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Disease-mediated alterations to drug disposition constitute a significant source of adverse drug reactions. Cisplatin (CDDP) elicits nephrotoxicity due to exposure in proximal tubule cells during renal secretion. Alterations to renal drug transporter expression have been discovered during nonalcoholic steatohepatitis (NASH), however, associated changes to substrate toxicity is unknown. To test this, a methionine- and choline-deficient diet-induced rat model was used to evaluate NASH-associated changes to CDDP pharmacokinetics, transporter expression, and toxicity. NASH rats administered CDDP (6 mg/kg, i.p.) displayed 20% less nephrotoxicity than healthy rats. Likewise, CDDP renal clearance decreased in NASH rats from 7.39 to 3.83 mL/min, renal secretion decreased from 6.23 to 2.80 mL/min, and renal CDDP accumulation decreased by 15%, relative to healthy rats. Renal copper transporter-1 expression decreased, and organic cation transporter-2 and ATPase copper transporting protein-7b increased slightly, reducing CDDP secretion. Hepatic CDDP accumulation increased 250% in NASH rats relative to healthy rats. Hepatic organic cation transporter-1 induction and multidrug and toxin extrusion protein-1 and multidrug resistance-associated protein-4 reduction may contribute to hepatic CDDP sequestration in NASH rats, although no drug-related toxicity was observed. These data provide a link between NASH-induced hepatic and renal transporter expression changes and CDDP renal clearance, which may alter nephrotoxicity., (© 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Objective: We wished to identify the prevalence, longitudinal trends, and associated risk factors for various birth weight categories by First Nations ethnicity in the province of Alberta., Methods: We performed a retrospective analysis of administrative data for the years 2000 to 2009 inclusive. Age-adjusted prevalence trends for high birth weight (HBW; > 4000g), very HBW (> 4500g), low birth weight (LBW; < 2500g), and very LBW (< 1500g) were compared via average annual percent change analyses. Logistic regression analysis was used to determine risk factors., Results: First Nations ethnicity was a significant independent predictor of HBW (OR 1.82 [95% CI 1.75, 1.89]), very HBW (OR 2.35 [95% CI 2.18, 2.52]), and very LBW (OR 1.35 [95% CI 1.23, 1.48]), but not of LBW (OR 0.98 [95% CI 0.93, 1.03]). However, HBW prevalence decreased and other birth weight categories remained stable over time in First Nations populations. Gestational diabetes and maternal weight ≥ 91 kg were potentially manageable risk factors for HBW. Potentially manageable risk factors for LBW included pre-gestational renal disease, hypertension, and maternal weight ≤ 45 kg, as well as smoking, illicit drug dependence, and alcohol consumption., Conclusion: Although HBW, very HBW, and very LBW remain more common in Alberta First Nations populations than in the general population, their prevalence is not increasing., (Copyright © 2016 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.)

Objective: Using a large administrative dataset we examined stillbirth epidemiology in First Nations and non-First Nations pregnancies in Alberta, focusing on previously unexplored longitudinal trends., Methods: We undertook a retrospective analysis of de-identified data from 426 945 delivery records for the years 2000 to 2009. Age-adjusted prevalence of antepartum and intrapartum stillbirth were calculated and compared by ethnicity, as were longitudinal changes via average annual percent change analyses. Risk factors were explored via multivariable logistic regression analysis., Results: Overall age-adjusted prevalence of antepartum and intrapartum stillbirth was significantly higher (P < 0.001) in First Nations pregnancies than in non-First Nations pregnancies, and prevalence remained stable over time in both groups. Pre-existing diabetes was a strong predictor of stillbirth., Conclusion: Stillbirth prevalence remains higher in First Nations pregnancies than in non-First Nations. Improved awareness of pre-existing diabetes and effective interventions are needed in First Nations women to decrease stillbirth risk.

The glucose and insulin responses to oral glucose tolerance tests and lipid values in normal women taking a triphasic pill containing norethindrone (Ortho 7/7/7) were performed. After three months, no significant changes in these metabolic indices were found. These results confirm and expand the knowledge regarding the metabolic safety of norethindrone-containing triphasic formulations.