ABSTRACT
Background & objectives: COVID-19 has been a global pandemic since early 2020. It has diverse clinical manifestations, but consistent immunological and metabolic correlates of disease severity and protection are not clear. This study was undertaken to compare seropositivity rate, antibody levels against nucleocapsid and spike proteins, virus neutralization and metabolites between adult and child COVID-19 patients. Methods: Plasma samples from naïve control (n=14) and reverse transcription (RT)-PCR positive COVID-19 participants (n=132) were tested for reactivity with nucleocapsid and spike proteins by ELISA, neutralization of SARS-CoV-2 infectivity in Vero cells and metabolites by 1H nuclear magnetic resonance (NMR) spectroscopy. Results: An ELISA platform was developed using nucleocapsid and spike proteins for COVID-19 serosurvey. The participants showed greater seropositivity for nucleocapsid (72%) than spike (55.3%), and males showed higher seropositivity than females for both the proteins. Antibody levels to both the proteins were higher in intensive care unit (ICU) than ward patients. Children showed lower seropositivity and antibody levels than adults. In contrast to ICU adults (81.3%), ICU children (33.3%) showed lower seropositivity for spike. Notably, the neutralization efficiency correlated with levels of anti-nucleocapsid antibodies. The levels of plasma metabolites were perturbed differentially in COVID-19 patients as compared with the naive controls. Interpretation & conclusions: Our results reflect the complexity of human immune response and metabolome to SARS-CoV-2 infection. While innate and cellular immune responses are likely to be a major determinant of disease severity and protection, antibodies to multiple viral proteins likely affect COVID-19 pathogenesis. In children, not adults, lower seropositivity rate for spike was associated with disease severity
ABSTRACT
Background: Quinidine is an antimalarial schizonticide and an antiarrhythmic agent with Class Ia activity. The present study was aimed at analyzing the bioequivalence of the proposed generic product Quinidine Gluconate 324mg Extended Release Tablets with the marketed product of Sun pharmaceuticals, USA.Methods: The design was an open, longitudinal, randomized, comparative study of two formulations in single dose of 324 mg, with a 5 days washout in between doses. The study was conducted in 12 healthy adult male and female Brazilian volunteers under fed conditions in Azidus Brasil, Valinhos, Brazil. Blood samples were collected post dose up to 36 hours for pharmacokinetic analysis and safety evaluation was done by assessing the adverse events and laboratory tests. A validated LC-MS/MS method was used to determine the plasma concentrations of Quinidine. Bioequivalence between the products was established by calculating 90% confidence intervals (90% CI) for the ratio of Cmax, AUC0-t and AUC0-? values for the proposed generic product and marketed product.Results: The 90% confidence intervals found for the relation Test/Reference, were Cmax 80.78% to 109.07%, AUC0-t 86.04% to 104.24% and AUC0-? 86.25% to 104.71%. There were no clinically relevant changes in the vital parameters and the QT, QTc were not adversely affected and both the drug products were found to be safe and tolerable at the given strength.Conclusions: According to FDA´s guidelines for Bioequivalence research, the confidence intervals for Cmax, AUC0-t and AUC0-? ranged between 80.00-125.00%. The above limits obtained were within the accepted bio-equivalence limits.
ABSTRACT
The tuberculosis control program is based on a felt need-oriented basis. The diagnosis is mainly microbiological. However, sputum smear-negative Acid Fast Bacilli [AFB] cases with suspected radiological findings can be problematic in diagnosis. To confirm the diagnosis of tuberculosis early, in smear-negative AFB cases by using a Fiberoptic Bronchoscope. We embarked on Fiberoptic Bronchoscopy [FOB] and Spot Scopy smear Microscopy [SSM[for 533 suspected Pulmonary Tuberculosis [PT] cases [sputum smear negative and radiologically suggestive] from February 2007 to May 2010. FOB was performed using a special device, a Trans Oro Pharyngeal Spacer [TOPS], as a conduit. The yield for positivity for AFB was 341 [64%] out of 533 cases. The specimens collected by using the fiberoptic bronchoscope confirmed the disease in the smear-negative cases. Hence, FOB was recommended in smear-negative cases, to avoid delay in the treatment of tuberculosis