Animals ; Male ; Muscle, Skeletal ; metabolism ; Myogenic Regulatory Factors ; metabolism ; Physical Conditioning, Animal ; Rats ; Rats, Sprague-Dawley ; Running

Objective To examine the effect of donepezil on cognitive function of Alzheimer's disease from a naturalistic observation in memory clinic.Methods From the subject pool in memory clinic,thirteen patients with mild to moderate Alzheimer's disease(meeting NINCDS-ADRDA criteria of probable AD)were enrolled in the naturalistic observation.Donepezil with dosage of 5 mg daily Was administered.Cognitive Ability Screening Instrument (CASI)Was used to assess the cognitive function,and was administered at baseline,3 and 6 months after treatment with donepezil.Resuits After 6-month treatment with donepezil,the change of score of verbal fluency from baseline Was significant[(4.3±3.1)vs(6.2±2.7),P＜0.05].There was a trend that constructional praxis was also improved after 6-month treatment(P=0.06).The change of scores of other cognitive domains remained the sanle(P＞0.05).Conclusion In the naturalistic observation at memory chnic,donepezil may improve verbal fluency of AD patients,and keep most cognitive function stable.

Objective To observe effects of aqueous extractive of Clarke boea herb on mice with gastric ulcer, and provide basis for clinical application.Methods Gastric ulcer model was induced by reserpine. The mice were divided into normal group, model group, ranitidine group, low and high dose of Clarke boea herb groups. Mice in treatment groups were given corresponding drugs by gavage, and the normal group and control group were given the same amount of saline for 4 weeks. The area of gastric ulcer, serum proinflammatory cytokines gastric juice volume, gastric juice acidity, iNOS and COX-2 gene expressions were detected.Results Compared with control group, the gastric ulcer area in low and high dose of Clarke boea herb groups decreased significantly. Clarke boea herb increased the SS and VIP, decreased the MOT and SP serum levels (P<0.05,P<0.01). Clarke boea herb reduced the levels of serum proinflammatory cytokines of IL-6, IL-12, TNF-α and IFN-γ(P<0.05,P<0.01). Clarke boea herb also decreased the genetic expressions of iNOS and COX-2 (P<0.05,P<0.01).ConclusionClarke boea herb has good gastric ulcer preventive effects, and the high dose of Clarke boea herb group showed the best efficiency.

The zinc chloride and cystine resistant strain of S.cerevisiae YZM-14(ZnCl2r,Cysr) was screened with the mutant processing of the protoplast of S.cerevisiae by combinative mutagens of ultraviolet and nitrite.The glutathione(GSH) production(84.72 mg/L),dry cell weight(7.63 g/L) and the intracellular GSH content(11.10 mg/g) of YZM-14 were 2.79,1.63 and 1.71 times compared with that of the initial strain.The biosynthetic process of GSH was divided into three phases according to the time course of the specific cell growth rate and GSH yielding coefficient.In the second phase,the metabolic flux of the pentose phosphate pathway and the GSH precursors biosynthetic pathway of the mutant strain increased by 8.1 mmol/(g?h),compared with that of the initial strain.Furthermore,the metabolic flux of the organic acids secretion of the mutant strain decreased.Through these mechanisms,the utilization efficiency of the carbon sources was enhanced and high production of GSH was obtained.

Streptozotocin-induced diabetic model was prepared in Wistar rats and the blood glucose levels were controlled at 3 levels of＜10,10-14 mmol/L or＞16.7 mmol/L by insulin,and changes of glucose transporter(GLUT)1 and 3 protein expressions of brain were observed in control rats and diabetic rats with different blood glucose levels by immunohistochemistry.The results showed that chronic hyperglycemia could decrease the protein expressions of GLUT 1 and GLUT3.

OBJECTIVETo study the effect of electroacupuncture on nitric oxide synthase (NOS) in rats with cerebral ischemia-reperfusion injury.

METHODSFocal cerebral ischemia-reperfusion model was established using modified intravascular suture technique. The NO content in the brain tissue was detected by nitrite reduction and the expressions of nNOS and iNOS were detected by immunohistochemistry. Eighty rats in this experiment were divided into the normal group, the cerebral ischemia-reperfusion injury model group (as the model group), the cerebral ischemia-reperfusion injury + electroacupuncture group (as the acupuncture group), and the cerebral ischemia-reperfusion injury + phosphatidylinositol 3 kinase (PI3-K) inhibitor group (as the inhibitor group). Each group consisted of twenty rats. Five microL PI3-K inhibitor LY294002 (400 microL) was slowly injected at the lateral cerebral ventricle of rats in the inhibitor group at a constant speed using microinjector according to Konig Klippel atlas of the stereotaxis instrument. Shuigou (DU26) and Chengjiang (RN24) were selected to determine levels of NO and NOS.

RESULTSAfter 24-h ischemia-reperfusion, the NO levels of the hippocampus and the cerebral cortex increased abnormally, and the expressions of nNOS and iNOS increased, showing significant difference when compared with those of the normal group (P<0.05). By electroacupuncture at Shuigou (DU26) and Chengjiang (RN24), the ischemic cerebral ischemia-reperfusion injury neuron loss was inhibited. Meanwhile, the high levels of NO, nNOS and iNOS in the cerebral cortex and the hippocampus were significantly inhibited (P<0.05). The abnormally increased expressions of nNOS and iNOS were reversed, showing significant difference when compared with the model group (P<0.05). But when compared with the normal group, there was no significant difference (P>0.05). The effects of electroacupuncture reversed the abnormally increased NO levels of the hippocampus and the cerebral cortex and expressions of nNOS and iNOS after LY294002 oppressed anti-PI3K to block the TrkA acceptor circuit. The NO levels of the hippocampus and the cerebral cortex and expressions of nNOS and iNOS increased again, showing significant difference when compared with the acupuncture group (P<0.05).

CONCLUSIONSAcupuncture fought against cerebral ischemia and reperfusion in the loss of neurons, at the same time, the abnormal regulation of NOS had reverse effect partly through TrkA/PI3K mediated signal transduction pathway.

Animals ; Brain Ischemia ; metabolism ; Electroacupuncture ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type I ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; metabolism ; Signal Transduction

Objective:To study the effects of cyclosporine A coadministrated with azathioprine,mycophenolate, mizorihine,rapamycin and/or prednisone on liver function in renal transplant recipients.Method:The drug history records of 600 renal transplant recipients in 1995 to 2005 were retrospectively investigated.Biochemical indexes before and after the treatment with cyclosporine A coadministrated with other immunosuppressants were analyzed.Result:The liver damage was found in 109 cases(18.2%)among 600 cases.The blood concentrations of cyclosporine A in the group with abnormal liver functions were significantly higher than those in the group with normal liver functions(P

Objective To observe prospectively and systematically the effect and safety of rhendostati injection (endostar) combined with FOLFOX as a second line chemotherapy for advanced/metastatic colorectal cancer. Methods 23 patients with histological confirmed advanced/metastatic colorectal cancer after first line chemotherapy failure were observed. The dosage of 15 mg/time of endostar solved in 500ml normal saline was slowly intravenously dropped 4 h from day 1 to day 14. Oxaliplatin 85 mg/m~2 iv 2-3 h dl, d15. CF 200 mg/m~2 iv 2 h followed by 5-Fu 400 mg iv bolus and 5-Fu 600 mg/m~2 iv 22 h dl-2, d15-16 were given, every 4 weeks as one cycle. Efficacy was evaluated after 2 cycles according to RECIST criteria. Results 23 cases had been completed totally 56 cycles. Among 23 cases, 8 cases were PR, 12 cases SD, and 3 cases PD. The objective response rate (RR) was 34.8 % (8/23), and the disease control rate (DCR) was 87.0 % (20/23). The median time to progression was 7 months. The 1-year survival rate were 50.0 %. The 2-year survival rate was 40.0 %. The occurrence rate of G3/4 toxicities was low, including neutropenia(21.7 %), anemia(4.3 %), thrombocytopenia (13.0 %). Those toxicities were mainly related with the chemotherapy agents. Meanwhile transient electrocardiogram changes mild ST-T of changes occurred in 3 cases. 2 cases were mild hypertension and were symptomatically controlled. Conclusion There are better efficacies of endostar combined with FOLFOX chemotherapy for advanced/metastatic colorectal cancer, and it is low toxic and tolerable. It is worth of further clinical observation. More experiences need to be accumulated.

Objective To investigate the instant clinical efficacy of intra-arterial infusion of fasudil combined with routine anti-vasospasm for symptomatic cerebral vasospasm (SCVS). Methods The clinical data of 21 patients with subarachnoid hemorrhage (SAH) due to ruptured aneurysm, who were admitted to authors' hospital during the period from May 2010 and February 2014, were retrospectively analyzed. The lesions included Fisher gradeⅡ(n=2), gradeⅢ (n=16) and gradeⅣ (n=3). Endovascular embolization of the aneurysm was carried out within 48 hours after the confirmation of the diagnosis with total cerebral DSA;no bleeding occurred during the operation and routine anti-vasospasm therapy was given. Within 4-9 days after the onset of the disease, all 21 patients presented SCVS. Half dose systemic heparinization, superselective intra-arterial infusion of fasudil (30 mg fasudil+250 ml saline, lasting for 30 min) were adopted. Reexamination of angiography performed at 15 min after fasudil infusion was employed, and the results were evaluated with NIHSS score by comparing the preoperative findings. Results Imaging examination performed after the treatment showed that significant improvement was obtained in 15 patients and no obvious changes in 6 patients. Clinical symptoms were remarkably improved in 11 patients, partially improved in 4 patients and remained unchanged in 6 patients. The mean NIHSS score was improved from preoperative 28.6 to postoperative 21.2. Conclusion For the treatment of symptomatic cerebral vasospasm, superselective intra-arterial infusion of fasudil is effective and safe, and it has good clinical application value.

BACKGROUNDThe delivery of glucose from the blood to the brain involves its passage across the endothelial cells of the blood-brain barrier (BBB), which is mediated by the facilitative glucose transporter protein 1 (GLUT(1)), and then across the neural cell membranes, which is mediated by GLUT(3). This study aimed to evaluate the dynamic influence of hyperglycemia on the expression of these GLUTs by measuring their expression in the brain at different blood glucose levels in a rat model of diabetes. This might help to determine the proper blood glucose threshold level in the treatment of diabetic apoplexy.

METHODSDiabetes mellitus was induced with streptozotocin (STZ) in 30 rats. The rats were randomly divided into 3 groups: diabetic group without blood glucose control (group DM1), diabetic rats treated with low dose insulin (group DM2), and diabetic rats treated with high dose insulin (group DM3). The mRNA and protein levels of GLUT(1) and GLUT(3) were assayed by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively.

RESULTSCompared with normal control rats, the GLUT(1) mRNA was reduced by 46.08%, 29.80%, 19.22% (P < 0.01) in DM1, DM2, and DM3 group, respectively; and the GLUT(3) mRNA was reduced by 75.00%, 46.75%, and 17.89% (P < 0.01) in DM1, DM2, and DM3 group, respectively. The abundance of GLUT(1) and GLUT(3) proteins had negative correlation with the blood glucose level (P < 0.01). The density of microvessels in the brain of diabetic rats did not change significantly compared with normal rats.

CONCLUSIONSChronic hyperglycemia downregulates GLUT(1) and GLUT(3) expression at both mRNA and protein levels in the rat brain, which is not due to the decrease of the density of microvessels. The downregulation of GLUT(1) and GLUT(3) expression might be the adaptive reaction of the body to prevent excessive glucose entering the cell that may lead to cell damage.

Animals ; Blood Glucose ; analysis ; Brain ; metabolism ; Diabetes Mellitus, Experimental ; metabolism ; Glucose Transporter Type 1 ; analysis ; genetics ; Glucose Transporter Type 3 ; analysis ; genetics ; Glycated Hemoglobin A ; analysis ; Male ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Streptozocin