Septic arthritis caused by Haemophilus influenzae associated with endocarditis.

Septic arthritis with Haemophilus influenzae is infrequent in adults and often associated with an extra-articular septic focus. We report the case of a septic arthritis caused by H. influenzae in an elderly (89-year-old) female patient in whom an transoesophageal echocardiogram showed an aortic valve endocarditis

Endothelium-dependent relaxation is resistant to inhibition of nitric oxide synthesis, but sensitive to blockade of calcium-activated potassium channels in essential hypertension

In human essential hypertension ( EH), endothelium-dependent relaxation can occur independent of nitric oxide ( NO) and prostacyclin (PGI(2)). Recent in vivo data suggest that rapid compensatory upregulation of endothelial cytochrome P450 epoxygenase 2C9 occurs to preserve vasorelaxation under conditions of decreased NO bioavailability. As one of the vascular actions of CYP2C9 is to modulate small and intermediate conductance endothelial calcium-activated potassium channels (SKCa and IKCa), we examined whether endothelium-dependent relaxation is sensitive to inhibitors of these channels ( apamin and charybdotoxin) in resistance-sized vessels from human with EH. Subcutaneous gluteal biopsies were performed on 12 humans with EH and 12 matched control subjects. Resistance arteries were dissected and relaxation responses to carbachol were assessed ex vivo using wire myography in the presence of: (i) N-G-nitro-L-arginine (L-NOARG)/indomethacin; and (ii) apamin/charybdotoxin. Maximal carbachol relaxation was impaired in EH vs control subjects. No differences in responses were observed with the endothelium-independent agonist, Snitroso-N-acetyl- penicillamine. Relaxation to carbachol was attenuated following incubation with L-NOARG/ indomethacin in vessels from control subjects (P < 0.01 analysis of variance ( ANOVA)), but not in vessels from patients with EH. The reverse pattern was seen following apamin/charybdotoxin with carbachol relaxation attenuated only in EH vessels (P < 0.001 ANOVA). Endothelium-dependent relaxation is resistant to endothelial nitric oxide synthase inhibition but sensitive to blockade of calcium-activated potassium channels in human EH. Studies with more specific inhibitors are required to determine whether this response is mediated by endothelial potassium channel subtypes (SKCa and IKCa)

Proenkephalin assists stress-activated apoptosis through transcriptional repression of NF-B- and p53-regulated gene targets

NOTE: THE SPECIAL CHARACTERS IN THIS ABSTRACT CANNOT BE DISPLAYED CORRECTLY. PLEASE REFER TO THE THE PUBLISHER'S WEBSITE FOR AN ACCURATE DISPLAY. The respective pro- and antiapoptotic functions of the transcription factors p53 and nuclear factor jB (NF-jB), and their potential impact on tumorigenesis and response to tumor therapy are well recognized. The capacity of the RelA(p65) subunit of NF-jB to specify a pro-apoptotic outcome in response to some stimuli is less well recognized, but needs to be understood if rational manipulation of the NF-jB pathway is to be deployed in cancer therapy. In this report, we provide evidence that the growth responsive nuclear protein, proenkephalin (Penk), is required, in part, for apoptosis induction, in response to activation ooverexpression of p53 and RelA(p65). We describe UV-C-inducible physical associations between endogenous Penk and p53 and RelA(p65) in mammalian cell lines. Depletion of Penk by RNA interference (RNAi) substantially preserves viable cell number following exposure to UV-C irradiation or hydrogen peroxide and confers transient protection in cells exposed to the genotoxin etoposide. In virally transformed and human tumor cell lines, overexpression of nuclear Penk with overabundant or activated p53, or RelA(p65) even in the absence of p53, enhances apoptosis to the point of synergy. We have further shown that Penk depletion by RNAi substantially derepresses transcription of a range of antiapoptotic gene targets previously implicated in repression-mediated apoptosis induction by NF-jB and p53. Physical association of endogenous Penk with the transcriptional co-repressor histone deacetylase suggests that it may be a component of a transcriptional repression complex that contributes to a pro-apoptotic outcome, following activation of the NF-jB and p53 pathways, and could therefore help to facilitate an antitumor response to a broad range of agents