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Effect of Genetic Variants on Rosuvastatin Pharmacokinetics in Healthy Volunteers: Involvement of , and .

Int J Mol Sci

December 2024

Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-Princesa), 28006 Madrid, Spain.

Statins are the primary drugs used to prevent cardiovascular disease by inhibiting the HMG-CoA reductase, an enzyme crucial for the synthesis of LDL cholesterol in the liver. A significant number of patients experience adverse drug reactions (ADRs), particularly musculoskeletal problems, which can affect adherence to treatment. Recent clinical guidelines, such as those from the Clinical Pharmacogenetics Implementation Consortium (CPIC) in 2022, recommend adjusting rosuvastatin doses based on genetic variations in the and genes to minimize ADRs and improve treatment efficacy.

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Background: Early neurological deterioration (END) is a critical determinant influencing the short-term prognosis of acute ischemic stroke (AIS) patients and is associated with increased mortality rates among hospitalized individuals. AIS frequently coexists with coronary heart disease (CHD), complicating treatment and leading to more severe symptoms and worse outcomes. Shared risk factors between CHD and AIS, especially elevated low-density lipoprotein cholesterol (LDL-C), contribute to atherosclerosis and inflammation, which worsen brain tissue damage.

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The research focuses on the characterization and evaluation of drug delivery efficiency of a microwave-assisted, free-radical synthesized polyacrylamide-grafted Assam Bora rice starch (ABRS) graft copolymer (ABRS-g-PAM). Percentage grafting efficiency (% GE) and intrinsic viscosity were chosen as the optimization parameters. The optimized ABRS-g-PAM Grade Formulation 4 (GF4) was found to be the best grade.

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Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder of complex pathogenesis and multiple interacting signaling pathways where amyloidal-β protein (Aβ) clearance plays a crucial role in cognitive decline. Herein, the current study investigated the possible modulatory effects of memantine/ rosuvastatin therapy on TGF-β1/p-Smad/p21 signaling pathway and their correlation to the blood brain barrier transporters involved in Aβ-clearance and microRNAs as a novel molecular mechanism in AD treatment. AD was induced by a single intracerebroventricular streptozotocin injection (ICV-STZ, 3 mg/kg) in rats and drug therapy was continued for 28 days after AD induction.

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Background/aims: Research has indicated that treatment with rosuvastatin can improve liver pathology in metabolic-associated fatty liver disease (MAFLD) patients and that treatment with Bifidobacterium can improve MAFLD. Therefore, the effects of Bifidobacterium, rosuvastatin, and their combination on related indices in a rat model of diet-induced MAFLD need to be investigated.

Methods: Forty rats were divided into five groups: the normal diet group (N), high-fat diet (HFD) model group (M), HFD + probiotic group (P), HFD + statin group (S), and HFD + probiotic + statin group (P-S).

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