Administration, Inhalation ; Animals ; Female ; Male ; Pesticides ; analysis ; toxicity ; Rats ; Rats, Wistar

OBJECTIVETo evaluate the effect of adenosine on endothelin-1 (ET-1) after acute myocardial infarction (AMI) and reperfusion and explore the possible mechanism of no-reflow.

METHODSTwenty-four mini-swine were randomized into three study groups: control group (n=8), adenosine treated group (n=8), and sham-operated group (n=8). The mini-swine in the groups were subjected to 3 hours of coronary occlusion, followed by 60 minutes of reperfusion except those in the sham-operated group. The levels of ET-1 in blood sample, normal, infracted reflow and no-reflow myocardium were evaluated by radioimmuno-assay (RIA). The gene expressions of ET-1 in normal, infracted reflow and no-reflow myocardium were quantified by reverse transcription-polymerase chain reaction.

RESULTSIn both control group and adenosine group, compared with that at the baseline, ET-1 in blood sample significantly increased at 5 minutes and 180 minutes of left anterior descending coronary artery occlusion, as well as 5 and 60 minutes of reperfusion (all P < 0.01). In adenosine group, the levels of ET-1 were significantly lower than those in the control group (P < 0.05, P < 0.01). In both control group and adenosine group, compared with that in normal myocardium, ET-1 levels in both infarcted reflow and no-reflow myocardium significantly increased (both P < 0.01), with the level of ET-1 in no-reflow myocardium significantly higher than that in infarcted reflow myocardium (P < 0.01). In adenosine group, the level of ET-1 in infarcted reflow myocardium was significantly lower than that in the control group (P < 0.01). In both control and adenosine groups, compared with that in normal myocardium, the gene expression of ET-1 in infarcted reflow myocardium was significantly up-regulated (P < 0.01), while that of ET-1 in. no-reflow myocardium significantly down-regulated (P < 0.01). In adenosine group, the level of ET-1 in infarcted reflow myocardium was significantly lower than that in the control group (P < 0.01).

CONCLUSIONThe endothelium injury may be one of the important mechanisms for no-reflow phenomenon. Adenosine cay prevent endothelium from injury to reduce no-reflow.

Adenosine ; pharmacology ; therapeutic use ; Animals ; Disease Models, Animal ; Endothelin-1 ; genetics ; metabolism ; Female ; Male ; Myocardial Infarction ; drug therapy ; physiopathology ; Myocardial Reperfusion ; Swine ; Swine, Miniature

AIM:To observe the effect of thyroxine on the expression of T-type calcium channels Cav3. 1, Cav3. 2 and Cav3. 3 in rat myocardium, and to explore the possible biological mechanism between the changes of the ex-pression of T-type calcium channels and the arrhythmia in hyperthyroid heart disease. METHODS:Healthy SD rats (n=20) were randomly divided into normal control group (n=10) and hyperthyroid heart disease group (n=10). The animal model was established by intraperitoneal injection of levothyroxine for 35 d. The contents of T3 and T4 in serum, the heart-to-body weight ratio, the diameter of cardiac myocytes and electrocardiograph were measured to evaluate hyperthyroid heart disease. Moreover, the mRNA and protein expression levels of T-type calcium channels in the myocardium were measured by RT-PCR, immunohistochemistry and Western blot. RESULTS:After intraperitoneal injection of levothyroxine for 35 d, compared with the normal control group, the serum contents of T3 and T4, the heart-to-body weight ratio and the diameter of cardiac myocytes were significantly increased in hyperthyroid heart disease group (P<0.05), and arrhythmia occurred in hyperthyroid heart disease group. By immunohistochemistry and Western blot, the protein expression of Cav3. 1 in-creased significantly (P<0.05), while the protein expression of Cav3.2 decreased significantly (P<0.01). However, no change of the Cav3. 3 protein was observed. The results of RT-PCR were the same as immunohistochemistry and Western blot. CONCLUSION:Thyroxine promotes the expression of Cav3. 1 in the myocardium but inhibits the expression of Cav3. 2 at mRNA and protein levels, which might be involved in arrhythmia in hyperthyroid heart disease.

OBJECTIVETo study the oral chronic toxicity of 97% isopropyl thioxanthone (97% ITX) in rats, determine the no-observed adverse effect levels (NOAEL).

METHODSFour groups of rats were fed with foodstuff containing 97% ITX in the dosage of 1000.0, 250.0, 62.5 mg/kg respectively for 2 years. The general behavior, body weight, food availability ect. were observed during the experiment. At the end of the experiment, blood and urine samples were collected for routine and biochemical assays. The internal organs were taken for calculating their organ coefficients and histopathological examinations.

RESULTSDuring the experimental period, no obvious abnormality were found in the experimental animals. The body weight and the total food availability rate in the high dosage group of male were lower than that of control (P < 0.05). Hematology examination showed that the quantity of Hb and RBC in high dosage groups of both the male and female and Hb in the male middle group were all lower than the control group (P < 0.01 or P < 0.05). Analysis of correlation indicated that r = -0.433, P < 0.01 in male, r = -0.337, P < 0.01 in female of Hb; r = -0.266, P < 0.05 in male, r = -0.317, P < 0.01 in female of RBC. There were obviously negative correlation. Serum biochemistry examination showed the concentration of CHO in the high and middle dosage treated rats of male and female were higher than that of the control (P < 0.01 or P < 0.05). Analysis of correlation indicated that r = 0.497, P < 0.01 in male, r = 0.417, P < 0.01 in female. No abnormality were found in urine examination. The organ weight and organ coefficient such as liver, were higher than control group (P < 0.01). The result of histopathological examinations displayed that the renal tubule Cast and the tubulointerstitial nephritis in the treated groups were higher than that of control group (P < 0.01).

CONCLUSION97% ITX could obviously interfere with the animals' physical condition, and reduce the number of RBC and the concentration of Hb in the blood, interact metabolism of lipoid and induce the concentration of CHO in the serum. The livers of the treated rats are compensatory enlarged. And kidneys of the poisoning animals are damaged. The 2 years oral NOAEL of 97% ITX in rats are more than 4.63 mg/kg for female rats, and larger than 4.06 mg/kg for male rats.

Administration, Oral ; Animals ; Female ; Male ; No-Observed-Adverse-Effect Level ; Rats ; Rats, Wistar ; Toxicity Tests, Chronic ; Xanthones ; toxicity

OBJECTIVETo investigate whether the phosphorylation (functionally inhibitive) of eukaryotic initiation factor 2-alpha (eIF2-a) affects the molecular mechanism of cisplatin-induced cellular apoptosis in human hepatocellular carcinoma (HCC).

METHODSThe human HCC cultured cell lines SMMC-7221 and HepG2 were treated with cisplatin alone (controls; 24 h) or in combination with pre-transfection of a dominant-negative eIF2-a mutant (eIF2aS51A) or pre-exposure to an eIF2-a-specific phosphatase inhibitor (salubrinal) to decrease or increase the phosphorylation level, respectively. Changes in expression of apoptosis markers were quantitatively and qualitatively assessed by flow cytometry and western blot analysis. The significance of differences among groups was assessed by analysis of variance testing and of differences between groups was assessed by t-test.

RESULTSCisplatin treatment induced the appropriate functional-inhibitive phosphorylation of eIF2-a on serine 51. Cisplatin treatment (10 mg/ml) induced significant apoptosis in the eIF2aS51A pre-transfected SMMC-7721 (control: 21.7 +/- 1.5% vs. 50.7 +/- 2.1%, t = 19.454, P less than 0.05) and HepG2 (21.0 +/- 1.0% vs. 57.3 +/- 2.1%, t = 27.250, P less than 0.05). Salubrinal pre-treatment significantly inhibited the cisplatin (15 mg/ml)-induced apoptosis in SMMC-7721 (control: 50.3 +/- 2.5% vs. 16.3 +/- 2.1%, t = 18.031, P less than 0.05) and HepG2 (42.0 +/- 2.6% vs. 12.0 +/- 2.0%, t = 15.667, P less than 0.05).

CONCLUSIONPhosphorylation of eIF2-a may act to inhibit cisplatin-induced apoptosis of HCC.

Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; Cell Line, Tumor ; Cisplatin ; pharmacology ; Eukaryotic Initiation Factor-2 ; metabolism ; Humans ; Liver Neoplasms ; Phosphorylation

Objectives To analyze the fatality and causes of death related to comprehensive prevention and care programs among HIV-infected patients in Dehong prefecture of Yunnan province,from 1989 to 2010. Methods Data on HIV/AIDS death cases in Dehong prefecture were extracted from the "Chinese National Comprehensive HIV/AIDS Prevention and Care Information System" and were analyzed. Results From 1989 to the end of 2010,a total of 13 493 HIV/AIDS cases registered as local residents or currently living m Dehong, had been reported. Among them, 8569 were reported as HIV cases with 2036 deaths and the other 4924 were reported as AIDS cases with 2251 deaths. A few of the cases had survived for 15-20 years. By the end of 2010, the number of deaths was higher than the number of survivors among HIV/AIDS cases reported before 2004, whereas the number of survivors was higher than the number of deaths among HIV/AIDS cases reported in 2004 and there after. During the twenty years' period,the proportion of reported HIV/AIDS cases died in the same year showed a secular trend of being low-highest-low, rising up to ＞ 10.0％ in 200 1, peaking at 18.9％in 2003 and then continuously going down to 5.8％ in 2010. The proportion of HIV/AIDS cases who survived at the beginning but died later in the year was going down since 2007. The proportion of HIV/ AIDS deaths died directly from AIDS was increasing whereas the proportion of HIV/AIDS deaths dying directly from overuse of drugs was decreasing in the recent years. Among HIV/AIDS deaths, the proportion of ever received CD4 + T-cell testing and the proportion of ever having received antiretroviral treatment were also increasing in the past years, reaching to 89.9％ and 25.5％ in 2010,respectively. Conclusion The case fatality of HIV/AIDS was decreasing in the past years in Dehong prefecture. More efforts were needed to scale up the CD4 + T-cell count testing and antiretroviral treatment in order to further reduce both morbidity and mortality among HIV/AIDS patients in Dehong prefecture. It is critical to improve surveillance program on HIV/AIDS deaths in the rural

Objective To determine the adherence to and its determinants of methadone maintenance treatment (MMT) among heroin addicts in Dehong prefecture in Yunnan province from 2005 to 2009. Methods A dynamic cohort analysis was conducted with the time of treatment initiation as the time of cohort entry, to calculate the proportion of adhering to the treatment at different time points after initiation of the treatment, and to study the determinants of adherence.Results A total of 3758 had been treated. Among them, 95.8% were males, 75.8% aged between 20-39 years, 90.4% were peasants or unemployed, 57.0% were ethnic minorities, 35.0% were single and 55.5% were married with spouses, 43.9% were illiterate or educated at most primary school. The age of first using drugs averaged at 23.93 years. About 96.3% of the study subjects had used heroin and 21.7% were HIV-infected. The minimum time under MMT was less than 1 month and the maximum 61 months. The median methadone dose at first delivery was 25 ml, with the minimum 1 ml and the maximum 330 ml. By the end of the study or observation period, a total of 1798 patients had withdrawn from treatment and 1960 were still under treatment. The proportions of adherence to or still being under the treatment after 1,3,6,9, 12,24, 36,48 and 60 months treatment were 0.919,0.847,0.756, 0.690, 0.637, 0.519, 0.417, 0.360 and 0.321, respectively. Multiple regression analysis using Cox proportional hazard model indicated that withdraw from the methadone maintenance treatment was significantly associated with location of the treatment clinics, year of treatment initiation, marital status, HIV infection status, methadone dose of first delivery and the result of last urine test for heroin use. Conclusion MMT attendants in Dehong prefecture had a relatively high withdraw rate and low adherence rate. More efforts are needed to provide tailored counseling and education to MMT attendants, to provide family and community support, appropriate methadone dose at first delivery, and to better coordinate with local police department.

Objective To determine the incidence and risk factors of HIV infection among heroin addicts receiving methadone maintenance treatment(MMT)in Dehong prefecture,Yunnan province.Methods All heroin addicts who were HIV negative at the initiation of MMT in June 2005 and through June 2011,in Dehong prefecture were included in the cohort analysis.HIV incidence was calculated and related risk factors determined by using Cox proportional hazard regression model.Results A total of 3154 MMT clinic attendants were qualified for this cohort study.By June 2011,1023(32.4％)of them had never received any follow-up HIV testing so were thus referred as loss to follow-up.The other 2131(67.6％)members had received at least one follow-up HIV testing and were observed for a total of 4615.86 person-years.During the period,22 new HIV infections or seroconverters were identified,making the overall HIV incidence as 0.48/100 person-years.The HIV incidence was higher among those who were unemployed,never married,self-reported being injecting drug users(IDUs)and HCV positive at entry into the MMT program.None of those who were always negative on follow-up-urine-testing of morphine was discovered as HIV newly infected during the follow-up period.Data from multiple regression analysis under Cox proportional hazard model indicated that after controlling for confounding variables,non-IDUs at the entry point for the MMT program,were less likely to be HIV newly-infected or seroconverted than IDUs(HR=0.29,95％CI:0.11-0.76).Conclusion MMT prograqm in Dehong prefecture was demonstrated to be fairly effective in reducing HIV transmission through drug use.Those HIV negative attendants at the MMT clinic who were IDUs or keep using drugs during the treatment,were at higher risk of HIV seroconvertion.More efforts were needed to improve the follow-up and HIV testing programs for the MMT clinic attendants.

OBJECTIVETo evaluate the effects of ischemic preconditioning (IPC) on myocardial no-reflow in a mini-swine model of acute myocardial infarction (AMI) and reperfusion.

METHODSTwenty-four mini-swines were randomized into 3 study groups: 8 in control, 8 in IPC and 8 in sham-operated. Animals in the former two groups were subjected to 3 hours of coronary occlusion followed by 1 hour of reperfusion. Data on hemodynamics and coronary blood flow volume (CBV) were collected, and the area of no-reflow (ANR) was evaluated with both myocardial contrast echocardiography (MCE) in vivo and pathological means. Necrosis area (NA) was measured with triphenyltetrazolium chloride (TTC) staining.

RESULTSIn control group, left ventricular systolic pressure (LVSP), the maximum change rate of left ventricular pressure rise and fall (+/-dp/dtmax) and cardiac output (CO) significantly declined (P < 0.05, P < 0.01), while left ventricular end-diastolic pressure (LVEDP) significantly increased at the end of 3 hours of left anterior descending coronary artery occlusion (both P < 0.01), with +/-dp/dtmax further significantly declined (both P <0.05) at 1 hour of reperfusion. In IPC group, LVSP, +/-dp/dtmax, CO and LVEDP significantly recovered at 1 hour of reperfusion, compared with those in control group. In IPC group, the coronary ligation area was similar on both MCE in vivo and pathological evaluation (P > 0.05), and ANR was both also similarly as high as (16.4 +/- 2.24) % and (17.5 +/- 2.87) %, respectively, with final necrosis area (NA) reaching (78.4 +/- 3.62) %. In IPC group, ANR and final NA were significantly lower than those in control group (P < 0.05, P < 0.01). In the control group, coronary blood flow volumn immediately after release of 3 hours occlusion and at 1 hour of reperfusion were significantly lower than the baseline (both P < 0.01). In IPC group, coronary blood flow volumn were significantly higher than those in the control group (both P < 0.01).

CONCLUSIONIPC is effective to prevent myocardial no-reflow, improve left ventricular function and decrease infarct area.

Animals ; Blood Flow Velocity ; Coronary Circulation ; physiology ; Echocardiography ; Hemodynamics ; Ischemic Preconditioning ; Myocardial Infarction ; diagnostic imaging ; physiopathology ; Myocardial Reperfusion ; methods ; Myocardial Reperfusion Injury ; diagnostic imaging ; physiopathology ; prevention & control ; Random Allocation ; Swine ; Swine, Miniature

OBJECTIVETo investigate the therapeutic effectiveness of intracoronary implantation of autologous bone marrow mononuclear cells (BM-MNC) in miniswine model of reperfused myocardial infarction.

METHODSSixteen miniswine myocardial ischemic reperfusion injury models made by ligation of the distal one third segment of left anterior descending artery for 90 minutes were randomized into 2 groups. In BM-MNC group (n = 9), (3.54 +/- 0.90) X 10(8) BM-MNC were intracoronary injected, and in the control group (n = 7), phosphate buffered saline was injected by the same way. Echocardiographic and hemodynamic results, vessel density, and myocardial infarction size were evaluated and compared before and 4 weeks after cell transplantation.

RESULTSIn BM-MNC group, there were no differences between before and 4 weeks after transplantation in aspects of left ventricular ejection fraction (LVEF), interventricular septal thickness, left ventricular lateral and anterior septal wall thickness, cardiac output, or +dp/dtmax. In control group, LVEF, interventricular septal thickness, left ventricular lateral and anterior septal wall thickness, cardiac output, and +dp/dtmax decreased significantly 4 weeks after transplantation (P < 0.05). Left ventricular end-diastolic pressure and -dp/dtmax, did not change significantly before and after cell transplantation in both groups. Capillary density in BM-MNC group was greater than that in control group [(13.39 +/- 6.96)/high power field vs. (3.50 +/- 1.90)/high power field, P < 0.05]. Infarction area assessed by tetrazolium red staining and the infarction percentage decreased in BM-MNC group compared with those in control group (P < 0.05).

CONCLUSIONSTransplantation of BM-MNC into myocardium with ischemic reperfusion injury increases capillary density and decreases infarction area. It has significantly beneficial effect on cardiac systolic function rather than on diastolic function.

Animals ; Bone Marrow Cells ; cytology ; physiology ; Bone Marrow Transplantation ; Capillaries ; physiology ; Echocardiography ; Heart ; anatomy & histology ; physiology ; physiopathology ; Hemodynamics ; Myocardial Ischemia ; Random Allocation ; Swine ; Systole ; physiology ; Transplantation, Autologous ; physiology