The Effect of Maternal Diet with Fish Oil on Oxidative Stress and Inflammatory Response in Sow and New-Born Piglets.

Pregnancy is an oxidative stress and immune challenge for the mother. Fish oil is rich in EPA and DHA, which can partly inhibit aspects of inflammation and restore antioxidant capacity. In the present study, we investigated the effect of maternal diet with fish oil during the late gestation period on oxidative stress and inflammatory response in sows and their progenies. Twelve second-parity sows were allocated equally into two groups. Sows were fed either the soybean oil diet (SD) or soybean oil+fish oil diet (FD) during the gestation period. The plasma of sows, cord blood, and new-born piglets were collected. Full-term placentas and livers of new-born piglets were also sampled. The activities of glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) in the plasma of sows on farrowing day were higher, and the concentrations of interleukin-6 (IL-6) and prostaglandin-endoperoxide synthase 2 (PGE2) in the plasma of sows on farrowing day and interleukin-1ß (IL-1ß) in the plasma of cord blood were lower in the FD group than those in the SD group (P < 0.05). The FD downregulated the expression of SOD, IL-1ß, IL-6, and transforming growth factor-ß-activated kinase 1 binding protein 1 (TAB1) mRNA but upregulated the expression of lipoxygenase enzyme 5 (ALOX5) and interleukin-10 (IL-10) mRNA in placentas (P < 0.05). The FD downregulated the protein expression level of p-JNK/JNK in placentas (P < 0.05). In the livers of new-born piglets, the FD upregulated the expression of ALOX5 (P < 0.05) and G-protein-coupled receptor 120 (GPR120) (P < 0.05) mRNA. Our results suggest that the maternal diet with fish oil might alleviate oxidative stress in sows on farrowing day and modulate inflammatory response in full-term placentas by inhibiting the JNK signal pathway. Moreover, the maternal diet with fish oil might partly regulate the neonatal immune response of their progenies.

Assessment of drug-drug interactions between daclatasvir and methadone or buprenorphine-naloxone.

Hepatitis C virus (HCV) infection is common among people who inject drugs, including those managed with maintenance opioids. Pharmacokinetic interactions between opioids and emerging oral HCV antivirals merit evaluation. Daclatasvir is a potent pangenotypic inhibitor of the HCV NS5A replication complex recently approved for HCV treatment in Europe and Japan in combination with other antivirals. The effect of steady-state daclatasvir (60 mg daily) on stable plasma exposure to oral opioids was assessed in non-HCV-infected subjects receiving methadone (40 to 120 mg; n = 14) or buprenorphine plus naloxone (8 to 24 mg plus 2 to 6 mg; n = 11). No relevant interaction was inferred if the 90% confidence interval (CI) of the geometric mean ratio (GMR) of opioid area under the plasma concentration-time curve over the dosing interval (AUCτ) or maximum concentration in plasma (C max) with versus without daclatasvir was within literature-derived ranges of 0.7 to 1.43 (R- and S-methadone) or 0.5 to 2.0 (buprenorphine and norbuprenorphine). Dose-normalized AUCτ for R-methadone (GMR, 1.08; 90% CI, 0.94 to 1.24), S-methadone (1.13; 0.99 to 1.30), and buprenorphine (GMR, 1.37; 90% CI, 1.24 to 1.52) were within the no-effect range. The norbuprenorphine AUCτ was slightly elevated in the primary analysis (GMR, 1.62; 90% CI, 1.30 to 2.02) but within the no-effect range in a supplementary analysis of all evaluable subjects. Dose-normalized C max for both methadone enantiomers, buprenorphine and norbuprenorphine, were within the no-effect range. Standardized assessments of opioid pharmacodynamics were unchanged throughout daclatasvir administration with methadone or buprenorphine. Daclatasvir pharmacokinetics were similar to historical data. Coadministration of daclatasvir and opioids was generally well tolerated. In conclusion, these data suggest that daclatasvir can be administered with buprenorphine or methadone without dose adjustments.

A comparison of the pharmacokinetics of two different formulations of extended-release niacin.

OBJECTIVE: The objective of this study was to compare pharmacokinetic parameters of niacin extended-release tablets (NER uncoated) and niacin extended-release caplet formation (NER coated). RESEARCH DESIGN AND METHODS: Twenty-five healthy male and female subjects were enrolled in a four-period, open-label, randomized, crossover study. Both NER uncoated and NER coated were given as 1 x 1000 mg or 2 x 500 mg tablets. Similarity of NER coated 1 x 1000 mg and NER uncoated 2 x 500 mg was declared if 90% confidence intervals for the geometric mean ratio (GMR) for nicotinuric acid (NUA) Cmax fell within the pre-specified bounds of [0.7, 1.43]. RESULTS: The GMRs for NUA Cmax demonstrated similarity in the pharmacokinetics of NER uncoated 2 x 500 mg, NER coated 1 x 1000 mg, and NER coated 2 x 500 mg. Although less stringent comparability bounds were prespecified for the primary pharmacokinetic endpoint (i.e., Cmax of plasma NUA), inspection of the primary comparison of interest indicated that a hypothesis with more stringent bioequivalence bounds of [0.8, 1.25] would have been satisfied. The NUA Cmax for NER uncoated 1 x 1000 mg was approximately 40% higher than that seen for the other three treatments. In contrast, total urinary excretion of niacin and its metabolites, an approximate measure of bioavailability, was similar for all four treatments. CONCLUSION: The pharmacokinetic profile of the original NER uncoated formulation dosed as 2 x 500 mg was similar to the new film-coated formulation, NER coated, dosed as 1 x 1000 mg.