Modulation of catecholamine release and cortisol secretion by social interactions in the rainbow trout,Oncorhynchus mykiss

The objective of the present study was to investigate the effect of social status on the ability of rainbow trout to secrete the stress hormones, cortisol, and catecholamines. Rainbow trout were confined in pairs for six days to permit the formation of dominance hierarchies. An in situ saline-perfused posterior cardinal vein (PCV) preparation was then used to assess cortisol secretion or release of the catecholamine hormones, adrenaline and noradrenaline, in response to the inclusion of appropriate secretagogues in the perfusate. Fish identified as subordinate on the basis of their behaviour showed a characteristic elevation of circulating plasma cortisol concentrations when compared with dominant fish. When the interrenal cells were stimulated in situ with adrenocorticotropic hormone, subordinate fish displayed a significantly lower rate of cortisol secretion than dominant fish. However, social status had no significant effect on either adrenaline or noradrenaline secretion rates upon stimulation of the chromaffin cells in situ with acetylcholine. These results suggest that the chronic elevation of plasma cortisol associated with subordinate social status in rainbow trout reduces the sensitivity of the cortisol-secreting interrenal cells, presumably through negative feedback mechanisms.     

Arteriovenous malformations of the intestine.

Arteriovenous malforamtions of the intestine are recognized as an uncommon cause of chronic gastrointestinal bleeding. In previous reports, the role of selective mesenteric angiography in the localization of the lesion has been emphasized; with confirmation by in vitro injection of radioopaque dye into the resected specimen. The histologic appearances of arteriovenous malformations are well recognized, although terminology is still confused. In this report, two distinct entities of small vessel malformation are described and the terms submucosal endothelial angiodysplasia and submucosal fibromuscular angiodysplasia are offered.     

Vaccination with a modified vaccinia virus Ankara (MVA)-vectored HIV-1 immunogen induces modest vector-specific T cell responses in human subjects

We investigated whether vaccination of healthy HIV-seronegative and HIV-1-seropositive antiretroviral therapy-treated subjects with recombinant modified vaccinia virus Ankara expressing an HIV-1 immunogen (MVA.HIVA) induced MVA-specific T cell responses. Using IFN-γ Elispot assays, we observed new or increased responses to MVA virus in 52% of HIV-seronegative subjects and 93% HIV-1 seropositive subjects; MVA-specific T cell frequencies were generally low and correlated poorly with T cell responses to the HIV-1 immunogen. In two vaccinees, responses were mapped to CD8+ T cell epitopes present in replication-competent vaccinia virus. These data support further evaluation of MVA as a viral vector for HIV-1 immunogens.     

The Effect of a Low Fructose and Low Glycemic Index/Load (FRAGILE) Dietary Intervention on Indices of Liver Function,Cardiometabolic Risk Factors,and Body Composition in Children and Adolescents With Nonalcoholic Fatty Liver Disease (NAFLD)

Background: Nonalcoholic fatty liver disease (NAFLD) is a common liver disease in obese children. Diets high in added fructose (high fructose corn syrup; HFCS) and glycemic index (GI)/glycemic load (GL) are associated with increased risk of NAFLD. Lifestyle modification is the main treatment, but no guidelines regarding specific dietary interventions for childhood NAFLD exist. We hypothesized that reductions in dietary fructose (total, free, and HFCS)/GI/GL over 6 months would result in improvements in body composition and markers of liver dysfunction and cardiometabolic risk in childhood NAFLD. Methods: Children and adolescents with NAFLD (n = 12) and healthy controls (n = 14) 7–18 years were studied at baseline and 3 and 6 months post–dietary intervention. Plasma markers of liver dysfunction (ALT, AST, γGT), cardiometabolic risk (TG, total cholesterol, LDL‐HDL cholesterol, Apo‐B100, Apo‐B48, Apo‐CIII, insulin, homeostasis model of assessment of insulin resistance [HOMA‐IR]), inflammation (TNF‐α, IL‐6, IL‐10), anthropometric, and blood pressure (BP) were studied using validated methodologies. Results: Significant reductions in systolic BP (SBP), percentage body fat (BF), and plasma concentrations of ALT (P = .04), Apo‐B100 (P < .001), and HOMA‐IR were observed in children with NAFLD at 3 and 6 months (P < .05). Dietary reductions in total/free fructose/HFCS and GL were related to reductions in SBP (P = .01), ALT (P = .004), HOMA‐IR (P = .03), and percentage BF in children with NAFLD. Reductions in dietary GI were associated with reduced plasma Apo‐B100 (P = .02) in both groups. With the exception of Apo‐B100, no changes in laboratory variables were observed in the control group. Conclusion: Modest reductions in fructose (total/free, HFCS) and GI/GL intake result in improvements of plasma markers of liver dysfunction and cardiometabolic risk in childhood NAFLD.     

Diesel Exhaust Enhanced Susceptibility to Influenza Infection is Associated with Decreased Surfactant Protein Expression

We have previously shown that exposure of respiratory epithelial cells to diesel exhaust (DE) enhances susceptibility to influenza infection and increases the production of interleukin (IL)-6 and interferon (IFN)-β. The purpose of this study was to confirm and expand upon these in vitro results by assessing the effects of DE exposure on the progression of influenza infection and on development of associated pulmonary immune and inflammatory responses in vivo. BALB/c mice were exposed to air or to DE containing particulate matter at concentrations of 0.5 or 2 mg/m³ for 4 h/day for 5 days and subsequently instilled with influenza A/Bangkok/1/79 virus. Exposure to 0.5 mg/m³ (but not the higher 2-mg/m³ dose) of DE increased susceptibility to influenza infection as demonstrated by a significant increase in hemagglutinin (HA) mRNA levels, a marker of influenza copies, and greater immunohistochemical staining for influenza virus protein in the lung. The enhanced susceptibility to infection observed in mice exposed to 0.5 mg/m³ of DE was associated with a significant increase in the expression of IL-6, while antiviral lung IFN levels were unaffected. Analysis of the expression and production of surfactant proteins A and D, which are components of the interferon-independent antiviral defenses, showed that these factors were decreased following exposure to 0.5 mg/m³ of DE but not to the higher 2-mg/m³ concentration. Taken together, the results demonstrate that exposure to DE enhances the susceptibility to respiratory viral infections by reducing the expression and production of antimicrobial surfactant proteins.     

The Severity of Dependence Scale (SDS) in an adolescent population of cannabis users: reliability, validity and diagnostic cut-off

The Severity of Dependence Scale (SDS) is a five-item scale that has been reported to be a reliable and valid screening instrument for dependence and a measure of dependence severity in adults across several substance classes. To date no data have been reported on its performance in a population of adolescent cannabis users. The current study assessed the psychometric properties of the SDS in a community sample of 14-18-year-old adolescent cannabis users (n=100). Internal consistency (alpha=0.83) and test-retest coefficients (ICC=0.88) were high and a principal components analysis of the scale found all items to load on a single factor. Total SDS score correlated significantly with frequency of cannabis use and number of DSM-IV dependence criteria met, indicating good concurrent validity. Receiver Operating Characteristic curve analysis was used to determine the most appropriate SDS cut-off score for use as an indicator of cannabis dependence, with optimal discrimination at an SDS score of 4. These findings indicate that the SDS is a reliable and valid measure of severity of cannabis dependence among adolescents, has high diagnostic utility, and that an SDS score of 4 may be indicative of cannabis dependence.     

AMPA receptor potentiation can prevent ethanol-induced intoxication.

We present a substantial series of behavioral and imaging experiments, which demonstrate, for the first time, that increasing AMPA receptor-mediated neurotransmission via administration of potent and selective biarylsulfonamide AMPA potentiators LY404187 and LY451395 reverses the central effects of an acutely intoxicating dose of ethanol in the rat. Using pharmacological magnetic resonance imaging (phMRI), we observed that LY404187 attenuated ethanol-induced reductions in blood oxygenation level dependent (BOLD) in the anesthetized rat brain. A similar attenuation was apparent when measuring local cerebral glucose utilization (LCGU) via C14-2-deoxyglucose autoradiography in freely moving conscious rats. Both LY404187 and LY451395 significantly and dose-dependently reversed ethanol-induced deficits in both motor coordination and disruptions in an operant task where animals were trained to press a lever for food reward. Both prophylactic and acute intervention treatment with LY404187 reversed ethanol-induced deficits in motor coordination. Given that LY451395 and related AMPA receptor potentiators/ampakines are tolerated in both healthy volunteers and elderly patients, these data suggest that such compounds may form a potential management strategy for acute alcohol intoxication.