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  • basic medicine
  • 3. Good health

  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: María C. Estévez; José O. Bonilla; Liliana Beatriz Villegas; Liliana Beatriz Villegas; +2 Authors

    The purpose of this study was to investigate the influence of increasing sulfate concentrations on chromium removal, to evaluate the effect of the presence of Cr(VI) on sulfate removal by Streptomyces sp. MC1 and to analyze the differential protein expression profile in the presence of this metal for the identification of proteins repressed or overexpressed. In the presence of Cr(VI) but in the absence of sulfate ions, bacterial growth was negligible, showing the Cr(VI) toxicity for this bacterium. However, the sulfate presence stimulated bacterium growth and Cr(VI) removal, regardless of its concentrations. Streptomyces sp. MC1 showed ability to remove chromium and sulfate simultaneously. Also, the sulfate presence favored the decrease of total chromium concentration from supernatants reaching a decrease of 50% at 48 h. In presence of chromium, seven proteins were down‐expressed and showed homology to proteins involved in protein biosynthesis, energy production and free radicals detoxification while two proteins involved in oxidation‐reduction processes identified as dihydrolipoamide dehydrogenase and S‐adenosyl‐l‐methionine synthase were overexpressed.

    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Journal of Basic Mic...arrow_drop_down
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Journal of Basic Microbiology
    Article . 2016 . Peer-reviewed
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Journal of Basic Mic...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      Journal of Basic Microbiology
      Article . 2016 . Peer-reviewed
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  • Authors: Christopher W. Loomis; J. F. Brien; J. E. Peachey;

    Each of 4 male alcoholic subjects received 0.7 mg/kg calcium carbimide (CC) orally 12 hr before ingestion of 0.25 gm/kg ethanol on 3 separate occasions. The CC-ethanol interaction consisted of increased blood acetaldehyde level and elevated heart rate. For each individual there was small variability in the area under the curve (AUC) values of the blood ethanol level--time course profiles for the 3 experiments, indicating a consistent extent of ethanol absorption. For subjects 1, 2, and 3 there was appreciable intraindividual variability in the AUC and the peak blood acetaldehyde levels of the blood acetaldehyde level--time course curves; the variation in these parameters was small for subjects 4. The intraindividual variability in the peak heart rate response was small for subjects 1 and 2 and appreciable for subjects 3 and 4. Regression analysis of the blood acetaldehyde level--heart rate data for each of the 3 experiments conducted on the 4 subjects revealed that there were positive, linear correlations. There was appreciable intraindividual variability in the slope values for the 3 experiments. The results of this study, conducted on 4 male alcoholics, suggest that for other alcoholic subjects there could be appreciable intraindividual variability in the intensity of the CC-ethanol interaction.

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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Yung Hyun Choi; Sung Hyun Choi; Su Hyun Hong; Sung Ok Kim; +5 Authors

    The leaves of Aster yomena (Kitam.) Honda have long been used as a traditional herb for treating disorders including coughs, asthma, and insect bites. According to recent studies, A. yomena leaf extracts have several pharmacological properties, including anti-inflammatory, antioxidant, and anti-asthmatic activities. However, little information is available regarding their anti-obesity effect. In this study, we investigated the inhibitory effect of the ethanol extracts of A. yomena leaves (EEAY) on adipocyte differentiation and adipogenesis using 3T3-L1 preadipocytes. When 3T3-L1 preadipocytes were treated with various concentrations of EEAY (ranging from non-toxic), the number of lipid droplets, lipid content, and triglyceride production, the typical characteristics of adipocytes, were suppressed in a concentration-dependent manner. During this process, EEAY significantly reduced the expression of adipogenic transcription factors, including peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding protein α and β, and sterol regulatory element-binding protein-1c. In addition, EEAY was also found to potently inhibit the expression of adipocyte-specific genes, including adipocyte fatty acid-binding protein and leptin. In particular, EEAY treatment effectively enhanced the activation of the AMP-activated protein kinase (AMPK) signaling pathway; however, the co-treatment with compound C, an inhibitor of AMPK, significantly restored the EEAY-induced inhibition of pro-adipogenic transcription factors and adipocyte-specific genes. These results indicate that EEAY may exert an anti-obesity effect by controlling the AMPK signaling pathway, suggesting that the leaf extract of A. yomena may be a potential anti-obesity agent.

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    Drug Discoveries & Therapeutics
    Article . 2017 . Peer-reviewed
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      Drug Discoveries & Therapeutics
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Fouad M.F. Elshaghabee; Fouad M.F. Elshaghabee; Wilhelm eBockelmann; Diana eMeske; +4 Authors

    Pour obtenir un aperçu spécifique des rôles que les micro-organismes pourraient jouer dans la stéatose hépatique non alcoolique (NAFLD), certaines bactéries intestinales et lactiques et une levure (Anaerostipes caccae, Bacteroides thetaiotaomicron, Bifidobacterium longum, Enterococcus fecalis, Escherichia coli, Lactobacillus acidophilus, Lactobacillus fermentum, Lactobacillus plantarum, Weissella confusa, Saccharomyces cerevisiae) ont été caractérisées par une chromatographie liquide haute performance pour la production d'éthanol lorsqu'elles sont cultivées sur différents glucides : hexoses (glucose et fructose), pentoses (arabinose et ribose), disaccharides (lactose et lactulose) et inuline. Les quantités les plus élevées d'éthanol ont été produites par S. cerevisiae, L. fermentum et W. confusa sur le glucose et par S. cerevisiae et W. confusa sur le fructose. En raison de la mannitol-déshydrogénase exprimée dans L. fermentum, la production d'éthanol sur le fructose a été significativement réduite (P < 0,05). Le pyruvate et le citrate, deux accepteurs d'électrons potentiels pour la régénération du NAD+/NADP+, ont considérablement réduit la production d'éthanol avec de l'acétate produit à la place dans L. fermentum cultivé sur glucose et W. confusa cultivé sur glucose et fructose, respectivement. Dans les boues fécales préparées à partir des matières fécales de quatre volontaires en surpoids, on a constaté que l'éthanol était produit lors de l'ajout de fructose. L'ajout d'A. caccae, L. acidophilus, L. fermentum, ainsi que de citrate et de pyruvate, respectivement, a aboli la production d'éthanol. Cependant, l'ajout de W. confusa a entraîné une augmentation significative (P < 0,05) de la production d'éthanol. Ces résultats indiquent que des micro-organismes comme W. confusa, une bactérie lactique hétéro-fermentaire, négative à la mannitol-déshydrogénase, peuvent favoriser la NAFLD par l'éthanol produit à partir de la fermentation du sucre, tandis que d'autres bactéries intestinales et des bactéries lactiques homo- et hétéro-fermentaires mais positives à la mannitol-déshydrogénase peuvent ne pas favoriser la NAFLD. En outre, nos études indiquent que les facteurs alimentaires interférant avec le microbiote gastro-intestinal et le métabolisme microbien peuvent être importants dans la prévention ou la promotion de la NAFLD. Para obtener información específica sobre los roles que podrían desempeñar los microorganismos en la enfermedad del hígado graso no alcohólico (NAFLD, por sus siglas en inglés), algunas bacterias intestinales y del ácido láctico y una levadura (Anaerostipes caccae, Bacteroides thetaiotaomicron, Bifidobacterium longum, Enterococcus fecalis, Escherichia coli, Lactobacillus acidophilus, Lactobacillus fermentum, Lactobacillus plantarum, Weissella confusa, Saccharomyces cerevisiae) se caracterizaron por cromatografía líquida de alto rendimiento para la producción de etanol cuando se cultivaron en diferentes carbohidratos: hexosas (glucosa y fructosa), pentosas (arabinosa y ribosa), disacáridos (lactosa y lactulosa) e inulina. Las cantidades más altas de etanol fueron producidas por S. cerevisiae, L. fermentum y W. confusa en glucosa y por S. cerevisiae y W. confusa en fructosa. Debido a la manitol-deshidrogenasa expresada en L. fermentum, la producción de etanol en fructosa se redujo significativamente (P < 0.05). El piruvato y el citrato, dos aceptores de electrones potenciales para la regeneración de NAD+/NADP+, redujeron drásticamente la producción de etanol con acetato producido en su lugar en L. fermentum cultivado en glucosa y W. confusa cultivado en glucosa y fructosa, respectivamente. En suspensiones fecales preparadas a partir de heces de cuatro voluntarios con sobrepeso, se encontró que el etanol se producía tras la adición de fructosa. La adición de A. caccae, L. acidophilus, L. fermentum, así como citrato y piruvato, respectivamente, abolió la producción de etanol. Sin embargo, la adición de W. confusa resultó en un aumento significativo (P < 0.05) de la producción de etanol. Estos resultados indican que microorganismos como W. confusa, una bacteria de ácido láctico hetero-fermentativa, negativa para manitol-deshidrogenasa, pueden promover NAFLD a través del etanol producido a partir de la fermentación de azúcar, mientras que otras bacterias intestinales y bacterias de ácido láctico homo- y hetero-fermentativas pero positivas para manitol-deshidrogenasa pueden no promover NAFLD. Además, nuestros estudios indican que los factores dietéticos que interfieren con la microbiota gastrointestinal y el metabolismo microbiano pueden ser importantes para prevenir o promover la EHGNA. To gain some specific insight into the roles microorganisms might play in non-alcoholic fatty liver disease (NAFLD), some intestinal and lactic acid bacteria and one yeast (Anaerostipes caccae, Bacteroides thetaiotaomicron, Bifidobacterium longum, Enterococcus fecalis, Escherichia coli, Lactobacillus acidophilus, Lactobacillus fermentum, Lactobacillus plantarum, Weissella confusa, Saccharomyces cerevisiae) were characterized by high performance liquid chromatography for production of ethanol when grown on different carbohydrates: hexoses (glucose and fructose), pentoses (arabinose and ribose), disaccharides (lactose and lactulose), and inulin. Highest amounts of ethanol were produced by S. cerevisiae, L. fermentum and W. confusa on glucose and by S. cerevisiae and W. confusa on fructose. Due to mannitol-dehydrogenase expressed in L. fermentum, ethanol production on fructose was significantly (P < 0.05) reduced. Pyruvate and citrate, two potential electron acceptors for regeneration of NAD+/NADP+, drastically reduced ethanol production with acetate produced instead in L. fermentum grown on glucose and W. confusa grown on glucose and fructose, respectively. In fecal slurries prepared from feces of four overweight volunteers, ethanol was found to be produced upon addition of fructose. Addition of A. caccae, L. acidophilus, L. fermentum, as well as citrate and pyruvate, respectively, abolished ethanol production. However, addition of W. confusa resulted in significantly (P < 0.05) increased production of ethanol. These results indicate that microorganisms like W. confusa, a hetero-fermentative, mannitol-dehydrogenase negative lactic acid bacterium, may promote NAFLD through ethanol produced from sugar fermentation, while other intestinal bacteria and homo- and hetero-fermentative but mannitol-dehydrogenase positive lactic acid bacteria may not promote NAFLD. Also, our studies indicate that dietary factors interfering with gastrointestinal microbiota and microbial metabolism may be important in preventing or promoting NAFLD. لاكتساب بعض الأفكار المحددة حول الأدوار التي قد تلعبها الكائنات الحية الدقيقة في مرض الكبد الدهني غير الكحولي (NAFLD)، تميزت بعض بكتيريا حمض الأمعاء واللاكتيك وخميرة واحدة (Anaerostipes caccae، Bacteroides thetaiotaomicron، Bifidobacterium longum، Enterococcus fecalis، Escherichia coli، Lactobacillus acidophilus، Lactobacillus fermentum، Lactobacillus plantarum، Weissella confusa، Saccharomyces cerevisiae) بتصوير سائل عالي الأداء لإنتاج الإيثانول عند زراعته على كربوهيدرات مختلفة: hexoses (الجلوكوز والفركتوز)، pentoses (الأرابينوز والريبوز)، disaccharides (اللاكتوز واللاكتولوز)، و inulin. تم إنتاج أعلى كميات من الإيثانول بواسطة S. cerevisiae و L. fermentum و W. confusa على الجلوكوز و S. cerevisiae و W. confusa على الفركتوز. بسبب نازعة هيدروجين المانيتول المعبر عنها في L. fermentum، انخفض إنتاج الإيثانول على الفركتوز بشكل كبير (P < 0.05). قلل البيروفات والسيترات، وهما مستقبلان محتملان للإلكترون لتجديد NAD +/NADP+، بشكل كبير من إنتاج الإيثانول مع الأسيتات المنتجة بدلاً من ذلك في L. fermentum المزروع على الجلوكوز و W. confusa المزروع على الجلوكوز والفركتوز، على التوالي. في الملاط البرازي الذي تم تحضيره من براز أربعة متطوعين يعانون من زيادة الوزن، وجد أن الإيثانول يتم إنتاجه عند إضافة الفركتوز. إضافة A. caccae، L. acidophilus، L. fermentum، وكذلك السترات والبيروفات، على التوالي، ألغت إنتاج الإيثانول. ومع ذلك، أدت إضافة W. confusa إلى زيادة كبيرة في إنتاج الإيثانول (P < 0.05). تشير هذه النتائج إلى أن الكائنات الحية الدقيقة مثل W. confusa، وهي بكتيريا حمض اللاكتيك السلبية غير المتجانسة، قد تعزز NAFLD من خلال الإيثانول المنتج من تخمير السكر، في حين أن البكتيريا المعوية الأخرى وبكتيريا حمض اللاكتيك الإيجابية غير المتجانسة ولكن غير المتجانسة قد لا تعزز NAFLD. أيضًا، تشير دراساتنا إلى أن العوامل الغذائية التي تتداخل مع الكائنات الحية الدقيقة في الجهاز الهضمي والتمثيل الغذائي الميكروبي قد تكون مهمة في منع أو تعزيز NAFLD.

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      https://dx.doi.org/10.60692/fk...
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  • Authors: Julio Caballero; Fernando D. González Nilo; Ariela Vergara Jague; Jans Alzate-Morales;

    N2 and O6 substituted guanine derivatives are well-known as potent and selective CDK2 inhibitors. The ability of molecular docking using the program AutoDock3 and the hybrid method ONIOM, to obtain some quantum chemical descriptors with the aim to successfully rank these inhibitors, was assessed. The quantum chemical descriptors were used to explain the affinity, of the series studied, by a model of the CDK2 binding site. The initial structures were obtained from docking studies and the ONIOM method was applied with only a single point energy calculation on the protein-ligand structure. We obtained a good correlation model between the ONIOM derived quantum chemical descriptor "H-bond interaction energy" and the experimental biological activity, with a correlation coefficient value of R = 0.80 for 75 compounds. To the best of our knowledge, this is the first time that both methodologies are used in conjunction in order to obtain a correlation model. The model suggests that electrostatic interactions are the principal driving force in this protein-ligand interaction. Overall, the approach was successful for the cases considered, and it suggests that could be useful for the design of inhibitors in the lead optimization phase of drug discovery.

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    Authors: R. J. Reiffenstein; Manuel Mah;

    Ethanol has been claimed to potentiate greatly the lethality of propoxyphene, although published clinical data suggest only an additive effect. Mice were treated intraperitoneally with various doses of propoxyphene hydrochloride and ethanol. Isobolograms of the data show the combination to be less-than-additive for lethality and loss of motor coordination and, at worst, simply additive for sedation.

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    Canadian Journal of Physiology and Pharmacology
    Article . 1984 . Peer-reviewed
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      Canadian Journal of Physiology and Pharmacology
      Article . 1984 . Peer-reviewed
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  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Ali-Reza Khalili; Keyvan Amirshahrokhi;

    Excessive ethanol ingestion causes gastric mucosal damage through the inflammatory and oxidative processes. The present study was aimed to evaluate the protective effect of thalidomide on ethanol-induced gastric mucosal damage in mice. The animals were pretreated with vehicle or thalidomide (30 or 60 mg/kg, orally), and one hour later, the gastric mucosal injury was induced by oral administration of acidified ethanol. The animals were euthanized one hour after ethanol ingestion, and gastric tissues were collected to biochemical analyzes. The gastric mucosal lesions were assessed by macroscopic and histopathological examinations. The results showed that treatment of mice with thalidomide prior to the administration of ethanol dose-dependently reduced the gastric ulcer index. Thalidomide pretreatment significantly reduced the levels of pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6], malondialdehyde (MDA) and myeloperoxidase (MPO) activity. In addition, thalidomide significantly inhibited ethanol-induced nitric oxide (NO) overproduction in gastric tissue. Histological observations showed that ethanol-induced gastric mucosal damage was attenuated by thalidomide pretreatment. It seems that thalidomide as an anti-inflammatory agent may have a protective effect against alcohol-induced mucosal damage by inhibition of neutrophil infiltration and reducing the production of nitric oxide and inflammatory cytokines in gastric tissue.

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    Chemico-Biological Interactions
    Article . 2015 . Peer-reviewed
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      Chemico-Biological Interactions
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    Authors: Patrick, Sheila; McDowell, Andrew; Lee, Andrew; Frau, Alessandra; +4 Authors

    Aims The aim of this study was to determine whether the sequential application of povidone iodine-alcohol (PVI) followed by chlorhexidine gluconate-alcohol (CHG) would reduce surgical wound contamination to a greater extent than PVI applied twice in patients undergoing spinal surgery. Patients and Methods A single-centre, interventional, two arm, parallel group randomised controlled trial was undertaken, involving 407 patients who underwent elective spinal surgery. For 203 patients, the skin was disinfected before surgery using PVI (10% [w/w (1% w/w available iodine)] in 95% industrial denatured alcohol, povidone iodine; Videne Alcoholic Tincture) twice, and for 204 patients using PVI once followed by CHG (2% [w/v] chlorhexidine gluconate in 70% [v/v] isopropyl alcohol; Chloraprep with tint). The primary outcome measure was contamination of the wound determined by aerobic and anaerobic bacterial growth from samples taken after disinfection. Results The detection of viable bacteria in any one of the samples taken after disinfection (culture-positive) was significantly lower in the group treated with both PVI and CHG than in the group treated with PVI alone (59 (29.1%) versus 85 (41.7%), p = 0.009; odds ratio 0.574; 95% confidence interval, 0.380 to 0.866). Conclusions Antisepsis of the skin with the sequential application of PVI and CHG more effectively reduces the contamination of a surgical wound than PVI alone. Cite this article: Bone Joint J 2017;99-B:1354–65.

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    The Bone & Joint Journal
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      The Bone & Joint Journal
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    Authors: Clark W. Bird; Glenna J. Chavez; Megan J. Barber; C. Fernando Valenzuela;

    ABSTRACTPrenatal ethanol exposure causes a variety of cognitive deficits that have a persistent impact on quality of life, some of which may be explained by ethanol-induced alterations in interneuron function. Studies from several laboratories, including our own, have demonstrated that a single binge-like ethanol exposure during the equivalent to the third trimester of human pregnancy leads to acute apoptosis and long-term loss of interneurons in the rodent retrosplenial cortex (RSC). The RSC is interconnected with the hippocampus, thalamus, and other neocortical regions and plays distinct roles in visuospatial processing and storage, as well as retrieval of hippocampal-dependent episodic memories. Here we used slice electrophysiology to characterize the acute effects of ethanol on GABAergic neurotransmission in the RSC of neonatal mice, as well as the long-term effects of neonatal ethanol exposure on parvalbumin-interneuron mediated neurotransmission in adolescent mice. Mice were exposed to ethanol using vapor inhalation chambers. In postnatal day (P) 7 mouse pups, ethanol unexpectedly failed to potentiate GABAAreceptor-mediated synaptic transmission. Binge-like ethanol exposure of P7 mice expressing channel rhodopsin in parvalbumin-positive interneurons enhanced the peak amplitudes, asynchronous activity and total charge, while decreasing the rise-times of optically-evoked GABAAreceptor-mediated inhibitory postsynaptic currents in adolescent animals. These effects could partially explain the learning and memory deficits that have been documented in adolescent and young adult mice exposed to ethanol during the third trimester-equivalent developmental period.

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    Scientific Reports
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    Authors: A. M. de Oliveira; Eurode Legros; Sérgio Akira Uyemura; Jean-Claude Honoré; +5 Authors

    Background and purpose:The contribution of endothelin‐1 (ET‐1) to vascular hyper‐reactivity associated with chronic ethanol intake, a major risk factor in several cardiovascular diseases, remains to be investigated.Experimental approach:The biphasic haemodynamic responses to ET‐1 (0.01–0.1 nmol kg−1, i.v.) or to the selective ETB agonist, IRL1620 (0.001–1.0 nmol kg−1, i.v.), with or without ETA or ETB antagonists (BQ123 (c(DTrp‐Dasp‐Pro‐Dval‐Leu)) at 1 and 2.5 mg kg−1 and BQ788 (N‐cis‐2,6‐dimethyl‐piperidinocarbonyl‐L‐γ‐methylleucyl1‐D‐1methoxycarbonyltryptophanyl‐D‐norleucine) at 0.25 mg kg−1, respectively) were tested in anaesthetized rats, after 2 weeks' chronic ethanol treatment. Hepatic parameters and ET receptor protein levels were also determined.Key results:The initial hypotensive responses to ET‐1 or IRL1620 were unaffected by chronic ethanol intake, whereas the subsequent pressor effects induced by ET‐1, but not by IRL1620, were potentiated. BQ123 at 2.5 but not 1 mg kg−1 reduced the pressor responses to ET‐1 in ethanol‐treated rats. Conversely, BQ788 (0.25 mg kg−1) potentiated ET‐1‐induced increases in mean arterial blood pressure in control as well as in ethanol‐treated rats. Interestingly, in the latter group, increases in heart rate, induced by ET‐1 at a dose of 0.025 mg kg−1 were enhanced following ETB receptor blockade. Finally, we observed higher levels of ETA receptor in the heart and mesenteric artery and a reduction of ETB receptor protein levels in the aorta and kidney from rats chronically treated with ethanol.Conclusions and implications:Increased vascular reactivity to ET‐1 and altered protein levels of ETA and ETB receptors could play a role in the pathogenesis of cardiovascular complications associated with chronic ethanol consumption.British Journal of Pharmacology (2008) 154, 971–981; doi:10.1038/bjp.2008.157; published online 12 May 2008

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    British Journal of Pharmacology
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      British Journal of Pharmacology
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  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: María C. Estévez; José O. Bonilla; Liliana Beatriz Villegas; Liliana Beatriz Villegas; +2 Authors

    The purpose of this study was to investigate the influence of increasing sulfate concentrations on chromium removal, to evaluate the effect of the presence of Cr(VI) on sulfate removal by Streptomyces sp. MC1 and to analyze the differential protein expression profile in the presence of this metal for the identification of proteins repressed or overexpressed. In the presence of Cr(VI) but in the absence of sulfate ions, bacterial growth was negligible, showing the Cr(VI) toxicity for this bacterium. However, the sulfate presence stimulated bacterium growth and Cr(VI) removal, regardless of its concentrations. Streptomyces sp. MC1 showed ability to remove chromium and sulfate simultaneously. Also, the sulfate presence favored the decrease of total chromium concentration from supernatants reaching a decrease of 50% at 48 h. In presence of chromium, seven proteins were down‐expressed and showed homology to proteins involved in protein biosynthesis, energy production and free radicals detoxification while two proteins involved in oxidation‐reduction processes identified as dihydrolipoamide dehydrogenase and S‐adenosyl‐l‐methionine synthase were overexpressed.

    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Journal of Basic Mic...arrow_drop_down
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Journal of Basic Microbiology
    Article . 2016 . Peer-reviewed
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Journal of Basic Mic...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      Journal of Basic Microbiology
      Article . 2016 . Peer-reviewed
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  • Authors: Christopher W. Loomis; J. F. Brien; J. E. Peachey;

    Each of 4 male alcoholic subjects received 0.7 mg/kg calcium carbimide (CC) orally 12 hr before ingestion of 0.25 gm/kg ethanol on 3 separate occasions. The CC-ethanol interaction consisted of increased blood acetaldehyde level and elevated heart rate. For each individual there was small variability in the area under the curve (AUC) values of the blood ethanol level--time course profiles for the 3 experiments, indicating a consistent extent of ethanol absorption. For subjects 1, 2, and 3 there was appreciable intraindividual variability in the AUC and the peak blood acetaldehyde levels of the blood acetaldehyde level--time course curves; the variation in these parameters was small for subjects 4. The intraindividual variability in the peak heart rate response was small for subjects 1 and 2 and appreciable for subjects 3 and 4. Regression analysis of the blood acetaldehyde level--heart rate data for each of the 3 experiments conducted on the 4 subjects revealed that there were positive, linear correlations. There was appreciable intraindividual variability in the slope values for the 3 experiments. The results of this study, conducted on 4 male alcoholics, suggest that for other alcoholic subjects there could be appreciable intraindividual variability in the intensity of the CC-ethanol interaction.

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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Yung Hyun Choi; Sung Hyun Choi; Su Hyun Hong; Sung Ok Kim; +5 Authors

    The leaves of Aster yomena (Kitam.) Honda have long been used as a traditional herb for treating disorders including coughs, asthma, and insect bites. According to recent studies, A. yomena leaf extracts have several pharmacological properties, including anti-inflammatory, antioxidant, and anti-asthmatic activities. However, little information is available regarding their anti-obesity effect. In this study, we investigated the inhibitory effect of the ethanol extracts of A. yomena leaves (EEAY) on adipocyte differentiation and adipogenesis using 3T3-L1 preadipocytes. When 3T3-L1 preadipocytes were treated with various concentrations of EEAY (ranging from non-toxic), the number of lipid droplets, lipid content, and triglyceride production, the typical characteristics of adipocytes, were suppressed in a concentration-dependent manner. During this process, EEAY significantly reduced the expression of adipogenic transcription factors, including peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding protein α and β, and sterol regulatory element-binding protein-1c. In addition, EEAY was also found to potently inhibit the expression of adipocyte-specific genes, including adipocyte fatty acid-binding protein and leptin. In particular, EEAY treatment effectively enhanced the activation of the AMP-activated protein kinase (AMPK) signaling pathway; however, the co-treatment with compound C, an inhibitor of AMPK, significantly restored the EEAY-induced inhibition of pro-adipogenic transcription factors and adipocyte-specific genes. These results indicate that EEAY may exert an anti-obesity effect by controlling the AMPK signaling pathway, suggesting that the leaf extract of A. yomena may be a potential anti-obesity agent.

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    Drug Discoveries & Therapeutics
    Article . 2017 . Peer-reviewed
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Drug Discoveries & T...arrow_drop_down
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      Drug Discoveries & Therapeutics
      Article . 2017 . Peer-reviewed
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Fouad M.F. Elshaghabee; Fouad M.F. Elshaghabee; Wilhelm eBockelmann; Diana eMeske; +4 Authors

    Pour obtenir un aperçu spécifique des rôles que les micro-organismes pourraient jouer dans la stéatose hépatique non alcoolique (NAFLD), certaines bactéries intestinales et lactiques et une levure (Anaerostipes caccae, Bacteroides thetaiotaomicron, Bifidobacterium longum, Enterococcus fecalis, Escherichia coli, Lactobacillus acidophilus, Lactobacillus fermentum, Lactobacillus plantarum, Weissella confusa, Saccharomyces cerevisiae) ont été caractérisées par une chromatographie liquide haute performance pour la production d'éthanol lorsqu'elles sont cultivées sur différents glucides : hexoses (glucose et fructose), pentoses (arabinose et ribose), disaccharides (lactose et lactulose) et inuline. Les quantités les plus élevées d'éthanol ont été produites par S. cerevisiae, L. fermentum et W. confusa sur le glucose et par S. cerevisiae et W. confusa sur le fructose. En raison de la mannitol-déshydrogénase exprimée dans L. fermentum, la production d'éthanol sur le fructose a été significativement réduite (P < 0,05). Le pyruvate et le citrate, deux accepteurs d'électrons potentiels pour la régénération du NAD+/NADP+, ont considérablement réduit la production d'éthanol avec de l'acétate produit à la place dans L. fermentum cultivé sur glucose et W. confusa cultivé sur glucose et fructose, respectivement. Dans les boues fécales préparées à partir des matières fécales de quatre volontaires en surpoids, on a constaté que l'éthanol était produit lors de l'ajout de fructose. L'ajout d'A. caccae, L. acidophilus, L. fermentum, ainsi que de citrate et de pyruvate, respectivement, a aboli la production d'éthanol. Cependant, l'ajout de W. confusa a entraîné une augmentation significative (P < 0,05) de la production d'éthanol. Ces résultats indiquent que des micro-organismes comme W. confusa, une bactérie lactique hétéro-fermentaire, négative à la mannitol-déshydrogénase, peuvent favoriser la NAFLD par l'éthanol produit à partir de la fermentation du sucre, tandis que d'autres bactéries intestinales et des bactéries lactiques homo- et hétéro-fermentaires mais positives à la mannitol-déshydrogénase peuvent ne pas favoriser la NAFLD. En outre, nos études indiquent que les facteurs alimentaires interférant avec le microbiote gastro-intestinal et le métabolisme microbien peuvent être importants dans la prévention ou la promotion de la NAFLD. Para obtener información específica sobre los roles que podrían desempeñar los microorganismos en la enfermedad del hígado graso no alcohólico (NAFLD, por sus siglas en inglés), algunas bacterias intestinales y del ácido láctico y una levadura (Anaerostipes caccae, Bacteroides thetaiotaomicron, Bifidobacterium longum, Enterococcus fecalis, Escherichia coli, Lactobacillus acidophilus, Lactobacillus fermentum, Lactobacillus plantarum, Weissella confusa, Saccharomyces cerevisiae) se caracterizaron por cromatografía líquida de alto rendimiento para la producción de etanol cuando se cultivaron en diferentes carbohidratos: hexosas (glucosa y fructosa), pentosas (arabinosa y ribosa), disacáridos (lactosa y lactulosa) e inulina. Las cantidades más altas de etanol fueron producidas por S. cerevisiae, L. fermentum y W. confusa en glucosa y por S. cerevisiae y W. confusa en fructosa. Debido a la manitol-deshidrogenasa expresada en L. fermentum, la producción de etanol en fructosa se redujo significativamente (P < 0.05). El piruvato y el citrato, dos aceptores de electrones potenciales para la regeneración de NAD+/NADP+, redujeron drásticamente la producción de etanol con acetato producido en su lugar en L. fermentum cultivado en glucosa y W. confusa cultivado en glucosa y fructosa, respectivamente. En suspensiones fecales preparadas a partir de heces de cuatro voluntarios con sobrepeso, se encontró que el etanol se producía tras la adición de fructosa. La adición de A. caccae, L. acidophilus, L. fermentum, así como citrato y piruvato, respectivamente, abolió la producción de etanol. Sin embargo, la adición de W. confusa resultó en un aumento significativo (P < 0.05) de la producción de etanol. Estos resultados indican que microorganismos como W. confusa, una bacteria de ácido láctico hetero-fermentativa, negativa para manitol-deshidrogenasa, pueden promover NAFLD a través del etanol producido a partir de la fermentación de azúcar, mientras que otras bacterias intestinales y bacterias de ácido láctico homo- y hetero-fermentativas pero positivas para manitol-deshidrogenasa pueden no promover NAFLD. Además, nuestros estudios indican que los factores dietéticos que interfieren con la microbiota gastrointestinal y el metabolismo microbiano pueden ser importantes para prevenir o promover la EHGNA. To gain some specific insight into the roles microorganisms might play in non-alcoholic fatty liver disease (NAFLD), some intestinal and lactic acid bacteria and one yeast (Anaerostipes caccae, Bacteroides thetaiotaomicron, Bifidobacterium longum, Enterococcus fecalis, Escherichia coli, Lactobacillus acidophilus, Lactobacillus fermentum, Lactobacillus plantarum, Weissella confusa, Saccharomyces cerevisiae) were characterized by high performance liquid chromatography for production of ethanol when grown on different carbohydrates: hexoses (glucose and fructose), pentoses (arabinose and ribose), disaccharides (lactose and lactulose), and inulin. Highest amounts of ethanol were produced by S. cerevisiae, L. fermentum and W. confusa on glucose and by S. cerevisiae and W. confusa on fructose. Due to mannitol-dehydrogenase expressed in L. fermentum, ethanol production on fructose was significantly (P < 0.05) reduced. Pyruvate and citrate, two potential electron acceptors for regeneration of NAD+/NADP+, drastically reduced ethanol production with acetate produced instead in L. fermentum grown on glucose and W. confusa grown on glucose and fructose, respectively. In fecal slurries prepared from feces of four overweight volunteers, ethanol was found to be produced upon addition of fructose. Addition of A. caccae, L. acidophilus, L. fermentum, as well as citrate and pyruvate, respectively, abolished ethanol production. However, addition of W. confusa resulted in significantly (P < 0.05) increased production of ethanol. These results indicate that microorganisms like W. confusa, a hetero-fermentative, mannitol-dehydrogenase negative lactic acid bacterium, may promote NAFLD through ethanol produced from sugar fermentation, while other intestinal bacteria and homo- and hetero-fermentative but mannitol-dehydrogenase positive lactic acid bacteria may not promote NAFLD. Also, our studies indicate that dietary factors interfering with gastrointestinal microbiota and microbial metabolism may be important in preventing or promoting NAFLD. لاكتساب بعض الأفكار المحددة حول الأدوار التي قد تلعبها الكائنات الحية الدقيقة في مرض الكبد الدهني غير الكحولي (NAFLD)، تميزت بعض بكتيريا حمض الأمعاء واللاكتيك وخميرة واحدة (Anaerostipes caccae، Bacteroides thetaiotaomicron، Bifidobacterium longum، Enterococcus fecalis، Escherichia coli، Lactobacillus acidophilus، Lactobacillus fermentum، Lactobacillus plantarum، Weissella confusa، Saccharomyces cerevisiae) بتصوير سائل عالي الأداء لإنتاج الإيثانول عند زراعته على كربوهيدرات مختلفة: hexoses (الجلوكوز والفركتوز)، pentoses (الأرابينوز والريبوز)، disaccharides (اللاكتوز واللاكتولوز)، و inulin. تم إنتاج أعلى كميات من الإيثانول بواسطة S. cerevisiae و L. fermentum و W. confusa على الجلوكوز و S. cerevisiae و W. confusa على الفركتوز. بسبب نازعة هيدروجين المانيتول المعبر عنها في L. fermentum، انخفض إنتاج الإيثانول على الفركتوز بشكل كبير (P < 0.05). قلل البيروفات والسيترات، وهما مستقبلان محتملان للإلكترون لتجديد NAD +/NADP+، بشكل كبير من إنتاج الإيثانول مع الأسيتات المنتجة بدلاً من ذلك في L. fermentum المزروع على الجلوكوز و W. confusa المزروع على الجلوكوز والفركتوز، على التوالي. في الملاط البرازي الذي تم تحضيره من براز أربعة متطوعين يعانون من زيادة الوزن، وجد أن الإيثانول يتم إنتاجه عند إضافة الفركتوز. إضافة A. caccae، L. acidophilus، L. fermentum، وكذلك السترات والبيروفات، على التوالي، ألغت إنتاج الإيثانول. ومع ذلك، أدت إضافة W. confusa إلى زيادة كبيرة في إنتاج الإيثانول (P < 0.05). تشير هذه النتائج إلى أن الكائنات الحية الدقيقة مثل W. confusa، وهي بكتيريا حمض اللاكتيك السلبية غير المتجانسة، قد تعزز NAFLD من خلال الإيثانول المنتج من تخمير السكر، في حين أن البكتيريا المعوية الأخرى وبكتيريا حمض اللاكتيك الإيجابية غير المتجانسة ولكن غير المتجانسة قد لا تعزز NAFLD. أيضًا، تشير دراساتنا إلى أن العوامل الغذائية التي تتداخل مع الكائنات الحية الدقيقة في الجهاز الهضمي والتمثيل الغذائي الميكروبي قد تكون مهمة في منع أو تعزيز NAFLD.

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      https://dx.doi.org/10.60692/fk...
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  • Authors: Julio Caballero; Fernando D. González Nilo; Ariela Vergara Jague; Jans Alzate-Morales;

    N2 and O6 substituted guanine derivatives are well-known as potent and selective CDK2 inhibitors. The ability of molecular docking using the program AutoDock3 and the hybrid method ONIOM, to obtain some quantum chemical descriptors with the aim to successfully rank these inhibitors, was assessed. The quantum chemical descriptors were used to explain the affinity, of the series studied, by a model of the CDK2 binding site. The initial structures were obtained from docking studies and the ONIOM method was applied with only a single point energy calculation on the protein-ligand structure. We obtained a good correlation model between the ONIOM derived quantum chemical descriptor "H-bond interaction energy" and the experimental biological activity, with a correlation coefficient value of R = 0.80 for 75 compounds. To the best of our knowledge, this is the first time that both methodologies are used in conjunction in order to obtain a correlation model. The model suggests that electrostatic interactions are the principal driving force in this protein-ligand interaction. Overall, the approach was successful for the cases considered, and it suggests that could be useful for the design of inhibitors in the lead optimization phase of drug discovery.

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    Authors: R. J. Reiffenstein; Manuel Mah;

    Ethanol has been claimed to potentiate greatly the lethality of propoxyphene, although published clinical data suggest only an additive effect. Mice were treated intraperitoneally with various doses of propoxyphene hydrochloride and ethanol. Isobolograms of the data show the combination to be less-than-additive for lethality and loss of motor coordination and, at worst, simply additive for sedation.

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    Canadian Journal of Physiology and Pharmacology
    Article . 1984 . Peer-reviewed
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      Canadian Journal of Physiology and Pharmacology
      Article . 1984 . Peer-reviewed
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  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Ali-Reza Khalili; Keyvan Amirshahrokhi;

    Excessive ethanol ingestion causes gastric mucosal damage through the inflammatory and oxidative processes. The present study was aimed to evaluate the protective effect of thalidomide on ethanol-induced gastric mucosal damage in mice. The animals were pretreated with vehicle or thalidomide (30 or 60 mg/kg, orally), and one hour later, the gastric mucosal injury was induced by oral administration of acidified ethanol. The animals were euthanized one hour after ethanol ingestion, and gastric tissues were collected to biochemical analyzes. The gastric mucosal lesions were assessed by macroscopic and histopathological examinations. The results showed that treatment of mice with thalidomide prior to the administration of ethanol dose-dependently reduced the gastric ulcer index. Thalidomide pretreatment significantly reduced the levels of pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6], malondialdehyde (MDA) and myeloperoxidase (MPO) activity. In addition, thalidomide significantly inhibited ethanol-induced nitric oxide (NO) overproduction in gastric tissue. Histological observations showed that ethanol-induced gastric mucosal damage was attenuated by thalidomide pretreatment. It seems that thalidomide as an anti-inflammatory agent may have a protective effect against alcohol-induced mucosal damage by inhibition of neutrophil infiltration and reducing the production of nitric oxide and inflammatory cytokines in gastric tissue.

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    Chemico-Biological Interactions
    Article . 2015 . Peer-reviewed
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      Chemico-Biological Interactions
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    Authors: Patrick, Sheila; McDowell, Andrew; Lee, Andrew; Frau, Alessandra; +4 Authors

    Aims The aim of this study was to determine whether the sequential application of povidone iodine-alcohol (PVI) followed by chlorhexidine gluconate-alcohol (CHG) would reduce surgical wound contamination to a greater extent than PVI applied twice in patients undergoing spinal surgery. Patients and Methods A single-centre, interventional, two arm, parallel group randomised controlled trial was undertaken, involving 407 patients who underwent elective spinal surgery. For 203 patients, the skin was disinfected before surgery using PVI (10% [w/w (1% w/w available iodine)] in 95% industrial denatured alcohol, povidone iodine; Videne Alcoholic Tincture) twice, and for 204 patients using PVI once followed by CHG (2% [w/v] chlorhexidine gluconate in 70% [v/v] isopropyl alcohol; Chloraprep with tint). The primary outcome measure was contamination of the wound determined by aerobic and anaerobic bacterial growth from samples taken after disinfection. Results The detection of viable bacteria in any one of the samples taken after disinfection (culture-positive) was significantly lower in the group treated with both PVI and CHG than in the group treated with PVI alone (59 (29.1%) versus 85 (41.7%), p = 0.009; odds ratio 0.574; 95% confidence interval, 0.380 to 0.866). Conclusions Antisepsis of the skin with the sequential application of PVI and CHG more effectively reduces the contamination of a surgical wound than PVI alone. Cite this article: Bone Joint J 2017;99-B:1354–65.

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    The Bone & Joint Journal
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      The Bone & Joint Journal
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    Authors: Clark W. Bird; Glenna J. Chavez; Megan J. Barber; C. Fernando Valenzuela;

    ABSTRACTPrenatal ethanol exposure causes a variety of cognitive deficits that have a persistent impact on quality of life, some of which may be explained by ethanol-induced alterations in interneuron function. Studies from several laboratories, including our own, have demonstrated that a single binge-like ethanol exposure during the equivalent to the third trimester of human pregnancy leads to acute apoptosis and long-term loss of interneurons in the rodent retrosplenial cortex (RSC). The RSC is interconnected with the hippocampus, thalamus, and other neocortical regions and plays distinct roles in visuospatial processing and storage, as well as retrieval of hippocampal-dependent episodic memories. Here we used slice electrophysiology to characterize the acute effects of ethanol on GABAergic neurotransmission in the RSC of neonatal mice, as well as the long-term effects of neonatal ethanol exposure on parvalbumin-interneuron mediated neurotransmission in adolescent mice. Mice were exposed to ethanol using vapor inhalation chambers. In postnatal day (P) 7 mouse pups, ethanol unexpectedly failed to potentiate GABAAreceptor-mediated synaptic transmission. Binge-like ethanol exposure of P7 mice expressing channel rhodopsin in parvalbumin-positive interneurons enhanced the peak amplitudes, asynchronous activity and total charge, while decreasing the rise-times of optically-evoked GABAAreceptor-mediated inhibitory postsynaptic currents in adolescent animals. These effects could partially explain the learning and memory deficits that have been documented in adolescent and young adult mice exposed to ethanol during the third trimester-equivalent developmental period.

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    Scientific Reports
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    Authors: A. M. de Oliveira; Eurode Legros; Sérgio Akira Uyemura; Jean-Claude Honoré; +5 Authors

    Background and purpose:The contribution of endothelin‐1 (ET‐1) to vascular hyper‐reactivity associated with chronic ethanol intake, a major risk factor in several cardiovascular diseases, remains to be investigated.Experimental approach:The biphasic haemodynamic responses to ET‐1 (0.01–0.1 nmol kg−1, i.v.) or to the selective ETB agonist, IRL1620 (0.001–1.0 nmol kg−1, i.v.), with or without ETA or ETB antagonists (BQ123 (c(DTrp‐Dasp‐Pro‐Dval‐Leu)) at 1 and 2.5 mg kg−1 and BQ788 (N‐cis‐2,6‐dimethyl‐piperidinocarbonyl‐L‐γ‐methylleucyl1‐D‐1methoxycarbonyltryptophanyl‐D‐norleucine) at 0.25 mg kg−1, respectively) were tested in anaesthetized rats, after 2 weeks' chronic ethanol treatment. Hepatic parameters and ET receptor protein levels were also determined.Key results:The initial hypotensive responses to ET‐1 or IRL1620 were unaffected by chronic ethanol intake, whereas the subsequent pressor effects induced by ET‐1, but not by IRL1620, were potentiated. BQ123 at 2.5 but not 1 mg kg−1 reduced the pressor responses to ET‐1 in ethanol‐treated rats. Conversely, BQ788 (0.25 mg kg−1) potentiated ET‐1‐induced increases in mean arterial blood pressure in control as well as in ethanol‐treated rats. Interestingly, in the latter group, increases in heart rate, induced by ET‐1 at a dose of 0.025 mg kg−1 were enhanced following ETB receptor blockade. Finally, we observed higher levels of ETA receptor in the heart and mesenteric artery and a reduction of ETB receptor protein levels in the aorta and kidney from rats chronically treated with ethanol.Conclusions and implications:Increased vascular reactivity to ET‐1 and altered protein levels of ETA and ETB receptors could play a role in the pathogenesis of cardiovascular complications associated with chronic ethanol consumption.British Journal of Pharmacology (2008) 154, 971–981; doi:10.1038/bjp.2008.157; published online 12 May 2008

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    British Journal of Pharmacology
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      British Journal of Pharmacology
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