Dexamethasone affects the chemotaxis and phagocytic activity of neutrophils for boar spermatozoa and the quality of liquid preserved boar semen in vitro.

This study aimed to investigate the effect of dexamethasone (DEX) on chemotaxis and phagocytic activity of neutrophils for spermatozoa and semen quality of preserved boar semen. The different concentrations of dexamethasone were added to boar semen dilutions to detect its effects on the chemotaxis of neutrophils and phagocytosis of neutrophils and sperm motility sperm malformation rate, plasma membrane integrity, mitochondrial activity, and spermatozoa motility parameters. The study results showed that the experimental groups of DEX significantly inhibited the phagocytosis and chemotaxis of PMNs for spermatozoa. With the increased concentration of DEX, there was an inhibition effect on PMNs activity. In addition, under 17 °C storage conditions, the addition of DEX 1 × 10-6 mol/mL concentration has the best preservation effect on boar semen, which can effectively improve the sperm motility, movement parameters, plasma membrane integrity, mitochondrial activity, T-AOC activity, and significantly reduce the sperm malformation rate and H2O2 content. Therefore, the most suitable concentration of DEX to preserve boar semen at 17 °C is 1 × 10-6 mol/mL. The significant increase of conception rate of sows and litter size of piglets proved that DEX has practical application value. Thus, it is shown that the use of DEX to inhibit uterine inflammation is effective and feasible for sperm damage providing new methods for developing low-dose artificial insemination technology.

Integrated pharmacokinetic/viral dynamic model for daclatasvir/asunaprevir in treatment of patients with genotype 1 chronic hepatitis C.

In order to develop an integrated pharmacokinetic/viral dynamic (PK/VD) model to predict long-term virological response rates to daclatasvir (DCV) and asunaprevir (ASV) combination therapy in patients infected with genotype 1 (GT1) chronic hepatitis C virus (HCV), a systematic publication search was conducted for DCV and ASV administered alone and/or in combination in healthy subjects or patients with GT1 HCV infection. On the basis of a constructed meta-database, an integrated PK/VD model was developed, which adequately described both DCV and ASV PK profiles and viral load time curves. The IC50 values of DCV and ASV were estimated to be 0.041 and 2.45 µg/L, respectively, in GT1A patients. A sigmoid Emax function was applied to describe the antiviral effects of DCV and ASV, depending on the drug concentrations in the effect compartment. An empirical exponential function revealed that IC50 changing over time described drug resistance in HCV GT1A patients during DCV or ASV monotherapy. Finally, the PK/VD model was evaluated externally by comparing the expected and observed virological response rates during and post-treatment with DCV and ASV combination therapy in HCV GT1B patients. Both the rates were in general agreement. Our PK/VD model provides a useful platform for the characterization of pharmacokinetic/pharmacodynamic relationships and the prediction of long-term virological response rates to aid future development of direct acting antiviral drugs.