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 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

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

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 ultrastructure of small artery wall in patients with spontaneous rupture of hepatocellular carcinoma (HCC).

METHODSTransmission electron microscopy was used to study 11 specimens from ruptured HCC and 11 cases with non-ruptured HCC.

RESULTSThe phenomenon of activated phagocytosis in macrophage could be found in 3 cases with ruptured HCC and 10 cases with non-ruptured HCC, respectively (P < 0.05). In 9 specimens with ruptured HCC, the evidence of vascular injury characterized as less cell junctions and larger fenestrae in endothelial cells, broken elastic lamina, proliferated and fragmented elastin and damaged structure of collagen was found in small arteries. The phenomenon of electron-dense deposit in the elastic lamina, and signs of more protein synthesis in endothelial cells were also present in these specimens. In the patients with non-ruptured HCC, the evidence of vascular injury can be found only in 2 cases (P < 0.01). Less cell junctions and larger fenestrae could increase the permeability of vascular wall. The electron-dense deposition in elastic lamina may represent the deposition of antigen-antibody complex in elastic membrane which had been found in our previous study. The vascular injury was postulated to be caused by the deposition of antigen-antibody complex in vascular wall which was identified by our previous study. The vascular wall in the patient with ruptured HCC could become stiff and weak due to the proliferated fragment elastin and damaged collagen which would make the blood vessels more prone to splitting and result in hemorrhage and the rupture of HCC.

CONCLUSIONSThe vascular injury caused by antigen-antibody complex deposition might related to the spontaneous rupture of HCC.

Carcinoma, Hepatocellular ; pathology ; ultrastructure ; Humans ; Liver Neoplasms ; pathology ; ultrastructure ; Macrophages ; immunology ; Microscopy, Electron ; Rupture, Spontaneous ; pathology

OBJECTIVETo study the effects of progressive loading on implants placed into extraction sockets.

METHODSBilateral 3rd, 4th and 2nd premolar of 4 beagle dogs were extracted and the implants were immediately inserted at 0, 14 and 21 days. The progressive loading procedure was conducted after 24 hours. The vertical bone loss (VBL) and the bone/biomaterials reactions were detected by X-ray and SEM.

RESULTSThe VBL in control groups was larger than that for the experimental groups at 14, 21 and 28 days (P<0.05). Scan electron microscopy detected that the mineralization speed of experimental groups was many times as faster as the control groups.

CONCLUSIONProgressive loading of implants placed into extraction sockets can be performed without disturbing the osseointegration process. The potential of new bone formation in the extraction sockets and the physical strains can congenerously promote osseointegration.

Animals ; Bicuspid ; Dental Implantation, Endosseous ; Dental Implants ; Dogs ; Osseointegration ; Tooth Extraction ; Tooth Socket

OBJECTIVETo observe the difference in fatty degree, glucose-lipid disorder and adipose-hormones between diet induced obesity (DIO) rats and diet induced obesity resistance (DIO-R) rats, and to explore the effect and acting mechanism of Chinese drugs for strengthening Pi (CD-SP) and those for both strengthening Pi and dissolving phlegm (CD-SPDP) in inhibiting obesity.

METHODSExcepting eight rats allocated in the blank control group, the other 54 rats were fed with high-lipid forage for 12 weeks to establish models of obesity. Finally, 30 DIO rats and 8 DIO-R rats (shown by their body weight) were obtained. The DIO rats were divided into three groups, which were given gastric perfusion, respectively, with normal saline (Group A), CD-SP (Group B), and CD-SPDP (Group C). Fourteen weeks later, the animals' body weight (BW), length (BL), blood levels of fasting insulin (FIn), fasting glucose (FBG), triglyceride (TG), cholesterol (TC), leptin (LP), neuropeptide Y (NPY), C-reactive protein (CRP), tumor necrosis factor-alpha(TNF-alpha), adiponectin (AN), and resistin (RS) were measured; insulin resistance index (IRI) was calculated, and the degree of obesity and lipid content in abdominal cavity of rats were estimated. Moreover, the levels of LP, CRP, TNF-alpha, AN and RS in homogenate of rats' adipose tissues (ATH) were determined.

RESULTSAfter 12 weeks of high-lipid diet, the BW of DIO rats was higher than that of normal or DIO-R rats. After a 14-week continuous high-lipid diet feeding, in DIO rats, BW, lipid coefficient (LC), and IRI were significantly increased (P<0.01); serum levels of TNF-alpha, LP and AN were lower, NPY was higher, while the ATH levels of LP and AN were lower and TNF-alpha was higher in DIO rats than in DIO-R rats (P<0.05 or P<0.01); blood levels of FBG and lipids in DIO rats showed an increasing trend but was statistically insignificant (P>0.05); no significant difference was found in serum levels of CRP and RS due to the overly high data dispersion. Comparisons of the 3 DIO groups showed that BW, body weight index (BWI), LC and IRI were significantly lowered after treatment (P<0.01) in Group C, while these indexes were not significantly different between Group A and B; the serum levels of TNF-alpha, LP, and AN increased, NPY decreased in Group B and C, ATH levels of LP and AN increased, and TNF-alpha decreased in the two groups; but NPY, LP, and AN in blood and ATH were higher in Group C than those in Group B (P<0.05 or P<0.01).

CONCLUSIONCD-SPDP could inhibit DIO and IR, showing that the effect is better than that of CD-SP, and its mechanism is related to promotion of LP and AN secretion and elevation of serum NPY.

Adipokines ; blood ; Animals ; Blood Glucose ; analysis ; C-Reactive Protein ; analysis ; Diet, Atherogenic ; Dietary Fats ; adverse effects ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Leptin ; blood ; Male ; Neuropeptide Y ; blood ; Obesity ; blood ; etiology ; pathology ; prevention & control ; Random Allocation ; Rats ; Rats, Wistar ; Syndrome ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo study the distribution of variable numbers of tandem repeat (VNTR) polymorphism in the intron 2 and the single nucleotide polymorphism (SNP) at position +8006 in the exon 2 of IL-1RN in healthy Chinese Han Population of Wuhan province and to analyze their correlation with the serum lipoprotein level.

METHODSIL-1RN (VNTR) and IL-1RN (+8006) polymorphisms were detected by PCR and PCR-RFLP methods in 251 healthy Chinese Han Population of Wuhan, and the levels of serum lipoprotein, IL-1 and IL-1Ra were inspected simultaneously.

RESULTSIn IL-1RN (VNTR), allele I appeared most common, then allele II, and allele IV was rare. At the position of IL-1RN (+8006), allele T was most commonly seen followed by allele C. Allele II of IL-1RN (VNTR) always existed with allele C of IL-1RN (+8006). The levels of serum lipoprotein, IL-1 and IL-1Ra were not different among the different genotypes of the two polymorphisms.

CONCLUSIONThere were two gene polymorphisms in the intron 2 and exon 2 of IL-1RN, which were not correlated with the levels of serum lipoprotein, IL-1 and IL-1Ra. However, there seemed to be a linkage disequilibrium between IL-1RN (VNTR) and IL-1RN (+8006).

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Exons ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Humans ; Hyperlipidemias ; blood ; genetics ; Interleukin 1 Receptor Antagonist Protein ; Introns ; genetics ; Lipoproteins ; blood ; Male ; Middle Aged ; Minisatellite Repeats ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Sialoglycoproteins ; genetics