Aim To investigate the effect of prenatal alcohol on insulin sensitivity of rat offspring and its underlying mechanism. Methods Female Sprague Dawley rats were given ethanol 4 g?kg-1?d-1 by gavage throughout pregnancy. At 16 wk of age, the rat offsrping underwent intravenous glucose tolerance test. The mRNA level of adipose leptin, resistin and adiponectin were determined by RT-PCR. Serum leptin, resistin and adiponectin were measured with RIA kits. Results Newborn ethanol rats had lower birth weight than control [(5.7?0.1) g vs (6.9?0.1) g,P

Calcium Channel Blockers ; pharmacology ; therapeutic use ; Cerebral Infarction ; drug therapy ; Coronary Disease ; drug therapy ; Humans ; Pyrazines ; pharmacology ; therapeutic use ; Vasodilator Agents ; pharmacology ; therapeutic use

Animals ; China ; Elapidae ; Humans ; Male ; Snake Bites ; Snake Venoms ; poisoning ; Young Adult

Objective:To discuss the influence and curative effect of intensive lipid-lowering with atorvastatin on blood fat and ser-um inflammatory factors levels in the patients with acute cerebral infarction. Methods:Totally 94 cases of patients with acute cerebral infarction were divided into the intensive group(n=47) and the ordinary group (n=47). The patients in the two groups were given the basic medical treatment, such as reducing intracranial pressure and dehydration, controlling blood pressure and blood sugar, anti-platelet aggregation, neural protection and etc. The patients in the ordinary group were orally given 20mg atorvastatin calcium tablets, once a day, while the patients in the intensive group were additionally given 40mg atorvastatin calcium tablets, once a day, and the treatment course was 8 weeks. The changes of blood fat index and serum inflammatory factors of hs-CRP, TNF-αand IL-10 in the two groups before and after the medical treatment were detected, and the clinical curative effect was compared as well. Results:After the 8-week medical treatment, TC, TG and LDL-C levels in the two groups were declined at different degree, while HDL-C levels were in-creased at different degree (P<0. 05 or P<0. 01), and the changes in the intensive group was more notable than those in the ordinary group (P<0. 05). After the treatment, the serum hs-CRP and TNF-αlevels in the two groups were declined at different degree, while serum IL-10 levels were increased at different degree (P<0. 05 or P<0. 01), and the changes in the intensive group was more signifi-cant than those in the ordinary group (P<0. 05). Meanwhile, the total clinical efficiency in the intensive group (95. 74%) was much higher than that in the ordinary group (80. 85%, P<0. 05). Respectively 2 and 4 cases of untoward effect were appeared in the ordi-nary group and the intensive group without statistical difference between the two groups(P>0. 05). Conclusion:Intensive lipid-lower-ing with atorvastatin has significant curative effect with favorable security on acute cerebral infarction, which can obviously improve the degree of neural function defect, and the mechanism may related with reducing blood fat, serum hs-CRP and TNF-αlevels, increasing serum IL-10 levels and inhibiting topical inflammatory reactions.

Photoaffinity labeling is widely applied to demonstrate targets of small molecule ligands. In this paper, biotin photoaffinity labeled molecule with propargyl group 1 has been designed and synthesized, followed it's labeling of N2-acetyl-2'-O-propargyl guanosine 9 by "click chemistry". This technology presents delight development potential in labeling of second messenger cyclic nucleotide, antisense oligonucleotide or siRNA.
Biotin ; chemistry ; Click Chemistry ; Guanosine ; chemical synthesis ; chemistry ; Ligands ; Photoaffinity Labels

Objective To investigate the clinical results of the primary total hip replacement (THR) and the secondary THR after failed internal fixation in the elderly patients with displaced femoral neck fracture so as to find the optimal treatment for displaced femoral neck fractures in the elderly patients. Methods From April 2001 to April 2007,16 patients (Study Group) treated with a secondary THR after failed internal fixation and 20 patients (Control Group) treated with a primary THR were enrolled in the study and followed up. There were seven males and nine females, at average age of 66. 5 years (50-85 years) and with mean follow-up period of 58. 25 months (24-96 months) in the Study Group. There were six males and 14 females, at average age of 68.1 years (51-83 years) and with mean follow-up period of 49.50 months (24-70 months) in the Control Group. All patients were active and lucid before they suffered fractures. Blood loss and operation duration in THR were compared. Hip function (Harris score) and health-related quality of life (HRQoL, KPS index score) were assessed during the follow-up after THR. Results Operative duration was (115.63 ±34.35) minutes in Study Group and (91.25 ±15.80) minutes in Control Group (P<0.05). Blood loss was (546.86 ±377.04) ml in Study Group and (320.00 ±155.94) ml in Control Group (P<0.05). At follow up, Harris score and KPS index score were (87. 25 ±7. 53) points and (95. 00 ±5. 16) points respectively in Study Group, and (90.20±5.46) points and (96.00 ±0.73) points respectively in Control Group (P>0.05). There were no infections or re-operations in two groups, but with one death in each group during the follow-up. Conclusions THR is the optimal treatment for displaced femoral neck fractures in the elderly patients.The secondary THR after failed internal fixation has higher risks in operation compared with the primary THR for a displaced femoral neck fracture in the elderly patient.

OBJECTIVETo observe the inhibitory effect of Tongxinluo (TXL) on coronary vaso spasm in small swine in vivo, and to investigate its possible acting mechanism.

METHODSThe model of coronary atherosclerosis in 16 male small swines was established by left thoracotomy after anesthesia, isolated the sections of left anterio-descending branch and proximal end of rotator branch with similar outer diameter, and encapsulated them with paper-towel holding 2.5 microg interleukin-1beta. Two weeks later, the condition of coronary vasospasm induced by catheter intra-coronary injection of 5-hydroxytryptamine (5-HT, 10 microg/kg) was observed through coronary artery contrast examination. The 12 swines with successfully formed coronary vaso spasm were randomly divided into 2 groups, the TXL group and the control group. They were fed with special diet, but TXL 1 g/(kg d) was administered additionally to the TXL group for 4 weeks. The observation on coronary vasospasm was repeated 1 week after discontinuation of TXL treatment, then the animals were sacrificed, their vascular sections enclosed with IL-1beta was taken to conduct the pathologic examination and to detect the expressions of Rho kinase mRNA and its substrate myosin- binding subunit phosphorylation (MBS-P) by RT-PCR and Western blot method.

RESULTSCoronary artery contrast showed that local coronary stenosis occurred in the 12 model swines to different extents (20% - 30%, and vascular spasm on them could be induced by 5-HT. At the time of repeating examination, 11 vascular sections in the control group still maintain their positive spasm reaction to 5-HT, but only 2 in the TXL group did so, the reaction turned to negative in 1 and 10 in the two groups respectively. Pathological examination showed that different degrees of macrophage aggregation could be found in both groups. The degree of lumen stricture and endometrial hyperplasia in the TXL group was obviously attenuated than those in the control group. The expressions of Rho kinase mRNA and MBS-P in the control group were up-regulated obviously. As compared with those in the control group, they were inhibited significantly in the TXL group, as (71.5 +/- 2.4) vs (98.2 +/- 7.7)% and 16,633 +/- 1,390 vs 25,818 +/- 4,745, respectively (all P < 0.05).

CONCLUSIONTXL could obviously inhibit the coronary intimal hyperplasia mediated by IL-1beta and coronary vasospasm induced by 5-HT, one of its mechanisms is possibly the inhibition on the intracellular Rho kinase mRNA expression in the IL-1beta enclosed vascular section to decrease the level of MBS-P.

Animals ; Coronary Vasospasm ; chemically induced ; drug therapy ; genetics ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Gene Expression ; drug effects ; Humans ; Interleukin-1beta ; genetics ; metabolism ; Male ; Random Allocation ; Serotonin ; adverse effects ; Swine ; rho-Associated Kinases ; genetics ; metabolism

OBJECTIVETo investigate the distribution of ER isoforms in endometriosis and eutopic endometrium.

METHODSTissue samples of patients with ovarian endometriosis, treated in People's Liberation Army General Hospital from January 2004 to December 2006, were retrieved. A total of 60 cases of ovarian endometriotic cysts with their corresponding eutopic endometrium (30 cases of proliferation phase and 30 of secretary phase eutopic endometrium) and 30 cases of normal endometrium (15 proliferative and 15 secretary phase endometrial samples respectively) were included. Expressions of ERalpha and ERbeta were analyzed using immunohistochemistry and the expression ratio was statistically analyzed by using SPSS 12.0 software.

RESULTSExpressions of both ERalpha and ERbeta in epithelial cells were positively correlated with that of the stromal cells. The expression of ERalpha in eutopic endometrium (73.3% in epithelium and 76.7% in stroma) was significantly higher than that in ovarian endometriotic cysts (43.3% in epithelium and 46.7% in stroma), or normal control (56.7% in epithelium and 50.0% in stroma, respectively, each P < 0.05. However, the expression of ERbeta (90.0% in epithelium and 76.7% in stroma) was higher in ovarian endometriotic cysts than that in the eutopic endometrium (68.0% in epithelium and 63.3% in stroma respectively, P < 0.05), and ERbeta expression in eutopic endometrium was higher than that in the normal control endometrium (36.7% in epithelium and 26.7% in stroma, respectively, P < 0.05). The expressions of both ERalpha and ERbeta changed periodically in eutopic and normal endometrium, whereas ERalpha and ERbeta level were less variable in the ectopic endometrium. The expression of ERbeta was statistically higher than that of ERalpha (P < 0.05) in ectopic endometrium, whereas no significant difference was seen between the two isoforms in the eutopic or normal endometrium.

CONCLUSIONSBoth ERalpha and ERbeta have higher expression levels in eutopic endometrium of patients with ovarian endometriotic cysts. ERbeta is predominantly expressed in endometriotic cysts, where the expression of ERalpha is limited. The different distribution of ERalpha and ERbeta may play an important role in the development of ovarian endometriosis.

Adult ; Choristoma ; pathology ; Endometriosis ; metabolism ; pathology ; Endometrium ; metabolism ; pathology ; Epithelium ; Estrogen Receptor alpha ; analysis ; Estrogen Receptor beta ; analysis ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Protein Isoforms ; analysis ; Receptors, Estrogen ; analysis ; Stromal Cells ; metabolism

OBJECTIVEThe structure-activity relationship between traditional Chinese medicine (TCM) compounds and antibacterial activity was studied by chemoinformatics approach.

METHODCytoscape and its plug-in ChemViz were applied to compute the 2D chemical structure similarity and topological parameter TPSA (topological molecular polar surface area), which measures cell permeability of chemicals, between TCM compounds and clinical antibacterials. The overall degree of structure similarity was then calculated and represented by E-value for the eight categories of TCM compounds and the known antibacterials.

RESULTOur results indicated that flavonoids showed good structural similarity with antibacterials and appropriate cell permeability, compared with those of the TCM compounds of the other categories. As flavonoids were featured by good drug safety, it suggested that they can be regarded as the preferred lead compounds skeleton structure source for further antibacterials synthesis.

CONCLUSIONThe application of chemoinformatics helps explore the structure-activity relationship between TCM compounds and the antibacterial activity and search for suitable antibacterial lead compounds skeleton structure source.

Anti-Bacterial Agents ; chemistry ; pharmacology ; Informatics ; methods ; Medicine, Chinese Traditional ; Software ; Statistics as Topic ; Structure-Activity Relationship

OBJECTIVETo study the effects of carbamazepine on serum metabolic profiles in rats using nuclear magnetic resonance (NMR) spectroscopy.

METHODSTwenty-four healthy male Wistar rats were randomized into 4 groups (n=6) for daily intragastric administration of high-, medium- or low-dose carbamazepine or distilled water (control) for 7 days. Blood samples were collected from the abdominal aortic under anesthesia after the treatment to determine serum carbamazepine concentration using high-performance liquid chromatography. ¹H nuclear magnetic resonance (¹H NMR) spectra were acquired for pattern recognition analysis. Histopathological changes of the renal and liver tissues of the rats were also examined.

RESULTSSteady-state blood concentration of carbamazepine in high-, medium- and low-dose groups were 14.64 ± 1.41, 8.54 ± 1.19, and 4.56 ± 0.64 µg/ml, respectively. Slight liver swelling was found in high-dose group, but none of the groups showed renal pathologies. Compared with the control group, the high-dose carbamazepine group showed lowered serum concentrations of 1,3-diaminopropane, deoxycorticosterone, 7-dehydrocholesterol, betaine, beta-alanine, L-cystathionine, 4-methyl-2-oxovaleric acid, and creatine with increased levels of saccharides, lactate, succinic acid, acetyl phosphate, and adipic acid. Principal component analysis revealed significant differences of the metabolites between carbamazepine-treated groups and the control group. The metabolic profiles showed no differences in the kinds of metabolites although the concentrations of the metabolites varied between the carbamazepine groups.

CONCLUSIONSCarbamazepine significantly affects metabolism in normal rats. This finding provides evidence for clinical drug monitoring and drug safety of carbamazepine. NMR technique has important values for pharmacodynamic and toxicological evaluation of drugs.

Animals ; Carbamazepine ; blood ; Kidney ; pathology ; Liver ; pathology ; Magnetic Resonance Spectroscopy ; Male ; Metabolomics ; Principal Component Analysis ; Rats ; Rats, Wistar