = 0.0002) and 2 and 3 years (1 RCT); ΔBCVA at 1 year (7 RCTs, −0.10 [−0.14, −0.06], P < 0.00001); and Δ CCT at 1 year (2 RCTs) and 3 years (1 RCT). Compared to conventional CXL (C-CXL), deterioration in Δ Kmax, ΔBCVA and endothelial cell density was seen at long term in the transepithelial CXL (TE-CXL, chemical enhancer). Up to 2 years, there was no difference between TE-CXL using iontophoresis (T-ionto) and C-CXL. At 2 and 4 years, C-CXL performed better compared to accelerated CXL (A-CXL) in terms of improving Kmax. Although CCT was higher in the A-CXL arm at 2 years, there was no difference at 4 years. While exploring heterogeneity among studies, selection of control eye (fellow eye of the same patient vs. eye of different patient) and baseline difference in Kmax were important sources of heterogeneity. CONCLUSION: CXL outperforms placebo/control in terms of enhancing Kmax and CCT, as well as slowing disease progression over time (till 3 years). T-ionto protocol, on the other hand, performed similarly to C-CXL protocol up to 2 years

Structural-Based Virtual Screening of FDA-Approved Drugs Repository for NSP16 Inhibitors, Essential for SARS-COV-2 Invasion Into Host Cells: Elucidation From MM/PBSA Calculation

NSP16 is one of the structural proteins of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) necessary for its entrance to the host cells. It exhibits 2’O-methyl-transferase (2’O-MTase) activity of NSP16 using methyl group from S-adenosyl methionine (SAM) by methylating the 5-end of virally encoded mRNAs and shields viral RNA, and also controls its replication as well as infection. In the present study, we used in silico approaches of drug repurposing to target and inhibit the SAM binding site in NSP16 using Food and Drug Administration (FDA)-approved small molecules set from Drug Bank database. Among the 2 456 FDA-approved molecules, framycetin, paromomycin, and amikacin were found to be significant binders against the SAM binding cryptic pocket of NSP16 with docking score of –13.708, –14.997 and –15.841 kcal/mol, respectively. Classical molecular dynamics (MD) simulation and molecular mechanics Poisson−Boltzmann surface area (MM/PBSA)-based binding free energy calculation depicted that all these three framycetin, paromomycin, and amikacin might be promising therapeutic leads towards SARS-CoV-2 infections via host immune escape inhibition pathway