To study the function and mechanism of the NgR-Rhoa- Rock signal pathways which exists in the retinal ganglion cells apoptosis in diabetes mellitus (DM) rats.
● METHODS: Some healthy SD rats were operated by means of single intraperitoneal injection of 1%streptozotocin based on the standard of 50mg/ kg wight, after that the blood sugar value was greater than 16. 7mmol/ L as DM model, then randomly divided into 3 groups, each group was 10 rats. ln addition to take 10 healthy SD rats as control group. Four groups of rats were bilaterally eyeball intravitreal injection in turn with NgR-siRNA virus 10μ L (siRNA group), NgR-siRNA virus diluted 10μ L ( DM group), NgR - siRNA virus - negative -control solution 10μ L (siRNA blank group), NgR- siRNA virus diluted 10μ L ( normal control group ), and fed normally. During that time, some life indexes like blood glucose, body mass, etc. were measured and recorded. After 12wk, the expression of NgR and Rhoa, HE staining, and TUNNEL staining were detected by Western blot analysis.
● RESULTS: Western blot analysis: compared with normal control group, the expression of NgR and Rhoa in DM group and siRNA blank group increased significantly (P<0. 01), while siRNA group was no significant change (P > 0. 05); compared with DM group and siRNA blank group, the expression of those proteins significantly lowered in siRNA group. HE staining: compared with normal control group, some extent ganglion cells arranged disorder, irregular shape, spacing not consistent were all found in three groups of model rats;compared with DM group and siRNA blank group, there was some improvement in siRNA group of ganglion cells about the order and shape size. TUNEL staining:compared with normal control group, there were retinal ganglion cells apoptosis in all of three groups of model rats. Compared with DM group and siRNA blank group, the number of retinal ganglion cells apoptotic cells was less, and the shape of cells had improved significantly in siRNA group.
●CONCLUSlON: ln the DM phase, the expression of NgR and Rhoa were up - regulation, the condition of diabetic retinal ganglion cell apoptosis was improved after that the NgR-Rhoa-Rock signal pathways had been inhibited.

Animals ; Guanylate Cyclase ; metabolism ; Hypercapnia ; metabolism ; Hypoxia ; metabolism ; Lung ; metabolism ; physiopathology ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Cytoplasmic and Nuclear ; metabolism ; Soluble Guanylyl Cyclase

Objective To study the efficacy of rituximab in the treatment of pemphigus vulgaris (PV) and its underlying mechanism. Methods A 38-year-old female with PV presented with refractory, painful oral ulcers and erosions. Since she was poorly responsive to prednisone 80 mg daily, intravenous ritu-ximab of 500 mg once a week was given for successive 3 weeks followed by 5 successive days of intra-venous gamma globulin at a dose of 400 mg/kg per day, and a total of two treatment sessions were conducted. ELISA was used to detect the serum titer of anti-Dsg3 antibodies and their IgG subtypes (IgG1 and IgG4) as well as serum level of interferon-gamma (IFN-gamma), interleukin-4 (IL-4), interleukin-10 (IL-10). Results Three months after the end of two treatment sessions, the symptom was obviously improved, and lesions subsided; alter another 1 month, clinical symptom fully disappeared. During the 1-year follow-up, no lesions recurred. The anti-Dsg3 antibody titer was 253.33 U/mL before treatment, plateaued at 250 U/mL within 4 weeks after the initial infusion, decreased till 3 months after the withdrawal, and reached 26.06 U/mL 7 months after the withdrawal, and remained within normal range till the time of this writing. The serum titer of IgGl subclass of anti-Dsg3 antibodies dropped dramatically fight after the first infusion, but that of IgG4 subclass remained at a high level at early stage of medication, began to decline until 3 months after the with-drawal, and finally reached the normal range following clinical remission. Also, serum level of IFN-garnma and IL-10 correlated with the severity of PV. Conclusions Combined rituximab is effective for the control of PV, likely by eliminating Dsg3-specific antibodies, especially IgG4 subclass of them.

Objective To analyze the cost of capsule endoscopy in diagnosing small bowel bleeding and to compare it with traditional diagnostic methods.Methods The patients suspected with small bowel bleeding were divided into group A(n=58,collected during 1998 to 2005)diagnosed with traditional processes and group B (n=93,collected during 2002 to January 2005)diagnosed with capsule endoscopy.The diagnostic yield,specific treatments,examination costs and other accumulated costs of two groups was compared.The examination cost ratio and the integration cost ratio were evaluated.The sensitivity analysis was performed.Results The diagnostic yield of small bowel bleeding in group A and group B were 22.4%(13/58) and 86%(80/93),respectively.The total of examination costs were 133 750 RMB and 790 500 RMB,respectively.The examination costs in group B(RMB 9881.3/each) was slightly lower than group A(RMB 10 288.5/each).Furthermore,as the diagnostic yield of group B was significantly higher than group A(P=0.001).The specific treatments based on the results of the diagnosis was 37.4% higher in group B(49.5%) than group A(12.1%).That means the cost of repeat- ed consultations,emergencies room visit,examinations,supporting treatments and hospitalizations in group B were significantly decreased.After the adjustment,the cost in group B(RMB 9881/patient) was lower than group A(16 361.5 RMB in one month—97 424.0 over 5 years/patient).The total cost of each patient in group A was 6480.2—87 542.7 RMB more than group B,which represented 1.7—9.9 folds increase.Conclusions The patients who suspected with small bowel bleeding and had a negative results of gastroscopy and colonoscopy were recommended to have capsule endoscopy which yields early diagnosis and less cost.

Objective To evaluate the effects of capsule endoscopy in the diagnosis and prognosis of small bowel tumors.Methods Three hundred and fifty-eight consecutive patients who underwent capsule endoscopy for suspected small bowel disease during May 2002 to Feb.2007 were examined.The final diagnosis was confirmed pathologically.Results Thirty-three(9.22%) out of 358 patients were identified as small bowel tumors[male 14/female 19,mean age(51?17)years].Of them,23(69.70%) patients had malignant tumors and ten(30.30%) had benign tumors.Obscure gastrointestinal bleeding were found in 26 cases,bleeding with abdominal pain in 2 cases,bleeding with diarrhea in 1 case,abdominal pain in 2 cases,abdominal pain with diarrhea in 1 case and vomiting in 1 case.All patients with benign tumors underwent surgery for their tumor.No further bleeding or abdominal pain after resection was found in all but one patient.Of the patients with malignant tumors,all expect two underwent surgery.Three patients accepted palliative surgery while eighteen patients received a curative resection.The locations of the tumor detected by capsule endoscopy were correlated well with the results of surgery.Conclusions Capsule endoscopy promises a higher diagnostic yield in small bowel tumors. h may improve the diagnosis of small bowel tumors and alter management thoroughly.

Abstract?AIM: To compare the changes in epithelial thickness profile following TransPRK and Epi-LASIK for myopia.? METHODS: In this prospective non -randomized controlled study, 76 right eyes of 76 myopic patients with the spherical equivalent refraction -1.25 to -6.00D were included under the informed consent. The eyes were divided into TransPRK group for 43 eyes and Epi-LASIK group for 33 eyes. Epithelial thickness was measured using spectral-domain optical coherence tomography at different corneal zones ( central, 2mm; paracentral, 2-5mm;and mid-peripheral, 5-6mm) preoperatively and at 1, 3, and 6mo postoperatively. The results were compared between the two groups.?RESULTS: The epithelium were thicker at 3 and 6mo after surgery compared to preoperative measurements in the two groups (all P<0.05).In TransPRK group, the epithelial thickness at 3 and 6mo demonstrated a negative meniscus-like lenticular pattern with lesser thickening centrally and progressively great thickening centrifugally (F3mo =-2.687,P=0.027;F6mo =-2.908,P=0.000).No statistically significant change was detected among the three zones in Epi-LASIK group (F=1.365, P=0.237). The epithelial thickness was thicker in the TransPRK group compared to the Epi-LASIK group mid-peripherally ( P<0.05) .? CONCLUSION: Significant epithelial thickening was observed after TransPRK and Epi-LASIK.It was showed a lenticular change with more thickening mid-peripherally after TransPRK than Epi -LASIK. Wound healing and inflammation may account for differences in the effect on epithelial thickness change by both surgeries.

This study was aimed to observe different forms of β-amyloid peptide (Aβ) and insulin degrading enzyme (IDE) in the hippocampus and cortex in order to further explore the role of Aβ and IDE on spleen yin deficiency di-abetes-associated cognitive decline (DACD), and the effect of Zi-Bu Pi-Y in method. The rats were randomly divided into five groups, which were the blank control (Cont) group, diabetes (DM) group, spleen yin deficiency (pi) group, spleen yin deficiency diabetes (piDM) group and Zi-Bu Pi-Y in recipe (ZBPYR) group. Soluble and insoluble Aβ in the hippocampus and cortex of rats were extracted by gradient centrifugation, and then measured by ELISA. The ex-pression of IDE was observed by western blot. The results showed that the content of soluble and insoluble Aβ1-42 in the hippocampus and cortex of the DM group and piDM group were higher than the Cont group. The soluble and in-soluble Aβ1-42 content in the hippocampus and cortex of the ZBPYR group were reduced compared with the DM group and the piDM group. The soluble Aβ1-40 in the cortex of the DM group, pi group and piDM group were in-creased compared with the Cont group (P < 0.05). The soluble Aβ1-40 content of the ZBPYR group was decreased compared with the DM group and the piDM group (P < 0.05). The expression of IDE protein was decreased in the hippocampus of the DM group and the piDM group compared with the Cont group (P< 0.05), and the IDE protein level in the hippocampus of the ZBPYR group was increased compared with the DM group and the piDM group (P<0.05). The expression of IDE protein in the cortex of the DM group, pi group and piDM group was lower than the Cont group (P< 0.05). The IDE protein level in the cortex of the ZBPYR group was reduced compared to the DM group (P< 0.05). It was concluded that the increased Aβ1-42 in brain may be a major pathological change of DACD and spleen yin deficiency DACD. The decreased IDE expression may be one of the reasons to induce increasing of Aβ1-42 level. The Zi-Bu Pi-Y in method may decrease the Aβ1-42 content by upregulating IDE protein expression.

To develop a parent-metabolite pharmacokinetic model for risperidone (RIP) and its major active metabolite (9-hydroxyrisperidone) and investigate their pharmacokinetics characteristics in healthy male volunteers, twenty-two healthy volunteers were orally given a single dose of 2 mg RIP. Plasma samples were collected in the period of 96 hours and concentrations of RIP and 9-hydroxyrisperidone were measured by a validated HPLC/MS method. CYP2D6 phenotypes were identified by the T1/2 of RIP and 9-hydroxyrisperidone according to the literature. Model structure identifiability analysis was performed by the similarity transformation approach to investigate whether the unknown parameters of the proposed model could be estimated from the designed experiment. Pharmacokinetics parameters were estimated using weighted least squares method, and the final pharmacokinetics model were tested and evaluated by Monte Carlo simulation. Eighteen volunteers were phenotyped as extensive metabolizers (EM) and four volunteers were identified as intermediate metabolizers (IM). The final model included central and peripheral compartment for both parent (RIP) and metabolite (9-hydroxyrisperidone) respectively. Model structure identifiability analysis indicated that the proposed model was local identifiable. However, if the ratio of RIP converted to 9-hydroxyrisperidone was assumed to be 32% in EM, and 22% in IM, the model could be globally identifiable. The predicted time-concentration curve and AUC(0-t), C(max), T(max) of RIP and 9-hydroxyrisperidone estimated by the established model were in agreement with the observations and noncompartment analysis. Rate constant of RIP conversion to 9-hydroxyrisperidone was (0.12 +/- 0.08) h(-1) and (0.014 +/- 0.007) h(-1) for EM and IM, respectively. Elimination rate constants of RIP were (0.25 +/- 0.18) and (0.05 +/- 0.23) h(-1) for EM and IM, respectively. Model validation result showed that all parameters derived from the concentration data fitted well with the theoretical value, with mean prediction error of most PK parameter within +/- 15%. The established model well defined the disposition of RIP and 9-hydroxyrisperidone simultaneously and showed large inter-individual pharmacokinetics variation in different CYP2D6 phenotype. The model also provide a useful approach to characterize pharmacokinetics of other parent-metabolite drugs.
Adult ; Cytochrome P-450 CYP2D6 ; physiology ; Humans ; Isoxazoles ; pharmacokinetics ; Male ; Models, Biological ; Monte Carlo Method ; Paliperidone Palmitate ; Pyrimidines ; pharmacokinetics ; Risperidone ; pharmacokinetics

In this paper, fourteen new L-proline derivatives were designed and synthesized, and their acetlcholinesterase (AChE) inhibitory activities were also investigated in vitro. New L-proline derivatives were prepared from substituted 2-bromo-1-acetophenones through four-step reaction; and their bioactivities as AChE inhibitors were measured by Ellman spectrophotometry. The results showed that the target compounds had a certain AChE inhibitory activity to in vitro. The bioactivity of compound 8b was the best of them, and its IC50 value was 5.45 µmol.L-1, which was better than that of rivastigmine. So the acetylcholinesterase inhibitory activities of new L-proline derivatives were worth to be further studied.
Acetylcholinesterase ; Cholinesterase Inhibitors ; chemical synthesis ; chemistry ; Drug Design ; Proline ; analogs & derivatives ; Rivastigmine ; chemistry ; Structure-Activity Relationship

The target compounds were prepared from 5-aminobenzimidazolone by two steps reaction, and their AChE inhibitory activities were measured by Ellman method in vitro. The AChE inhibitory activity of compound 4d is the best of them, and its IC50 value is equal to 7.2 μmol·L(-1), which is better than that of rivastigmine; moreover the 4d had no inhibitory activities to BuChE. Therefore, the inhibitory activities of 5-aminobenzimidazolone derivatives to acetylcholinesterase are worth further researching.
Acetylcholinesterase ; metabolism ; Benzimidazoles ; chemical synthesis ; chemistry ; Cholinesterase Inhibitors ; chemical synthesis ; chemistry ; Drug Design ; Phenylcarbamates ; chemistry ; Rivastigmine ; Structure-Activity Relationship