Abstract-Akt is a central regulator of cardiomyocyte survival after ischemic injury in vitro and in vivo, but the mechanisms regulating Akt activity in the postischemic cardiomyocyte are not known. Furthermore, although much is known about the detrimental role that the c-Jun N-terminal kinases (JNKs) play in promoting death of cells exposed to various stresses, little is known of the molecular mechanisms by which JNK activation can be protective. We report that JNKs are necessary for the reactivation of Akt after ischemic injury. We identified Thr450 of Akt as a residue that is phosphorylated by JNKs, and the phosphorylation status of Thr450 regulates reactivation of Akt after hypoxia, apparently by priming Akt for subsequent phosphorylation by 3-phosphoinositide-dependent protein kinase. The reduction in Akt activity that is induced by JNK inhibition may have significant biological consequences, as we find that JNKs, acting via Akt, are critical determinants of survival in posthypoxic cardiomyocytes in culture. Furthermore, in contrast to selective p38 -mitogen-activated protein kinase inhibition, which was cardioprotective in vivo, concurrent inhibition of both JNKs and p38 -mitogen-activated protein kinases increased ischemia/reperfusion injury in the heart of the intact rat. These studies demonstrate that reactivation of Akt after resolution of hypoxia and ischemia is regulated by JNKs and suggest that this is likely a central mechanism of the myocyte protective effect of JNKs. (Circ Res. 2006;98:111-118.)Key Words: Akt Ⅲ apoptosis Ⅲ c-Jun NH2-terminal kinase Ⅲ hypoxia Ⅲ ischemia Ⅲ signal transduction T he families of stress-activated protein kinases (SAPKs) consist of the c-Jun N-terminal kinase (JNK) family and the p38 -mitogen-activated protein kinase (MAPK) family. 1 They are potently activated by a number of cellular stresses and produce a number of biological responses that vary by the stimulus and the cell type. These kinases are activated by ischemia (especially p38-MAPKs 2 ) and by reperfusion of ischemic tissues (JNKs and to a lesser extent p38-MAPKs 3 ).Recently, a potent and relatively selective inhibitor of the ␣ and  p38-MAPK isoforms has demonstrated reductions in ischemic injury in animal models of myocardial infarction and stroke. 4,5 In addition, overexpression of dominant negative mutants of components of the p38-MAPK pathway in transgenic mice protected hearts from ischemia/reperfusion (I/R) injury. 6 However, the roles played by the JNKs in ischemic injury are much less clear than those of p38-MAPKs. This is due in large part to the fact that potent and selective inhibitors of the JNKs have only very recently been developed, are not widely available, and, to our knowledge, have not been used to study I/R injury either in vivo or in cultured cardiomyocytes.In support of a deleterious role for JNKs in ischemic injury, studies in mice in which the JNK3 gene has been deleted and studies with a peptide inhibitor of JNKs demonstrated markedly reduced ischemic injury and excitotoxicity in th...
Background and Aims:Various drugs are used for providing favorable intubation conditions during awake fiberoptic intubation (AFOI). However, most of them cause respiratory depression and airway obstruction leading to hypoxemia. The aim of this study was to compare intubation conditions, and incidence of desaturation between dexmedetomidine and fentanyl group during AFOI.Material and Methods:This randomized double-blind prospective study was conducted on a total of 60 patients scheduled for elective laparotomies who were randomly allocated into two groups: Group A received dexmedetomidine 1 mcg/kg and Group B received fentanyl 2 mcg/kg over 10 min. Patients in both groups received glycopyrrolate 0.2 mg intravenous, nebulization with 2% lidocaine 4 ml over 20 min and 10% lidocaine spray before undergoing AFOI. Adequacy of intubation condition was evaluated by cough score and post-intubation score. Incidence of desaturation, hemodynamic changes and sedation using Ramsay sedation scale (RSS) were noted and compared between two groups.Results:Cough Score (1-4), post-intubation Score (1-3) and RSS (1-6) were significantly favorable (P < 0.0001) along with minimum hemodynamic responses to intubation (P < 0.05) and less oxygen desaturation (P < 0.0001) in Group A than Group B.Conclusion:Dexmedetomidine is more effective than fentanyl in producing better intubation conditions, sedation along with hemodynamic stability and less desaturation during AFOI.
being the predominant organism causing SSIs, MRSA needs the attention for its resistance to commonly used antibiotics in the hospital like penicillin, cephalosporin group of drugs. Regular monitoring of the MRSA, involved in the SSI of a particular setup is the basic requirement to trim down the incidence of the postoperative wound infections by proper antibiotic prophylaxis.
Background:Onychomycosis manifests itself in various forms, notably onychodystrophy, onycholysis, subungual hyperkeratosis, or nail-plate discoloration. Not necessarily nail changes mentioned here should always be of fungal origin.Objective:The present study is planned to get an idea about etiological agent and clinical correlation in fingernail onychomycosis.Materials and Methods:Nail-clipping and subungual debris of patients with above mentioned nail changes were subjected to KOH preparation. Culture was done on SDA and SDCCA media. Species identification was done by colony character, pigment production, LCB staining, and some special tests like germ tube test, etc.Results:Out of 85 cases, 44 cases showed the growth of fungus, amounting to 51.76% positivity. Among those 44 cases, the infective fungal agents were predominantly dermatophytes (50%), and the rest were due to yeasts (27.27%) and moulds (22.72%). Among the different species, Trichophyton rubrum (29.54%) accounted for the majority of dermatophytes; Candida albicans (11.78%) was the predominant yeast; and Aspergillus niger (18.18%) the commonest mold. No significant association could be established between the different fungal species and various clinical manifestations. Positive results were found more with fungal culture (95.45%) than KOH preparation (63.64%).Conclusion:The results show that nail changes are not always a reliable marker for predicting the causative organism, and relying only on the clinical manifestation (i.e., pattern of nail changes) in the diagnosis of onychomycosis is often misleading. The present study highlights the need for microbiological confirmation in case of onychomycosis.
IA-HLH is important because it can obscure the typical clinical features of the underlying primary disease, thus delaying the diagnosis and having a negative effect on the outcome. Although bone marrow haemophagocytosis is not a mandatory diagnostic criterion, we found it to be a useful tool together with biochemical parameters for early recognition of HLH, especially in developing countries lacking molecular and flow laboratories. The severity of pancytopenia and derangement in biochemical markers were significantly higher in the patients who died.
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