Agonist Binding to α2-Adrenoceptors Is Elevated in the Locus Coeruleus from Victims of Suicide

Abstract: The binding of an agonist, p-[¹²⁵I]iodoclonidine, and an antagonist, [³H]yohimbine, to α₂-adrenoceptors was measured autoradiographically in the locus coeruleus from 10 pairs of antidepressant-free victims of suicide and age-matched controls. Agonist binding to α₂-adrenoceptors was significantly greater in the locus coeruleus from victims of suicide compared with control subjects. In contrast, antagonist binding to α₂-adrenoceptors in the locus coeruleus did not differ significantly between control and suicide subjects. HPLC analysis of norepinephrine in tissue sections of the locus coeruleus did not reveal any differences between control subjects and suicide victims, suggesting that differences in agonist binding are not a result of differences in retention of the endogenous agonist norepinephrine in tissue sections. The increase in agonist binding to α₂-adrenoceptors in the locus coeruleus of victims of suicide links an altered expression of the high-affinity state of autoinhibitory α₂-adrenoceptors with suicide.     

Simplified methods for monitoring petroleum‐contaminated ground water and soil vapor

Portable meters and simplified gas Chromatographic (GC) techniques were investigated for monitoring volatile hydrocarbon (HC), CO₂, and O₂, concentrations in groundwater, exhaust gases, and soil vapor during in situ remediation using soil vapor extraction (SVE) and air sparging (AS). Results of groundwater samples analyzed in‐house using a headspace technique compared well to split samples analyzed by a certified analytical laboratory (r² = 0.94). SVE exhaust gas HC and CO₂ concentrations measured using a GT201 portable HC/O₂ meter and a RA‐411A meter (GasTech), respectively, were highly correlated with in‐house laboratory GC analyses (r² = 0.91). O₂ concentrations fell in a small range and meter analyses were not well correlated with laboratory analyses. Results of soil gas monitoring were not as well correlated as those for exhaust gases for HC, CO₂, or O₂, perhaps due to environmental conditions such as changes in relative humidity or the wider range of soil gas values. Overall, the meters were good indicators of vapor contamination, they greatly simplified estimates of total HC mass removal, and they allowed estimates of the biological contribution to contaminant removal during the remediation process.     

Existence of Three Subtypes of Bradykinin B2 Receptors in Guinea Pig

We describe the binding of [3H]bradykinin to homogenates of guinea pig brain, lung, and ileum. Analysis of [3H]bradykinin binding kinetics in guinea pig brain, lung, and ileum suggests the existence of two binding sites in each tissue. The finding of two binding sites for [3H]bradykinin in ileum, lung, and brain was further supported by Scatchard analysis of equilibrium binding in each tissue. [3H]Bradykinin binds to a high-affinity site in brain, lung, and ileum (KD = 70-200 pM), which constitutes approximately 20% of the bradykinin binding, and to a second, lower-affinity site (0.63-0.95 nM), which constitutes the remaining 80% of binding. Displacement studies with various bradykinin analogues led us to subdivide the high- and lower-affinity sites in each tissue and to suggest the existence of three subtypes of B2 receptors in the guinea pig, which we classify as B2a, B2b, and B2c. Binding of [3H]bradykinin is largely to a B2b receptor subtype, which constitutes the majority of binding in brain, lung, and ileum and represents the lower-affinity site in our binding studies. Receptor subtype B2c constitutes approximately 20% of binding sites in the brain and lung and is equivalent to the high-affinity site in brain and lung. We suggest that a third subtype of B2 receptor (high-affinity site in ileum), B2a, is found only in the ileum. All three subtypes of B2 receptors display a high affinity for bradykinin, whereas they show different affinities for various bradykinin analogues displaying agonist or antagonist activities.(ABSTRACT TRUNCATED AT 250 WORDS)     

New erythrina alkaloids of Cocculus laurifolia

Four abnormal Erythrina alkaloids have been isolated from the leaves of Cocculus laurifolia. Of these, two new bases, isococculidine and coccoline, have been assigned the structures (3S,5S)-3,15-dimethoxyerythrin-1-ene and (3R,5S)-15-hydroxy-3-methoxyerythrin-1-en-8-one respectively.     

Investigations on the biosynthesis of steroids and terpenoids: XI. The 24-methylene sterol 24(28)-reductase of Saccharomyces cerevisiae

The microsomal fraction of Saccharomyces cerevisiae has been shown to catalyse the NADPH-dependent reduction of ergosta-5,7,22,24(28)-tetraen-3β-ol to ergosterol. This cell-free system together with whole-cell cultures of polyene-resistant mutants has been used to compare the rates of reduction of other 24-methylene sterols. The results indicate that the enzyme involved exhibits a marked specificity for ergosta-5,7,22,24(28)-tetraen-3β-ol and support the concept of a major terminal step in ergosterol biosynthesis.     

Respiratory Viruses Associated Hospitalization among Children Aged <5 Years in Bangladesh: 2010-2014

Background

We combined hospital-based surveillance and health utilization survey data to estimate the incidence of respiratory viral infections associated hospitalization among children aged < 5 years in Bangladesh.

Methods

Surveillance physicians collected respiratory specimens from children aged <5 years hospitalized with respiratory illness and residing in the primary hospital catchment areas. We tested respiratory specimens for respiratory syncytial virus, parainfluenza viruses, human metapneumovirus, influenza, adenovirus and rhinoviruses using rRT-PCR. During 2013, we conducted a health utilization survey in the primary catchment areas of the hospitals to determine the proportion of all hospitalizations for respiratory illness among children aged <5 years at the surveillance hospitals during the preceding 12 months. We estimated the respiratory virus-specific incidence of hospitalization by dividing the estimated number of hospitalized children with a laboratory confirmed infection with a respiratory virus by the population aged <5 years of the catchment areas and adjusted for the proportion of children who were hospitalized at the surveillance hospitals.

Results

We estimated that the annual incidence per 1000 children (95% CI) of all cause associated respiratory hospitalization was 11.5 (10–12). The incidences per 1000 children (95% CI) per year for respiratory syncytial virus, parainfluenza, adenovirus, human metapneumovirus and influenza infections were 3(2–3), 0.5(0.4–0.8), 0.4 (0.3–0.6), 0.4 (0.3–0.6), and 0.4 (0.3–0.6) respectively. The incidences per 1000 children (95%CI) of rhinovirus-associated infections among hospitalized children were 5 (3–7), 2 (1–3), 1 (0.6–2), and 3 (2–4) in 2010, 2011, 2012 and 2013, respectively.

Conclusion

Our data suggest that respiratory viruses are associated with a substantial burden of hospitalization in children aged <5 years in Bangladesh.     

A potent and selective nonpeptide antagonist of CXCR2 inhibits acute and chronic models of arthritis in the rabbit

Much evidence implicates IL-8 as a major mediator of inflammation and joint destruction in rheumatoid arthritis. The effects of IL-8 and its related ligands are mediated via two receptors, CXCR1 and CXCR2. In the present study, we demonstrate that a potent and selective nonpeptide antagonist of human CXCR2 potently inhibits (125)I-labeled human IL-8 binding to, and human IL-8-induced calcium mobilization mediated by, rabbit CXCR2 (IC(50) = 40.5 and 7.7 nM, respectively), but not rabbit CXCR1 (IC(50) = >1000 and 2200 nM, respectively). These data suggest that the rabbit is an appropriate species in which to examine the anti-inflammatory effects of a human CXCR2-selective antagonist. In two acute models of arthritis in the rabbit induced by knee joint injection of human IL-8 or LPS, and a chronic Ag (OVA)-induced arthritis model, administration of the antagonist at 25 mg/kg by mouth twice a day significantly reduced synovial fluid neutrophils, monocytes, and lymphocytes. In addition, in the more robust LPS- and OVA-induced arthritis models, which were characterized by increased levels of proinflammatory mediators in the synovial fluid, TNF-alpha, IL-8, PGE(2), leukotriene B(4), and leukotriene C(4) levels were significantly reduced, as was erythrocyte sedimentation rate, possibly as a result of the observed decreases in serum TNF-alpha and IL-8 levels. In vitro, the antagonist potently inhibited human IL-8-induced chemotaxis of rabbit neutrophils (IC(50) = 0.75 nM), suggesting that inhibition of leukocyte migration into the knee joint is a likely mechanism by which the CXCR2 antagonist modulates disease.