Objective To investigate calcineurin signaling pathway which mediates myocardium apoptosis of right heart in rats with chronic hypoxia and the potential mechanisms of it.Methods A rat model of right ventricular hypertrophy(RVH) was established induced by chronic hypoxia(95-105 mL?L-1 O2).Used randomized block design based on different brood,30 rats were divided into 3 groups:treatment group with cyclosporine A(CsA,10 mg?kg-1?d-1,intraperitoneal injection),chronic hypoxia group,normal control group(with normal oxygen).The rats in CsA treatment group and chronic hypoxia group were exposed to normobaric chronic hypoxia(95-105 mL?L-1 O2,21 days).Apoptotic index(AI),calcineurin A?(CnA?) mRNA levels,Bcl-2 mRNA levels and the protein expression levels of CnA?,nuclear factor 3 of activated T cells(NFAT3) and Bcl-2 in right ventricle were investigated.Results 1.The AI of treatment group with CsA was higher than that in chronic hypoxia group(P

Animals ; Asthma ; drug therapy ; metabolism ; Genistein ; pharmacology ; therapeutic use ; Guinea Pigs ; Interleukin-4 ; genetics ; metabolism ; Janus Kinase 1 ; genetics ; metabolism ; Lung ; metabolism ; Male ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use

Acute Disease ; Animals ; Female ; Hypoxia ; physiopathology ; Male ; Microcirculation ; physiology ; Rats ; Splanchnic Circulation ; physiology ; Superoxide Dismutase ; blood

The metabolic characteristics of ligustrazin (TMPz) in liver microsomes were investigated in the present study. The reaction phenotyping of TMPz metabolism was also identified by in vitro assessment using recombinant human cytochrome P450 enzymes (CYP) and UDP glucuronosyltransferases (UGT). TMPz was incubated at 37 degrees C with human (HLM) and rat liver microsomes (RLM) in the presence of different co-factors. The metabolic stability and enzyme kinetics of TMPz were studied by determining its remaining concentrations with a LC-MS/MS method. TMPz was only metabolically eliminated in the microsomes with NADPH or NADPH+UDPGA. In the HLM and RLM with NADPH+UDPGA, t1/2, K(m) and V(max) of TMPz were 94.24 +/- 4.53 and 105.07 +/- 9.44 min, 22.74 +/- 1.89 and 33.09 +/- 2.74 micromol x L(-1), 253.50 +/- 10.06 and 190.40 +/- 8.35 nmol x min(-1) x mg(-1) (protein), respectively. TMPz showed a slightly higher metabolic rate in HLM than that in RLM. Its primary oxidative metabolites, 2-hydroxymethyl-3, 5, 6-trimethylpyrazine (HTMP), could undergo glucuronide conjugation. The CYP reaction phenotyping of TMPz metabolism was identified using a panel of recombinant CYP isoforms (rCYP) and specific CYP inhibitors in HLM. CYP1A2, 2C9 and 3A4 were found to be the major CYP isoforms involved in TMPz metabolism. Their individual contributions were assessed b) using the method of the total normalized rate to be 19.32%, 27.79% and 52.90%, respectively. It was observed that these CYP isoforms mediated the formation of HTMP in rCYP incubation. The UGT reaction phenotyping of HTMP glucuronidation was also investigated preliminarily by using a panel of 6 UGT isoforms (rUGT). UGT1A1, 1A4 and 1A6 were the predominant isoforms mediated the HTMP glucuronidation. The results above indicate that the metabolism of TMPz involves multiple enzymes mediated phase I and phase II reactions.
Animals ; Cytochrome P-450 CYP1A2 ; metabolism ; Cytochrome P-450 CYP2C9 ; metabolism ; Cytochrome P-450 CYP3A ; metabolism ; Cytochrome P-450 Enzyme Inhibitors ; Cytochrome P-450 Enzyme System ; metabolism ; Drug Interactions ; Glucuronosyltransferase ; metabolism ; Humans ; Ligusticum ; chemistry ; Microsomes, Liver ; enzymology ; NADP ; metabolism ; pharmacology ; Pyrazines ; metabolism ; pharmacokinetics ; Rats ; Uridine Diphosphate Glucuronic Acid ; metabolism ; pharmacology

Applying multi-media combined with case teaching method to optimize pediatric dermatology teaching and clinical practice.The data of typical cases were collected by multi-media method,which can visually describe the characteristics of the cases and help students master the knowledge of pediatric dermatology by personal involvement.It can also cultivate students′ ability to analyze and solve problems as well as alleviate the conflicts between the clinical practice and lack of teaching case resources under the intense doctor-patient relationship.In conclusion,it is a teaching reform which deserves extending and applying.

Objective To evaluate the capacity of atopy patch test in diagnosis of food allergy in children with atopic dermatitis (AD).Methods Egg and milk,as the most common food allergens among Chinese children,were employed in this study.Skin prick test (SPT) and atopy patch test (APT) with fresh egg and milk were carried out in 68 children with AD.Oral food challenges in an open style were performed to confirm the diagnosis of food allergy.Resuits Of these patients,58(85.3%)were sensitive to egg,40(58.8%)to milk and 34(50.0%) to both.Of 98 patients with positive challenge,47 showed late response,10 immediate reactions.and 41 mixed reactions.The sensitivity,specificity,positive predictive value (PPV),negative predictive value (NPV) and the agreement with food challenges in diagnosis of egg/milk allergy were 96.6%/67.5%.90.0%/82.1%,98.2%/84.4%,81.8%/63.9% and 95.6%/73.5%,respectively for APT alone,37.9%/30.0%,100%/89.3%,100%/80.0%,21.7%/47.2% and 47.1%/54.4%,respectively for SPT alone.APT was found to be more sensitive in diagnosis of late-phase reactions than SPT (P<0.01).No significant difference was found in the sensitivity between APT alone and the combination of APT and SPT in parallel algorithm for diagnosis of egg or milk allergy (x2=0.509,0.549,both P>0.05) or in the specificity between APT alone and that in serial algorithm( P=1.000;x2=3.514,P>0.05).Conclusions APT is superior to SPT in diagnosis of late responses to food,and the combination of SPT and APT does not facilitate the diagnosis of food or milk allergy compared with APT alone.

Objective To study the mechanisms of Curcumin-induced apoptosis on human gastric cancer cell line SGC-7901.Methods SC,C-7901 cells were treated with various concentrations of Curcumin and the growth inhibition rates of it were accessed by MTT method.Apoptosis of gastric cancer cells were in- spected by flow cytometry.The expression of Fas and survivin in gastric cancer cells were evaluated by west- ern blot.Results Curcumin could effectively inhibit the growth of gastric cancer cells in dose-dependent and time-dependent manners,the sub-peak appeared and the apoptotic rate was increased.The expressions of Fas was higher in Western blot,meanwhile,the expressions of survivin was decreased.Conclusion Curcumin could significantly inhibit the growth and induce apoptosis of gastric cancer cells(SGC-7901),Curcumin could probably through up-regulating Fas and down-regulating surviving to induce apoptosis.

objective To explore the role of cytokines and dendritic cells (DCs) in rat high-risk corneal allograft survival pro- longed by superantigen Staphylococcal Enterotoxin B (SEB) and to compare the different effects between SEB and glucocorticoid. Design Experimental study.Participants Fisher 344 and Lewis rats.Methods The Fisher 344 and Lewis inbred rats were used for high-risk penetrating keratoplasty model.All of the Lewis rat recipients were divided into three groups by blinded fashion.GroupⅠand GroupⅡrats were injected intraperitoneally with 0.2ml saline buffer or SEB (75?g/ml) respectively at 4-day intervals on three occasions before transplantation.GroupⅢrats were injected subconjunctivally with 0.1ml dexamethasone (1mg/ml) daily from the first day after surgery for 2 weeks.The allograft survival was examined under slit-lamp.The concentration of interleukin IL-1?,IL-2,IL-4,IL-5,IL-6, IL-10,TNF-?in rat aqueous humor and peripheral blood were measured by liquichip and the cytokine and CD11c,CD80,MHC-Ⅱex- pression in corneal grafts were examined by immunohistochemestry staining.Main Octcome Measures Mean survival time of the allo- grafts,the level of cytokines in aqueous humor,peripheral blood and corneal grafts.Results Compared with group control,the grafts mean survival time was delayed about 3.8d in group SEB (P=0.00) and 7.1d in group dexamethasone(P=0.01).But there was no signifi- cant difference between group SEB and dexamethone (P=0.26).Liquichip test showed that the level of IL-1?in aqueous humor was re- duced and IL-4,IL-6 and IFN-?,ascended.Only IFN-?,and IL-6 could be found in peripheral blood,and the changing shift of them was similar to that in aqueous humor.The immunohistochemistry staining showed that the expression of IL-2 in rat corneal grafts was signif- icantly decreased but IL-4,IL-6 and IL-10 elevated.The expression of DCs in group SEB was similar to that in group control,which was elevated after keratoplasty,but the phenotype of DCs was not the same.There were predominantly mature DCs in group control while immature DCs in group SEB.Conclusions The immunological inhibiting effect of SEB is same to glucocorticoid,but the mecha- nism is different.SEB can modulate immune response,which might induce immune inhibition via the local production of cytokines and effect on DCs maturation involving corneal graft rejection prevention.

To investigate and analyze the epidemiology of serious corneal ulcer.
● METHODS: A total of 133 serious corneal ulcercases from June 2010 to December 2013 in Xiangya Hospital Affiliated to Central South University were retrospectively reviewed for risk factors, demographic characteristics and diagnosis.
●RESULTS: There were 91 male patients (68. 4%) in the 133 patients. A peak incidence age was from 41 to 60 years old (82 cases, 44. 4%). Most of patients were peasant (77 cases, 57. 9%) and the percentage of the low schooling patients was 85. 0% (113 cases). The number of patients who had been sick was 73 before hospitalization (54. 9%) in all cases. The peak incidence season was January (34. 6%). Average length of stay was 9. 84d. The number of emergency cases was 44 (33. 1%). Most of patient were not only corneal ulcer cases but the hypopyon (92 cases, 69. 2%). The figure of inpatients who received operations was 102 cases ( 76. 7%). And the most of operations was amniotic membrane transplantation (31 cases, 39. 2%). Additionally, this data was classified regard to gender differences.
● CONCLUSlON: The peasant of the middle age and elderly represents a distinct clinical group in the serious corneal ulcer in hospital. Severity, ocular trauma in agriculture and health awareness are the major predisposing factors.

Background Optic neuropathy is one of the diabetic eye complications.Rosiglitazone,a peroxisome proliferator activated receptor γ(PPARγ) agonist,plays a very important role in arresting the pathogenesis and development of diabetes.However,the role of PPARγ in diabetic optic neuropathy is unclear.Objective This study was to investigate the protective effect of rosiglitazone against diabetic optic neuropathy and its mechanism.Methods Male Sprague-Dawley rats were randomly divided into the control group,diabetic group and rosiglitazone group,with 10 rats for each group.Diabetic models were induced by injecting 50 mg/kg of streptozotocin via the caudal vein,and rosiglitazone(5 ng/[kg· d])was used in the rats of the rosiglitazone group by intragastric administration every day for four weeks.At the end of the experiment,the fasting blood sugar(FBS) was tested in all the animals.The level of vascular endothelial growth factor(VEGF) in the blood plasma was detected by ELISA.Optical neural tissues were obtained from the rats of each group,and Lauck fast Blue myelin stain was used to examine the morphology of the optical myelin.The expression of neural cell adhesion molecule (NCAM) mRNA and protein in the optic nerve was detected by real time PCR and Western blot,respectively.Results The levels of FBS,blood plasma VEGF,NCAM mRNA and protein in the optic nerve were significantly different among the control group,diabetic model group and the rosiglitazone group after the administration of 5 nmg/(kg · d) rosiglitazone for 4 weeks (F =6.12,P＜0.01 ; F =5.14,P＜0.05 ; F =4.75,P＜0.05 ; F =4.87,P＜0.05).Compared with the control group,the level of FBS significantly increased in the diabetic model group(t =2.26,P＜O.05),and that in the rosiglitazone group significantly declined in comparison with the diabetic model group(t=2.08,P＜0.05).The optic nerve exhibited a normal morphology in the control group as revealed by the Lauck fast Blue myelin staining;however,severe demyelination of the optic nerve and proliferation of glial cells were found in the diabetic model group,and mild demyelination of the optic nerve and proliferation of glial cells were seen in the rosiglitazone group.Blood plasma VEGF was(28.76±4.21)ng/L in the control group and(134.28±11.36)ng/L in the diabetic model group,showing a significant difference between them (t=2.36,P ＜ 0.05).Compared with the model group,the blood plasma VEGF was significantly lower in the rosiglitazone group ([42.67 ± 5.83] ng/L) than that in the diabetic model group (t =2.17,P＜ 0.05).Expression of NCAM mRNA and protein in the optic nerve significantly decreased in the diabetic model group compared with the control group(t =2.21,t =2.58,both at P＜0.05);while those in the rosiglitazone group were significantly elevated in comparison with the diabetic model group(t =2.19,t =2.67,both at P＜O.05).Conclusions Rosiglitazone can protect optic nerve from damage in diabetic rats mainly by downregulating blood plasma VEGF level and upregulating NCAM expression.