To investigate the pharmacokinetic characteristics and absolute bioavailability of ginkgolide A (GA), ginkgolide B (GB) and bilobalide (BB) in rats. In this experiment, a high-performance liquid chromatography-tandem mass spectrometry (LC-MS/ MS) method was established to determine the plasma concentrations of GA, GB and BB in rats after rats were administrated with the three drugs through ig and iv respectively. The main pharmacokinetic parameters and absolute bioavailability of three ginkgolide compounds were obtained by using pharmacokinetic software DAS 2. 0. After the inject of GA, GB and BB, the results showed Cmax at (513.9 ± 116.9), (701.3 ± 76.0), (5,255.6 ± 476.8) µg · L(-1) and AUC0.24h of (960.9 ± 268.5), (779.5 ± 140.6), (7,409.3 ± 1,181.1) µg · h · L(-1), respectively; after the oral administration, the results showed Cmax at (522.9 ± 39.9), (146.8 ± 31.6), (2,711.9 ± 588.9) µg · L(-1) and AUC0-24 h of (1,760.4 ± 300.7), (636.6 ± 180.3), (16,651.4 ± 1,306.5) µg · h · L(-1), respectively. The absolute bioavailability of GA, GB and BB in rats was (61.1 ± 10.4)%, (27.2 ± 7.7)%, (56.2 ± 4.4)%, respectively. The method established in this experiment has a good specificity and sensitivity and so can be used to study the pharmacokinetics and absolute bioavailability of GA, GB and BB in rats.
Animals ; Biological Availability ; Chromatography, High Pressure Liquid ; Cyclopentanes ; pharmacokinetics ; Furans ; pharmacokinetics ; Ginkgolides ; pharmacokinetics ; Lactones ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry

0.05). Conclusions Biofeedback and pelvic electric stimulation could be used to treat stress incontinence. Menopause status,BMI and severity of stress incontinence can not obvious affect the outcomes of biofeedback and pelvic electric stimulation.

OBJECTIVETo study the effect of arsenic trioxide (As2O3) and all-trans retinoic acid (ATRA) on human cervical carcinoma HeLa cell line.

METHODSHeLa cells were treated with As2O3 and ATRA. The cell proliferation was evaluated by MTT assay. The expressions of NDRG-1 protein and mRNA were determined by Western blot and RT-PCR analysis.

RESULTSMTT assay showed that As2O3 and ATRA inhibited the growth of human cervical carcinoma HeLa cells in vitro in a dose- and time-dependent manner. Western blot and RT-PCR techniques showed that As2O3 and ATRA down-regulated the expressions of NDRG-1 protein and mRNA (P < 0.05).

CONCLUSIONAs2O3 and ATRA can significantly inhibit the growth and proliferation of HeLa cells. The reason of these changes may be related with the down-regulation of expression of NDRG-1.

Antineoplastic Agents ; administration & dosage ; pharmacology ; Arsenicals ; administration & dosage ; pharmacology ; Blotting, Western ; Cell Cycle Proteins ; genetics ; metabolism ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; HeLa Cells ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; metabolism ; Oxides ; administration & dosage ; pharmacology ; RNA, Messenger ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tretinoin ; administration & dosage ; pharmacology

OBJECTIVETo study the mechanism of spontaneous rupture of hepatocellular carcinoma (HCC).

METHODSThe specimens of 30 patients with ruptured HCC and 30 patients with non-ruptured HCC were collected. Immunofluorescence, immunohistochemical and flow cytometry techniques were used to detect the phagocytosis of macrophages and the deposition of immune complex (IC) on vascular wall.

RESULTSIn this study, the poor function of macrophage phagocytosis was found in patients with ruptured HCC, which could results in the cumulating of IC and deposition on vascular wall. The IC, which composed of hepatitis B virus e1 antigen (HBeAg/1), complement C1q and immunoglobulins, was found deposited in the elastic membrane of arteries. Likely as a result of IC deposition, vascular injury occurs mainly in the small arteries where the deposition of IC was present. As the small arteries were the blood vessels with predominant injury, they would likely to be the ones to split and cause hemorrhage and rupture of HCC during vascular load increase.

CONCLUSIONSWe would conclude that the poor function of macrophage phagocytosis, which lead to the IC deposition and vascular injury may be the factors involved in the pathogenesis of ruptured HCC.

Adult ; Antigen-Antibody Complex ; metabolism ; Carcinoma, Hepatocellular ; immunology ; pathology ; Complement C1q ; metabolism ; Female ; Flow Cytometry ; Hepatitis B e Antigens ; metabolism ; Humans ; Immunoglobulins ; metabolism ; Immunohistochemistry ; Liver Neoplasms ; immunology ; pathology ; Macrophages ; immunology ; Male ; Middle Aged ; Rupture, Spontaneous ; immunology

China ; epidemiology ; Female ; Humans ; Liver Diseases, Alcoholic ; epidemiology ; etiology ; Male ; Obesity ; complications ; Risk Factors ; Sex Factors

Objective To explore the association between polymorphisms of adiponectin gene and the risk of ischemic stroke in Han population from the Northern parts of China.Methods TaqMan probe of RT-PCR was applied to detect the genotype frequency of single nucleotide polymorphism(SNPs)(rs266729 and rs2241766)of adiponectin gene in 357 ischemic stroke cases who developed the episode at first time and with 345 healthy controls.Logistic regression analysis was used to evaluate the relationship of each genotype of SNPs and ischemic stroke.Results Mutation of rs2241766(T＞G)increased the risk of ischemic stroke among all the samples(0R=1.55,P=0.01)and it was still the risk factor of ischemic stroke when analyzed by multi-factors logistic regression after each factor was adjusted(OR=1.55,P=0.00).The polymorphism of rs266729 was not related to the risk of ischemic stroke among all the samples(OR=1.13,P=0.57).However,the genotype GG of rs266729 increased the risk of ischemic stroke among female population(OR=3.25,P=0.04).Conclusion The variance of rs2241766 in adiponectin gene was related to the risk of ischemic stroke in Han population from the Northern parts of China and the genotype GG of rs266729 could possibly increase the risk of ischemic stroke in women of Han population from the Northern parts of the country.

OBJECTIVETo investigate the changes in circulating bone marrow stem cells in pregnant rabbits after AMI (AMI) and their relationship with estradiol.

METHODSThree groups of rabbits were used, namely pregnancy and AMI group, AMI group without pregnancy, and sham operation group with pregnancy. The ratio of CD90(+) cells in the peripheral blood was determined with flow cytometry in all the rabbits, and serum estradiol level measured. Four weeks after AMI, hemodynamic measurements were carried out. The morphological changes of the myocardial tissues were examined with ImageJ 1.31.

RESULTS AND CONCLUSIONFour weeks after AMI, the two pregnancy groups showed a higher Left ventricular end systolic pressure(LVESP) and+dp/dtmax, lower left ventricular end-diastolic pressure (LVEDP) and -dp/dtmax and high levels of CD90(+) cells in peripheral blood than AMI group without pregnancy (P<0.01). The ratio of circulating CD90(+) cells increased gradually with gestational age and peaked at the end stage of pregnancy. After delivery the circulating CD90+ cell ratio decreased sharply, showing a significant correlation with serum estradiol level (r=0.725, P<0.01). Four weeks after AMI, the pregnancy group had smaller myocardial infarction (MI) volume than the non-pregnant group (22.17+/-6.34% vs 38.86+/-5.97%, P<0.05). Circulating bone marrow stem cells increased during pregnancy with gestational age and peaked at the end stage of pregnancy. Ten days after delivery, the stem cells resumed basically the normal level. The proportion of circulating bone marrow stem cells was significantly correlated with the level of serum estradiol during pregnancy, and mobilization of the bone marrow stem cells induced by acute ischemic event in pregnant rabbits was advanced. 4 weeks after AMI, the pregnant rabbits showed better heart contraction and diastolic function than the non-pregnant ones.

Animals ; Bone Marrow Cells ; cytology ; Estradiol ; blood ; Female ; Hematopoietic Stem Cells ; cytology ; Myocardial Contraction ; Myocardial Infarction ; blood ; physiopathology ; Pregnancy ; Pregnancy Complications, Cardiovascular ; blood ; Rabbits ; Thy-1 Antigens ; blood ; Time Factors

Migraine is a complex and heterogeneous disorder. Although several genetic models has been proposed including autosomal-dominant/autosomal recessive, sex-linked, sex-limited, mitochondrial, and multi-gene, none of these models can well-explain the transmission of the disease. We hypothesied that migraine is a sex-conditioned inherited disorder (autosomal dominant in females and autosomal recessive in males). This hypothesis is supported by the evidence such as the locations of genes associated with familial hemiplegic migraine, possibly "typical" migraine as well (dominantly on chromosome 19p, 1q, and 2q), male:female ratio of prevalence (1:2-1:4), the mostly youth-onset, the provocation by the contraceptives, the induction by menstruation, and the self-limitation after menopause. Female sex-hormones appear to be the key contributor to a higher prevalence of migraine in female. Socio-environmental factors may also play an important role.
Age of Onset ; China ; epidemiology ; Female ; Genes, Dominant ; genetics ; Genetic Predisposition to Disease ; epidemiology ; genetics ; Gonadal Steroid Hormones ; metabolism ; Humans ; Inheritance Patterns ; genetics ; Male ; Menstrual Cycle ; genetics ; Migraine Disorders ; epidemiology ; genetics ; Sex Factors

OBJECTIVETo evaluate the safety and efficacy between endoscopic papillary balloon dilatation (EPBD) and endoscopic sphincteropapillotomy ( EST) for common bile duct stones using meta-analysis method.

METHODSRandomizd controlled trials comparing EPBD with EST for common bile duct stones and published from January 1990 to July 2012 were recruited. This meta-analysis was conducted to estimate short-term and long-term complications. Fixed random effect model or random effect model was established to analyze the data.

RESULTSTwelve randomizd controlled trials were included in this analysis. These studies included 1865 patients, 925 of them were treated with EPBD and 940 were treated with EST. The analysis of basic characteristics of these included studies showed that: compared to EST, patients in the EPBD group were younger (OR = -1.16, 95% CI: -1.49 to -0.84, P = 0.00), while in two groups, there were no significant difference (P > 0.05) in gender proportion, average size of stones, number of gallstones, previous cholecystectomy, the number of merged duodenal diverticulum, common bile duct diameter, the total follow-up time. Also, compared to EST, the overall stone clearance in the EPBD group was lower (OR = 0.64, 95% CI: 0.42 to 0.96, P = 0.03), pancreatitis incidence was higher (OR = 2.67, 95% CI: 1.61 to 4.43, P = 0.00), incidence of bleeding (OR = 0.12, 95% CI: 0.04 to 0.34, P = 0.00), acute cholecystitis (OR= 0.39, 95% CI: 0.18 to 0.84, P = 0.02), total long-term complication rate (OR = 0.53, 95% CI: 0.36 to 0.77, P = 0.01), stone recurrence rate more than a year were lower (OR= 0.48, 95% CI: 0.26 to 0.90, P = 0.02). While in two groups, there were no significant difference (P > 0.05) in the stone removal on 1 '' attempt, the total near-term complications and acute cholangitis.

CONCLUSIONSOn the basis of lower rates of bleeding, EPBD seems to be preferred strategy over EST for endoscopic remove of common bile duct stones in patients who have coagulopathy. Although stone recurrence rate more than a year of EPBD is lower, but the overall stone clearance rate is lower and the risk of pancreatitis is higher than that of EST.

Dilatation ; Gallstones ; surgery ; Humans ; Postoperative Complications ; epidemiology ; Randomized Controlled Trials as Topic ; Sphincterotomy, Endoscopic ; Treatment Outcome

OBJECTIVETo study mechanism of the apoptosis of rat pancreas islet β cell strain (INS-1 cells) induced by sodium arsenite.

METHODSINS-1 cells were exposed to sodium arsenite at the different concentrations. MTT assay was used to detect the viability of INS-1 cells. The potentials on mitochondrial membrane and lysosome membrane of INS-1 cells were determined with the fluorescence spectrophotometer. The apoptotic levels of INS-1 cells exposed to sodium arsenite were observed by a fluorescence microscope and flow cytometry.

RESULTSAfter exposure to sodium arsenite, the viability of INS-1 cells significantly decreased with the doses of sodium arsenite. At 24 h after exposure, the OD values of the mitochondrial membrane potentials declined observably with the doses of sodium arsenite (P < 0.01). At 48 h after exposure, the OD values of the lysosome membrane potentials significantly increased with the doses of sodium arsenite (P < 0.01). At 72 h after exposure, the apoptotic cells were observed under a fluorescence microscope and enhanced with the doses of sodium arsenite. The apoptosis cells with light blue, karyopyknosis, karyorrhexis, apoptotic body and chromatin concentration appeared. The results detected with flow cytometry indicated that after exposure, the apoptotic INS-1E cells significantly increased with the doses of sodium arsenite.

CONCLUSIONSThe sodium arsenite can induce the apoptosis of INS-1 cells through the mitochondria-lysosome pathway.

Animals ; Apoptosis ; drug effects ; Arsenites ; toxicity ; Cells, Cultured ; Insulin-Secreting Cells ; drug effects ; Lysosomes ; metabolism ; Membrane Potentials ; drug effects ; Mitochondria ; metabolism ; Rats ; Sodium Compounds ; toxicity