OBJECTIVETo investigate the electrophysiological effect of Xin' an granule (XAG) on ventricular muscle cell in ischemic rabbits.

METHODSA total of 48 rabbits were divided into the normal group and the ischemic group, and then subdivided into three groups, the control group, the high and low-dose XAG groups, 8 in each group. Rabbits in the low-dose XAG group and the high-dose XAG group were gastrogavaged XAG at the daily dose of 0. 85 g/kg and 3.40 g/kg, while the others in the control group were given the equal dosage of normal saline. All the rabbits were treated three times per day for successive 10 days. The rabbit model of ischemia was established by intravenous injected with 2. 5 U/kg posterior pituitary injection. Five minutes later, the monophasic action potential (MAP) and electrocardiogram (ECG) of each rabbit in the different groups were recorded and compared.

RESULTS(1) To normal rabbits, XAG could significantly shorten the action 50% and 90% potential duration (APD)50 and APD90 of ventricular muscle cell (P < 0.05 ), and high-dose of XAG could significantly increased the Vmax of MAP(P <0. 05). (2) While to ischemic rabbits, XAG could significantly prolong APD50 and APD90, and significantly increased the action potential amplitude (APA) and Vmax of MAP (P < 0. 05).

CONCLUSION(1) XAG can significantly shorten APD50 and APD90 of ventricular muscle cell, and high-dose XAG significantly increase the Vmax of MAP of normal rabbits. (2) XAG can delay and alleviate the manifestation characteristics of action potential of ventricular muscle cell during ischemia.

Action Potentials ; drug effects ; Animals ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Electrocardiography ; Heart Ventricles ; cytology ; drug effects ; Medicine, Chinese Traditional ; Myocardial Ischemia ; physiopathology ; Myocytes, Cardiac ; drug effects ; physiology ; Rabbits

The interaction between Gliotoxin and bovine serum albumin (BSA) was studied by the fluo-rescence, Circular Dichroism (CD) and ultraviolet visible (UV-Vis) techniques. The fluorescent experiment showed that the intrinsic fluorescence of BSA was quenched by the binding of gliotoxin in a static quenching procedure, with an association constant of 7.2?103 L/mol and in hydropobic forces. And the CD spectrum revealed that gliotoxin effected the conformation of BSA by increased the mass of ?-helix.

Cutaneous Fistula ; Digestive System Abnormalities ; therapy ; Endoscopy, Gastrointestinal ; methods ; Female ; Humans ; Infant ; Treatment Outcome

A systematic review was undertaken, including studies that evaluated the incidence of the blood system adverse events of Tripterygium wilfordii (TWP). Medline, Embase and the Cochrane library were searched for relevant studies, including RCT, cohort studies and case series, of patients treated with TWP published in English and Chinese from inception up until May 25th, 2013 with the keywords including "Tripterygium wilfordii", "toxicity", "reproductive", "side effect", "adverse", "safety" and "tolerability". Relevant information was extracted and the incidence of the blood system adverse events was pooled with MetaAnalyst software. Besides, subgroup and sensitivity analyses were performed based on age, mode of medicine, observation time and disease system. According to inclusion and exclusion criteria, a total of 49 articles were included in the meta-analysis, they were split into 54 researches incorporated in the analysis. There is a large degree of heterogeneity among the studies, so data was analyzed using random-effects model and the summary estimates of incidence of the blood system adverse events was 6.1%. The weighted combined incidence of three major blood system adverse events were white-blood cells decreasing 5.6% (95% CI, 4.3% - 7.3%), hemoglobin decreasing 1.7% (95% CI, 0.5% - 5.0%) and platelet decreasing 1.8% (95% CI, 1.0% - 3.1%), respectively . Sensitivity analyses based on 45 studies with high quality showed the combined value was close to the summary estimate of total 54 studies. The current evidence indicates that the incidence of the blood system adverse events induced by TWP was high; attentions should be paid on to the prevention and treatment of the blood system adverse events.
Blood Cells ; drug effects ; Hemoglobins ; analysis ; Humans ; Tripterygium ; adverse effects

AIMTo study the pharmacokinetics of genistein at different doses in Beagle dogs.

METHODSSuspended in 0.5% CMC-Na solution, genistein was orally administered to Beagle dogs at doses of 2.67, 5.34 and 10.68 mg.kg(-1). At various time intervals, 1.5 mL of blood was drawn from the femoral vein of dogs in their front legs. The plasma was treated with beta-glucuronidase. The genistein in plasma was extracted twice by vortexing with 2.0 mL mixture of methyl tert-tubtyl ether and pentane (v/v = 8:2). The organic phase was removed into the tubes and then evaporated in ventilation cabinet. The residue was dissolved in 50 microL of methanol. 20 microL solution was drawn and detected by high-performance liquid chromatography. The pharmacokinetic parameters were calculated by 3P97 software.

RESULTSThe plasma drug concentration-time data were fitted to the two-compartment model. When the dose was 2.67 mg.kg(-1), the MRT and AUC of parent compound were 52.9 min and 6.7 mg.min. L(-1), respectively. When the dose rose to 5.34 mg.kg(-1), the MRT and AUC of parent compound became 224.8 min and 26.1 mg.min.L(-1), respectively. However, when the dose increased to 10.68 mg .kg(-1), the MRT and AUC of parent compound increased to 267.7 min and 33.2 mg.min L(-1), respectively. The AUC of glucuronidated genistein was 33.9, 70.1 and 140.5 mg.min.L(-1) at the dose of 2.67, 5.34 and 10.68 mg.kg(-1), respectively.

CONCLUSIONDue to significant first pass metabolism, the drug was mainly existed in the form of glucuronidated genistein in the plasma. With the increase of dose, the absorption of genistein became saturated and the half life prolonged.

Animals ; Anticarcinogenic Agents ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Dogs ; Dose-Response Relationship, Drug ; Female ; Genistein ; administration & dosage ; blood ; pharmacokinetics ; Glucuronides ; blood ; pharmacokinetics ; Male

Chemical constituents of Leonurus japonicus were isolated and purified by a combination of various chromatographic techniques including column chromatography over silica gel, Sephadex LH-20, MCI, and Rp C18. Structures of the isolates were determined by spectroscopic analysis as 10 coumarins: bergapten (1), xanthotoxin (2), isopimpinellin (3), isogosferal (4), imperatorin (5), meransin hydrate(6), isomeranzin(7), murrayone(8) , auraptenol(9), and osthol(10). In addition to compound 9, the others were isolated from the genus Leonurus for the first time. In the in vitro assay, compounds 4 and 8 significantly inhibited the abnormal increase of platelet aggregation induced by ADP.
Blood Platelets ; drug effects ; Coumarins ; chemistry ; pharmacology ; Leonurus ; chemistry ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; chemistry ; pharmacology

Non-alcoholic fatty liver disease(NAFLD)is one of the common chronic liver diseases in the world.The molecular mechanism of NAFLD is complex,involving many signal molecules,and the vitamin D(VD)/VDBP/vitamin D receptor(VDR)axis is also involved.VD is a lipid-soluble steroid,which can participate in the regula-tion of lipid metabolism,insulin secretion,immune function,inflammatory response and other biological processes.Stud-ies have shown that VD deficiency is closely related to liver lipid accumulation,inflammation,insulin resistance,oxida-tive stress,intestinal flora imbalance,autophagy,apoptosis,pyroptosis and fibrosis,and plays an important role in the oc-currence and development of NAFLD.This paper reviews the research progress on Vitamin D in recent years in the field of NAFLD,including the physiological characteristics of VD and its role in the NAFLD mechanism,so as to provide referenc-es for the prevention and treatment of NAFLD.

Objective To investigate the effects of sodium nitroprussiate on neurological function and Janus family of tyrosine kinases/signal transduction and transcription activator 3 (JAK2/STAT3) pathway in rats with experimental intracerebral hemorrhage. Methods Sixty rats were randomly divided into control group,model group and test group,20 rats in each group. The model in model group and test group were given collagenase and heparin mixture to establish experimental cerebral hemorrhage,while control group was given the same amount of 0. 9％ NaCl. The test group received intraperitoneal injection with sodium nitroprussiate(1 mg·kg-1) at 6,24,72 and 120 h after modeling,and the rats in model group and control group received intraperitoneal injection with the same amount of 0. 9％ NaCl. The brain water content of each group was measured by weighing method was calculated; TdT-mediated dUTP nick- end labeling (TUNEL) method was used to detect apoptosis of rat brain tissue,and Western blotting (WB) method was used to detect the expression of JAK2/STAT3 pathway-related protein in rat brain tissue. Results At 72 h after modeling,there were significant differences among the control group,model group and test group in the brain water content [(76. 05 ±2. 04) ％ vs (84. 91 ±2. 58) ％ vs (79. 68 ±3. 01) ％],the rate of apoptotic neurons [(7. 52 ± 1. 86) ％ vs (50. 23 ± 2. 43) ％ vs (26. 24 ± 2. 37) ％],the relative expression of p- JAK2 protein in the brain tissues [(0. 07 ± 0. 13) vs (1. 26 ± 0. 05) vs (0. 33 ± 0. 05) ]and the relative expression of p-STAT3 protein [(0. 20 ± 0. 03) vs (0. 38 ± 0. 06) vs (0. 26 ± 0. 09) ](all P < 0. 05). Conclusion Sodium nitroprussiate has protective effect on brain injury in experimental cerebral hemorrhage rats,which may be related to regulate JAK2/STAT3 pathway and reduce apoptosis of brain tissue.

AIMTo study the metabolic kinetics of MN9202 in Beagle dog liver microsome.

METHODSBeagle dog liver microsomes were prepared by using ultracentrifuge method. After incubating 0.4 micromol x L(-1) MN9202 with 1 g x L(-1) microsomes for 30 min at 37 degrees C, the reaction was terminated by adding 0.5 mL alkalization. The RP-HPLC was used to determine the drug in the incubation mixture. The Michaelis-Menten parameters Km, and Vmax in Beagle dog liver microsomes were initially estimated by analyzing Lineweave-Brurk plot. Various selective CYP inhibitors were used to investigate their inhibitory effect on the metabolism of MN9202.

RESULTSThe Km, Vmax and CLint of MN9202 were (22.6 +/- 8.0) micromol x L(-1), (0.54 +/- 0.17) micromol x g(-1) x min(-1) and (0.0242 +/- 0.0009) L x g(-1) x min(-1), respectively. The metabolism of MN9202 was significantly inhibited by ketoconazole (Ket) and troleandomycin (Tro) in Beagle dog liver microsomes. Tranylcypromine (Tra) could inhibit the metabolism of drug as well. While other inhibitors showed little inhibitory effect on the metabolism of MN9202.

CONCLUSIONIt was shown that CYP3A and CYP2C19 were involved in MN9202 metabolism. The inhibitors of human CYP3A and CYP2C19 may have potential interaction with MN9202, and this can reduce the metabolism rate and increase the toxicity of MN9202.

Animals ; Aryl Hydrocarbon Hydroxylases ; antagonists & inhibitors ; Calcium Channel Blockers ; metabolism ; pharmacokinetics ; Cytochrome P-450 CYP2C19 ; Cytochrome P-450 CYP3A Inhibitors ; Dihydropyridines ; metabolism ; pharmacokinetics ; Dogs ; Ketoconazole ; pharmacology ; Microsomes, Liver ; metabolism ; Mixed Function Oxygenases ; antagonists & inhibitors ; Nitrobenzenes ; metabolism ; pharmacokinetics ; Tranylcypromine ; pharmacology ; Troleandomycin ; pharmacology

AIMTo study the pharmacokinetics of m-nifedipine (m-Nif) in Beagle dogs.

METHODSThe Beagle dogs were divided into two groups. m-Nif was intravenously administered to the Beagle dogs in group 1 at the dose of 0. 288 mg x kg(-1), and it was orally administered to the Beagle dogs in group 2, 3 and 4 at the dose of 1.152, 3.456 and 10.370 mg x kg(-1), respectively. m-Nif in plasma was detected by reversed phase high performance liquid chromatography. The pharmacokinetic parameters were calculated by 3P97 software.

RESULTSWhen m-Nif was intravenously administered, the plasma concentration-time curve was fit to a two-compartment model and T1/2beta was 117 min. When m-Nif was orally administered, the plasma concentration-time curve was fit to a one-compartment model. T1/2 (Ke) and Cmax were 147 min and 20 microg x L(-1); at the low dose of 1.152 mg x kg(-1). T1/2 (Ke) was 122 min and Cmax was 36 microg x L(-1) at the middle dose of 3.456 mg x kg(-1). T1/2 (Ke) was 144 min and Cmax was 69 microg x L(-1) at the high dose of 10.37 mg x kg(-1), respectively.

CONCLUSIONIt was showed that the speed of elimination of m-Nif was high in Beagle dogs. The absolute bioavailability of m-Nif given orally was very low.

Administration, Oral ; Animals ; Area Under Curve ; Biological Availability ; Calcium Channel Blockers ; administration & dosage ; pharmacokinetics ; Dogs ; Injections, Intravenous ; Isomerism ; Nifedipine ; administration & dosage ; pharmacokinetics