Norepinephrine constricts the canine coronary bed via postsynaptic alpha 2-adrenoceptors

The effect of alpha 2-blockade (0.3 mg/kg i.v. rauwolscine) and alpha 1-blockade (1.2 mg/kg i.v. prazosin) on coronary constrictions induced by intracoronary injections of azepexole (B-HT 933, alpha 2-agonist, 0.1-10 microgram/kg), phenylephrine (0.3-3 microgram/kg) and norepinephrine (0.001-0.1 microgram/kg) were studied in dog hearts perfused in situ under beta-blockade. Constrictions by azepexole (antagonized by rauwolscine, yet resistant to prazosin and methysergide) demonstrated coronary alpha 2-adrenoceptors. Norepinephrine-induced constrictions were more attenuated (22-fold) by alpha 2-blockade than by alpha 1-blockade (2.6-fold) and thus were mediated mainly by activation of postsynaptic alpha 2-receptors.     

Differential diagnosis of early opacification of the portal vein and its tributaries during arteriography

Twenty-two cases with communication of an artery and the portal vein or one of its tributaries are discussed. Four conditions in which relatively significant arterio-portal shunts may exist can be differentiated: (1) angiodysplasias or arteriovenous malformations, (3) traumatic and postoperative lesions, and (4) benign and malignant tumors. The significance of the portal vein's early opacification during arteriographic examinations of the abdominal organs is discussed, and the findings are compared to those reported in the literature.     

Multidrug-resistant tuberculosis detection, Latvia

To improve multidrug-resistant tuberculosis (MDR-TB) detection, we successfully introduced the rpoB gene mutation line probe assay into the national laboratory in Latvia, a country with epidemic MDR-TB. The assay detected rifampin resistance with 91% sensitivity and 96% specificity within 1 to 5 days (vs. 12-47 days for BACTEC).     

Neuregulin receptors erbB2 and erbB4 in failing human myocardium

Membrane–bound and secreted neuregulin isoforms induce growth, survival and differentiation by activating erbB tyrosine kinase receptors. In cultured cardiomyocytes, erbB2 and erbB4 receptors regulate apoptosis by controlling bcl–x splicing, and conditional elimination of erbB2 induces dilative cardiomyopathy in vivo. Therefore, we analyzed expression and activation of erbB receptors in left ventricular myocardium from 32 heart failure patients, from 10 organ donors, and from 15 heart failure patients prior to and following unloading by ventricular assist devices. ErbB receptors, expressed in cardiomyocytes and noncardiomyocytes, are downregulated in failing myocardium as mRNA (which is renormalized by hemodynamic unloading) and as protein (erbB2: –25%; erbB4: –70%), their phosphorylation is reduced and bcl–x splicing is shifted towards 6.7–fold augmentation of proapoptotic Bcl–xS, compatible with attenuated erbB signaling. However, secreted and membrane–anchored neuregulin–1 isoforms, preferentially expressed in microvascular endothelium, are induced and not lowered with heart failure, while expression of erbB–inhibitory neuregulin isoforms or of autoinhibitory soluble erbB isoforms could not be demonstrated as potential causes of erbB receptor inhibition. We conclude that erbB receptor inactivation by unknown mechanisms results in altered splicing of bcl–x towards enhanced formation of proapoptotic Bcl–xS, thereby contributing to enhanced apoptotic susceptibility of failing human myocardium.     

Health and economic impact of HIV/AIDS on South African households: a cohort study

Background  

South African households are severely affected by human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) but health and economic impacts have not been quantified in controlled cohort studies.     

Remifentanil in the horse: identification and detection of its major urinary metabolite

Remifentanil (4-methoxycarbonyl-4-[(1-oxopropyl)phenylamino]-1-piperidinepropionic acid methyl ester) is a mu-opioid receptor agonist with considerable abuse potential in racing horses. The identification of its major equine urinary metabolite, 4-methoxycarbonyl-4-[(1-oxopropyl)phenylamino]-1-piperidinepropionic+ ++ acid, an ester hydrolysis product of remifentanil is reported. Administration of remifentanil HCl (5 mg, intravenous) produced clear-cut locomotor responses, establishing the clinical efficacy of this dose. ELISA analysis of postadministration urine samples readily detected fentanyl equivalents in these samples. Mass spectrometric analysis, using solid-phase extraction and trimethylsilyl (TMS) derivatization, showed the urine samples contained parent remifentanil in low concentrations, peaking at 1 h. More significantly, a major peak was identified as representing 4-methoxycarbonyl-4-[(1-oxopropyl)phenylamino]-1-piperidinepropionic+ ++ acid, arising from ester hydrolysis of remifentanil. This metabolite reached its maximal urinary concentrations at 1 h and was present at up to 10-fold greater concentrations than parent remifentanil. Base hydrolysis of remifentanil yielded a carboxylic acid with the same mass spectral characteristics as those of the equine metabolite. In summary, these data indicate that remifentanil administration results in the appearance of readily detectable amounts of 4-methoxycarbonyl-4-[(1-oxopropyl)phenylamino]-1-piperidinepropionic+ ++ acid in urine. On this basis, screening and confirmation tests for this equine urinary metabolite should be optimized for forensic control of remifentanil.