Pharmacokinetics of cantide, an antisense oligonucleotide, and its metabolites in rhesus monkeys / 药学学报

To study the pharmacokinetics of cantide, an antisense oligonucleotide, and its metabolites after iv gtt administration in rhesus monkeys, a dual solid phase extraction pretreatment method coupling with non-gel sieving capillary electrophoresis analysis method was used for determination of cantide and its metabolites in plasma and their pharmacokinetic parameters were calculated. The pharmacokinetic behavior of cantide and its metabolites (M1 and M2) after iv gtt administration (8, 16 and 24 mg kg(-1)) in rhesus monkeys were investigated. After iv gtt administration of cantide to rhesus monkeys, cantide in plasma was eliminated rapidly and the terminal elimination half-life (t1/2) was 57.91-77.97 min, the correlation coefficients (r) to the dose of Cmax AUC(o-inf) and AUC(0-t) of the prototype was 0.9918, 0.9568 and 0.9773, respectively. The metabolites of cantide reached the Cmax following cantide immediately and the Cmax of metabolites were lower than that of the prototype. The CL(S) of cantide and its metabolites (M1 and M2) were 1.60-2.19, 5.92-8.58 and 6.07-8.78 mL min(-1) kg(-1), respectively. So, it is concluded that the Cmax of cantide and its metabolites increased with the dose, which is the same as their AUC(0-inf) and AUC(0-t). The CL(S) of metabolites were higher than that of the prototype. The MRT and t1/2 of metabolites in the high dose group increased obviously.

Effect of IFN-lambda2 on apoptotic protein in the myocardium in mice with viral myocarditis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>INF-lambda has anti-viral and anti-tumor activities. Its application in viral myocarditis (VMC) has not been reported. This study investigated the role of INF-lambda in acute VMC in mice.</p><p><b>METHODS</b>Forty mice were randomly divided into three groups: VMC (n=15), IFN-lambda2-treated VMC (n=15) and control (n=10). VMC was induced by an intraperitoneal injection of Coxsackievirus B3 (CVB3).The control group was intraperitoneally injected with 2% PBS. The IFN-lambda2-treated VMC group was administered with 400 ng IFN-lambda2 (0.1 mL) by subcutaneous injections daily, for 5 days. The control and the VMC groups were given equal amount of nomal saline.The surviving mice were sacrificed 9 days after IFN-lambda2 treatment. The pathological changes of heart tissues were examined under a light microscope. Bcl-2 and Bax expression in heart tissues was determined by immunohistochemistry.</p><p><b>RESULTS</b>The control group presented normal heart tissues. The INF-lambda2-treated VMC group showed significantly a lower pathological score (1.5+/-0.5) than the untreated VMC group (2.8+/-0.8) (P<0.01). Bcl-2 expression decreased (P<0.01), in contrast, Bax expression increased (P<0.01) in the untreated VMC group compared with that in the control group. INF-lambda2 treatment resulted in an increased Bcl-2 expression (P<0.01) and a decreased Bax expression (P<0.01) compared to the untreated VMC group.</p><p><b>CONCLUSIONS</b>INF-lambda2 may alleviate myocardial injuries and inhibit cardiomyocytic apoptosis, thus providing protective effects on myocardial cells in mice with acute VMC.</p>

Mitochondria Injury due to Viral Myocarditis Improved by Different Doses of Captopril in Mice / 实用儿科临床杂志

Objective To further understand the cellular events of myocarditis,we have examined the myocardial mitochondria structure and activity of ATPase in mice with myocarditis,and observe the interventional effect of different doses of carptopril.Methods Sixty male Balb/c mice were randomly divided into 5 groups:infected coxsackie B3 virus(CVB3)group,infected CVB3 and treated with carptopril(in a dose of 10,30,or 100 mg/kg,twice a day)groups and control group.Captopril was administered after infection.The activity of Na+-K+-adenosine triphosphatase(Na+-K+-ATPase)and Ca2+-adenosine triphosphatase(Ca2+-ATPase)of myocardial mitochondrial as well as the morphological of myocardial mitochondrial were investigated on day 14.Results The activity of mitochondrial Na+-K+-ATPase and Ca2+-ATPase were significantly higher(Pa0.05).Conclusions The favorable effects of captopril exerts on myocyte mitochondria were shown in a dose-dependent manner.Thirty and 100 mg/kg,twice a day captopril protecs the membrane integrity and thus plays a role at the recovery of depressed mitochondrial Na+-K+-ATPase and Ca2+-ATPase activity and also in myocytes injury.