Intraischemic Modest Hypothermia Does Not Prevent Onset of Locomotor Inactivity After Transient Forebrain Ischemia in Rats.

Although modest hypothermia of 35°C has been demonstrated to provide histological neuroprotection in a rodent model of cerebral ischemia, the long-term behavioral outcome is still not clear. This study was designed to investigate whether modest hypothermia of 35°C provides sustained histological and behavioral neuroprotection following transient forebrain ischemia in rats. Male Sprague-Dawley rats were randomly assigned to one of three groups: sham, control, and modest hypothermia group. Each group contained eight rats. Ten-minute transient forebrain ischemia was produced by bilateral carotid artery occlusion plus hemorrhagic hypotension (mean arterial pressure = 40 mmHg). The hypothermic group was cooled to 35°C in preischemic period, and the cooling was continued for 1 hour postischemia. To evaluate behavioral outcome, spontaneous alternation behavior and locomotor activity were assessed using Y-maze test on a weekly basis. The rats were sacrificed after 28 days, and the number of intact neurons per 1 mm in the hippocampal CA1 subfield was counted microscopically. There was significant difference between the control [19(24.5)/mm: median (interquartile range)] and hypothermia groups [116(24)/mm; p < 0.01] in the intact CA1 neuron count. In the control and modest hypothermia groups, the locomotor activities were gradually decreased, and reached significantly lower levels in comparison with the sham group at 14 days postischemia. This study indicates that intraischemic modest hypothermia provided long-term histological neuroprotection, but did not reverse the onset of locomotor inactivity in a rat transient forebrain ischemia model.

[Postoperative analgesia with morphine with or without diclofenac after shoulder surgery].

Balanced analgesia using a narcotic and a nonsteroidal anti-inflammatory drug has been successfully tested for postoperative analgesia. This study was designed to examine the efficacy of such combination therapy after shoulder surgeries. Twenty ASA physical status I or II patients, scheduled for shoulder surgeries under general anesthesia, were randomly assigned to either morphine (M) group (n = 10), who received IV morphine patient-controlled analgesia (PCA) alone (2 mg as a bolus, lock-out interval of 10-minutes, and 10 mg as 1-hour limit for 48 hours), or morphine + diclofenac (M + D) group (n = 10), who received, in addition to morphine PCA, diclofenac suppositories 50 mg.8 h-1 starting immediately before surgical incision for 48 hours. Postoperative analgesic profiles, such as visual analog scale (VAS) at rest and on movement, and cumulative morphine consumption, the incidence and extent of side effects (nausea, vomiting, and time till the first bowel movement), and other complications were recorded. The two groups were similar demographically. Patients in the M + D group required 15.1 +/- 9.0 mg of morphine within 48 hours after surgery, while those in the M group required 30.5 +/- 21.0 mg of morphine (P < 0.05). No significant differences in VAS at rest and on movement were observed between the two groups. The time till the first bowel movement was significantly shorter in the M + D group. Our data suggest that diclofenac suppositories 50 mg.8 h-1 starting immediately before surgery for 48 h are effective adjuvant in reducing post-shoulder surgery morphine requirement and retardation of bowel movement.

Anti-vascular endothelial growth factor receptor-2 (Flk-1/KDR) antibody suppresses contact hypersensitivity.

The angiogenic mediator vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) have been studied extensively in neoplastic disease and some inflammatory conditions. Contact hypersensitivity (CHS) is a prototypic Langerhans' cell-dependent, T-helper (Th) 1 cell-mediated inflammatory skin disease that is now also thought to involve angiogenic mediators. The purpose of our study was to examine the role of angiogenesis and VEGF in CHS. We demonstrated that VEGF production is up-regulated in murine skin after challenge with dinitrofluorobenzene. Administration of a monoclonal antibody directed against the VEGFR-2 (DC101) resulted in a 28.8% decrease in CHS response (P < 0.001). Examination of the DC101-treated mouse skin 24 h after challenge revealed decreases in dermal inflammatory cellular infiltrates and total vessel area. Furthermore, mRNA and protein of the Th1-type cytokine interferon (IFN)-gamma was significantly down-regulated in skin of DC101-treated animals 24 h after challenge. The results of the study demonstrate that VEGFR-2 blockade significantly reduces vascular enlargement and edema formation and effects IFN-gamma expression in the skin during challenge in CHS. Our findings suggest that DC101 could function by reducing inflammatory cell migration and hence IFN-gamma expression during the CHS response.