The production conditions of glutathione with shaking flask fermentation by the mutant Saccharomyces J-X25, a methionine-defected strain were studied, and the optimum culture conditions are as follows: initial pH6. 0, temperature 30℃, 100ml in 500ml flask, the inoculum size 10% and agitation rate 220r/min. The emphasis was on the stimulating effect on the cells by dioxogen and the sodium lactate as surfactant. Both of which were added at the logarithmic phase of fermentation, and the GSH production was up to 0. 253g/L , 52% higher than the control without the additions. Compared with the production of GSH initial strain that by the mutant in optimum conditions was increased by 79%.

OBJECTIVE:To observe the efficacy and safety of eprosartan in the treatment of hypertensive patients with coro-nary heart disease. METHODS:160 hypertensive patients with coronary heart disease randomly divided into observation group and control group. All patients were given aspirin,nitroglycerin,low molecular weight heparin,statins and other conventional treat-ment;control group was additioanlly given 50 mg Losartan potassium tablet,orally,once a day. Observation group was additional-ly given 600 mg Eprosartan tablet,orally,once a day. The treatment course for both groups was 6 months. Clinical efficacy,sit-ting systolic blood pressure and diastolic blood pressure,alanine aminotransferase(ALT),aspartate aminotransferase(AST),urea (UREA),creatinine(Cr),uric acid(UA),total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol (LDL-C),the Mini-Mental status (MMSE) scale and activities of daily living (ADL) scale scores before and after treatment and incidence of adverse reactions in 2 groups were observed. RESULTS:There was no signifi-cant difference in the total effective rate between 2 groups(P>0.05). After treatment,the sitting systolic blood pressure and diastol-ic blood pressure,MMSE and ADL scale scores in 2 groups were significantly lower than before,and sitting systolic blood pres-sure in observation group was lower than control group,the differences were statistically significant(P<0.05),and there were no significant differences in sitting diastolic blood pressure,MMSE and ADL scale scores between 2 groups(P>0.05),and no signifi-cant differences in ALT,AST,UREA,Cr,UA,TC,TG,HDL-C and LDL-C between 2 groups before and after treatment(P>0.05). There were no obvious adverse reactions during treatment. CONCLUSIONS:Eprosartan can effectively reduce sitting systol-ic blood pressure in hypertensive patients with coronary heart disease,and improve cognitive function,with good safety.

OBJECTIVE:To study the effects and mechanism of propranolol on the myocardial abnormal electrophysiology sta-tion in diabetic model rats. METHODS:SD rats were randomly divided into normal control(normal saline)group,diabetic(nor-mal saline)group,PD98059(ERK inhibitor,10 mg/kg)group and propranolol low-dose,medium-dose and high-dose(1,20,50 mg/kg)groups,with 8 rats in each group. Except for normal control group,rats were given alloxan(20 mg/kg)intravenously via tail vein to induce diabetic model. They were given relevant medicine intragastrically,once a day,for consecutive 42 days. The car-diac index,electrocardiogram and action potential durations (APD) of rats were analyzed;the expression of TNF-α,IL-2,IL-6 and IL-10 protein in serum were detected,and the expression of Ras,Raf,ERK kinase(MEK)and ERK1/2 in myocardial tissue were detected. RESULTS:Compared with normal control group,cardiac index increased in diabetes group;heart rate decreased;QT interval and APD were prolonged;the relative expression of TNF-α,IL-2,IL-6,IL-10,Ras,Raf,MEK and ERK1/2 protein increased (P<0.01). Compared with diabetes group,cardiac index decreased in propranolol medium-dose and high-dose groups and PD98059 group,heart rate increased,QT interval and APD were shortened;the relative expression of TNF-α,IL-2,IL-6, IL-10,Ras,Raf,MEK and ERK1/2 protein decreased(P<0.05 or P<0.01). CONCLUSIONS:Propranolol can improve myocar-dial abnormal electrophysiology station of diabetic model rats by down-regulating inflammatory reactions in serum and inhibiting the activation of MEK/ERK signaling pathway.

Antihypertensive Agents ; therapeutic use ; Humans ; Hypertension ; therapy ; Practice Guidelines as Topic

Tumorous cells are characterized by distinctive metabolic reprogramming and living conditions. Understanding drug metabolizing features in tumor cells will not only favor the estimation of metabolic rate, elimination half life and the assessment of potency, but also facilitate the optimal design of anti-tumor drugs/prodrugs. This article reviewed the expression and activity features of major drug metabolizing enzymes (DMEs) in solid tumorous tissues, such as liver, intestine, breast and lung, and the difference from the correspondingly normal tissues, exemplified by the metabolic properties of some classic antitumor-agents in tumorous tissues. In combination with the data retrieved in vitro tumor cell lines, we discussed the similarities and differences of DMEs expression and function between tumor tissues (in vivo) and tumor cells (in vitro), and proposed the possible factors that cause the differences.
Antineoplastic Agents ; pharmacokinetics ; Cell Line, Tumor ; Humans ; Inactivation, Metabolic ; Liver ; metabolism ; Neoplasms ; enzymology ; Prodrugs ; pharmacokinetics

Objective To establish the methodology of uncertainty evaluation with reference measurement procedure by Monte Carlo method (MCM).Methods According to JCGM 101:2008,we established the methodology of uncertainty evaluation by MCM in the example of GGT reference measurement procedure.We could calculate an estimate of GGT concentration,the associated standard uncertainty and a coverage interval with a specified probability by MATLAB software,setting the uncertainty evaluation by GUM method as a control.Results When the uncertainty was evaluated by GUM method,the results of sample A and Sample B were (95.8 ±2.4) U/L (k =2) with coverage interval [93.4 U/L,98.2 U/L] and (180.0 ± 3.9) U/L (k =2) with coverage interval [176.1 U/L,183.9 U/L] respectively,while using MCM method,the uncertainty evaluation result of sample A and Sample B were (95.8 ± 2.4) U/L (k =2) with coverage interval [93.4 U/L,98.2 U/L] and (180.0 ± 3.9) U/L with symmetrical 95％ coverage interval [176.2 U/L,183.8 U/L].The output quantity simulated by MCM was normal distributed.Conclusions When the distribution of the output quantity is normal,the measurement uncertainty evaluated by both MCM and GUM method is nearly the same.When the distribution of the output quantity is unknown,MCM can be used as a verification of GUM method.

Objective To investigate the epidemiology of respiratory viruses in children from Wuxi area.Methods A total of 2 747 cases of children diagnosed with acute respiratory infection in Wuxi during 2011 —2014 were collected.Reverse transcription-polymerase chain reaction was used to detect nine kinds of respiratory viruses,including influenza virus A (Flu A),influenza virus B (Flu B),parainfluenza virus (PIV)Ⅰ-Ⅳ,adenovirus (ADV),respiratory sycytial virus (RSV),human metaneumovirus (hMPV), human bocavirus (HBov),human coronaviruses (hCov)and human rhinovirus (HRV).The categorical data were compared using chi square test.Results A total of 856 among the 2 747 samples were tested positive for respiratory virus nucleic acid,with the positive rate of 31 .16%.The viral distribution was uneven in different seasons,and the infection peaked in winter and spring.The virus detection rate was highest in age 1 to 2 year group (up to 40.18%),and followed by age 6 to 12 year group (32.63%).Flu A virus was the most frequently detected virus,accounting for 7.54% (207/2 747);followed by PIV, accounting for 6.95 % (191/2 747);and Flu B accounted for 4.22%(116/2 747).There were 84 cases of mixed infection of two or more kinds of respiratory viruses,with positive rate of 3.06% (84/2 747 ). Conclusions Our study suggests that Flu A is the most common pathogen in children with acute respiratory infections in Wuxi area during 2011 —2014;virus detection rate is highest in age 1 to 2 year group;and parainfluenza virus is almost detected throughout the year,while the rest of respiratory viruses are commonly seen in winter and spring.

Objective To observe the expression of heparanase(HPA)in kidney of diabetic nephropathy(DN)rats and to investigate the role of HPA in the pathogenesis of proteinuria in DN rals. Methods DM rat models induced by intraperitoneal injection with streptozotocin were constnmted.Twenty-six rats were randomly divided into heahhy control group(n=6),DM6-week group(n=10)and DM 12-week group(n=10).Relative kidney weight(RKW),blood glucose,BUN,Scr,24-hour urine volume and(t 24-hour proteinuria quantilation were measured,and renal morphology was observed after 6 and 12 weeks.The expression of HPA was examined by immunohistochemistry and reverse transcription PCR. Results (1)Conq)ared with the control group,RKW,blood glucose,BUN,24-hour urine volume and 24-hour proteinuria quantitation of DM groups increased markedly(P＜0.05 orP＜0.01).(2)Compared to the control group,the expression of HPA mRNA and protein in DM groups increused significantly(P＜0.01).(3)HPA protein and mRNA were positively correlated with the quantification of urinary prolein (r=0.783,P＜0.01;r=0.793,P＜0.01). Conclusion The increased expression of HPA maybe parlicipate in the pathogenesis of proteinuria in DN.

Objective To explore the association between inflammatory cytokines and islet β-cell function in chronic persistent asthma patients. Methods 112 adults with persistent asthma and 60 healthy volunteers were enrolled in this study. According to the severity of disease, all subjects were divided into persistent-mild group and persistent-moderate group. Plasma tumor necrosis factor-α(TNF-α), interleukin6(IL-6) and C-reactive protein (CRP) were determined. Oral glucose tolerance and insulin releasing test were performed. The ratio of the area under the curve of insulin to area under the curve of glucose ( AUC1/AUCG ), homeostasis model assessment for insulin resistance ( HOMA-IR), insulin sensitivity index( ISI),homeostasis model assessment for β-cell function (HBCI) and early insulin secretion index(△I30/△G30)were calculated. The values of forced expiratory volume in l second ( FEV1 ), forced vital capacity(FVC)and FEV1/FVC were recorded. Results In patient groups, the values for plasma TNF-α, IL-6, CRP,AUC1, AUC1/AUCG, HOMA-IR, HBCI significantly increased compared with those in control group, while ISI declined ( t =2. 02～13.62, P ＜0. 05). Multiple step regression analysis showed that HOMA-IR was positively correlated with CRP, LDL-C, BMI, AUC1, TNF-α( P ＜0. 01 orP ＜0. 05), but negatively correlated with FEV1 ( P ＜ 0. 05 ). Conclusion The results indicated that inflammatory cytokines ( TNF-α,IL-6,CRP) might result in insulin resistance in asthma patients who had hyperinsulinism at the same time.

Peroxisome proliferator-activated receptors (PPARs) are nuclear transcriptional factors closely related to glucose and lipid metabolism, insulin sensitivity. Activation of PPARs targets treated type 2 diabetes, obesity, hypertension and other metabolic diseases by insulin resistance. Recently, a variety of active ingredients of traditional Chinese medicines (TCMs) have been proved to activate PPARs targets for improving insulin resistance, which has attracted widespread attention at home and abroad. In this paper, we reviewed the pathological mechanisms between insulin resistance and PPARs, and summarized the active ingredients of TCMs improved insulin resistance based on PPARs targets. This paper may provide some theoretical guidance for the development of new drugs and TCMs.
Animals ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Insulin Resistance ; Metabolic Diseases ; drug therapy ; genetics ; metabolism ; Peroxisome Proliferator-Activated Receptors ; antagonists & inhibitors ; genetics ; metabolism