BackgroundThe α2-adrenoreceptor agonist dexmedetomidine is known to provide renoprotection against ischemia and reperfusion (I/R) injury. However the underlying molecular mechanisms remain unclear. The purpose of this study was to investigate whether the Janus kinase and signal transducer and activator of transcription (JAK/STAT) signaling pathway plays a role in dexmedetomidine’s renoprotection.MethodsI/R model was induced by bilateral renal pedicle clamping for 45 min followed by 48 h of reperfusion in male Wistar rat. Sham laparotomy served as controls. Animals received dexmedetomidine (50 μg/kg, i.p.) in the absence or presence of atipamezole (250 μg/kg, i.p.), or vehicle (DMSO) in the absence or presence of selective JAK2 inhibitor tyrphostin AG490 (10 mg/kg, i.p.) before ischemia. Renal function, histology, apoptosis, expression of cleaved caspase 3 protein, intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1) and phosphorylations of JAK2, STAT1 and STAT3 were assessed.ResultsThe animals treated with either dexmedetomidine or AG490 exhibited an improved renal functional recovery, attenuated histological lesions and reduced number of apoptotic tubular epithelial cells. Either dexmedetomidine or AG490 inhibited the phosphorylations of JAK2 and its downstream molecule STAT1 and STAT3, accompanied by down-regulation the expression of cleaved caspase 3, ICAM-1 and MCP-1 proteins, and significantly ameliorated renal I/R injury.ConclusionsDexmedetomidine protects kidney against I/R injury, at least in part, through its inhibitory effects on injury-induced activation of JAK/STAT signaling pathway. If our data can be extrapolated to clinical setting, then dexmedetomidine may therefore serve as a clinical strategy to treat/prevent perioperative renal I/R injury.

Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine.

SummaryA controlled rhndomised double-blind design was used to study the effect of lignocaine on the pain produced by intravenous injection of propofol. Patients received a 2-ml pretreatment solution with temporary venous occlusion, followed by an induction solution. One hundred and three patients were assigned to one of jive groups: saline pretreatment, followed by induction with propofid plus saline 2 ml; lignocaine 20 mg pretreatment, followed by induction with propofol plus saline 2 ml; lignocaine 40 mg pretreatment, ,followed by induction with propofol plus saline 2 ml; saline pretreatment, followed by induction with propofol plus lignocaine 20 mg; or saline pretreatment, followed by induction with propofol plus lignocaine 40 mg. Pain was reduced significantly in all groups in which lignocaine was used and a dose of 40 mg was more eflective than 20 mg. There were no significant differences in the incidence of pain among the groups which received lignocaine as pretreatment and the groups which received lignocaine mixed with propofol. Sixty-eight percent of patients who experienced pain or discomfort recalled it in the postoperative period.

Summary

Diabetic retinopathy is the major cause of premature blindness amongst adults in the western world [1].Characterised by microvascular occlusion and leakage due to endothelial and pericyte cell damage and basement membrane thickening, macular oedema, neovascularisation and vitreous haemorrhage can eventually result in blindness [1]. Sustained hyperglycaemia results in retinal under perfusion, hypoxia and retinal ischaemia. These changes induce the production of AbstractDiabetic retinopathy is the leading cause of blindness in the industrialized world. Hyperglycaemia induces retinal hypoxia that upregulates a range of vasoactive factors which may lead to macular oedema and/or angiogenesis and hence potentially sight threatening retinopathy. In this study, we have focused on the association of CD105 and vascular endothelial growth factor (VEGF) with the development and progression of diabetic retinopathy by means of quantifying their expression in the plasma and vitreous of diabetic patients. CD105 levels were quantified in the plasma of 38 type I diabetic patients at various stages of retinopathy and 15 non-diabetic controls. In an additional cohort of 11 patients with advanced proliferative retinopathy and 23 control subjects, CD105 and VEGF were measured in the vitreous. The values were expressed as median (range) and statistical analysis was carried out using the non-parametric Mann-Whitney U test. Plasma CD105 levels were significantly increased in diabetic patients [1.8 (1.1-2.4) ng/ml] compared with non-diabetic controls [0.7 (0.3-1.8) ng/ml] (p<0.01). Plasma CD105 levels were elevated in diabetic patients with all stages of retinopathy, the highest level was observed in background retinopathy [2.3 (2.1-2.5) ng/ml] followed by proliferative retinopathy [2.1 (0.9-2.8) ng/ml] and advanced proliferative retinopathy [1.4 (0.6-1.8) ng/ml]. Vitreous contents of CD105 did not differ between controls and patients with advanced proliferative retinopathy, but vitreous levels of VEGF were elevated by ~3-fold in patients with advanced proliferative retinopathy [7.2 (1.90-15.60) ng/ml] compared with the control subjects [1.80 (1.10-2.210)] (p<0.01). These observations indicate that plasma levels of CD105 and vitreous levels of VEGF are associated with diabetic retinopathy, suggesting that CD105 and the angiogenic factor VEGF may play a critical role in the development and progression of diabetic retinopathy. Further studies are required to determine whether circulating CD105 levels could serve as a surrogate marker for early stage retinopathy and for monitoring disease progression.