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Clinical Trials That Have Changed Clinical Practice and Care of Pregnant People With HIV.
Clin Obstet Gynecol
June 2024
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology.
Over the last 4 decades, significant advances in the care of HIV during pregnancy have successfully reduced, and nearly eliminated, the risk of perinatal HIV transmission. The baseline risk of transmission without intervention (25% to 30%) is now <1% to 2% in the United States with contemporary antepartum, intrapartum, and postnatal interventions. In this review, we discuss 3 landmark clinical trials that substantially altered obstetric practice for pregnant individuals with HIV and contributed to this extraordinary achievement: 1) the Pediatric AIDS Clinical Trials Group 076 Trial determined that antepartum and intrapartum administration of antiretroviral drug zidovudine to the pregnant individual, and postnatally to the newborn, could reduce the risk of perinatal transmission by approximately two-thirds; 2) the European Mode of Delivery Collaboration Trial demonstrated performance of a prelabor cesarean birth before rupture of membranes among pregnant people with viremia reduced the risk of perinatal transmission compared with vaginal birth; and 3) the International Maternal Pediatric Adolescent AIDS Clinical Trials Network 2010 Trial identified that dolutegravir-containing, compared with efavirenz-containing, antiretroviral regimens during pregnancy achieved a significantly higher rate of viral suppression at delivery with shorter time to viral suppression, with fewer adverse pregnancy outcomes.
View Article and Find Full Text PDFMethods for Inferring Cell Cycle Parameters Using Thymidine Analogues.
Biology (Basel)
June 2023
Unidad de Citología e Histología, Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia, Facultad de Biociencias, Institut de Neurociències, Universidad Autónoma de Barcelona, Bellaterra, 08193 Barcelona, Spain.
Tritiated thymidine autoradiography, 5-bromo-2'-deoxyuridine (BrdU) 5-chloro-2'-deoxyuridine (CldU), 5-iodo-2'-deoxyuridine (IdU), and 5-ethynyl-2'-deoxyiridine (EdU) labeling have been used for identifying the fraction of cells undergoing the S-phase of the cell cycle and to follow the fate of these cells during the embryonic, perinatal, and adult life in several species of vertebrate. In this current review, I will discuss the dosage and times of exposition to the aforementioned thymidine analogues to label most of the cells undergoing the S-phase of the cell cycle. I will also show how to infer, in an asynchronous cell population, the duration of the G, S, and G phases, as well as the growth fraction and the span of the whole cell cycle on the base of some labeling schemes involving a single administration, continuous nucleotide analogue delivery, and double labeling with two thymidine analogues.
View Article and Find Full Text PDFMethods to Assess Proliferation of Stimulated Human Lymphocytes In Vitro: A Narrative Review.
Cells
January 2023
Laboratory of Toxicology, Unit of Environment & Health, Department of Public Health and Primary Care, KU Leuven, 3000 Leuven, Belgium.
The ability to monitor lymphocyte responses is critical for developing our understanding of the immune response in humans. In the current clinical setting, relying on the metabolic incorporation of [H] thymidine into cellular DNA via a lymphocyte proliferation test (LPT) is the only method that is routinely performed to determine cell proliferation. However, techniques that measure DNA synthesis with a radioactive material such as [H] thymidine are intrinsically more sensitive to the different stages of the cell cycle, which could lead to over-analyses and the subsequent inaccurate interpretation of the information provided.
View Article and Find Full Text PDFSynthesis, antimicrobial, molecular docking and molecular dynamics studies of lauroyl thymidine analogs against SARS-CoV-2: POM study and identification of the pharmacophore sites.
Bioorg Chem
August 2022
Laboratory of Carbohydrate and Nucleoside Chemistry, Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, Bangladesh. Electronic address:
Nucleoside precursors and nucleoside analogs occupy an important place in the treatment of viral respiratory pathologies, especially during the current COVID-19 pandemic. From this perspective, the present study has been designed to explore and evaluate the synthesis and spectral characterisation of 5́-O-(lauroyl) thymidine analogs 2-6 with different aliphatic and aromatic groups through comprehensive in vitro antimicrobial screening, cytotoxicity assessment, physicochemical aspects, molecular docking and molecular dynamics analysis, along with pharmacokinetic prediction. A unimolar one-step lauroylation of thymidine under controlled conditions furnished the 5́-O-(lauroyl) thymidine and indicated the selectivity at C-5́ position and the development of thymidine based potential antimicrobial analogs, which were further converted into four newer 3́-O-(acyl)-5́-O-(lauroyl) thymidine analogs in reasonably good yields.
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