Toll-Like Receptor 3 is Associated With the Risk of HCV Infection and HBV-Related Diseases.

There are inconsistent data on the association of risk of hepatitis virus infection and hepatitis virus-related diseases with the toll-like receptor 3 (TLR3) gene.Several common polymorphism sites were targeted to assess the risk of HBV infection, HCV infection, and HBV-related diseases.Meta-analysis combining data for 3547 cases and 2797 controls from 8 studies was performed in this study. Pooled ORs were calculated to measure the risk of hepatitis virus infection and hepatitis virus-related diseases. Fixed-effects pooled ORs were calculated using the Mantel-Haenszel method.The TLR3 gene was associated with a significantly increased risk of HBV-related diseases among 1355 patients and 1130 controls ([pooled OR, [95%CI]: 1.30, [1.15-1.48] for dominant; 1.77, [1.35-2.31] for recessive; 1.28 [1.16-1.41] for allele frequency). Subgroup analyses by a polymorphism site indicated an increased risk of HCV infection in relation to the TT/CT genotypes of rs3775291 (1.50 [1.11-2.01]), and a decreased risk ascribed to the T allele (0.20 [0.16-0.25]). We also noted an association between rs3775291 and significantly increased risk of HBV-related diseases (2.23 [1.55-3.21]). No significant inter-study heterogeneity or publication bias was detected in the analyses.These data suggest a likely effect on the risk to infect HCV and develop HBV-related diseases for the TLR3 gene. Large-scale studies with racially diverse populations are required to validate these findings.

Pharmacokinetics of ambroxol and clenbuterol tablets in healthy Chinese volunteers.

OBJECTIVE: To investigate the pharmacokinetics of Ambroxol and Clenbuterol Tablets in Chinese healthy volunteers after a single or multiple dosages oral administration. METHODS: A total of 9 healthy adult subjects were given Ambroxol and Clenbuterol Tablets in a single dosage or multiple dosages respectively. LC/MS/MS were used for the determination of Ambroxol and Clenbuterol of in plasma. The important pharmacokinetic parameters were calculated by DAS 2.0 software (compartment model). RESULTS: Single and multiple dosage groups of Ambroxol and Clenbuterol were all fitted two-compartment model. The pharmacokinetics fitted first order kinetics process. No difference in pharmacokinetics of Ambroxol in single and multiple dosage groups volunteers was observed, Which showed no marked changes, suggesting that multiple dosing did not influence the velocity of drug metabolism. Moreover, parameters of Clenbuterol had significant difference between the single and multiple dosage groups (P<0.05), showing there was accumulation in the body. 9 subjects had completed single or multiple dosages oral administration test, with no adverse drug reactions appeared during the test. CONCLUSION: There was no obvious accumulation of Ambroxol after repeated dosing. But obvious accumulation of Clenbuterol was noted in multiple-dose administration. The established method is sensitive, accurate, reliable and specific, and it can meet the requirement of clinical pharmacokinetic trial.

[Changes in plasma endotoxin content due to cholinesterase inhibitor VX intoxication and therapeutic effect of benthiaczine in mice].

OBJECTIVE: To investigate the therapeutic effect and its mechanisms of benthiaczine on cholinesterase inhibitor VX poisoning by observing on the changes in plasma endotoxin content in mice. METHODS: Three hundred and six male Kunming mice were randomly assigned to five groups: normal group, VX poisoning (model) group, benthiaczine, atropine or 654-2 pretreatment group. The above mentioned drugs were respectively given 10 minutes before hypodermic injection of VX in a dose of 0.02 mg/kg. The plasma concentration of endotoxin was measured at 1.5, 3, 6, 24, 48 and 72 hours after VX poisoning. RESULTS: After VX injection, the endotoxin concentration in model group was significantly increased compared with normal group (all P < 0.01). The endotoxin concentration in model group was (5.36+/-1.62) kEU/L at 1.5 hours, which was almost twice of that of normal group [(1.90+/-0.41) kEU/L]. It increased gradually to (11.47+/-3.90) kEU/L at 24 hours, which was 5 fold of that of the normal group (all P < 0.01), and it maintained on the abnormally high level until 48 hours, then declined to the level of normal group after 72 hours. The endotoxin concentration of benthiaczine pretreatment group was significantly lower than that of model group at 1.5 hours and 3 hours after VX injection [(3.73+/-0.71) kEU/L, (3.95+/-1.26) kEU/L, respectively, P < 0.01 and P < 0.05], but there was no significant difference between two groups at 6 hours [(8.77+/-1.85) kEU/L] and 24 hours [(11.47+/-2.51) kEU/L], though it was significantly higher than normal group (both P < 0.01). It lowered to the normal level at 48 hours. The endotoxin concentration in atropine pretreatment group was significantly higher than model group at 1.5-24 hours after VX injection (P < 0.05 or P < 0.01), while that of 654-2 pretreatment group reached a peak at 6 hours, which was significantly higher than that of the model group (P < 0.01). CONCLUSION: The increased endotoxin concentration induced by VX in mice 1.5-48 hours after poisoning can be reversed by pretreatment of benthiaczine, but aggravated by pretreatment of atropine or 654-2. The administration of benthiaczine could alleviate the injury to the gut barrier function thus delay translocation of endotoxin into blood, and also shorten the time of endotoxemia.