Bee venom acupuncture therapy ameliorates neuroinflammatory alterations in a pilocarpine-induced epilepticus model

Metabolic Brain Disease - Bee venom (BV) is applied in different traditional medicinal therapies and is used worldwide to prevent and treat many acute and chronic diseases. Epilepsy has various...     

Eating habits are associated with subjective sleep quality outcomes among university students: findings of a cross-sectional study

Sleep and Breathing - This study investigated the relationships between eating habits and sleep quality among university students. In a cross-sectional study, university students completed a...     

Release of neurotensin by selective perfusion of the jejunum with oleic acid in dogs

Plasma neurotensin concentrations are rapidly elevated after oral ingestion or intraduodenal infusion of fat, apparently before fat reaches the ileum where neurotensin is highly concentrated. The purpose of this study was to investigate the site of neurotensin release and to determine whether neurotensin is released by direct luminal stimulation by fat in conscious dogs. Dogs were prepared with isolated jejunal or ileal segments and portal vein catheters. Release of neurotensin into the portal venous blood was examined by selective perfusion of each intestinal segment with sodium oleáte. The results of this study show that selective perfusion of the jejunum, but not the ileum, with sodium oleate, caused a significant release of neurotensin. We speculate that release of ileal neurotensin is not due to direct luminal stimulation, but is mediated by local neural or humoral intermediates.     

Antiviral activity of 1-docosanol, an inhibitor of lipid-enveloped viruses including herpes simplex.

This article reports that 1-docosanol, a 22-carbon-long saturated alcohol, exerts a substantial inhibitory effect on replication of certain viruses (e.g., herpes simplex virus and respiratory syncytial virus) within primary target cells in vitro. To study the basis for its viral inhibitory activity, a suspension of 1-docosanol was formulated in an inert and nontoxic surfactant, Pluronic F-68; this suspension exerted potent inhibitory activity on the ability of susceptible viruses to infect cultured target cells. Susceptible viruses included wild-type herpes simplex viruses 1 and 2 as well as acyclovir-resistant herpes simplex virus 2 and also respiratory syncytial virus--all of which are lipid-enveloped. In contrast, nonenveloped poliovirus was not susceptible to the inhibitory action of 1-docosanol. Although the precise mechanism has yet to be defined, current evidence suggests that 1-docosanol inhibits viral replication by interfering with the early intracellular events surrounding viral entry into target cells. It is possible that interaction between the highly lipophilic compound and components of target cell membranes renders such target cells less susceptible to viral fusion and/or entry. If this mechanism proves to be correct, 1-docosanol may provide a broad spectrum activity against many different viruses, especially those with lipid-containing envelopes.     

Indeterminate biliary strictures: a simplified approach

Introduction: Pre-operative evaluation of biliary strictures remains challenging. The dilemma that exists is how to balance the risk of failing to detect malignancy and the potential morbidity caused by unnecessary surgery in patients with benign etiologies. With emerging novel diagnostic modalities, this study aims to assess the efficacy of diagnostic techniques and facilitate a clinical approach to indeterminate biliary strictures.

Areas covered: Conventional imaging modalities are crucial in identifying the location of a stricture and are helpful for choosing further diagnostic modalities. Utilization of endoscopic techniques, including endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS), is key in establishing a diagnosis. The emergence of novel diagnostic modalities, such as fluorescence in-situ hybridization (FISH), peroral cholangioscopy (POC), intraductal endoscopic ultrasound (IDUS) and confocal laser endomicroscopy (CLE), enhance the diagnostic yield in the evaluation of indeterminate biliary strictures.

Expert commentary: More reliable and validated visual criteria for differentiating malignancy from benign biliary conditions, utilizing advanced imaging modalities such as POC and CLE, need to be established. It is of significance to further evaluate these novel diagnostic modalities through ongoing trials and to develop a diagnostic algorithm that reconciles cost-effectiveness with diagnostic accuracy.     

Gross and histological studies of immediate, Arthus, and delayed skin test responses to schistosome antigen, and of delayed response to ubiquitous antigens in Egyptians

Gross studies of skin reactions to adult antigen of Schistosoma mansoni were made on 156 hospitalized patients with schistosomiasis and 114 subjects from the nonendemic area of Hurghada in Egypt. Wheal areas equal to or greater than 1.0 cm2 indicated a positive immediate (15-min) reaction to adult worm antigen; the criterion of positivity for both 24-hour and 48-hour delayed reactions was an area of induration equal to or greater than 0.6 cm2. Immediate reactions with adult worm antigen were observed in 99% of the patients with schistosomiasis and 11% of the subjects from Hurghada: the percentages with delayed reaction were 58% and 2%, respectively. Biopsies of skin test sites at various intervals after antigen injection were done on 87 individuals. Eosinophilic and mononuclear infiltrates were characteristic of immediate and delayed skin responses, respectively. Biopsies from 22 patients with marked skin reactions 5 hours after antigen injection showed that a neutrophilic response indicative of Arthus reactivity was present in only 18. Thus, Arthus reactivity could not be determined on gross appearance alone. The studies did not show any evidence of delayed basophilic hypersensitivity to schistosome antigen. Immunofluorescent studies on a small number of biopsies suggested that a late phase (5-hour) reaction due to IgE may occur in some patients. Delayed reactivity to mumps and/or monilia skin test antigens was observed in 91% of Egyptians in a nonendemic area of schistosomiasis. Delayed hypersensitivity to PPD was detected in 44% of the same group.     

Formation of 4-oestrene-3,17-dione (19-norandrostenedione) by porcine granulosa cells in vitro is inhibited by the aromatase inhibitor 4-hydroxyandrostenedione and the cytochrome P-450 inhibitors aminoglutethimide phosphate and ketoconazole

The origin and biosynthesis of 4-oestrene-3,17-dione (19-norandrostenedione), a major steroid in porcine ovarian follicular fluid, was investigated by culturing granulosa cells from 4-6 mm follicles of prepubertal gilts with radiolabelled androstenedione and 19-hydroxyandrostenedione. Steroid metabolites were purified by solvent extraction and lipophilic column chromatography, and analysed by C18 reverse-phase high-performance liquid chromatography. 19-Hydroxyandrostenedione, 19-norandrostenedione and oestradiol-17 beta were obtained as major metabolites from androstenedione, while 19-norandrostenedione and oestradiol-17 beta were the major products from 19-hydroxyandrostenedione. Serum alone or serum plus FSH significantly enhanced formation of 19-norandrostenedione and oestradiol-17 beta from each substrate, compared with controls. Micromolar concentrations (1 mumol/l) of 4-hydroxyandrostenedione, an aromatase inhibitor, significantly reduced formation of 19-norandrostenedione and oestradiol-17 beta by granulosa cells cultured with serum and FSH. Formation of 19-norandrostenedione and oestradiol-17 beta from androstenedione and 19-hydroxyandrostenedione was also significantly inhibited by aminoglutethimide phosphate, a cytochrome P-450 inhibitor known to block the conversion of androstenedione to oestrogens. Ketoconazole, an inhibitor of the cytochrome P-450 dependent 17,20-lysase, blocked formation of 19-norandrostenedione and oestradiol-17 beta only at millimolar concentrations. These results suggest that 19-norsteroid and oestrogen formation from C19 aromatizable androgens may share a common or overlapping pathway, and imply that 19-norsteroid and oestrogen synthesis is mediated by cytochrome P-450 dependent enzymes.     

SOD2 genetic polymorphism (rs4880) has no impact on 6‐month response to antidepressant treatment and inflammatory biomarkers in depressed patients

Two thirds of patients suffering from a major depressive episode (MDE) do not reach a complete response with antidepressant drugs. This lack of response is due to several factors, including genetic determinants. Since major depressive disorder is associated with inflammatory and oxidative stress abnormalities, the metabolism of superoxide anions might be involved in non‐response to antidepressant drugs. Superoxide anions are metabolized by manganese‐dependent superoxide dismutase (SOD2) in the mitochondria. A functional genetic polymorphism (SOD2, rs4880), responsible of a 40% reduction in enzyme activity, is associated with anti‐inflammatory response of rosuvastatin. We investigated the association of ala‐allele of SOD2 rs4880 and both antidepressant efficacy and inflammatory parameters in patients treated for a MDE with antidepressant drugs. The Hamilton Depression Rating Scale (HDRS) score and levels of plasma CRP and inflammatory cytokines were assessed at baseline, one month (M1), 3 months (M3) and 6 months (M6) after antidepressant treatment. They were compared according to SOD2 genetic polymorphism. Of the 484 patients studied, 361 (74.6%) carried the ala‐allele (Ala group), 123 (25.4%) of them had Val/Val genotype (Val/Val group). No significant difference was observed between the Ala and Val/Val groups neither for baseline clinical characteristics, nor for HDRS scores, response/remission rates, plasma CRP and cytokine levels throughout the study. The rs4880 SOD2 genetic polymorphism was not associated with the clinical response and cytokines levels after antidepressant treatment. These data suggest that SOD2 is not a major genetic determinant of antidepressant response. Other genes of the oxidative stress pathways should be explored in further studies.     

Anti-inflammatory effects of insulin regular and flunixin meglumine on endotoxemia experimentally induced by Escherichia coli serotype O55:B5 in an ovine model

Background

Endotoxemia is a major cause of mortality in large animals and there are several therapeutic regimens for the treatment of endotoxemia. Recent studies have suggested the anti-inflammatory effects of insulin in endotoxemic human and laboratory animal models but to the best of our knowledge there is no report on the possible therapeutic effect of insulin in large animal endotoxemia.

Objective

This experiment was conducted to evaluate the anti-inflammatory effects of insulin regular compared with flunixin meglumine on the treatment of endotoxemia in sheep.

Methods

Lipopolysaccharide from Escherichia coli was administered intravenously to ewes. Anti-inflammatory effects of flunixin meglumine (at 2.2 mg/kg) and insulin regular (at 1.5 and 3 IU/kg) were evaluated by determination of serum concentrations of acute phase proteins, inflammatory cytokines and oxidative stress biomarkers.

Results

Insulin regular at 3 IU/kg controlled the acute phase response following endotoxemia induction. The anti-inflammatory potency of insulin regular at 3 IU/kg was significantly higher than at 1.5 IU/kg and of flunixin meglumine at 2.2 mg/kg (P < 0.05).

Conclusion

Insulin regular induces its anti-inflammatory effects in a dose-dependent manner. Intravenous use of insulin regular can be a potential new therapeutic regimen for endotoxemia in large animal medicine.