Objective To study the antagonistic effect of N-acetylcysteine(NAC)on the damage of hepatic mitochondria of rats induced by cadmium in vitro.Methods The mitochondria were prepared from the clean Wistar rats' whole liver by using differ ential centfifugation.The mitochondria were incubated in the assay buffer containing different concentration of CdCl_2 (10,100,1 000,10 000 ?mol/L)at 37 ℃ for 1 h.The effect of NAC(500 ?mol/L)was studied at a CdCl_2 concentration of 1 000 ?mol/L.The incubation buffer was collected and the level of GSH,cytochrome C and the activity of Mn-SOD were determined. Results Compared with the control group,the level of GSH and Mn-SOD in 100,1 000,10 000 ?mol/L CdCl_2 groups were significantly decreased,the content of cytochrome C in 1 000,10 000 ?mol/L CdCl_2 groups were significantly increased(P

In order to improve the efficiency of drug screening on serotonin transporter (SERT) inhibitors, a high-throughput screening (HTS) model is established in RBL-2H3 cells. The RBL-2H3 cells are very similar to the serotonin genetic neuro, in modulation of post-receptor mechanisms and transduction pathway of SERT reactivated. Depending on a fluorescence substrate ASP+ used in detection method of inhibitor rates, it's convenient, quick, accurate and effective, not making the environmental biohazard compared with radioactive experiments. Furthermore, biological screening model combined with computer aided virtual screening technique describing high-throughput virtual screening (HTVS). Bayesian classification method and molecular fingerprint similarity were applied to virtual screening technique, for screening compounds in compound library. Some compounds have been found, and then validated further by biological screening model. Combination of HTS and HTVS improves the efficiency of screening SERT inhibitors.
Animals ; Bayes Theorem ; Cell Line ; Drug Evaluation, Preclinical ; High-Throughput Screening Assays ; Models, Biological ; Rats ; Serotonin Plasma Membrane Transport Proteins ; metabolism ; Serotonin Uptake Inhibitors ; pharmacology

Objective HupA is one of the potential drugs which can be used to treat Alzheimer's disease(AD).The aim of this study was to explore the pharmacokinetics and biodistribution of HupA in vivo by using 11C-HupA.Methods A total of 25 SD rats were studied.They were divided into 5 groups (5 rats in each group).All had intravenous injection of 22 MBq(in0.2 ml)11C-HupA through tail vein.Dynamic im-aging Was acquired from 5 to 90 minutes after injection.Venous blood and organ activities were collected at 5,15,30,60.and 90 minutes after injection.Percentage activity of injected dose per gram of tissue(%ID/g)was calculated to characterize the biodistribution of tracer in different brain regions: frontal,apical, temporal,occipital,cerebellum,hippocampus,striatum,thalamencephalon, and brain stem, Variance analysis using SPSS 11.5 software was performed and compared among the study groups.Results 11C-HupA was character-istic for its quick clearance from blood,with half time T1/2 of (14.61±1.77) min,and clearance rate (CL)macokinetics of 11C-HupA in rats corresponded to a one-compartment model.with an activity curve(area 11C-HupA distribution in different brain regions,being greater in cerebral cortex,hippocampus,hypothala-mus and brain stem. Conclusions Pharmacokinetic study of 11C-HupA in brain was fast.convenient and showed high specificity and sensitivity.Its ability to quantitatively evaluate brain function and its character-istic distribution in mice provided some evidence for monitoring therapy in AD patients.

Humans ; Sinus of Valsalva ; Death, Sudden, Cardiac/etiology* ; Coronary Stenosis/complications*

OBJECTIVETo evaluate the effect of vertebral height restoration of vertebroplasty for osteoporotic vertebra compression fractures (VCFs).

METHODSFrom October 2004 to June 2007, a total of 37 patients with 40 VCFs were treated by vertebroplasty. There were 12 males and 25 females with a mean age of (72.4 +/- 12.7) years (ranged, 48 to 87). Pain easement state was evaluated by visual analog scale (VAS) before and after operation, as well as in followed-up. Preoperative and postoperative vertebral height, kyphosis angle at fractured levels were measured on X-rays.

RESULTSAll of patients were followed-up for 12 to 47 months (averaged, 35.8 +/- 9.6). The VAS score was 8.4 +/- 1.6 before operative, 2.1 +/- 1.2 at the 2nd day after operative, there were significant difference between pre-and postoperative (P < 0.05); the average follow-up VAS was 1.6 +/- 0.9, there were significant difference as compared with the preoperative (P < 0.05). Lateral X-ray showed that the preoperative degree of vertebral height in the of anterior and middle vertebral were (72.0 +/- 10.6)% and (68.0 +/- 15.6)%, and postoperative were (76.0 +/- 8.6)% and (73.0 +/-6.1)%, respectively. There were no significant difference in vertebral height between preoperative and postoperative. The vertebral kyphosis angle was corrected from preoperative (7.8 +/- 2.7) degree to postoperative (8.1 +/- 2.3) degree.

CONCLUSIONVertebroplasty is a safe and effective method for treatment of osteoporotic VCFs, it can relieve the pain effectively. Failure to restore vertebaral height does not seem to interfere with the excellent pain management.

Aged ; Aged, 80 and over ; Female ; Fractures, Compression ; complications ; diagnostic imaging ; surgery ; Humans ; Male ; Middle Aged ; Osteoporosis ; complications ; Radiography ; Spinal Fractures ; complications ; diagnostic imaging ; surgery ; Spine ; diagnostic imaging ; pathology ; surgery ; Treatment Outcome ; Vertebroplasty ; methods

The emerging of network pharmacology and polypharmacology forces the scientists to recognize and explore new mechanisms of existing drugs. The drug target prediction can play a key significance on the elucidation of the molecular mechanism of drugs and drug reposition. In this paper, we systematically review the existing approaches to the prediction of biological targets of small molecule based on chemoinformatics, including ligand-based prediction, receptor-based prediction and data mining-based prediction. We also depict the strength of these methods as well as their applications, and put forward their developing direction.
Computational Biology ; Data Mining ; Drug Delivery Systems ; Drug Design ; Ligands

Amyloid Neuropathies, Familial ; genetics ; Cardiomyopathies ; Humans ; Mutation

OBJECTIVETo observe the effect of Zishen Huoxue Recipe (ZHR) on pathomorphology in coronary heart disease (CHD) rats with Shen deficiency blood stasis syndrome (SDBSS).

METHODSTotally 60 healthy Wistar rats were divided into the blank control group, the model group, high, middle, and low dose ZHR groups according to random digit table, 12 in each group. Myocardial ischemia SDBSS rat model was prepared by ligating the left anterior descending coronary artery and injecting hydrocortisone. ZHR physic liquor was administered to rats in high, middle, and low dose ZHR groups at the daily dose of 21.6, 10.8, 5.4 g/kg by gastrogavage for 7 successive days, equal volume of pure water was administered to rats in the blank control group and the model group by gastrogavage for 7 successive days. Rat heart was collected for pathomorphological observation under light microscope.

RESULTSIn the model group the heart muscle fiber was swollen and deformed with widened space, loose and dropsy tissues. Blood vessels in myocardial mesenchymal were dilated, infiltrated with more inflammatory cells. Myocardial cells were markedly swollen, degenerated, or necrotic, with caryolysis or disappearance of partial nuclear. A large amount of collagen fibrous tissue became hyperplasia. Endocardial blood vessels were swollen and degenerated with infiltration of few inflammatory cells. Epicardium tissue and structure were destroyed and got hyperplasia. Swollen, degenerated, or necrotic vessels could be seen, with infiltration of more inflammatory cells and collagen deposition. Pathomorphological injuries were alleviated in each ZHR group. The higher ZHR concentration, the milder the injury degree of myocardial tissue, the more limited range of damage.

CONCLUSIONZHR could attenuate pathomorphological injuries of myocardial ischemia rats with SDBSS and regulate myocardial function, thus improving myocardial ischemia in CHD rats with SDBSS.

Animals ; Coronary Artery Disease ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Medicine, Chinese Traditional ; Myocardial Ischemia ; Myocardium ; Rats ; Rats, Wistar

OBJECTIVETo explore the expression and clinical significance of Semaphorin4D (Sema4D) mRNA in peripheral blood lymphocyte, Sema4D on platelet surface, soluble Sema4D (sSema4D) in plasma in patients with cerebral infarction.

METHODSTaking 299 patients with cerebral infarction as the case group while 195 healthy adults as the control group. The mRNA expression of Sema4D was detected by Real-time PCR, and Sema4D expression on platelet by flow cytometry, sSema4D by ELISA. Then, the expression of Sema4D on platelet surface and the concentration of sSema4D in plasma of the 195 selected patients following 2 weeks' treatment were tested.

RESULTSThe expression of Sema4D mRNA significantly increased in the case group \[(2.23, 2.66)×10(4) IU/ml\] than in the control group \[(0.49, 0.53)×10(4)IU/ml\] (P < 0.01). The level of Sema4D on platelet surface in the case group (191.62 ± 46.56) significantly decreased than in the control group (303.33 ± 112.66) (P < 0.01). But the concentration of sSema4D in plasma in the case group \[(1.34 ± 0.56) µg/L\] was obviously higher than in the control group \[(0.61 ± 0.31) µg/L\] (P < 0.01). The expression of Sema4D on platelet was obviously relevant with the concentration of sSema4D in plasma in the case group with the correlation coefficient as 0.328 (P < 0.01). The expression of Sema4D on platelet obviously peaked up following 2 weeks' routine therapy in the case group, which was close to that in the control group. Meanwhile the concentration of sSema4D in plasma was downward corrected to the normal in the case group.

CONCLUSIONThe increased expressions and plasma levels, and reduced expressions on platelet of Sema4D in acute period, which returned to normal 2 weeks after treatment in the case group may be related to the occurrence of acute cerebral infarction, reflecting the development process of cerebral infarction.

Aged ; Antigens, CD ; blood ; metabolism ; Blood Platelets ; metabolism ; Case-Control Studies ; Cerebral Infarction ; blood ; Female ; Humans ; Lymphocytes ; metabolism ; Male ; Middle Aged ; Semaphorins ; blood ; metabolism

OBJECTIVETo investigate the relationship between gene polymorphism of CYP2E1, CYP1A1, IL-4 and susceptibility of medicamentosa-like dermatitis induced by trichloroethylene (TCE).

METHODS35 patients with medicamentosa-like dermatitis induced by TCE were chosen as the patient group, and 35 healthy workers as control group. The real-time quantitative polymerase chain reaction (PCR) with TaqMan minor groove binding (MGB) probes was used to test single nucleotide polymorphisms (SNP) of CYP2E1, CYP1A1 and IL-4 in the patients with medicamentosa-like dermatitis as well as in the control. The genotypes and the frequency of genotype or allele were compared between the patients and control with statistical analysis.

RESULTSThe frequency of allele G within CYP1A1 gene (rs1048943) was significantly higher in TCE patients (37.1%) than that in control (P<0.05); the frequency of allele T within CYP2E1-1053 C/T was significantly higher in TCE patients (41.4%) than that in control (P<0.01); the frequency of T/T within IL-4-588 C/T (rs2243250) was significantly higher in TCE patients (75.0%) than that in control (P<0.01), and the frequency of allele T within IL-4-588 C/T (rs2243250) was also significantly higher in TCE patients (87.5%) than that in control (P<0.01).

CONCLUSIONThe gene polymorphism of CYP2E1, CYP1A1, IL-4 is probably associated with hypersensitivity for the TCE patients with medicamentosa-like dermatitis, and could be one of the genetic factors related to the individual susceptibility to TCE exposure.

Cytochrome P-450 CYP1A1 ; genetics ; Cytochrome P-450 CYP2E1 ; genetics ; Dermatitis, Occupational ; genetics ; Genetic Predisposition to Disease ; Humans ; Interleukin-4 ; genetics ; Polymorphism, Single Nucleotide ; Trichloroethylene ; adverse effects