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Using PBPK modeling to supplement clinical data and support the safe and effective use of dolutegravir in pregnant and lactating women.
CPT Pharmacometrics Syst Pharmacol
November 2024
Certara Predictive Technologies Division, Sheffield, UK.
Optimal dosing in pregnant and lactating women requires an understanding of the pharmacokinetics in the mother, fetus, and breastfed infant. Physiologically-based pharmacokinetic (PBPK) modeling can be used to simulate untested scenarios and hence supplement clinical data to support dosing decisions. A PBPK model for the antiretroviral dolutegravir (mainly metabolized by UGT1A1) was verified using reported exposures in non-pregnant healthy volunteers, pregnant women, and the umbilical cord, lactating mothers, and breastfed neonates.
View Article and Find Full Text PDFExcretion of polybrominated diphenyl ethers and AhR activation in breastmilk among firefighters.
Toxicol Sci
February 2023
Department of Community, Environment and Policy, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona, US.
Excretion of toxicants accumulated from firefighter exposures through breastmilk represents a potential hazard. We investigated if firefighting exposures could increase the concentration of polybrominated diphenyl ethers (PBDEs) and aryl hydrocarbon receptor (AhR) activation in excreted breastmilk. Firefighters and non-firefighters collected breastmilk samples prior to any firefighting responses (baseline) and at 2, 8, 24, 48, and 72 hours after a structural fire (firefighters only).
View Article and Find Full Text PDFPerceptions of Work-Related Health and Cancer Risks Among Women Firefighters: A Qualitative Study.
J Occup Environ Med
December 2021
Department of Medicine, University of Miami, Leonard M. Miller School of Medicine, Miami, Florida (Dr Solle); Department of Public Health Sciences, University of Miami, Leonard M. Miller School of Medicine, Miami, Florida (Ms Santiago, Ms Louzado Feliciano, and Dr Caban-Martinez); Sylvester Comprehensive Cancer Center, University of Miami, Leonard M. Miller School of Medicine, Miami, Florida (Dr Solle and Dr Caban-Martinez); Division of Field Studies and Engineering (DFSE), National Institute for Occupational Safety and Health, Cincinnati, Ohio (Dr Calkins and Dr Fent); Center for Fire, Rescue & EMS Health Research, National Development & Research Institutes, Leawood, Kansas (Dr Jahnke); San Francisco Fire Department, SF, California (Ms Parks and Ms Buren); Fire Protection Research Foundation, Quincy, Massachusetts (Grant); Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona (Dr Burgess).
Objectives: We use a qualitative method to gain further insight into women firefighters' experiences, perceptions of cancer, health, and safety risks in the fire service.
Methods: We conducted six focus groups with U.S.
Involvement of Protein Kinase A in Oxytocin Neuronal Activity in Rat Dams with Pup Deprivation.
Neurochem Res
April 2021
Department of Physiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, 150081, China.
Oxytocin (OT) neuronal activity is the key factor for breastfeeding and it can be disrupted by mother-baby separation. To explore cellular mechanisms underlying OT neuronal activity, we studied the role of protein kinase A (PKA) in OT neuronal activity in the supraoptic nucleus (SON) using a rodent model of pup deprivation (PD) Intermittent (IPD) or continuous (CPD) PD significantly reduced suckling duration and number of milk ejections in lactating rats, particularly those with CPD. In Western blots of the SON, PD increased expressions of OT receptor (OTR) and its immediate downstream effectors, Gαq and Gβ subunits, particularly IPD, but reduced the expression of catalytic subunit of PKA (cPKA).
View Article and Find Full Text PDFKey Roles of Cyclooxygenase 2-Protein Kinase A-Hyperpolarization-activated Cyclic Nucleotide-gated Channel 3 Pathway in the Regulation of Oxytocin Neuronal Activity in Lactating Rats with Intermittent Pup-Deprivation.
Neuroscience
January 2021
Department of Physiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China. Electronic address:
Suckling-evoked pulsatile release of oxytocin (OT) from the posterior pituitary plays a key role in breastfeeding, which relies on burst-like discharges of OT neurons. To explore cellular mechanisms regulating OT neuronal activity, using lactating rats with pup-deprivation (PD) during postpartum day 1-5, we observed the involvement of prostaglandin, cyclic AMP/protein kinase A (PKA) and hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3) signaling pathway in OT neuronal activity. PD gradually reduced lactation efficiency.
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