These results provide specific behavioral and autonomic evidence of anxiolytic-like effects for oxytocin in males and, together with previously reported observations in females, suggest the potential utility of OTR agonism as a therapeutically relevant mechanism of action for novel anxiolytics in both sexes.

Background and Purpose-Hemodynamic factors are thought to play an important role in the initiation, growth, and rupture of cerebral aneurysms. However, the hemodynamic features in the residual neck of the partially embolized aneurysms and their influences on recanalization are rarely reported. In this study, we characterized the hemodynamics of partially occluded aneurysms, which were proven to undergo recanalization during follow-up using computational fluid dynamic analysis. Methods-From May 2007 to June 2009, we identified 11 partial aneurysms during follow-up, including 5 recanalized cases and 6 stable cases with 3-dimensional digital subtraction angiography. We retrospectively characterized the hemodynamic features around the residual aneurismal pouch using the available postprocedural digital subtraction angiography image data. The occluded part of the aneurysm was regarded as completely separated from the circulation. Results-The overall blood flow patterns before embolization were almost the same in the recanalized and stable groups.After occlusion, the flow pattern changes, wall shear stress (WSS), and velocity at the remnant neck demonstrated different changes between the 2 groups. Specifically, in the recanalized group, high WSS regions were found near the neck in all 5 cases, with 4 of them being even higher than those before occlusion. Interestingly, in all cases, the high WSS area of the remnant neck coincided with the location where the aneurysm recanalization occurred. In the stable group, 5 out of 6 cases demonstrated lower WSS and velocity at the remnant neck after occlusion. Conclusions-High

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The present study employed in-vivo microdialysis techniques in the freely moving rat to systematically compare the neurochemical effects of various antidepressant agents on extracellular concentrations of norepinephrine (NE) and serotonin (5-HT) in the frontal cortex. We found that acute administration of the tricyclic antidepressant, desipramine (3-30 mg/kg, s.c.) and the dual serotonin/norepinephrine reuptake inhibitor, venlafaxine (3-30 mg/kg, s.c.), produced dose-dependent and robust increases in cortical NE concentrations (498% and 403%, respectively). Conversely, acute injection of the selective serotonin reuptake inhibitors, fluoxetine (30 mg/kg, s.c.) and paroxetine (1-10 mg/kg, s.c.), did not alter forebrain NE concentrations. However, paroxetine did produce a significant increase in cortical NE concentrations (164%) when administered at 30 mg/kg. These changes in NE were not paralleled by 5-HT, which showed no increase following administration of desipramine, venlafaxine, paroxetine or fluoxetine. Combination treatment with the 5-HT1A receptor antagonist, WAY-100635 (0.3 mg/kg, s.c.), significantly enhanced extracellular 5-HT concentrations following venlafaxine (10 and 30 mg/kg), fluoxetine (30 mg/kg) and paroxetine (3-30 mg/kg). Alternatively, WAY-100635 produced no augmentation of the antidepressant-induced changes in extracellular NE. Collectively, these studies show that paroxetine, at low to intermediate doses, and fluoxetine are selective for 5-HT versus NE systems, whereas venlafaxine produces similar effects on both 5-HT and NE levels at the effective doses tested.

To enhance the cytocompatibility of polyvinylidene fluoride (PVDF) films, arginine-glycine-aspartic acid (RGD) peptide-click-poly(glycidyl methacrylate) (PGMA) polymer brushes were grafted onto the PVDF surface by the combination of surface-initiated atom transfer radical polymerization (ATRP) and click reaction. The direct initiation of the secondary fluorine atoms of PVDF backbone allowed for grafting of the PGMA brushes containing reactive epoxy groups. Subsequent introduction of the azide groups onto the side chain of PGMA brushes was achieved by the ring-open reaction of the epoxy groups with sodium azide. The cell adhesive RGD peptide was finally conjugated onto the PGMA brushes via alkyneazide click reaction. Kinetic studies revealed that the PGMA chain growth from the PVDF surface was consistent with a "controlled" process, and that the amount of immobilized RGD peptide on the PGMA brushes increased with the concentration of the pendant azide groups. The specificity of cellular interactions of adipose tissue-derived stem cells (ASCs) on the functionalized PVDF films was investigated. Results demonstrated that cell adhesion and proliferation of ASCs were significantly improved on the RGD-immobilized PVDF substrates, and this improvement was positively correlated with the surface concentration of covalently-bonded RGD peptide. With the inherent superior chemical and mechanical properties of PVDF films and the biocompatible nature of cell-adhesive peptides, surface functionalized PVDF films are potentially useful for biomedical and tissue engineering applications.

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In recent years a series of novel costimulatory molecules have been identified, including inducible costimulator (ICOS). In a fully major histocompatibility complex (MHC)-mismatched mouse model of islet transplantation, we demonstrate that while monotherapy with CTLA4-Ig, CD40 ligand monoclonal antibody (CD40L mAb) or rapamycin each improves islet allograft survival, graft rejection eventually develops. Immunohistologic analysis of rejected grafts revealed increased ICOS expression, suggesting a role for this costimulatory molecule as an alternate pathway for T-cell activation. The combination of a blocking anti-ICOS mAb with each of the above therapies resulted in significantly improved islet allograft survival, confirming the importance of ICOS signaling in islet allograft rejection. Mechanistic studies conducted in mice treated with anti-ICOS mAb and rapamycin demonstrated a lack of donor-specific immunological tolerance and an absence of regulatory T-cell activity. However, a dramatic effect was seen on acute anti-donor responses whereby anti-ICOS mAb and rapamycin significantly reduced the initial expansion and function of alloreactive T cells. These data demonstrate that blockade of the ICOS/B7RP-1 pathway has potential therapeutic benefit given its role in enhancing islet allograft survival and regulating acute alloresponses in vivo.

AIM:To investigate the etiology and clinical characteristics of severe acute pancreatitis (SAP) in elderly patients (≥ 60 years of age). METHODS:We reviewed retrospectively all the SAP cases treated in Xuanwu Hospital in Beijing between 2000 and 2007. RESULTS:In 169 patients with SAP, 94 were elderly and 16 died. Biliary and idiopathic etiologies were the first two causes that accounted for over 90% of SAP in the elderly. Biliary, hyperlipemic and alcoholic etiologies were the first three causes in the young. The proportion of comorbidity of cholelithiasis, biliary infection, hypertension and coronary heart disease in the aged was significantly higher than that in their young partners. The scores of APACHE Ⅱ and Ranson were also significantly higher in the elderly except the CT score. Organ failures were more common in the elderly, but the local pancreatic complications were not different between the two groups. Mortality of the aged was correlated with the severity of SAP, multiple co-morbidity and incidence of multiple organ dysfunction syndrome (MODS). MODS was the main cause of death. CONCLUSION:The etiology of SAP in the elderly is quite different from that in the young. Biliary and unknown factors are main causes in the aged. The elderly are subject to major organ failures but there is no difference in the occurrence of local pancreatic complications between the elderly and the young. It is crucial to monitor and improve the functions of major organs so as to prevent MODS in the aged with SAP.