Browsing by Subject "Physiological changes"

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    A Semi-Mechanistic Metabolism Model of CYP3A Substrates in Pregnancy: Predicting Changes in Midazolam and Nifedipine Pharmacokinetics
    (Wiley, 2012-09-26) Quinney, S. K.; Mohamed, A. N.; Hebert, M. F.; Haas, D. M.; Clark, S.; Umans, J. G.; Caritis, S. N.; Li, L.; Obstetric-fetal Pharmacology Research Unit Network; Obstetrics and Gynecology, School of Medicine
    Physiological changes in pregnancy, including changes in body composition and metabolic enzyme activity, can alter drug pharmacokinetics. A semi-mechanistic metabolism model was developed to describe the pharmacokinetics of two cytochrome P450 3A (CYP3A) substrates, midazolam and nifedipine, in obstetrics patients. The model parameters were optimized to fit the data of oral midazolam pharmacokinetics in pregnant women, by increasing CYP3A-induced hepatic metabolism 1.6-fold in the model with no change in gut wall metabolism. Fetal metabolism had a negligible effect on maternal plasma drug concentrations. Validation of the model was performed by applying changes in volume of distribution and metabolism, consistent with those observed for midazolam, to the pharmacokinetics parameters of immediate-release nifedipine in healthy volunteers. The predicted steady-state areas under the concentration-time curve (AUCs) for nifedipine were within 15% of the data observed in pregnant women undergoing treatment for preterm labor. This model predicts the pharmacokinetics of two CYP3A substrates in pregnancy, and may be applicable to other CYP3A substrates as well.
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    Maternal Diet Intervention Before Pregnancy Primes Offspring Lipid Metabolism in Liver
    (Springer Nature, 2020-04) Zhou, Yi; Peng, Hui; Xu, Huiting; Li, Jiangyuan; Golovko, Mikhail; Cheng, Henghui; Lynch, Ernest C.; Liu, Lin; McCauley, Naomi; Kennedy, Lindsey; Alpini, Gianfranco; Zhang, Ke K.; Xie, Linglin; Medicine, School of Medicine
    Nonalcoholic fatty liver disease (NAFLD) has a developmental origin and is influenced in utero. We aimed to evaluate if maternal diet intervention before pregnancy would be beneficial to reduce the risk of offspring NAFLD. In our study, female mice were either on a normal-fat diet (NF group), or a high-fat diet for 12 weeks and continued on this diet throughout pregnancy and lactation (HF group), or switched from HF-to-NF diet 1 week (H1N group), or 9 weeks (H9N group) before pregnancy. Compared with the NF offspring, the H1N and HF, but not the H9N offspring, displayed more severe hepatic steatosis and glucose intolerance. More specifically, an abnormal blood lipid panel was seen in the H1N offspring and abnormal hepatic free fatty acid composition was present in both the HF and H1N offspring, while the H9N offspring displayed both at normal levels. These physiological changes were associated with desensitized hepatic insulin/AKT signaling, increased expression of genes and proteins for de novo lipogenesis and cholesterol synthesis, decreased expression of genes and proteins for fatty acid oxidation, increased Pcsk9 expression, and hypoactivation of 5' AMP-activated protein kinase (AMPK) signaling in the HF and H1N offspring. However, these effects were completely or partially rescued in the H9N offspring. In summary, we found that early maternal diet intervention is effective in reducing the risk of offspring NAFLD caused by maternal HF diet. These findings provide significant support to develop effective diet intervention strategies and policies for prevention of obesity and NAFLD to promote optimal health outcomes for mothers and children.
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    Pulse Supplementation Improves Gut Health and Lowers Total Cholesterol in Postmenopausal Women
    (Elsevier, 2022) Orphan, Jessica; Alake, Sanmi; Keirns, Bryant; Ice, John; Smith, Brenda; Emerson, Sam; Lucas, Edralin; Obstetrics and Gynecology, School of Medicine
    Objectives: Menopause is associated with many physiological changes as well as increased risk of obesity, cardiovascular disease, type 2 diabetes, and gut-related diseases (i.e. irritable bowel syndrome, inflammatory bowel disease, colon cancer). Data regarding the use of pulse crops in alleviating health risks associated with menopause are limited. This study investigated the effects of pulse supplementation on markers of gut health and metabolic outcomes in postmenopausal women. Methods: Thirty-five postmenopausal (≥1 year without menstruation) women, ages 45–70 years old, who were not on hormone replacement therapy, probiotics, antibiotics, multiple supplements, or medications that affect lipids or glucose, were recruited for this clinical study. Study participants were asked to consume 100 g of pulses (alternate between chickpeas, kidney beans, pinto beans, black-eyed peas, and lentils) daily for 12 wks, and to maintain their normal diet and lifestyle. Anthropometric measures including body composition by dual-energy X-ray absorptiometry, plasma lipids and glucose, fecal short chain fatty acids (SCFAs), and stool characteristics (Bristol Stool Chart and the Cleveland Clinic Constipation Scoring System) were assessed before and at the end of 12-wk supplementation. P < 0.05 was considered statistically significant. Results: There were no differences in anthropometric measures and plasma glucose at the end of the 12-wk supplementation compared to baseline. However, a reduction in plasma total cholesterol (p = 0.039) and LDL-C (p = 0.026), but an increase in both VLDL-C (p = 0.031) and triglycerides (p = 0.033) were observed with pulse supplementation. Constipation score significantly improved (p = 0.003) but no change in stool quality were observed with pulse supplementation. Fecal acetic acid (p< 0.001), n-butyric (p = 0.038), n-caproic (p = 0.004) and total SCFAs (p = 0.001) were also significantly increased with pulse supplementation. Conclusions: Our findings demonstrate that 12 wks of pulse supplementation improved markers of gut health and lowers total- and LDL-cholesterol in postmenopausal women. This population who are at an increased risk for cardiovascular and gut-related diseases can benefit from regularly consuming pulses.