ABSTRACT
Objective To investigate the effect and mechanism of calcitonin(CT) in glutamate release from primary cultured neurons of midbrain periaqueductal gray matter(PAG).Methods Primary dissociated culture of PAG neurons was prepared from neonatal Sprague-Dawley (SD) rats.The cultured cells were divided into 4 groups:control group,salmon calcitonin (sCT) group,CT antagonist group (sCT8-32),and protein kinase C (PKC) inhibitor chelerythrine(Che) group.Each group was further divided into subgroups representing low,middle,and high levels of drugs.Glutamate release from the cultured PAG neurons evoked by sCT and/or other interfering factors was detected by using high-performance liquid chromatography (HPLC) assay.Results (1) Compared with the control group,sCT group yielded a time-dependent and concentration-dependent glutamate release from the cultured PAG neurons,and the most effective concentration of sCT was 20 nmol/L(P＜0.01).(2) sCT8-32,a selective antagonist of CT receptor,significantly reversed the effect of 20 nmol/L sCT on glutamate release from cultured PAG neurons,and the most effective concentration was 100nmol/L sCT8-32 (P＜0.01).(3) Incubation of the cultured neurons with Che inhibited the glutamate release from cultured PAG neurons evoked by 20 nmol/L sCT,and 100 μmol/L Che was most effective(P＜0.01).Conclusion CT receptors participates in the glutamate release from PAG neurons in which intracellular protein kinase C signaling pathway is involved.
ABSTRACT
The decoy receptor-3 ( DcR3 ) and glutamic acid decarboxylase-65 ( GAD65 ) recombinant adenovirus was construced and transduced into denlritic cells (DC). After the transduced DC were utilized to immunize NOD mice,the CD+8 T cells and blood glucose were analyzed. The results showed that recombinant adenovirus inhibited the proliferation and cytokine release of GAD65 specific T cells,and delayed the incidence of diabetes.Both interferon-γ[ (50.5±7.2)vs(95.4±6.9) and(91.2±6.5) pg/ml] and interleukin-2 [ (46.3±5.1 )vs ( 86.1 ±5.2 ) and ( 80.3 ± 7.3 ) pg/ml ] were decreased compared to those in negative and blank controls ( all P＜0.05 ).The results suggest that DcR3 and GAD65 recombinant adenovirus might provide a promising way for gene therapy of type 1 diabetes.
ABSTRACT
Objective To investigate the analgesic effect of salmon calcitonin(sCT)and its effect on expression of calcitonin receptor(CT-R)in periaqueductal gray(PAG). Methods Rat models of neuropathic pain were prepared by chronic constriction injury(CCI). Thermal withdrawal latency(TWL)and mechanical nociceptive threshold(MNT)were measured using hot plate test and yon Frey monofilaments test. The distribution of CT-R in PAG was detected by immunohistochemical method. CT-R protein was quantitatively determined by western blotting. Fourty male SD rats were randomized into 5 groups: normal group, sham-CCI group, CCI group, CCI plussubcutaneous sCT group, and CCI plus microinjection of sCT into PAG group. Results TWL, MNT, andexpression of CT-R in PAG showed no difference between normal group and sham-CCI group(P＞0. 05). TWL and MNT in CCI group were significantly lower than those in normal group(P＜0.05), and expression of CT-R in CCI group was significantly higher than that in normal group(P＜0.05). TWL, MNT and expression of CT-R in CCI rats increased significantly after sCT therapy(P＜0. 05), and the effect was more marked in PAG injection group than subcutaneous injection group(P＜0.05). Conclusions sCT raises the pain threshold and increase the expression of CT-R in PAG of CCI rats, while PAG injection showed more marked effect than subcutaneous injection.
ABSTRACT
OBJECTIVE:To investigate the effects of different kinds of hypoglycemic drugs on the QT interval dispersion in patients with type 2 diabetes mellitus. METHODS: The differences of QT interval dispersion (QTd) and corrected QT interval dispersion (QTcd) in 318 patients with type 2 diabetes (of which, 129 were assigned to receive insulin, 110 glibenclamide and 79 metformin) and 33 healthy volunteers (normal control) were compared. RESULTS: The QTd and QTcd were all significantly higher in glibenclamide group than in the other three groups(P0.05). CONCLUSION: The results suggest that glibenclamide and insulin may increase the QTd and QTcd in patients with type 2 diabetes.