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

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.

Toll-like receptors (TLRs) family may play important roles in inflammatory bowel disease. This study examined the expression of TLR2, TLR4 and TLR9 in the colonic tissues of patients with ulcerative colitis (UC) and explored their roles in the pathogenesis of UC. Colonic biopsies were taken from the colon of 30 patients with mild or moderate UC (at active phase) and 10 healthy controls during colonoscopy. TLR2, TLR4 and TLR9 protein expression levels were immunohistochemically detected. The mRNA expression levels of TLR2, TLR4 and TLR9 were assessed by reverse transcription polymerase chain reaction (RT-PCR). The disease activity index (DAI), colonoscopic and histologic grades and fecal microbial flora were determined. Histological examination showed that the intestinal mucous membrane of UC patients underwent acute inflammation changes. Immunohistochemistry exhibited that the expression levels of TLR2, TLR4 and TLR9 in colon epithelia and inflammatory cells were higher in UC patients than in control group (P<0.01). The mRNA expression levels of TLR2, TLR4 and TLR9 were increased in UC patients but were not detected in the normal controls. Expression levels of TLR2, TLR4 and TLR9 were positively correlated, and bore close correlation with DAI, colonoscopic and histologic grades and fecal microbial flora. An important mechanism of UC might be that abnormal activation of mucosal immunity by intestinal dysbacteriosis caused dysregulation of TLRS that mediates innate immunity.

?AlM: To observe the effect of Qingguang'an on elastic fiber, MMP-7, TlMP-1 in scarring area of filtration canal after glaucoma surgery through the four Qingguang'an effective groups and Qingguang'an granules, to discuss and compare their mechanism of action on scarring area of filtration canal.?METHODS:Four effective components of Qingguang'an were used in groups D, E, F, G and H after glaucoma surgery, compared with group A ( blank ) , group B (model) and group C ( MMC) to observe the effect of elastic fiber, MMP-7, TlMP-1 in scarring filtration canal.?RESULTS:Compared with the preoperative basic lOP and 2d , 1, 2, 4wk postoperative lOP of groups C, E and H, the lOP of three group rose up slower than other groups, and kept the lowest data at 28d. There was significant difference compared with the rest of A, B, D, F, G groups (P<0. 05). The area and density of elastic fiber in surgery group were significantly different with that of black control group ( P<0. 05 ), but there were no statistical differences between groups C and H, groups C and F, groups H and E (P>0. 05). The difference was statistically significant among other groups (P<0. 01).?CONCLUSlON:The scarring area of filtration canal after glaucoma surgery is the major reason which lead to the failure of surgery. Qingguang'an effective group 2, Qingguang'an granules and MMC could reduced the scar tissue by restrained the elastic fiber, TlMP - 1 and increased the MMP-7. By observing the experimental results that both Qingguang'an effective group 2 and Qingguang'an granules could restrained the scarring area of filtration canal, the effects were unbiased, Qingguang'an granules group is better than effective group 2.

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.

BACKGROUND:Many studies have showed that neural stem cells therapy is a new strategy for hypoxic-ischemic encephalopathy.
OBJECTIVE:To review and analyze the status of research, transplantation strategies and mechanism of neural stem cells therapy for treatment of hypoxic-ischemic encephalopathy.
METHODS:A computer-based retrieval was performed in PubMed and CNKI database to search papers published from August 2000 to August 2013 using the key words of“hypoxic-ischemic encephalopathy, neural stem cells”in English and Chinese. The papers with objective-independent and repetitive contents were excluded, and final y 39 papers were included for final analysis.
RESULTS AND CONCLUSION:Neural stem celltransplantation can promote recovery of neurological function, which brings new hope to hypoxic-ischemic encephalopathy patients. But the study is at a primary stage and limited in laboratory. There are many critical factors that hinder the clinical transplantation, such as delivery path, transplantation time, single or combined transplantation, mechanisms of action. Application of neural stem cells requires further investigation.

OBJECTIVE: To study surgical techniques and clinical applications of the intranasal endoscopic combined middle meatus and expand prelacrimal recess-maxillary ainus approach for orbital fracture treatment. METHOD: A retrospective clinical analysis of 3 patients whose admitted for orbital floor fractures or medial wall fractures operated by the intranasal endoscopic middle meatus with expand prelacrimal recess-maxillary ainus approach surgical treatment was studied, and the treatment effects and the postoperative complications were analyzed. RESULT: All patients had been followed up for 6 to 12 months. All cases of diplopia symptom were disappeared, enophthalmos were totally corrected, no cases of complication were found. CONCLUSION Endonasal endoscopic combined middle meatus and expand prelacrimal recess-maxillary ainus approach for orbital fracture treatment have great and clear view. This approach with less tissue damage and high therapeutic effect makes the cost lower than other methods and complications will be decreased as well, it has a great advantage in the orbital fracture treatment.
Diplopia ; etiology ; therapy ; Endoscopy ; Enophthalmos ; etiology ; therapy ; Humans ; Maxillary Sinus ; surgery ; Nose ; Ophthalmologic Surgical Procedures ; methods ; Orbital Fractures ; complications ; surgery ; Postoperative Complications ; Reconstructive Surgical Procedures ; methods ; Retrospective Studies