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Sample records for acute ethanol administration

  1. Effect of acute ethanol administration on zebrafish tail-beat motion.

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    Bartolini, Tiziana; Mwaffo, Violet; Butail, Sachit; Porfiri, Maurizio

    2015-11-01

    Zebrafish is becoming a species of choice in neurobiological and behavioral studies of alcohol-related disorders. In these efforts, the activity of adult zebrafish is typically quantified using indirect activity measures that are either scored manually or identified automatically from the fish trajectory. The analysis of such activity measures has produced important insight into the effect of acute ethanol exposure on individual and social behavior of this vertebrate species. Here, we leverage a recently developed tracking algorithm that reconstructs fish body shape to investigate the effect of acute ethanol administration on zebrafish tail-beat motion in terms of amplitude and frequency. Our results demonstrate a significant effect of ethanol on the tail-beat amplitude as well as the tail-beat frequency, both of which were found to robustly decrease for high ethanol concentrations. Such a direct measurement of zebrafish motor functions is in agreement with evidence based on indirect activity measures, offering a complementary perspective in behavioral screening.

  2. Liver necrosis induced by acute intraperitoneal ethanol administration in aged rats.

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    Giavarotti, Leandro; D'Almeida, Vania; Giavarotti, Karin A S; Azzalis, Ligia A; Rodrigues, Luciano; Cravero, Amerys A M; Videla, Luis A; Koch, Osvaldo R; Junqueira, Virginia B C

    2002-03-01

    It is generally agreed that the deleterious pathophysiological effects of ethanol are caused, at least partially by an increase in free radical production. However, little attention has been directed to the effects of ethanol upon elderly organisms. Male Wistar rats at ages 3, 6, 12, 18 and 24 months were treated either with a single i.p. dose of 35% ethanol (v/v) at 3 g ethanol/kg body weight or an isovolumetric amount of 0.9% saline solution. We then assessed the plasma levels of transaminases and hepatic levels of oxidative stress-related parameters, followed by liver histological evaluation. The younger rats (3 months old) were not affected by the treatment with ethanol with respect to any of the studied parameters except for a lowering of total hepatic GSH and an increase in hepatic thiobarbituric acid reactants (TBARS) formation, while animals older than 3 months were increasingly more affected by the treatment. Acute ethanol treatment elicited the similar responses to those in the 3 months-old group, plus a decrease in the hepatic and plasma levels of beta-carotene and the plasma level of alpha-tocopherol, as well as an increase in the activity of plasma transaminases. In the 12,18 and 24 months old groups, there was increasing liver necrosis. These findings suggest that liver damage induced by acute ethanol administration in elderly rats may involve a lack of antioxidants.

  3. The Effect of Acute Ethanol and Gabapentin Administration on Spatial Learning and Memory

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    Fahimeh Yeganeh

    2011-09-01

    Full Text Available  Introduction: Patients with epilepsy can have impaired cognitive abilities. Many factors contribute to this impairment, including the adverse effects of antiepileptic drugs like Gabapentin (GBP. Apart from anti-epilectic action, Gabapentin is used to relieve ethanol withdrawal syndrome. Because both GBP and ethanol act on GABA ergic system, the purpose of this study was to evaluate their effect and interaction on spatial learning and memory. Material and Methods: Male Sprague-Dawley rats were trained in the Morris water maze for 5 consecutive days. On the sixth day, a probe test was performed to assess the retention phase or spatial rats’ memory ability. Ethanol (1.5 g/kg i.p. and GBP (30 mg/kg i.p. was administered each day 30 and 40 minutes before testing respectively. Results: Acute ethanol administration selectively impaired spatial memory (p<0.05, yet it failed to impair the acquisition phase (learning. Contradictorily GBP selectively impaired learning on second and forth days. Conclusion: These findings demonstrate that GBP and acute ethanol impair different phases of learning probably by modifying different neuronal pathways in cognitive areas of the brain.

  4. Redox state and energy metabolism during liver regeneration: alterations produced by acute ethanol administration.

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    Gutiérrez-Salinas, J; Miranda-Garduño, L; Trejo-Izquierdo, E; Díaz-Muñoz, M; Vidrio, S; Morales-González, J A; Hernández-Muñoz, R

    1999-12-01

    Ethanol metabolism can induce modifications in liver metabolic pathways that are tightly regulated through the availability of cellular energy and through the redox state. Since partial hepatectomy (PH)-induced liver proliferation requires an oversupply of energy for enhanced syntheses of DNA and proteins, the present study was aimed at evaluating the effect of acute ethanol administration on the PH-induced changes in cellular redox and energy potentials. Ethanol (5 g/kg body weight) was administered to control rats and to two-thirds hepatectomized rats. Quantitation of the liver content of lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, and adenine nucleotides led us to estimate the cytosolic and mitochondrial redox potentials and energy parameters. Specific activities in the liver of alcohol-metabolizing enzymes also were measured in these animals. Liver regeneration had no effect on cellular energy availability, but induced a more reduced cytosolic redox state accompanied by an oxidized mitochondrial redox state during the first 48 hr of treatment; the redox state normalized thereafter. Administration of ethanol did not modify energy parameters in PH rats, but this hepatotoxin readily blocked the PH-induced changes in the cellular redox state. In addition, proliferating liver promoted decreases in the activity of alcohol dehydrogenase (ADH) and of cytochrome P4502E1 (CYP2E1); ethanol treatment prevented the PH-induced diminution of ADH activity. In summary, our data suggest that ethanol could minimize the PH-promoted metabolic adjustments mediated by redox reactions, probably leading to an ineffective preparatory event that culminates in compensatory liver growth after PH in the rat.

  5. The role of glycerol-3-phosphate dehydrogenase 1 in the progression of fatty liver after acute ethanol administration in mice

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    Sato, Tomoki, E-mail: s13220@u-shizuoka-ken.ac.jp [Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526 (Japan); Morita, Akihito, E-mail: moritaa@u-shizuoka-ken.ac.jp [Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526 (Japan); Mori, Nobuko, E-mail: morin@b.s.osakafu-u.ac.jp [Department of Biological Science, Graduate School of Science, Osaka Prefecture University, 1-2 Gakuen-cho, Naka-ku, Sakai 599-8570 (Japan); Miura, Shinji, E-mail: miura@u-shizuoka-ken.ac.jp [Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526 (Japan)

    2014-02-21

    Highlights: • Ethanol administration increased GPD1 mRNA expression. • Ethanol administration increased glucose incorporation into TG glycerol moieties. • No increase in hepatic TG levels was observed in ethanol-injected GPD1 null mice. • We propose that GPD1 is required for ethanol-induced TG accumulation in the liver. - Abstract: Acute ethanol consumption leads to the accumulation of triglycerides (TGs) in hepatocytes. The increase in lipogenesis and reduction of fatty acid oxidation are implicated as the mechanisms underlying ethanol-induced hepatic TG accumulation. Although glycerol-3-phosphate (Gro3P), formed by glycerol kinase (GYK) or glycerol-3-phosphate dehydrogenase 1 (GPD1), is also required for TG synthesis, the roles of GYK and GPD1 have been the subject of some debate. In this study, we examine (1) the expression of genes involved in Gro3P production in the liver of C57BL/6J mice in the context of hepatic TG accumulation after acute ethanol intake, and (2) the role of GPD1 in the progression of ethanol-induced fatty liver using GPD1 null mice. As a result, in C57BL/6J mice, ethanol-induced hepatic TG accumulation began within 2 h and was 1.7-fold greater than that observed in the control group after 6 h. The up-regulation of GPD1 began 2 h after administering ethanol, and significantly increased 6 h later with the concomitant escalation in the glycolytic gene expression. The incorporation of {sup 14}C-labelled glucose into TG glycerol moieties increased during the same period. On the other hand, in GPD1 null mice carrying normal GYK activity, no significant increase in hepatic TG level was observed after acute ethanol intake. In conclusion, GPD1 and glycolytic gene expression is up-regulated by ethanol, and GPD1-mediated incorporation of glucose into TG glycerol moieties together with increased lipogenesis, is suggested to play an important role in ethanol-induced hepatic TG accumulation.

  6. Acute psychomotor effects of MDMA and ethanol (co-) administration over time in healthy volunteers

    NARCIS (Netherlands)

    Dumont, G J H; Schoemaker, R C; Touw, D J; Sweep, F C G J; Buitelaar, J K; van Gerven, J M A; Verkes, R J

    2010-01-01

    In Western societies, a considerable percentage of young people use 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy'). The use of alcohol (ethanol) in combination with ecstasy is common. The aim of the present study was to assess the acute psychomotor and subjective effects of (co-) administrati

  7. Acute ethanol administration inhibits Toll-like receptor 4 signaling pathway in rat intestinal epithelia.

    Science.gov (United States)

    Zhou, Chao; Zhao, Ji; Li, Jing; Wang, Haiying; Tang, Chengwei

    2013-05-01

    Excess alcohol intake, as in binge drinking, increases susceptibility to microbial pathogens. Alcohol impairs macrophage function by suppression of the Toll-like receptor 4 (TLR4) pathway. This study investigated the effects of acute ethanol intake on the TLR4 pathway in rat intestinal epithelia, which usually encounters luminal antigens at first and participates in the development of intestinal immunity. Twenty Wistar rats were randomly assigned to an ethanol group given ethanol as a 25% (v/v) solution in water at 7.5 g/kg, or a control group given saline, by oral gavage daily for 3 days. The epithelial histology and ultrastructure, the intestinal microflora, peripheral and portal venous plasma lipopolysaccharide (LPS) levels, and somatostatin (SST) levels in the peripheral plasma and small intestine were evaluated. Somatostatin receptor 2 (SSTR2), TLR4, TANK binding kinase-1 (TBK1), activated nuclear factor-κB (NF-κB), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in the intestinal mucosa were assayed. LPS responsiveness with or without SST pretreatment was assayed in vitro by quantification of TLR4, TBK1, activated NF-κB, IFN-γ and TNF-α in isolated intestinal epithelia. Mucosal damage was observed in the ethanol group by light and electron microscopy. Escherichia coli cultures were unchanged in rat intestine of the ethanol group compared with controls, but lactobacilli cultures were reduced (p TNF-α were unchanged in the ethanol group. LPS treatment in vitro up-regulated the level of TLR4, TBK1 and nuclear NF-κB as well as the production of IFN-γ and TNF-α in isolated intestinal epithelia in the control (p inhibited by SST pretreatment (p < 0.05). The peripheral plasma and intestinal levels of SST and the mucosal expression of SSTR2 in the ethanol group were significantly higher than in the control group (p < 0.05). These findings suggest the hyposensitivity of intestinal epithelial TLR4 to LPS induced by acute alcohol abuse

  8. Comparative studies of oral administration of marine collagen peptides from Chum Salmon (Oncorhynchus keta) pre- and post-acute ethanol intoxication in female Sprague-Dawley rats.

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    Liang, Jiang; Li, Qiong; Lin, Bing; Yu, Yongchao; Ding, Ye; Dai, Xiaoqian; Li, Yong

    2014-09-01

    The present study aimed to evaluate the effect of an oral administration of marine collagen peptides (MCPs) pre- and post-acute ethanol intoxication in female Sprague-Dawley (SD) rats. MCPs were orally administered to rats at doses of 0 g per kg bw, 2.25 g per kg bw, 4.5 g per kg bw and 9.0 g per kg bw, prior to or after the oral administration of ethanol. Thirty minutes after ethanol treatment, the effect of MCPs on motor incoordination and hypnosis induced by ethanol were investigated using a screen test, fixed speed rotarod test (5 g per kg bw ethanol) and loss of righting reflex (7 g per kg bw ethanol). In addition, the blood ethanol concentrations at 30, 60, 90, and 120 minutes after ethanol administration (5 g per kg bw ethanol) were measured. The results of the screen test and fixed speed rotarod test suggested that treatment with MCPs at 4.5 g per kg bw and 9.0 g per kg bw prior to ethanol could attenuate ethanol-induced loss of motor coordination. Moreover, MCP administered both pre- and post-ethanol treatment had significant potency to alleviate the acute ethanol induced hypnotic states in the loss of righting reflex test. At 30, 60, 90 and 120 minutes after ethanol ingestion at 5 g per kg bw, the blood ethanol concentration (BEC) of control rats significantly increased compared with that in the 4.5 g per kg bw and 9.0 g per kg bw MCP pre-treated groups. However, post-treatment with MCPs did not exert a significant inhibitory effect on the BEC of the post-treated groups until 120 minutes after ethanol administration. Therefore, the anti-inebriation effect of MCPs was verified in SD rats with the possible mechanisms related to inhibiting ethanol absorption and facilitating ethanol metabolism. Moreover, the efficiency was better when MCPs were administered prior to ethanol.

  9. Acute ethanol administration reduces the antidote effect of N-acetylcysteine after acetaminophen overdose in mice

    DEFF Research Database (Denmark)

    Dalhoff, K; Hansen, P B; Ott, P;

    1991-01-01

    1. The combined antidote effect of N-acetylcysteine and ethanol on the toxicity of acetaminophen was investigated. 2. Fed male mice were given acetaminophen i.p. (600 mg kg-1) and after 5 min in addition ethanol i.p. (0.2 ml, 19% v/v), N-acetylcysteine i.p. (1.2 g kg-1, 0.2 ml), N-acetylcysteine ......1. The combined antidote effect of N-acetylcysteine and ethanol on the toxicity of acetaminophen was investigated. 2. Fed male mice were given acetaminophen i.p. (600 mg kg-1) and after 5 min in addition ethanol i.p. (0.2 ml, 19% v/v), N-acetylcysteine i.p. (1.2 g kg-1, 0.2 ml), N...

  10. Xanthohumol, a prenylated flavonoid from hops (Humulus lupulus L., protects rat tissues against oxidative damage after acute ethanol administration

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    Carmen Pinto

    2014-01-01

    Full Text Available Ethanol-mediated free radical generation is directly involved in alcoholic liver disease. In addition, chronic alcohol bingeing also induces pathological changes and dysfunction in multi-organs. In the present study, the protective effect of xanthohumol (XN on ethanol-induced damage was evaluated by determining antioxidative parameters and stress oxidative markers in liver, kidney, lung, heart and brain of rats. An acute treatment (4 g/kg b.w. of ethanol resulted in the depletion of superoxide dismutase, catalase and glutathione S-transferase activities and reduced glutathione content. This effect was accompanied by the increased activity of tissue damage marker enzymes (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and lactate dehydrogenase and a significant increase in lipid peroxidation and hydrogen peroxide concentrations. Pre-treatment with XN protected rat tissues from ethanol-induced oxidative imbalance and partially mitigated the levels to nearly normal levels in all tissues checked. This effect was dose dependent, suggesting that XN reduces stress oxidative and protects rat tissues from alcohol-induced injury.

  11. Induction of experimental acute ulcerative colitis in rats by administration of dextran sulfate sodium at low concentration followed by intracolonic administration of 30% ethanol

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Several models of experimental ulcerative colitis have been reported previously. However, none of these models showed the optimum characteristics. Although dextran sulfate sodium-induced colitis results in inflammation resembling ulcerative colitis, an obvious obstacle is that dextran sulfate sodium is very expensive. The aim of this study was to develop an inexpensive model of colitis in rats. Sprague-Dawley rats were treated with 2% dextran sulfate sodium in drinking water for 3 d followed by an intracolonic administration of 30% ethanol. The administration of 2% dextran sulfate sodium followed by 30% ethanol induced significant weight loss, diarrhea and hematochezia in rats. Severe ulceration and inflammation of the distal part of rat colon were developed rapidly. Histological examination showed increased infiltration of polymorphonuclear leukocytes,lymphocytes and existence of cryptic abscesses and dysplasia. The model induced by dextran sulfate sodium at lower concentration followed by 30% ethanol is characterized by a clinical course, localization of the lesions and histopathological features similar to human ulcerative colitis and fulfills the criteria set out at the beginning of this study.

  12. Estradiol increases expression of the brain-derived neurotrophic factor after acute administration of ethanol in the neonatal rat cerebellum.

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    Firozan, Bita; Goudarzi, Iran; Elahdadi Salmani, Mahmoud; Lashkarbolouki, Taghi; Rezaei, Arezou; Abrari, Kataneh

    2014-06-05

    Recently it has been shown that estradiol prevents the toxicity of ethanol in developing cerebellum. The neuroprotective effect of estradiol is not due to a single phenomenon but rather encompasses a spectrum of independent proccesses. According to the specific timing of Purkinje cell vulnerability to ethanol and several protective mechanisms of estradiol, we considered the neurotrophin system, as a regulator of differentiation, maturation and survival of neurons during CNS development. Interactions between estrogen and Brain derived neurotrophic factor (BDNF, an essential factor in neuronal survival) lead us to investigate involvement of BDNF pathway in neuroprotective effects of estrogen against ethanol toxicity. In this study, 17β-estradiol (300-900μg/kg) was injected subcutaneously in postnatal day (PD) 4, 30min prior to intraperitoneal injection of ethanol (6g/kg) in rat pups. Eight hours after injection of ethanol, BDNF mRNA and protein levels were assayed. Behavioral studies, including rotarod and locomotor activity tests were performed in PD 21-23 and histological study was performed after completion of behavioral tests in PD 23. Our results indicated that estradiol increased BDNF mRNA and protein levels in the presence of ethanol. We also observed that pretreatment with estradiol significantly attenuated ethanol-induced motoric impairment. Histological analysis also demonstrated that estradiol prevented Purkinje cell loss following ethanol treatment. These results provide evidence on the possible mechanisms of estradiol neuroprotection against ethanol toxicity.

  13. Effect of ethanol administration and withdrawal on GABA receptor binding in rat cerebral cortex

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    Volicer, L.; Biagioni, T.M.

    1982-01-01

    Sodium independent GABA receptor binding was measured in synaptosomes prepared from cerebral cortex of rats made ethanol dependent by three daily ethanol administrations. In rats sacrificed 1 hour after the last ethanol dose there was a lower number of low affinity binding sites and lower affinity of the high affinity binding than in controls. The decreased affinity was present only in rats who showed symptoms of ethanol withdrawal during the course of ethanol administration. In rats sacrificed during ethanol withdrawal the affinity of the high affinity binding was lower than in controls and other binding characteristics were unchanged. This decreased binding was normalized by repeated Triton X-100 incubations indicating involvement of an endogenous inhibitor in this ethanol effect. Acute ethanol administration did not change GABA receptor binding.

  14. Intravenous pyridoxine in acute ethanol intoxication.

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    Mardel, S; Phair, I; O'Dwyer, F; Henry, J A

    1994-05-01

    Intravenous pyridoxine was evaluated as an agent for the reversal of ethanol-induced central nervous depression in a randomised double blind controlled study of 108 patients presenting with a clinical diagnosis of acute ethanol intoxication to two accident and emergency departments. Level of consciousness, measured by a modified Glasgow coma scale, showed no significant change after a single 1 g dose of intravenous pyridoxine when compared to controls given saline. The mean fall in blood alcohol concentration after one hour was 33 mg dl-1 (7.2 mmol l-1) in both groups suggesting that pyridoxine has no antidotal action and no short term effect on the rate of metabolism of ethanol.

  15. Influence of zinc sulfate intake on acute ethanol-induced liver injury in rats

    Institute of Scientific and Technical Information of China (English)

    Sema Bolkent; Pelin Arda-Pirincci; Sehnaz Bolkent; Refiye Yanardag; Sevim Tunali; Sukriye Yildirim

    2006-01-01

    AIM: To investigate the role of metallothionein and proliferating cell nuclear antigen (PCNA) on the morphological and biochemical effects of zinc sulfate in ethanol-induced liver injury.METHODS: Wistar albino rats were divided into four groups. Group I; intact rats, group Ⅱ; control rats given only zinc, group Ⅲ; animals given absolute ethanol, group Ⅳ; rats given zinc and absolute ethanol.Ethanol-induced injury was produced by the 1 mL of absolute ethanol, administrated by gavage technique to each rat. Animals received 100 mg/kg per day zinc sulfate for 3 d 2 h prior to the administration of absolute ethanol.RESULTS: Increases in metallothionein immunoreactivity in control rats given only zinc and rats given zinc and ethanol were observed. PCNA immunohistochemistry showed that the number of PCNA-positive hepatocytes was increased significantly in the livers of rats administered ethanol + zinc sulfate. Acute ethanol exposure caused degenerative morphological changes in the liver. Blood glutathione levels decreased, serum alkaline phosphatase and aspartate transaminase activities increased in the ethanol group when compared to the control group. Liver glutathione levels were reduced, but lipid peroxidation increased in the livers of the group administered ethanol as compared to the other groups. Administration of zinc sulfate in the ethanol group caused a significant decrease in degenerative changes, lipid peroxidation, and alkaline phosphatase and aspartate transaminase activities, but an increase in liver glutathione.CONCLUSION: Zinc sulfate has a protective effect on ethanol-induced liver injury. In addition, cell proliferation may be related to the increase in metallothionein immunoreactivity in the livers of rats administered ethanol + zinc sulfate.

  16. Acute Ethanol Intake Induces NAD(P)H Oxidase Activation and Rhoa Translocation in Resistance Arteries

    Science.gov (United States)

    Simplicio, Janaina A.; Hipólito, Ulisses Vilela; do Vale, Gabriel Tavares; Callera, Glaucia Elena; Pereira, Camila André; Touyz, Rhian M; Tostes, Rita de Cássia; Tirapelli, Carlos R.

    2016-01-01

    Background The mechanism underlying the vascular dysfunction induced by ethanol is not totally understood. Identification of biochemical/molecular mechanisms that could explain such effects is warranted. Objective To investigate whether acute ethanol intake activates the vascular RhoA/Rho kinase pathway in resistance arteries and the role of NAD(P)H oxidase-derived reactive oxygen species (ROS) on such response. We also evaluated the requirement of p47phox translocation for ethanol-induced NAD(P)H oxidase activation. Methods Male Wistar rats were orally treated with ethanol (1g/kg, p.o. gavage) or water (control). Some rats were treated with vitamin C (250 mg/kg, p.o. gavage, 5 days) before administration of water or ethanol. The mesenteric arterial bed (MAB) was collected 30 min after ethanol administration. Results Vitamin C prevented ethanol-induced increase in superoxide anion (O2-) generation and lipoperoxidation in the MAB. Catalase and superoxide dismutase activities and the reduced glutathione, nitrate and hydrogen peroxide (H2O2) levels were not affected by ethanol. Vitamin C and 4-methylpyrazole prevented the increase on O2- generation induced by ethanol in cultured MAB vascular smooth muscle cells. Ethanol had no effect on phosphorylation levels of protein kinase B (Akt) and eNOS (Ser1177 or Thr495 residues) or MAB vascular reactivity. Vitamin C prevented ethanol-induced increase in the membrane: cytosol fraction ratio of p47phox and RhoA expression in the rat MAB. Conclusion Acute ethanol intake induces activation of the RhoA/Rho kinase pathway by a mechanism that involves ROS generation. In resistance arteries, ethanol activates NAD(P)H oxidase by inducing p47phox translocation by a redox-sensitive mechanism. PMID:27812679

  17. Ethanol co-administration moderates 3,4-methylenedioxymethamphetamine effects on human physiology.

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    Dumont, G J H; Kramers, C; Sweep, F C G J; Willemsen, J J; Touw, D J; Schoemaker, R C; van Gerven, J M A; Buitelaar, J K; Verkes, R J

    2010-02-01

    Alcohol is frequently used in combination with 3,4-methylenedioxymethamphetamine (MDMA). Both drugs affect cardiovascular function, hydration and temperature regulation, but may have partly opposing effects. The present study aims to assess the acute physiologic effects of (co-) administration of MDMA and ethanol over time. A four-way, double blind, randomized, crossover, placebo-controlled study in 16 healthy volunteers (9 male and 7 female) between the ages of 18 and 29. MDMA (100 mg) was given orally and blood ethanol concentration was maintained at pseudo-steady state levels of 0.6 per thousand by a three-hour 10% intravenous ethanol clamp. Cardiovascular function, temperature and hydration measures were recorded throughout the study days. Ethanol did not significantly affect physiologic function, with the exception of a short lasting increase in heart rate. MDMA potently increased heart rate and blood pressure and induced fluid retention as well as an increase in temperature. Co-administration of ethanol with MDMA did not affect cardiovascular function compared to the MDMA alone condition, but attenuated the effects of MDMA on fluid retention and showed a trend for attenuation of MDMA-induced temperature increase. In conclusion, co-administration of ethanol and MDMA did not exacerbate physiologic effects compared to all other drug conditions, and moderated some effects of MDMA alone.

  18. Gastroprotective effects of Leejung-tang, an oriental traditional herbal formula, on ethanol-induced acute gastric injury in rats.

    Science.gov (United States)

    Shin, In-Sik; Lee, Mee-Young; Lim, Hye-Sun; Seo, Chang-Seob; Ha, Hye-Kyung; Shin, Hyeun-Kyoo

    2013-01-01

    Leejung-tang (LJT, Rechu-to in Japanese and Lizhong-tang in Chinese) is an oriental traditional traditional herbal formula. LJT has been used for treatment of gastrointestinal disorders in Korea, Japan, and China for a long time. In present study, we investigated the protective effects of LJT against absolute ethanol induced gastric injuries. Rats in the control group were given PBS orally (5 mL/kg body weight) as the vehicle, and the absolute-ethanol group (EtOH group) received absolute ethanol (5 mL/kg body weight) by oral gavage. Rats in the positive control group were given omeprazole orally (50 mg/kg body weight) 2 h prior to the administration of absolute ethanol. The treatment groups received LJT (400 mg/kg body weight) 2 h prior to absolute ethanol administration. All rats were sacrificed 1 h after receiving the ethanol treatment. The stomach was excised for macroscopic examination and biochemical analysis. The administration of LJT protected gastric mucosa against ethanol-induced acute gastric injury, including hemorrhage and hyperemia. LJT reduced the increase in lipid peroxidation in ethanol-induced acute gastric lesions. LJT increased GSH content and activities of the antioxidant enzymes, catalase, glutathione-S-transferase, glutathione reductase, glutathione peroxidase, and superoxide dismutase. These results indicate that LJT protects gastric mucosa against ethanol-induced acute gastric injury by increasing their antioxidant content. We suggest that LJT can be developed as an effective drug for the treatment of acute gastric injury.

  19. Maternal metallothionein and zinc after acute ethanol exposure during gestation in the rat

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    Harris, J.E. (Univ. of Kansas, Kansas City (United States))

    1992-02-26

    Acute exposure of the rat fetus to ethanol at critical periods can cause growth retardation and brain damage; the mechanism(s) is not known. Ethanol may cause redistribution of maternal zinc which results in fetal zinc deficiency and subsequent interruption of growth and development. The purpose was to determine if acute ethanol administration to the pregnant rat alters Zn and the Zn binding protein metallothionein (MT) in selected tissues. On gestational day (gd) 14, eighteen pregnant Sprague-Dawley rats were divided into groups. By intragastric tube, ethanol treated dams were given ethanol and pairfed controls were given a 0.85% NaCl solution. On gd 15, intragastric feedings were repeated. Throughout, the Lieber-DeCarli control diet was fed (adlibitum to untreated controls and ethanol treated dams and in appropriate quantities to pair fed controls). Blood ethanol concentrations at 90 minutes after the ethanol dose were 154 {plus minus} 46 and 265 {plus minus} 110 mg% on gd 14 and 15, respectively.

  20. Acute ethanol intake induces superoxide anion generation and mitogen-activated protein kinase phosphorylation in rat aorta: A role for angiotensin type 1 receptor

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    Yogi, Alvaro; Callera, Glaucia E. [Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario (Canada); Mecawi, André S. [Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP (Brazil); Batalhão, Marcelo E.; Carnio, Evelin C. [Department of General and Specialized Nursing, College of Nursing of Ribeirão Preto, USP, São Paulo (Brazil); Antunes-Rodrigues, José [Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP (Brazil); Queiroz, Regina H. [Department of Clinical, Toxicological and Food Science Analysis, Faculty of Pharmaceutical Sciences, USP, São Paulo (Brazil); Touyz, Rhian M. [Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario (Canada); Tirapelli, Carlos R., E-mail: crtirapelli@eerp.usp.br [Department of Psychiatric Nursing and Human Sciences, Laboratory of Pharmacology, College of Nursing of Ribeirão Preto, USP, Ribeirão Preto, SP (Brazil)

    2012-11-01

    Ethanol intake is associated with increase in blood pressure, through unknown mechanisms. We hypothesized that acute ethanol intake enhances vascular oxidative stress and induces vascular dysfunction through renin–angiotensin system (RAS) activation. Ethanol (1 g/kg; p.o. gavage) effects were assessed within 30 min in male Wistar rats. The transient decrease in blood pressure induced by ethanol was not affected by the previous administration of losartan (10 mg/kg; p.o. gavage), a selective AT{sub 1} receptor antagonist. Acute ethanol intake increased plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity, plasma angiotensin I (ANG I) and angiotensin II (ANG II) levels. Ethanol induced systemic and vascular oxidative stress, evidenced by increased plasma thiobarbituric acid-reacting substances (TBARS) levels, NAD(P)H oxidase‐mediated vascular generation of superoxide anion and p47phox translocation (cytosol to membrane). These effects were prevented by losartan. Isolated aortas from ethanol-treated rats displayed increased p38MAPK and SAPK/JNK phosphorylation. Losartan inhibited ethanol-induced increase in the phosphorylation of these kinases. Ethanol intake decreased acetylcholine-induced relaxation and increased phenylephrine-induced contraction in endothelium-intact aortas. Ethanol significantly decreased plasma and aortic nitrate levels. These changes in vascular reactivity and in the end product of endogenous nitric oxide metabolism were not affected by losartan. Our study provides novel evidence that acute ethanol intake stimulates RAS activity and induces vascular oxidative stress and redox-signaling activation through AT{sub 1}-dependent mechanisms. These findings highlight the importance of RAS in acute ethanol-induced oxidative damage. -- Highlights: ► Acute ethanol intake stimulates RAS activity and vascular oxidative stress. ► RAS plays a role in acute ethanol-induced oxidative damage via AT{sub 1} receptor activation.

  1. Acute Ethanol Causes Hepatic Mitochondrial Depolarization in Mice: Role of Ethanol Metabolism

    Science.gov (United States)

    Zhong, Zhi; Ramshesh, Venkat K.; Rehman, Hasibur; Liu, Qinlong; Theruvath, Tom P.; Krishnasamy, Yasodha; Lemasters, John J.

    2014-01-01

    Background/Aims An increase of ethanol metabolism and hepatic mitochondrial respiration occurs in vivo after a single binge of alcohol. Here, our aim was to determine how ethanol intake affects hepatic mitochondrial polarization status in vivo in relation to ethanol metabolism and steatosis. Methods Hepatic mitochondrial polarization, permeability transition (MPT), and reduce pyridine nucleotides, and steatosis in mice were monitored by intravital confocal/multiphoton microscopy of the fluorescence of rhodamine 123 (Rh123), calcein, NAD(P)H, and BODIPY493/503, respectively, after gavage with ethanol (1–6 g/kg). Results Mitochondria depolarized in an all-or-nothing fashion in individual hepatocytes as early as 1 h after alcohol. Depolarization was dose- and time-dependent, peaked after 6 to 12 h and maximally affected 94% of hepatocytes. This mitochondrial depolarization was not due to onset of the MPT. After 24 h, mitochondria of most hepatocytes recovered normal polarization and were indistinguishable from untreated after 7 days. Cell death monitored by propidium iodide staining, histology and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was low throughout. After alcohol, mitochondrial NAD(P)H autofluorescence increased and decreased, respectively, in hepatocytes with polarized and depolarized mitochondria. Ethanol also caused steatosis mainly in hepatocytes with depolarized mitochondria. Depolarization was linked to ethanol metabolism, since deficiency of alcohol dehydrogenase and cytochrome-P450 2E1 (CYP2E1), the major ethanol-metabolizing enzymes, decreased mitochondrial depolarization by ∼70% and ∼20%, respectively. Activation of aldehyde dehydrogenase decreased depolarization, whereas inhibition of aldehyde dehydrogenase enhanced depolarization. Activation of aldehyde dehydrogenase also markedly decreased steatosis. Conclusions Acute ethanol causes reversible hepatic mitochondrial depolarization in vivo that may contribute to

  2. Effect of acute ethanol ingestion on fat absorption.

    Science.gov (United States)

    Boquillon, M

    1976-12-01

    A test meal (300 mg casein, 600 mg sucrose, 100 mg corn oil, tracer dose of 9.10(3)H oleic acid) was given to fasting adult rats with intestinal lymph fistulas. One group received an acute oral dose of ethanol (3.2 g/kg body weight) simultaneously with the test meal. Controls received 2.5 ml of water instead of ethanol. Ingestion of ethanol temporarily delayed the removal of lipid radioactivity from the stomachs. More than 25% of radioactivity fed remained 8 hr after feeding whereas with control rats less than 10% of lipid radioactivity fed remained 6 hr after feeding. In controls and ethanol-treated rats, the amounts of exogenous lipids in the intestinal lumen and mucosa were low and similar enough. Quantities of endogenous and exogenous lipids found in the lymph collected during 24 hr after feeding were similar in the two groups, but the fat absorption peak was found after 6 hr in alcoholic rats and before 6 hr in controls. This delay was probably due to the retention of lipids in the stomach. More of the exogenous lipid was always transported by small particles moving in the region of alpha1 globulins in cellulose acetate electrophoresis than by larger particles remaining at the origin. This proportion was enhanced in the ethanol-treated animals. The larger fat particles were richer in endogenous fatty acids in alcohol-treated rats than in controls.

  3. The combination of atorvastatin and ethanol is not more hepatotoxic to rats than the administration of each drug alone

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    D.T. Ito

    2007-03-01

    Full Text Available Animal studies and premarketing clinical trials have revealed hepatotoxicity of statins, primarily minor elevations in serum alanine aminotransferase levels. The combined chronic use of medicines and eventual ethanol abuse are common and may present a synergistic action regarding liver injury. Our objective was to study the effect of the chronic use of atorvastatin associated with acute ethanol administration on the liver in a rat model. One group of rats was treated daily for 5 days a week for 2 months with 0.8 mg/kg atorvastatin by gavage. At the end of the treatment the livers were perfused with 72 mM ethanol for 60 min. Control groups (at least 4 animals in each group consisted of a group of 2-month-old male Wistar EPM-1 rats exposed to 10% ethanol (v/v ad libitum replacing water for 2 months, followed by perfusion of the liver with 61 nM atorvastatin for 60 min, and a group of animals without chronic ethanol treatment whose livers were perfused with atorvastatin and/or ethanol. The combination of atorvastatin with ethanol did not increase the release of injury marker enzymes (alanine aminotransferase, aspartate aminotransferase, and lactic dehydrogenase from the liver and no change in liver function markers (bromosulfophthalein clearance, and oxygen consumption was observed. Our results suggest that the combination of atorvastatin with ethanol is not more hepatotoxic than the separate use of each substance.

  4. In Vivo Acute on Chronic Ethanol Effects in Liver: A Mouse Model Exhibiting Exacerbated Injury, Altered Metabolic and Epigenetic Responses.

    Science.gov (United States)

    Shukla, Shivendra D; Aroor, Annayya R; Restrepo, Ricardo; Kharbanda, Kusum K; Ibdah, Jamal A

    2015-11-20

    Chronic alcoholics who also binge drink (i.e., acute on chronic) are prone to an exacerbated liver injury but its mechanism is not understood. We therefore investigated the in vivo effects of chronic and binge ethanol ingestion and compared to chronic ethanol followed by three repeat binge ethanol on the liver of male C57/BL6 mice fed ethanol in liquid diet (4%) for four weeks followed by binge ethanol (intragastric administration, 3.5 g/kg body weight, three doses, 12h apart). Chronic followed by binge ethanol exacerbated fat accumulation, necrosis, decrease in hepatic SAM and SAM:SAH ratio, increase in adenosine levels, and elevated CYP2E1 levels. Histone H3 lysine acetylation (H3AcK9), dually modified phosphoacetylated histone H3 (H3AcK9/PS10), and phosphorylated H2AX increased after binge whereas phosphorylation of histone H3 ser 10 (H3S10) and H3 ser 28 (H3S28) increased after chronic ethanol-binge. Histone H3 lysine 4 and 9 dimethylation increased with a marked dimethylation in H3K9 in chronic ethanol binge group. Trimethylated histone H3 levels did not change. Nuclear levels of histone acetyl transferase GCN5 and histone deacetylase HDAC3 were elevated whereas phospho-CREB decreased in a distinctive manner. Taken together, acute on chronic ethanol ingestion caused amplification of liver injury and elicited characteristic profiles of histone modifications, metabolic alterations, and changes in nuclear protein levels. These findings demonstrate that chronic ethanol exposure renders liver more susceptible to repeat acute/binge ethanol induced acceleration of alcoholic liver disease.

  5. Adaptations in Basal and Hypothalamic–Pituitary–Adrenal-Activated Deoxycorticosterone Responses Following Ethanol Self-administration in Cynomolgus Monkeys

    Science.gov (United States)

    Jimenez, Vanessa A.; Porcu, Patrizia; Morrow, A. Leslie; Grant, Kathleen A.

    2017-01-01

    Acute ethanol activates the hypothalamic–pituitary–adrenal (HPA) axis, while long-term exposure results in a blunted neuroendocrine state, particularly with regards to the primary endpoint, cortisol, the primary glucocorticoid produced in the adrenal cortex. However, it is unknown if this dampened neuroendocrine status also influences other adrenocortical steroids. Plasma concentration of the mineralocorticoid and neuroactive steroid precursor deoxycorticosterone (DOC) is altered by pharmacological challenges of the HPA axis in cynomolgus monkeys. The present study investigated HPA axis regulation of circulating DOC concentration over the course of ethanol (4% w/v) induction and self-administration in non-human primates (Macaca fasciculata, n = 10). Plasma DOC, measured by radioimmunoassay, was compared at baseline (ethanol naïve), during schedule-induced polydipsia, and following 6-months of 22 h/day access to ethanol and water. The schedule induction of ethanol drinking did not alter basal DOC levels but selectively dampened the DOC response to pharmacological challenges aimed at the anterior pituitary (ovine corticotrophin-releasing hormone) and adrenal gland (post-dexamethasone adrenocorticotropin hormone), while pharmacological inhibition of central opioid receptors with naloxone greatly enhanced the DOC response during induction. Following 6 months of ethanol self-administration, basal DOC levels were increased more than twofold, while responses to each of the challenges normalized somewhat but remained significantly different than baseline. These data show that HPA axis modulation of the neuroactive steroid precursor DOC is markedly altered by the schedule induction of ethanol drinking and long-term voluntary ethanol self-administration. The consequences of chronic ethanol consumption on HPA axis regulation of DOC point toward allostatic modification of hypothalamic and adrenal function. PMID:28220108

  6. Postnatal Administration of Allopregnanolone Modifies Glutamate Release but Not BDNF Content in Striatum Samples of Rats Prenatally Exposed to Ethanol

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    Roberto Yunes

    2015-01-01

    Full Text Available Ethanol consumption during pregnancy may induce profound changes in fetal CNS development. We postulate that some of the effects of ethanol on striatal glutamatergic transmission and neurotrophin expression could be modulated by allopregnanolone, a neurosteroid modulator of GABAA receptor activity. We describe the acute pharmacological effect of allopregnanolone (65 μg/kg, s.c. administered to juvenile male rats (day 21 of age on the corticostriatal glutamatergic pathway, in both control and prenatally ethanol-exposed rats (two ip injections of 2.9 g/kg in 24% v/v saline solution on gestational day 8. Prenatal ethanol administration decreased the K+-induced release of glutamate regarding the control group. Interestingly, this effect was reverted by allopregnanolone. Regarding BDNF, allopregnanolone decreases the content of this neurotrophic factor in the striatum of control groups. However, both ethanol alone and ethanol plus allopregnanolone treated animals did not show any change regarding control values. We suggest that prenatal ethanol exposure may produce an alteration of GABAA receptors which blocks the GABA agonist-like effect of allopregnanolone on rapid glutamate release, thus disturbing normal neural transmission. Furthermore, the reciprocal interactions found between GABAergic neurosteroids and BDNF could underlie mechanisms operating during the neuronal plasticity of fetal development.

  7. Hepatoprotective Evaluation of Ganoderma lucidum Pharmacopuncture: In vivo Studies of Ethanol-induced Acute Liver Injury

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    Sun-Hee Jang

    2014-09-01

    Full Text Available Objectives: Alcohol abuse is a public issue and one of the major causes of liver disease worldwide. This study was aimed at investigating the protective effect of Ganoderma lucidum pharmacopuncture (GLP against hepatotoxicity induced by acute ethanol (EtOH intoxication in rats. Methods: Sprague-Dawley (SD rats were divided into 4 groups of 8 animals each: normal, control, normal saline pharmacopuncture (NP and GLP groups. The control, NP and GLP groups received ethanol orally. The NP and the GLP groups were treated daily with injections of normal saline and Ganoderma lucidum extract, respectively. The control group received no treatment. The rats in all groups, except the normal group, were intoxicated for 6 hours by oral administration of EtOH (6 g/kg BW. The same volume of distilled water was administered to the rats in the normal group. Two local acupoints were used: Qimen (LR14 and Taechung (LR3. A histopathological analysis was performed, and the liver function and the activities of antioxidant enzymes were assessed. Results: GLP treatment reduced the histological changes due to acute liver injury induced by EtOH and significantly reduced the increase in the alanine aminotransferase (ALT enzyme; however, it had an insignificant effect in reducing the increase in aspartate aminotransferase (AST enzyme. It also significantly ameliorated the superoxide dismutase (SOD and the catalase (CAT activities. Conclusion: The present study suggests that GLP treatment is effective in protecting against ethanol-induced acute hepatic injury in SD rats by modulating the activities of ethanol metabolizing enzymes and by attenuating oxidative stress.

  8. Water-insoluble fractions of botanical foods lower blood ethanol levels in rats by physically maintaining the ethanol solution after ethanol administration

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    Shunji Oshima

    2015-11-01

    Full Text Available Background: Several studies have analyzed the functions of foods and dietary constituents in the dynamics of alcohol metabolism. However, few studies have reported the function of dietary fibers in the dynamics of alcohol metabolism. Objective: We assessed the effects of botanical foods that contain dietary fibers on alcohol metabolism. Methods: The ability of the water-insoluble fraction (WIF of 18 kinds of botanical foods to maintain 15% (v/v ethanol solution was examined using easily handled filtration. A simple linear regression analysis was performed to examine the correlation between the filtered volumes and blood ethanol concentration (BEC in F344 rats 4 h after the ingestion of 4.0 g/kg of ethanol following dosage of 2.5% (w/v WIF of the experimental botanical foods. Furthermore, the supernatant (6.3 Brix; water-soluble fraction and precipitate (WIF of tomato, with a strong ethanol-maintaining ability, were obtained and BEC and the residual gastric ethanol in rats were determined 2 h after the administration of 4.0 g/kg of ethanol and the individuals fractions. Results: The filtered volumes of dropped ethanol solutions containing all the botanical foods tested except green peas were decreased compared with the ethanol solution without WIF (control. There was a significant correlation between the filtered volumes and blood ethanol concentration (BEC. There was no significant difference in the residual gastric ethanol between controls and the supernatant group; however, it was increased significantly in the WIF group than in controls or the supernatant group. Consistent with this, BEC reached a similar level in controls and the supernatant group but significantly decreased in the WIF group compared with controls or the supernatant group. Conclusions: These findings suggest that WIFs of botanical foods, which are mostly water-insoluble dietary fibers, possess the ability to absorb ethanol-containing solutions, and this ability correlates

  9. Sub-acute toxicity of a hydro-ethanolic whole plant extract of Synedrella nodiflora (L Gaertn in rats

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    Samuel Adjei

    2014-01-01

    Full Text Available Objectives: Synedrella nodiflora (L Gaertn (family Asteraceae is traditionally used in Ghana for the management of epilepsy, hiccup and threatened abortion. The anticonvulsant and other related neuro-pharmacological effects of a hydro-ethanolic extract in murine models have been established. To this end, we evaluated a sub-acute toxicity of the hydro-ethanolic whole plant extract in rats. Materials and Methods: The effects of a continuous 14-day oral administration of the extract (100, 300 and 1000 mg/kg on haematological and serum biochemical parameters were measured. Results: The extract produced no mortality in the rats treated during the study period. The extract also did not significantly affect any of the haematological and serum biochemical indices measured. Conclusion: This result suggests that a 14-day oral administration of the hydro-ethanolic extract of Synedrella nodiflora is relatively safe in Sprague-Dawley male rats under the present laboratory conditions.

  10. Evaluation of the antinociceptive activity and acute oral toxicity of standardized ethanolic extract of the rhizome of Curcuma xanthorrhiza Roxb.

    Science.gov (United States)

    Devaraj, Sutha; Esfahani, Azadeh Sabetghadam; Ismail, Sabariah; Ramanathan, Surash; Yam, Mun Fei

    2010-04-22

    Ethanolic extract of Curcuma xanthorrhiza was used to evaluate the analgesic and toxicity effects in vivo. The extract was standardized using GC-MS, which showed that 1 mg of Curcuma xanthorrhiza ethanolic extract contains 0.1238 mg of xanthorrhizol. The analgesic activity was studied in rats using three different models, namely the hot plate test, tail flick test and formalin-induced pain test. The acute oral toxicity was examined by the oral administration of standardized Curcuma xanthorrhiza ethanolic extract in mice at doses ranging from 300-5,000 mg/kg and observation for 14 days. Standardized Curcuma xanthorrhiza ethanolic extract did not show significant analgesic effect in the hot plate and tail flick tests. However, in the formalin-induced pain test, Curcuma xanthorrhiza ethanolic extract significantly (P Curcuma xanthorrhiza ethanolic extract did not show any toxic effects in mice at 5 g/kg. These experimental results suggest that the standardized Curcuma xanthorrhiza ethanolic extract showed peripheral and central antinociceptive activity associated with neurogenic pain as well as a relative absence of toxic effects which could compromise the medicinal use of this plant in folk medicine.

  11. Effects of Withania somnifera on oral ethanol self-administration in rats.

    Science.gov (United States)

    Peana, Alessandra T; Muggironi, Giulia; Spina, Liliana; Rosas, Michela; Kasture, Sanjay B; Cotti, Elisabetta; Acquas, Elio

    2014-10-01

    Recent evidence has shown that Withania somnifera Dunal (Ashwagandha or Indian ginseng), a herbal remedy used in traditional medicine, impairs morphine-elicited place conditioning. Here, we investigated the effect of W. somnifera roots extract (WSE) on motivation for drinking ethanol using operant self-administration paradigms. Wistar rats were trained to self-administer ethanol (10%) by nose-poking. The effects of WSE (25-75 mg/kg) were evaluated on acquisition and maintenance, on ethanol breakpoint under a progressive-ratio schedule of reinforcement and on the deprivation effect and reinstatement of seeking behaviours. Moreover, on the basis of the recent suggestion of an involvement of GABAB receptors in WSE central effects, we studied the interaction between WSE and GABAB ligands. The effect of WSE on saccharin (0.05%) oral self-administration was also tested. The results show that WSE reduced the acquisition, maintenance and breakpoint of ethanol self-administration. WSE also reduced the deprivation effect, reinstatement of ethanol-seeking behaviours and saccharin reinforcement. Furthermore, the GABAB receptor antagonist, phaclofen, counteracted the ability of WSE to impair the maintenance of ethanol self-administration. These findings show that WSE, by an action that may involve GABAB receptors, impairs motivation for drinking ethanol and suggest that further investigations should be performed to determine whether W. somnifera may represent a new approach for the management of alcohol abuse.

  12. Genetic dissection of acute ethanol responsive gene networks in prefrontal cortex: functional and mechanistic implications.

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    Aaron R Wolen

    Full Text Available Individual differences in initial sensitivity to ethanol are strongly related to the heritable risk of alcoholism in humans. To elucidate key molecular networks that modulate ethanol sensitivity we performed the first systems genetics analysis of ethanol-responsive gene expression in brain regions of the mesocorticolimbic reward circuit (prefrontal cortex, nucleus accumbens, and ventral midbrain across a highly diverse family of 27 isogenic mouse strains (BXD panel before and after treatment with ethanol.Acute ethanol altered the expression of ~2,750 genes in one or more regions and 400 transcripts were jointly modulated in all three. Ethanol-responsive gene networks were extracted with a powerful graph theoretical method that efficiently summarized ethanol's effects. These networks correlated with acute behavioral responses to ethanol and other drugs of abuse. As predicted, networks were heavily populated by genes controlling synaptic transmission and neuroplasticity. Several of the most densely interconnected network hubs, including Kcnma1 and Gsk3β, are known to influence behavioral or physiological responses to ethanol, validating our overall approach. Other major hub genes like Grm3, Pten and Nrg3 represent novel targets of ethanol effects. Networks were under strong genetic control by variants that we mapped to a small number of chromosomal loci. Using a novel combination of genetic, bioinformatic and network-based approaches, we identified high priority cis-regulatory candidate genes, including Scn1b, Gria1, Sncb and Nell2.The ethanol-responsive gene networks identified here represent a previously uncharacterized intermediate phenotype between DNA variation and ethanol sensitivity in mice. Networks involved in synaptic transmission were strongly regulated by ethanol and could contribute to behavioral plasticity seen with chronic ethanol. Our novel finding that hub genes and a small number of loci exert major influence over the ethanol

  13. Hepatoprotective effect of carob against acute ethanol-induced oxidative stress in rat.

    Science.gov (United States)

    Souli, Abdelaziz; Sebai, Hichem; Chehimi, Latifa; Rtibi, Kaïs; Tounsi, Haifa; Boubaker, Samir; Sakly, Mohsen; El-Benna, Jamel; Amri, Mohamed

    2015-09-01

    The present study was undertaken to determine whether subacute treatment with aqueous extract of carob (Ceratonia siliqua L.) pods (AECPs) protects against ethanol (EtOH)-induced oxidative stress in rat liver. Animals were divided into four groups: control, carob, EtOH and EtOH + carob. Wistar rats were intraperitoneally pretreated with AECP (600 mg/kg body weight (bw)) during 7 days and intoxicated for 6 h by acute oral administration of EtOH (6 g/kg bw) 24 h after the last injection. We found that acute administration of EtOH leads to hepatotoxicity as monitored by the increase in the levels of hepatic marker aspartate aminotransferase and alanine aminotransferase as well as hepatic tissue injury. EtOH also increased the formation of malondialdehyde in the liver, indicating an increase in lipid peroxidation and depletion of antioxidant enzyme activities as superoxide dismutase, catalase and glutathione peroxidase. Subacute carob pretreatment prevented all the alterations induced by EtOH and returned their levels to near normal. Importantly, we showed that acute alcohol increased hepatic and plasmatic hydrogen peroxide and free iron levels. The carob pretreatment reversed EtOH effects to near control levels. These data suggest that carob could have a beneficial effect in inhibiting the oxidative damage induced by acute EtOH administration and that its mode of action may involve an opposite effect on plasma and tissue-free iron accumulation. Indeed, carob can be offered as a food additive to protect against EtOH-induced oxidative damage.

  14. Long-term ethanol exposure decreases the endotoxin-induced hepatic acute phase response in rats

    DEFF Research Database (Denmark)

    Glavind, Emilie; Vilstrup, Hendrik; Grønbaek, Henning

    2017-01-01

    -fed rats showed either no liver histopathological changes or varying degrees of steatosis. Ethanol feeding decreased the spontaneous liver mRNA expression of the prevailing acute phase protein alpha-2-macroglobulin by 30% (Ptumor necrosis factor...... an induced acute phase response is impaired in long-term ethanol-fed rats. METHODS: For six weeks, rats were either fed a Lieber-DeCarli ethanol-containing (36% as calories) liquid diet ad libitum or calorically pair-fed. Then, the rats were injected intraperitoneally with a low-dose of lipopolysaccharide...... (LPS) (0.5 mg/kg) to induce an acute phase response. Two hours after LPS, we measured the plasma concentrations of an array of inflammatory cytokines. Twenty-four hours after LPS, we measured the hepatic mRNA expression and serum concentrations of prominent rat acute phase proteins. RESULTS: Ethanol...

  15. Depression of contraction and the calcium transient in single cardiomyocytes with acute ethanol exposure

    Energy Technology Data Exchange (ETDEWEB)

    Rozanski, D.J.; Delaville, F.J.; Thomas, A.P. (Thomas Jefferson Univ., Philadelphia, PA (United States))

    1992-01-01

    The mechanism by which acute ethanol (ET) exposure causes reversible myocardial dysfunction is unknown. The purpose of this study was to examine the effects of ET exposure on contraction and cytosolic free Ca[sup 2+] ([Ca[sup 2+

  16. Biliopancreatic duct injection of ethanol as an experimental model of acute and chronic pancreatitis in rats.

    Science.gov (United States)

    Unal, Ethem; Atalay, Suleyman; Tolan, Huseyin Kerem; Yuksekdag, Sema; Yucel, Metin; Acar, Aylin; Basak, Fatih; Gunes, Pembegul; Bas, Gurhan

    2015-01-01

    In the present study, we described an easily reproducable experimental pancreatits model induced by biliopancreatic duct injection of ethyl alcohol. Seventy Wistar albino rats were divided equally into seven groups randomly: the control group (group 1), acute pancreatitis groups; induced by 20% ethanol (group 2), 48% ethanol (group 3), 80% ethanol (group 4), chronic pancreatitis groups; induced by 20% ethanol (group 5), 48% ethanol (group 6) and by 80% ethanol (group 7). Acute pancreatitis groups were sacrified on postoperative day 3, while the control group and chronic pancreatitis groups were killed on postoperative day 7. Histopathologic evaluation was done, and P acute pancreatitis (100%). Inflammatory infiltration of neutrophils and mononuclear cells, interstitial edema, and focal necrotic areas were seen in the pancreatic tissues. Similarly, all rats in group 6 developed chronic pancreatitis (100%). Interstitial fibrosis, lymphotic infiltration, ductal dilatation, acinar cell atrophy, periductal hyperplasia were seen in the pancreatic tissues. Mortality was seen only in group 7. The biliopancreatic ductal injection of 48% ethanol induced acute and chronic pancreatitis has 100% success rate.

  17. Drosophila highwire gene modulates acute ethanol sensitivity in the nervous system

    Institute of Scientific and Technical Information of China (English)

    Awoyemi A.AWOFALA

    2011-01-01

    Animals exhibit behavioral differences in their sensitivity to ethanol,a trait that is at least in part due to genetic predispositions.This study has implicated a large neuronal protein involving Highwire,a Drosophila E3 ubiquitin ligase (Hiw,a homolog of Pam,a protein associated with Myc found in humans) in acute sensitivity to ethanol sedation.Flies lacking Hiw were hypersensitive to the sedating effect of ethanol whereas those overexpressing Hiw showed decreased sensitivity to ethanol.Furthermore,RNAi functional knockdown of Hiw in adult neurons or ellipsoid body neurons showed increased sensitivity to ethanol sedation.None of these manipulations of the hiw gene caused changes in the rate of ethanol absorption and/or metabolism.These results suggest a previously unknown role for this highly conserved gene in regulating the behavioral responses to an addictive drug.

  18. Perillyl alcohol protects against ethanol induced acute liver injury in Wistar rats by inhibiting oxidative stress, NFκ-B activation and proinflammatory cytokine production.

    Science.gov (United States)

    Khan, Abdul Quaiyoom; Nafees, Sana; Sultana, Sarwat

    2011-01-11

    Oxidative stress and inflammation are two major etiological factors that are suggested to play key roles in the development of ethanol induced liver injury. Release of proinflammatory cytokine like tumor necrosis factor alpha (TNF-α) and activation of nuclear factor kappa-B (NFκ-B) may strongly intensify inflammation and cell damage. Additionally, reactive oxygen species (ROS) also exerts significant effect in this whole cell signaling machinery. The present study was designed to investigate the protective effects of perillyl alcohol (POH) on ethanol-induced acute liver injury in Wistar rats and its probable mechanism. We have successfully demonstrated that pre-treatment with POH, besides exerting antioxidant activity might be able to modulate TNF-α release and NFκ-B activation. Rats were divided into five groups and treated with ethanol or POH via an intragastric tube for one week. Control group was treated with vehicle, and ethanol treated group was given ethanol (5 g/kg body wt). Animal of treatment groups were pretreated with POH (50 & 100 mg/kg body wt) and have been given ethanol. Serum aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase and hepatic malondialdehyde were increased significantly by ethanol treatment. Ethanol administration decreased hepatic reduced glutathione content and various antioxidant enzymes activity. TNF-α production and NFκ-B activation was also found to be increased after ethanol administration. POH pre-treatment significantly ameliorates ethanol induced acute liver injury possibly by inhibition of lipid peroxidation, replenishment of endogenous enzymatic and non-enzymatic defense system, downregulation of TNF-α as well as NFκ-B.

  19. Developmental changes in the acute ethanol sensitivity of glutamatergic and GABAergic transmission in the BNST.

    Science.gov (United States)

    Wills, T A; Kash, T L; Winder, D G

    2013-11-01

    Glutamatergic and GABAergic transmission undergo significant changes during adolescence. Receptors for both of these transmitters (NMDAR, and GABAA) are known to be key targets for the acute effects of ethanol in adults. The current study set out to investigate the acute effects of ethanol on both NMDAR-mediated excitatory transmission and GABAergic inhibitory transmission within the bed nucleus of the stria terminalis (BNST) across age. The BNST is an area of the brain implicated in the negative reinforcing properties associated with alcohol dependence, and the BNST plays a critical role in stress-induced relapse. Therefore, assessing the developmental regulation of ethanol sensitivity in this key brain region is important to understanding the progression of ethanol dependence. To do this, whole-cell recordings of isolated NMDAR-evoked excitatory postsynaptic currents (eEPSCs) or evoked GABAergic inhibitory postsynaptic currents (eIPSCs) were performed on BNST neurons in slices from 4- or 8-week-old male C57BL/6J mice. Ethanol (50 mm) produced greater inhibition of NMDAR-eEPSCs in adolescent mice than in adult mice. This enhanced sensitivity in adolescence was not a result of shifts in function of the GluN2B subunit of the NMDAR, measured by Ro25-6981 inhibition and decay kinetics measured across age. Adolescent mice also exhibited greater ethanol sensitivity of GABAergic transmission, as ethanol (50 mm) enhanced eIPSCs in the BNST of adolescent but not adult mice. Collectively, this work illustrates that a moderate dose of ethanol produces greater inhibition of transmission in the BNST (through greater excitatory inhibition and enhancement of inhibitory transmission) in adolescents compared to adults. Given the role of the BNST in alcohol dependence, these developmental changes in acute ethanol sensitivity could accelerate neuroadaptations that result from chronic ethanol use during the critical period of adolescence.

  20. Acute extracellular ethanol load does not produce hyponatremia by internal osmoregulation

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, J.E.; Tzamaloukas, A.H.; Long, D.A.

    1986-03-05

    Hyponatremia is frequently present in subjects intoxicated with ethanol. To study whether an acute increase in extracellular osmolality by addition of ethanol creates any clinically appreciable osmotic shift of intracellular water extracellularly, they infused over 20 sec 11 mmol/kg of ethanol intravenously into 5 anesthetized dogs (2 with intact renal function, 3 anuric) and measured plasma sodium and ethanol concentrations and osmolality at frequent intervals for 100 min after the end of the infusion. For a range of ethanol concentration between 4 and 120 mmol/l, changes in osmolality were equal to ethanol concentration in plasma water (y = -0.49 + 1.06 x mosm/kg per mmol/l, r = 0.981, p < 0.01). Plasma sodium concentration remained unchanged from baseline throughout the experiments, even at 1 min post-infusion, when osmolality was 78 +/- 25 mosm/kg above the baseline. An acute increase in extracellular osmolality created by rapid intravenous infusion of a large dose of ethanol does not create any osmotic shift of intracellular water extracellularly, that can be detected by dilution of extracellular sodium. The mechanism of hyponatremia in ethanol intoxication is not internal osmoregulation, but abnormalities in external balance of body water and/or solute.

  1. Lesions of the lateral habenula increase voluntary ethanol consumption and operant self-administration, block yohimbine-induced reinstatement of ethanol seeking, and attenuate ethanol-induced conditioned taste aversion.

    Directory of Open Access Journals (Sweden)

    Andrew K Haack

    Full Text Available The lateral habenula (LHb plays an important role in learning driven by negative outcomes. Many drugs of abuse, including ethanol, have dose-dependent aversive effects that act to limit intake of the drug. However, the role of the LHb in regulating ethanol intake is unknown. In the present study, we compared voluntary ethanol consumption and self-administration, yohimbine-induced reinstatement of ethanol seeking, and ethanol-induced conditioned taste aversion in rats with sham or LHb lesions. In rats given home cage access to 20% ethanol in an intermittent access two bottle choice paradigm, lesioned animals escalated their voluntary ethanol consumption more rapidly than sham-lesioned control animals and maintained higher stable rates of voluntary ethanol intake. Similarly, lesioned animals exhibited higher rates of responding for ethanol in operant self-administration sessions. In addition, LHb lesion blocked yohimbine-induced reinstatement of ethanol seeking after extinction. Finally, LHb lesion significantly attenuated an ethanol-induced conditioned taste aversion. Our results demonstrate an important role for the LHb in multiple facets of ethanol-directed behavior, and further suggest that the LHb may contribute to ethanol-directed behaviors by mediating learning driven by the aversive effects of the drug.

  2. Systemic administration of D-penicillamine prevents the locomotor activation after intra-VTA ethanol administration in rats.

    Science.gov (United States)

    Martí-Prats, Lucía; Sánchez-Catalán, María José; Hipólito, Lucía; Orrico, Alejandro; Zornoza, Teodoro; Polache, Ana; Granero, Luis

    2010-10-11

    Although recently published studies seem to confirm the important role displayed by acetaldehyde (ACH), the main metabolite of ethanol, in the behavioral effects of ethanol, the origin of ACH is still a matter of debate. While some authors confer more importance to the central (brain metabolism) origin of ACH, others indicate that the hepatic origin could be more relevant. In this study we have addressed this topic using an experimental approach that combines local microinjections of ethanol into the ventral tegmental area (VTA) (which guarantees the brain origin of the ACH) to induce motor activation in rats together with systemic administration (i.p.) of several doses (0, 12.5, 25 and 50 mg/kg) of D-penicillamine (DP), a sequestering agent of ACH with contrasted efficiency to abolish the behavioral effects of the drug. Our results clearly show that DP prevented in a dose-dependent manner the motor activation induced by intra-VTA ethanol, being the 50 mg/kg dose the most efficient. DP per se did not affect the basal activity of the rats. In order to determine the specificity of the DP action, we also studied the effects of DP 50 mg/kg on the DAMGO-induced motor activation after the intra-VTA administration of this mu-opioid receptors agonist. DP did not significantly modify the motor activation induced by DAMGO thus confirming the specificity of the DP effects. Our results clearly suggest that the brain-derived ACH is necessary to manifest the activating effects resulting from ethanol administration.

  3. Optogenetic stimulation of VTA dopamine neurons reveals that tonic but not phasic patterns of dopamine transmission reduce ethanol self-administration

    Directory of Open Access Journals (Sweden)

    Caroline E Bass

    2013-11-01

    Full Text Available There is compelling evidence that acute ethanol exposure stimulates ventral tegmental area (VTA dopamine cell activity and that VTA-dependent dopamine release in terminal fields within the nucleus accumbens plays an integral role in the regulation of ethanol drinking behaviors. Unfortunately, due to technical limitations, the specific temporal dynamics linking VTA dopamine cell activation and ethanol self-administration are not known. In fact, establishing a causal link between specific patterns of dopamine transmission and ethanol drinking behaviors has proven elusive. Here, we sought to address these gaps in our knowledge using a newly developed viral-mediated gene delivery strategy to selectively express Channelrhodopsin-2 (ChR2 on dopamine cells in the VTA of wild-type rats. We then used this approach to precisely control VTA dopamine transmission during voluntary ethanol drinking sessions. The results confirmed that ChR2 was selectively expressed on VTA dopamine cells and delivery of blue light pulses to the VTA induced dopamine release in accumbal terminal fields with very high temporal and spatial precision. Brief high frequency VTA stimulation induced phasic patterns of dopamine release in the nucleus accumbens. Lower frequency stimulation, applied for longer periods mimicked tonic increases in accumbal dopamine. Notably, using this optogenetic approach in rats engaged in an intermittent ethanol drinking procedure, we found that tonic, but not phasic, stimulation of VTA dopamine cells selectively attenuated ethanol drinking behaviors. Collectively, these data demonstrate the effectiveness of a novel viral targeting strategy that can be used to restrict opsin expression to dopamine cells in standard outbred animals and provide the first causal evidence demonstrating that tonic activation of VTA dopamine neurons selectively decreases ethanol self-administration behaviors.

  4. Optogenetic stimulation of VTA dopamine neurons reveals that tonic but not phasic patterns of dopamine transmission reduce ethanol self-administration.

    Science.gov (United States)

    Bass, Caroline E; Grinevich, Valentina P; Gioia, Dominic; Day-Brown, Jonathan D; Bonin, Keith D; Stuber, Garret D; Weiner, Jeff L; Budygin, Evgeny A

    2013-01-01

    There is compelling evidence that acute ethanol exposure stimulates ventral tegmental area (VTA) dopamine cell activity and that VTA-dependent dopamine release in terminal fields within the nucleus accumbens plays an integral role in the regulation of ethanol drinking behaviors. Unfortunately, due to technical limitations, the specific temporal dynamics linking VTA dopamine cell activation and ethanol self-administration are not known. In fact, establishing a causal link between specific patterns of dopamine transmission and ethanol drinking behaviors has proven elusive. Here, we sought to address these gaps in our knowledge using a newly developed viral-mediated gene delivery strategy to selectively express Channelrhodopsin-2 (ChR2) on dopamine cells in the VTA of wild-type rats. We then used this approach to precisely control VTA dopamine transmission during voluntary ethanol drinking sessions. The results confirmed that ChR2 was selectively expressed on VTA dopamine cells and delivery of blue light pulses to the VTA induced dopamine release in accumbal terminal fields with very high temporal and spatial precision. Brief high frequency VTA stimulation induced phasic patterns of dopamine release in the nucleus accumbens. Lower frequency stimulation, applied for longer periods mimicked tonic increases in accumbal dopamine. Notably, using this optogenetic approach in rats engaged in an intermittent ethanol drinking procedure, we found that tonic, but not phasic, stimulation of VTA dopamine cells selectively attenuated ethanol drinking behaviors. Collectively, these data demonstrate the effectiveness of a novel viral targeting strategy that can be used to restrict opsin expression to dopamine cells in standard outbred animals and provide the first causal evidence demonstrating that tonic activation of VTA dopamine neurons selectively decreases ethanol self-administration behaviors.

  5. Evaluation of the acute and sub-acute toxicity of the ethanolic extract ofPericampylus glaucus (Lam.) Merr. in BALB/c mice

    Institute of Scientific and Technical Information of China (English)

    Muhammad Kifayatullah; Mohd. Shahimi Mustafa; Pinaki Senguptha; Md. Moklesur Rahman Sarker; Arindam Das; Sreemoy Kanti Das

    2015-01-01

    Objective: To evaluate the safety dose range of ethanolic extract from the leaves of Pericampylus glaucus(Lam.) Merr. by acute and sub-acute oral toxicity study on animal model. Methods: The acute and sub-acute toxicity study was carried out as per Organization for Economic Co-operation and Development guidelines 423 and 407. In acute toxicity study, the oral dose (300, 2 000 and 4 000 mg/kg) of tested plant extract was administered to three groups in single dose and general behavior, adverse effects and mortality were determined up to 72 h and compared to normal group. In sub-acute study, the tested crude plant extract was administered orally at doses of 600 and 1 000 mg/kg for 28 days to the two animals groups and their body weight, hematological, serum hepatic biochemical parameters were evaluated and compared to normal group by sacrificing all group animals. Results: In acute toxicity, all treated groups’ revealed neither mortality nor any significant alteration in behavior only drowsiness, sedation and lethargy were observed in two group, i.e. 2 000 and 4 000 mg/kg of the tested plant extract. In sub-acute toxicity study no change in hematological, biochemical parameter and organ body weight were observed during study compared to the normal group. The kidney function parameters [serum glutamic-oxaloacetic transaminase (aspartate transaminase), serum glutamic pyruvic transaminase (alanine transaminase)] were significantly increased following administration of tested crude plant extract (600, 1 000 mg/kg). Conclusions:The result indicates that the oral administration ofPericampylus glaucus (Lam.) Merr. extract did not produce any significant toxic effect in BALB/c mice. Hence, the extract can be utilized safely for therapeutic use in pharmaceutical formulations.

  6. Orexin-1 and orexin-2 receptor antagonists reduce ethanol self-administration in high-drinking rodent models

    Directory of Open Access Journals (Sweden)

    Rachel Ivy Anderson

    2014-02-01

    Full Text Available To examine the role of orexin-1 and orexin-2 receptor activity on ethanol self-administration, compounds that differentially target orexin (OX receptor subtypes were assessed in various self-administration paradigms using high-drinking rodent models. Effects of the OX1 antagonist SB334867, the OX2 antagonist LSN2424100, and the mixed OX1/2 antagonist almorexant (ACT-078573 on home cage ethanol consumption were tested in ethanol-preferring (P rats using a 2-bottle choice procedure. In separate experiments, effects of SB334867, LSN2424100, and almorexant on operant ethanol self-administration were assessed in P rats maintained on a progressive ratio operant schedule of reinforcement. In a third series of experiments, SB334867, LSN2424100, and almorexant were administered to ethanol-preferring C57BL/6J mice to examine effects of OX receptor blockade on ethanol intake in a binge-like drinking (drinking-in-the-dark model. In P rats with chronic home cage free-choice ethanol access, SB334867 and almorexant significantly reduced ethanol intake, but almorexant also reduced water intake, suggesting nonspecific effects on consummatory behavior. In the progressive ratio operant experiments, LSN2424100 and almorexant reduced breakpoints and ethanol consumption in P rats, whereas the almorexant inactive enantiomer and SB334867 did not significantly affect the motivation to consume ethanol. As expected, vehicle-injected mice exhibited binge-like drinking patterns in the drinking-in-the-dark model. All three OX antagonists reduced both ethanol intake and resulting blood ethanol concentrations relative to vehicle-injected controls, but SB334867 and LSN2424100 also reduced sucrose consumption in a different cohort of mice, suggesting nonspecific effects. Collectively, these results contribute to a growing body of evidence indicating that OX1 and OX2 receptor activity influences ethanol self-administration, although the effects may not be selective for ethanol

  7. Is acute dyspnea related to oxaliplatin administration?

    Institute of Scientific and Technical Information of China (English)

    LM Pasetto; S Monfardini

    2006-01-01

    The standard adjuvant treatment of colon cancer is fluorouracil plus leucovorin. Oxaliplatin improves the efficacy of this combination in patients with stage Ⅲ colon cancer and moreover its toxicity is well tolerable. We describe a rare clinical case of acute dyspnoea probably related to oxaliplatin at one month from the end of the adjuvant treatment. A 74-year-old man developed a locally advanced sigmoid carcinoma (pT3N1M0). A port a cath attached to an open-ended catheter was implanted in order to administer primary chemotherapy safely according to the FOLFOX4 schedule. One month following the end of the 6th cycle, the patient referred a persistent cough and moderate dyspnoea. Chest radiography displayed a change in the lung interstitium, chest CT scan confirmed this aspect of adult respiratory distress syndrome,spirometry reported a decreased carbon monoxide diffusion capacity. Antibiotic and corticosteroids were administered for 10 d, then a repeated chest X ray evidenced a progressive pulmonary infiltration. A transbronehial biopsy and cytology did not show an infective process,a CT scan reported radiological abnormalities including linear and nodular densities which were becoming confluents. Antimicotic and antiviral drugs did not evidence any benefit. The antiviral therapy was stopped and high dose metilprednisolone was started. The patient died of pulmonary distress after 10 d.

  8. Nephroprotective effect of ethanolic extract of abutilon indicum root in gentamicin induced acute renal failure

    Directory of Open Access Journals (Sweden)

    Jacob Jesurun RS

    2016-06-01

    Conclusions: The ethanolic extract of abutilon indicum root has nephron protective effect in gentamicin induced acute renal failure. Nephro protective action in this study could be due to the antioxidant and other phytochemical of abutilon indicum root. [Int J Basic Clin Pharmacol 2016; 5(3.000: 841-845

  9. Inhibitory Effect of Helicteres gardneriana Ethanol Extract on Acute Inflammation

    Directory of Open Access Journals (Sweden)

    Juliana Oliveira de Melo

    2012-01-01

    Full Text Available The anti-inflammatory effect of an ethanol extract of Helicteres gardneriana (Nees Castiglioni was assayed in experimental models of pleurisy and microcirculation in situ. Treatment of animals with 500 mg/kg body weight reduced the exudate volume (35% reduction induced by intrapleural injection of carrageenan and the migration of polymorphonuclear cells into the inflamed pleural cavity of rats (40%. Additionally, rolling and adhesion of leukocytes and the number of leukocytes that migrated toward the perivascular space in response to the carrageenan injection were decreased by the extract (500 mg/kg. These data demonstrate the anti-inflammatory effect of the ethanol extract of Helicteres gardneriana and imply that inhibition of leukocyte-endothelial interactions is important in the extract's mechanism of action.

  10. Serotonin-3 Receptors in the Posterior Ventral Tegmental Area Regulate Ethanol Self-Administration of Alcohol-Preferring (P) Rats

    Science.gov (United States)

    Rodd, Zachary A.; Bell, Richard L.; Oster, Scott M.; Toalston, Jamie E.; Pommer, Tylene J.; McBride, William J.; Murphy, James M.

    2015-01-01

    Several studies indicated the involvement of serotonin-3 (5-HT3) receptors in regulating alcohol-drinking behavior. The objective of this study was to determine the involvement of 5-HT3 receptors within the ventral tegmental area (VTA) in regulating ethanol self-administration by alcohol-preferring (P) rats. Standard two-lever operant chambers were used to examine the effects of 7 consecutive bilateral micro-infusions of ICS205-930 (ICS), a 5-HT3 receptor antagonist, directly into the posterior VTA on the acquisition and maintenance of 15% (v/v) ethanol self-administration. P rats readily acquired ethanol self-administration by the 4th session. The three highest doses (0.125, 0.25 and 1.25 ug) of ICS prevented acquisition of ethanol self-administration. During the acquisition post-injection period, all rats treated with ICS demonstrated higher responding on the ethanol lever, with the highest dose producing the greatest effect. In contrast, during the maintenance phase, the 3 highest doses (0.75, 1.0 and 1.25 ug) of ICS significantly increased responding on the ethanol lever; following the 7-day dosing regimen, responding on the ethanol lever returned to control levels. Micro-infusion of ICS into the posterior VTA did not alter the low responding on the water lever, and did not alter saccharin (0.0125% w/v) self-administration.. Micro-infusion of ICS into the anterior VTA did not alter ethanol self-administration. Overall, the results of this study suggest that 5-HT3 receptors in the posterior VTA of the P rat may be involved in regulating ethanol self-administration. In addition, chronic operant ethanol self-administration, and/or repeated treatments with a 5-HT3 receptor antagonist may alter neuronal circuitry within the posterior VTA. PMID:20682192

  11. Assessment of acute toxicity of the ethanolic extract of Lychnophora pinaster (Brazilian arnica

    Directory of Open Access Journals (Sweden)

    Simone A. Ferreira

    2014-10-01

    Full Text Available Species of the Lychnophora genus are plants native to Brazil, popularly known as "Brazilian arnica" and used in folk medicine as alcoholic and hydro-alcoholic preparations for the treatment of bruises, inflammation, pain, rheumatism and insect bites. The present study aimed to evaluate the safety of the use of Lychnophora pinaster Mart., Asteraceae. Acute toxicity of the crude ethanolic extract was evaluated by administration of the extract by oral route to male and female Swiss mice. A single extract dose of 125, 250 or 500 mg/kg was administered and the effects on spontaneous locomotor activity, exploratory behavior, muscle strength, body weight, food and water consumption, relative organ weight, histology, as well as hematological and biochemical parameters were evaluated. The three doses administered to the animals did not cause muscle tone alterations, but doses of 250 and 500 mg/kg induced a significant inhibition of the spontaneous locomotor activity and exploratory behavior of the animals in open-field test. There was no alteration to hematological parameters and consumption of water and food, body weight variation and organs relative weight. Changes were observed in AST and ALT during assessment of biochemical parameters. The histopathological evaluation showed that the extract provoked cellular alterations, such as vacuolar degeneration and inflammation in kidneys and liver at all doses. Liver morphometric analyses of male and female mice showed that the extract did not have dose-dependent effects. Although females showed a significant increase in inflammatory cells, the effect was not dose-dependent.

  12. Ethanol co-administration moderates 3,4-methylenedioxymethamphetamine effects on human physiology

    NARCIS (Netherlands)

    Dumont, G.J.H.; Kramers, C.; Sweep, F.C.G.J.; Willemsen, J.J.; Touw, D.J.; Schoemaker, R.C.; Van Gerven, J.M.A.; Buitelaar, J.K.; Verkes, R.J.

    2010-01-01

    Alcohol is frequently used in combination with 3,4- methylenedioxymethamphetamine (MDMA). Both drugs affect cardiovascular function, hydration and temperature regulation, but may have partly opposing effects. The present study aims to assess the acute physiologic effects of (co-) administration of M

  13. Effects of six weeks of chronic ethanol administration on the behavioral outcome of rats after lateral fluid percussion brain injury.

    Science.gov (United States)

    Zhang, L; Maki, A; Dhillon, H S; Barron, S; Clerici, W J; Hicks, R; Kraemer, P J; Butcher, J; Prasad, R M

    1999-03-01

    This study examined the effects of 6 weeks of chronic ethanol administration on the behavioral outcome in rats after lateral fluid percussion (FP) brain injury. Rats were given either an ethanol liquid diet (ethanol diet-groups) or a pair-fed isocaloric sucrose control diet (control diet groups) for 6 weeks. After 6 weeks, the ethanol diet was discontinued for the ethanol diet rats and they were then given the control sucrose diet for 2 days. During those 2 days, the rats were trained to perform a beam-walking task and subjected to either lateral FP brain injury of low to moderate severity (1.8 atm) or to sham operation. In both the control diet and the ethanol diet groups, lateral FP brain injury caused beam-walking impairment on days 1 and 2 and spatial learning disability on days 7 and 8 after brain injury. There were no significant differences in beam-walking performance and spatial learning disability between brain injured animals from the control and ethanol diet groups. However, a trend towards greater behavioral deficits was observed in brain injured animals in the ethanol diet group. Histologic analysis of both diet groups after behavioral assessment revealed comparable ipsilateral cortical damage and observable CA3 neuronal loss in the ipsilateral hippocampus. These results only suggest that chronic ethanol administration, longer than six weeks of administration, may worsen behavioral outcome following lateral FP brain injury. For more significant behavioral and/or morphological change to occur, we would suggest that the duration of chronic ethanol administration must be increased.

  14. Lycopene Pretreatment Ameliorates Acute Ethanol Induced NAD+ Depletion in Human Astroglial Cells

    Directory of Open Access Journals (Sweden)

    Jade Guest

    2015-01-01

    Full Text Available Excessive alcohol consumption is associated with reduced brain volume and cognition. While the mechanisms by which ethanol induces these deleterious effects in vivo are varied most are associated with increased inflammatory and oxidative processes. In order to further characterise the effect of acute ethanol exposure on oxidative damage and NAD+ levels in the brain, human U251 astroglioma cells were exposed to physiologically relevant doses of ethanol (11 mM, 22 mM, 65 mM, and 100 mM for ≤ 30 minutes. Ethanol exposure resulted in a dose dependent increase in both ROS and poly(ADP-ribose polymer production. Significant decreases in total NAD(H and sirtuin 1 activity were also observed at concentrations ≥ 22 mM. Similar to U251 cells, exposure to ethanol (≥22 mM decreased levels of NAD(H in primary human astrocytes. NAD(H depletion in primary astrocytes was prevented by pretreatment with 1 μM of lycopene for 3.5 hours. Unexpectedly, in U251 cells lycopene treatment at concentrations ≥ 5 μM resulted in significant reductions in [NAD(H]. This study suggests that exposure of the brain to alcohol at commonly observed blood concentrations may cause transitory oxidative damage which may be at least partly ameliorated by lycopene.

  15. Acute and subacute toxicity evaluation of ethanolic extract from fruits of Schinus molle in rats.

    Science.gov (United States)

    Ferrero, Adriana; Minetti, Alejandra; Bras, Cristina; Zanetti, Noelia

    2007-09-25

    Ethanolic and hexanic extracts from fruits and leaves of Schinus molle showed ability to control several insect pests. Potential vertebrate toxicity associated with insecticidal plants requires investigation before institutional promotion. The aim of the present study was to evaluate the acute and subacute toxicity of ethanolic extracts from fruits of Schinus molle in rats. The plant extract was added to the diet at 2g/kg body weight/day during 1 day to evaluate acute toxicity and at 1g/kg body weight/day during 14 days to evaluate subacute toxicity. At the end of the exposure and after 7 days, behavioral and functional parameters in a functional observational battery and motor activity in an open field were assessed. Finally, histopathological examinations were conducted on several organs. In both exposures, an increase in the arousal level was observed in experimental groups. Also, the landing foot splay parameter increased in the experimental group after acute exposure. Only the subacute exposure produced a significant increase in the motor activity in the open field. All these changes disappeared after 7 days. None of the exposures affected the different organs evaluated. Our results suggest that ethanolic extracts from fruits and leaves of Schinus molle should be relatively safe to use as insecticide.

  16. Effects of binge ethanol administration on the behavioral outcome of rats after lateral fluid percussion brain injury.

    Science.gov (United States)

    Prasad, R M; Doubinskaia, I; Singh, D K; Campbell, G; Mace, D; Fletcher, A; Dendle, P; Yurek, D M; Scheff, S W; Kraemer, P J

    2001-10-01

    This study examined the effects of 4 weeks of binge ethanol administration (BEAn) on the behavioral outcome in rats after lateral fluid percussion (FP) brain injury. Rats were intragastrically given 7.5 mL/kg of either 40% ethanol in 5% glucose solution (3 g ethanol/kg; binge ethanol group), or 5% glucose solution (vehicle group), twice on Thursday and Friday of 3 consecutive weeks. Then rats from both groups were subjected to either lateral FP brain injury of moderate severity (1.8 atm) or to sham operation. Postinjury behavioral measurements revealed that brain injury caused significant spatial learning disability in both groups. There were no significant differences in mean search latencies in the sham animals between the vehicle and binge ethanol groups. On the other hand, the mean search latency of the binge ethanol group was significantly higher than that of the vehicle group in trial blocks 2 and 4. There were no significant differences in the target visits (expressed as mean zone difference [MZD]) during the probe trial between the injured animals of binge ethanol and vehicle groups. However, there was only a minor trend towards worsened MZD score in the binge-injured animals. Histologic analysis of injured animals from both injured ethanol and vehicle groups revealed similar extents of ipsilateral cortical and observable hippocampal damage. These results suggest that 4 weeks of binge ethanol treatment followed by ethanol intoxication at the time of injury worsens some aspects of the spatial learning ability of rats. This worsening is probably caused by subtle, undetectable morphologic damage by binge ethanol administration.

  17. Acute Cor Pulmonale and Right Heat Failure Complicating Ethanol Ablative Therapy: Anesthetic and Radiologic Considerations and Management

    Energy Technology Data Exchange (ETDEWEB)

    Naik, Bhiken, E-mail: bin4n@virginia.edu [University of Virginia, Department of Anesthesiology (United States); Matsumoto, Alan H. [University of Virginia, Department of Radiology and Medical Imaging (United States)

    2013-10-15

    Ethanol is an effective ablative agent used for the treatment of certain solid organ tumors and vascular malformations (VMs). The egress of ethanol beyond the target tissue can be associated with significant changes to the cardiopulmonary system that can lead to cardiac arrest. This article reviews the contemporary role of ethanol in tumor and VM treatment and discusses the physiological mechanisms of acute pulmonary hypertension and cardiovascular collapse. The importance of periprocedural recognition of the hemodynamic changes that can occur with the use of ethanol and the treatment of this condition are discussed.

  18. Acute cor pulmonale and right heat failure complicating ethanol ablative therapy: anesthetic and radiologic considerations and management.

    Science.gov (United States)

    Naik, Bhiken; Matsumoto, Alan H

    2013-10-01

    Ethanol is an effective ablative agent used for the treatment of certain solid organ tumors and vascular malformations (VMs). The egress of ethanol beyond the target tissue can be associated with significant changes to the cardiopulmonary system that can lead to cardiac arrest. This article reviews the contemporary role of ethanol in tumor and VM treatment and discusses the physiological mechanisms of acute pulmonary hypertension and cardiovascular collapse. The importance of periprocedural recognition of the hemodynamic changes that can occur with the use of ethanol and the treatment of this condition are discussed.

  19. Acute effects of ethanol on hepatic uptake and distribution of narcotics in the isolated perfused rabbit liver

    Energy Technology Data Exchange (ETDEWEB)

    Kreek, M.J.; Rothschild, M.A.; Oratz, M.; Mongelli, J.; Handley, A.C.

    This study was performed as an initial step in systematically defining the hepatic interactions between ethanol and opioids using a controlled in vitro system. The acute effects of ethanol on the initial uptake and distribution of long- and short-acting narcotics were studied using isolated rabbit liver perfused with rabbit blood without or with ethanol. A pulse injection of 1.5 mg of 14C-labeled narcotic (methadone, 1-alpha-acetylmethadol (LAAM), morphine, or meperidine) was made into the portal vein cannula followed by perfusion for 2 min. Radioactivity was determined in liver homogenates and subcellular fractions; methadone and its metabolites were measured by thin-layer chromatography with zonal scanning in each fraction. Ethanol preperfusion and concomitant ethanol perfusion did not effect hepatic uptake of methadone, LAAM, morphine, or meperidine. Although subcellular localization of morphine and meperidine differed from that of methadone and LAAM, perfusion with ethanol did not alter the acute hepatic uptake and distribution of any of the narcotics. These findings suggest that acute exposure to ethanol does not alter the acute hepatic disposition of narcotics.

  20. Moderate (2%, v/v) Ethanol Feeding Alters Hepatic Wound Healing after Acute Carbon Tetrachloride Exposure in Mice.

    Science.gov (United States)

    Deshpande, Krutika T; Liu, Shinlan; McCracken, Jennifer M; Jiang, Lu; Gaw, Ta Ehpaw; Kaydo, Lindsey N; Richard, Zachary C; O'Neil, Maura F; Pritchard, Michele T

    2016-01-06

    Wound healing consists of three overlapping phases: inflammation, proliferation, and matrix synthesis and remodeling. Prolonged alcohol abuse can cause liver fibrosis due to deregulated matrix remodeling. Previous studies demonstrated that moderate ethanol feeding enhances liver fibrogenic markers and frank fibrosis independent of differences in CCl₄-induced liver injury. Our objective was to determine whether or not other phases of the hepatic wound healing response were affected by moderate ethanol after CCl₄ exposure. Mice were fed moderate ethanol (2% v/v) for two days and then were exposed to CCl₄ and euthanized 24-96 h later. Liver injury was not different between pair- and ethanol-fed mice; however, removal of necrotic tissue was delayed after CCl₄-induced liver injury in ethanol-fed mice. Inflammation, measured by TNFα mRNA and protein and hepatic Ly6c transcript accumulation, was reduced and associated with enhanced hepatocyte apoptosis after ethanol feeding. Hepatocytes entered the cell cycle equivalently in pair- and ethanol-fed mice after CCl₄ exposure, but hepatocyte proliferation was prolonged in livers from ethanol-fed mice. CCl₄-induced hepatic stellate cell activation was increased and matrix remodeling was prolonged in ethanol-fed mice compared to controls. Taken together, moderate ethanol affected each phase of the wound healing response to CCl₄. These data highlight previously unknown effects of moderate ethanol exposure on hepatic wound healing after acute hepatotoxicant exposure.

  1. Moderate (2%, v/v Ethanol Feeding Alters Hepatic Wound Healing after Acute Carbon Tetrachloride Exposure in Mice

    Directory of Open Access Journals (Sweden)

    Krutika T. Deshpande

    2016-01-01

    Full Text Available Wound healing consists of three overlapping phases: inflammation, proliferation, and matrix synthesis and remodeling. Prolonged alcohol abuse can cause liver fibrosis due to deregulated matrix remodeling. Previous studies demonstrated that moderate ethanol feeding enhances liver fibrogenic markers and frank fibrosis independent of differences in CCl4-induced liver injury. Our objective was to determine whether or not other phases of the hepatic wound healing response were affected by moderate ethanol after CCl4 exposure. Mice were fed moderate ethanol (2% v/v for two days and then were exposed to CCl4 and euthanized 24–96 h later. Liver injury was not different between pair- and ethanol-fed mice; however, removal of necrotic tissue was delayed after CCl4-induced liver injury in ethanol-fed mice. Inflammation, measured by TNFα mRNA and protein and hepatic Ly6c transcript accumulation, was reduced and associated with enhanced hepatocyte apoptosis after ethanol feeding. Hepatocytes entered the cell cycle equivalently in pair- and ethanol-fed mice after CCl4 exposure, but hepatocyte proliferation was prolonged in livers from ethanol-fed mice. CCl4-induced hepatic stellate cell activation was increased and matrix remodeling was prolonged in ethanol-fed mice compared to controls. Taken together, moderate ethanol affected each phase of the wound healing response to CCl4. These data highlight previously unknown effects of moderate ethanol exposure on hepatic wound healing after acute hepatotoxicant exposure.

  2. Acute but not chronic ethanol exposure impairs retinol oxidation in the small and large intestine of the rat

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Ellendt, K.; Lindros, K.;

    2005-01-01

    BACKGROUND AND AIM: Ethanol has been shown to inhibit retinol oxidation at the level of alcohol dehydrogenase in liver and colon but not previously in the small intestine. In the present study we investigated how chronic alcohol feeding and acute ethanol exposure affects retinol dehydrogenase...... activity in the colon and small intestine of the rat. METHODS: Rats were fed ethanol in a liquid diet for six weeks. Control rats received a similar diet but with ethanol isocalorically replaced by carbohydrates. Retinol dehydrogenase was analyzed from cell cytosol samples from the small and the large...... higher, respectively). While chronic alcohol feeding did not affect these parameters, acute ethanol exposure reduced V(max) and V(max)/K(m) dose-dependently (p retinol...

  3. Beneficial effects of Foeniculum vulgare on ethanol-induced acute gastric mucosal injury in rats

    Institute of Scientific and Technical Information of China (English)

    Fatih Mehmet Birdane; Mustafa Cemek; Yavuz Osman Birdane; (I)lhami Gül(c)in; Mehmet Emin Büyükokuro(g)lu

    2007-01-01

    AIM: To examine the anti-ulcerogenic and antioxidant effects of aqueous extracts of Foeniculum vulgare (FVE) on ethanol-induced gastric lesions in rats.METHODS: FVE was administered by gavage at doses of 75, 150 and 300 mg/kg, and famotidine was used at the dose of 20 mg/kg. Following a 60 min period, all the rats were given 1 mL of ethanol (80%) by gavage. One hour after the administration of ethanol, all groups were sacrificed, and the gastric ulcer index was calculated;whole blood malondialdehyde (MDA) and reduced glutathione (GSH), serum nitrate, nitrite, ascorbic acid,retinol and β-carotene levels were measured in all the groups.RESULTS: It was found that pretreatment with FVE significantly reduced ethanol-induced gastric damage.This effect of FVE was highest and statistically significant in 300 mg/kg group compared with the control (4.18 ± 2.81 vs 13.15 ± 4.08, P < 0.001). Also, pretreatment with FVE significantly reduced the MDA levels, while significantly increased GSH, nitrite, nitrate, ascorbic acid,retinol and β-carotene levels.CONCLUSION: FVE has clearly a protective effect against ethanol-induced gastric mucosal lesion, and this effect, at least in part, depends upon the reduction in lipid peroxidation and augmentation in the antioxidant activity.

  4. [Corticosteroid administration for acute respiratory distress syndrome : therapeutic option?].

    Science.gov (United States)

    Möhnle, P; Briegel, J

    2012-04-01

    Despite a number of clinical trials there is still controversy about the role of corticosteroid therapy in acute respiratory distress syndrome (ARDS). In addition recent meta-analyses differed markedly in the conclusions. This review is intended to provide a short practical guide for the clinician. Based on the available literature, high-dose and pre-emptive administration of corticosteroids is hazardous and not indicated. A low-dose corticosteroid regime given for 4 weeks may potentially be helpful and can be considered in acute or unresolved ARDS in less than 14 days after onset of ARDS, if a close infection surveillance program is available, if neuromuscular blockade can be avoided and if a stepwise dose reduction of corticosteroids is performed. The total daily dose at the beginning of treatment should not exceed 2 mg/kg body weight (BW) methylprednisolone.

  5. Acute caffeine administration affects zebrafish response to a robotic stimulus.

    Science.gov (United States)

    Ladu, Fabrizio; Mwaffo, Violet; Li, Jasmine; Macrì, Simone; Porfiri, Maurizio

    2015-08-01

    Zebrafish has been recently proposed as a valid animal model to investigate the fundamental mechanisms regulating emotional behavior and evaluate the modulatory effects exerted by psychoactive compounds. In this study, we propose a novel methodological framework based on robotics and information theory to investigate the behavioral response of zebrafish exposed to acute caffeine treatment. In a binary preference test, we studied the response of caffeine-treated zebrafish to a replica of a shoal of conspecifics moving in the tank. A purely data-driven information theoretic approach was used to infer the influence of the replica on zebrafish behavior as a function of caffeine concentration. Our results demonstrate that acute caffeine administration modulates both the average speed and the interaction with the replica. Specifically, zebrafish exposed to elevated doses of caffeine show reduced locomotion and increased sensitivity to the motion of the replica. The methodology developed in this study may complement traditional experimental paradigms developed in the field of behavioral pharmacology.

  6. Acute Ethanol Gavage Attenuates Hemorrhage/Resuscitation-Induced Hepatic Oxidative Stress in Rats

    Directory of Open Access Journals (Sweden)

    B. Relja

    2012-01-01

    Full Text Available Acute ethanol intoxication increases the production of reactive oxygen species (ROS. Hemorrhagic shock with subsequent resuscitation (H/R also induces ROS resulting in cellular and hepatic damage in vivo. We examined the role of acute ethanol intoxication upon oxidative stress and subsequent hepatic cell death after H/R. 14 h before H/R, rats were gavaged with single dose of ethanol or saline (5 g/kg, EtOH and ctrl; H/R_EtOH or H/R_ctrl, resp.. Then, rats were hemorrhaged to a mean arterial blood pressure of 30±2 mmHg for 60 min and resuscitated. Two control groups underwent surgical procedures without H/R (sham_ctrl and sham_EtOH, resp.. Liver tissues were harvested at 2, 24, and 72 h after resuscitation. EtOH-gavage induced histological picture of acute fatty liver. Hepatic oxidative (4-hydroxynonenal, 4-HNE and nitrosative (3-nitrotyrosine, 3-NT stress were significantly reduced in EtOH-gavaged rats compared to controls after H/R. Proapoptotic caspase-8 and Bax expressions were markedly diminished in EtOH-gavaged animals compared with controls 2 h after resuscitation. EtOH-gavage increased antiapoptotic Bcl-2 gene expression compared with controls 2 h after resuscitation. iNOS protein expression increased following H/R but was attenuated in EtOH-gavaged animals after H/R. Taken together, the data suggest that acute EtOH-gavage may attenuate H/R-induced oxidative stress thereby reducing cellular injury in rat liver.

  7. A possible role of atrial natriuretic peptide in ethanol-induced acute diuresis

    Energy Technology Data Exchange (ETDEWEB)

    Colantonio, D.; Casale, R.; Mammarella, M.; Pasqualetti, P. (Univ. of L' Aquila (Italy)); Desiati, P.; De Michele, G. (General Hospital of Coppito, L' Aquila (Italy))

    1991-01-01

    The acute effects of ethanol on plasma atrial natriuretic peptide levels were investigated in 4 clinically healthy males, aged 24-26 years, consumed either 750 ml of water as a control study, or the same beverage with 1 ml/kg alcohol added, which increased the plasma alcohol concentration to 99.12{plus minus}15.10 mg/dl at 60 min. Plasma atrial natriuretic peptide levels were significantly higher in the alcohol study compared to the control study at each time point, and with a peak at 10 min. Atrial natriuretic peptide levels showed a positive significant correlation with plasma antidiuretic hormone in the control group, while no relationship was found between the two peptides in the alcohol study. Moreover, a significant correlation exists between plasma atrial natriuretic peptide levels and systolic arterial blood pressure, and heart rate, and between the variations in atrial natriuretic peptide values and the variations in plasma sodium, serum ethanol, and plasma osmolality in the alcohol study. Acute ethanol intake causes an increase in urinary volume, and a decrease in urinary potassium excretion and urinary osmolality, and no change in urinary sodium excretion.

  8. In vitro anti oxidant activity and acute oral toxicity of Terminalia paniculata bark ethanolic extract on Sprague Dawley rats

    Institute of Scientific and Technical Information of China (English)

    Ramgopal Mopuri; Balaji Meriga

    2014-01-01

    Objective: To ensure the safety and evaluate the anti oxidant activity of Terminalia paniculata (T.paniculata) ethanolic extract in Sprague Dawley rats. Methods: The solvent extracts (hexane, ethyl acetate and ethanol) of T. paniculata were subjected to phytochemical analysis and their DPPH radical scavenging activity was assayed. The oral acute toxicity was evaluated using ethanolic extract of T. paniculata. Results:Ethyl acetate and ethanolic extracts showed more phytochemicals, whereas highest DPPH scavenging activity was found in ethanolic extract. In an acute toxicity study, T. paniculata ethanolic extract was orally administered (1 000 mg/kg body weight) to rats and observed for 72 h for any toxic symptoms and the dose was continued up to 14 d. On the 15th day rats were sacrificed and blood samples were collected from control and test animals and analyzed for some biochemical parameters. We did not observe any behavioral changes in test groups in comparison with their controls. Also, there were no significant alterations in biochemical, hematological (hemoglobin content and blood cells count) and liver function parameters such as serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase, total proteins, albumin and bilirubin levels between T. paniculata ethanolic extract treated and normal control groups. Conclusions:Together our results demonstrated that T. paniculata ethanolic possessed potent antioxidant activity and it was safer and non toxic to rats even at higher doses and therefore could be well considered for further investigation for its medicinal and therapeutic efficacy.

  9. Acute antidepressant drug administration and autobiographical memory recall

    DEFF Research Database (Denmark)

    Papadatou-Pastou, Marietta; Miskowiak, Kamilla W; Williams, J Mark G

    2012-01-01

    Antidepressants affect memory and neural responses to emotionally valenced stimuli in healthy volunteers. However, it is unclear whether this extends to autobiographical memory for personally experienced events. The current study investigated the effects of acute administration of the antidepress......Antidepressants affect memory and neural responses to emotionally valenced stimuli in healthy volunteers. However, it is unclear whether this extends to autobiographical memory for personally experienced events. The current study investigated the effects of acute administration...... of the antidepressant reboxetine on emotional autobiographical retrieval in healthy volunteers (14 men, 10 women). Functional magnetic resonance imaging was used in a double-blind between-groups investigation with reboxetine (4 mg) and placebo. Consistent with previous reports using lab-based stimuli, neural activation...... of reboxetine on emotional memory extends to recall of personally experienced events. Such effects may be relevant to the cognitive improvements found with recovery from depression and with the mechanism of action of contemporary antidepressant drugs. (PsycINFO Database Record (c) 2012 APA, all rights reserved)....

  10. Acute and chronic tramadol administration impair spatial memory in rat

    Science.gov (United States)

    Hosseini-Sharifabad, Ali; Rabbani, Mohammad; Sharifzadeh, Mohammad; Bagheri, Narges

    2016-01-01

    Tramadol hydrochloride, a synthetic opioid, acts via a multiple mechanism of action. Tramadol can potentially change the behavioral phenomena. The present study evaluates the effect of tramadol after single or multiple dose/s on the spatial memory of rat using object recognition task (ORT). Tramadol, 20 mg/kg, was injected intraperitoneally (i.p) as a single dose or once a day for 21 successive days considered as acute or chronic treatment respectively. After treatment, animals underwent two trials in the ORT. In the first trial (T1), animals encountered with two identical objects for exploration in a five-minute period. After 1 h, in the T2 trial, the animals were exposed to a familiar and a nonfamiliar object. The exploration times and frequency of the exploration for any objects were recorded. The results showed that tramadol decreased the exploration times for the nonfamiliar object in the T2 trial when administered either as a single dose (P<0.001) or as the multiple dose (P<0.05) compared to the respective control groups. Both acute and chronic tramadol administration eliminated the different frequency of exploration between the familiar and nonfamiliar objects. Our findings revealed that tramadol impaired memory when administered acutely or chronically. Single dose administration of tramadol showed more destructive effect than multiple doses of tramadol on the memory. The observed data can be explained by the inhibitory effects of tramadol on the wide range of neurotransmitters and receptors including muscarinic, N-methyl D-aspartate, AMPA as well as some second messenger like cAMP and cGMP or its stimulatory effect on the opioid, gama amino butyric acid, dopamine or serotonin in the brain. PMID:27051432

  11. Acute Oral Toxicity Studies of Ethanol Leaf Extracts Of Derris Scandens & Pulicaria Wightiana In Albino Rats

    Directory of Open Access Journals (Sweden)

    Vidya Sabbani

    2015-02-01

    Full Text Available Objective: The present study was designed to find out LD50 and to ascertain the safety of ethanol extracts of leaves of Derris scan dens and Pulicaria wightiana by acute oral toxicity study in female rats as per OECD guideline 425.Methods: Rats were sequentially administered with ethanol leaf extracts of Derris scandens (Ds & Pulicaria wightiana(Pw  in single dosages of 175, 550, and 2000 mg/kg of body weight. All the animals were individually studied for mortality, wellness parameters and body weight for 14 days.Results: No mortality and no significant changes were observed in body weight and wellness parameters at 175, 550 and 2000 mg/kg body wt. doses of both Derris scandens and Pulicaria wightiana , which reveal the safety of these plants  in the doses up to 2000 mg/kg body weight.Conclusion: Conclusively, LD50 value of ethanol extracts of leaves of Derris scandens and Pulicaria wightiana were found to be more than 2000 mg/kg body weight.

  12. Carnosic acid attenuates acute ethanol-induced liver injury via a SIRT1/p66Shc-mediated mitochondrial pathway.

    Science.gov (United States)

    Tian, Xinyao; Hu, Yan; Li, Mingzhu; Xia, Kun; Yin, Jiye; Chen, Juan; Liu, Zhaoqian

    2016-04-01

    Ethanol-induced liver injury is associated with oxidative stress and hepatocyte apoptosis. We previously demonstrated that SIRT1/p66Shc pathway activation attenuates hepatocyte apoptosis in liver ischemia/reperfusion. The current study aimed to investigate whether carnosic acid (CA), a natural antioxidant, can inhibit acute ethanol-induced apoptosis of hepatocytes and to determine the effect of SIRT1/p66Shc on this process. Our results showed that CA pretreatment significantly reduced ethanol-induced histologic damage, serum aminotransferase activity, and oxidative stress in rats. Importantly, CA pretreatment increased SIRT1 expression following ethanol exposure. Furthermore, p66Shc expression was negatively correlated with SIRT1 expression. Consistent with the results demonstrating p66Shc inhibition, CA pretreatment inhibited the release of cytochrome C and apoptosis-inducing factor (AIF) from mitochondria. After exposing L02 cells to ethanol, the increased SIRT1 expression induced by CA was abrogated by pharmacologic SIRT1 inhibition or the use of siRNA against SIRT1. Additionally, SIRT1 inhibition significantly abrogated the suppression of p66Shc expression and mitochondrial translocation induced by CA. Accordingly, CA-induced decreases in the release of cytochrome C and AIF and in mitochondrial apoptosis were nearly abolished by SIRT1 knockdown. These data indicated that CA-activated SIRT1 is protective against ethanol treatment. In summary, CA attenuates acute ethanol-induced liver injury via a SIRT1/p66Shc-mediated mitochondrial pathway.

  13. Acute delirium in an elderly woman following zoledronate administration

    Directory of Open Access Journals (Sweden)

    Mohammad Nasiruddin

    2014-01-01

    Full Text Available Zoledronate is a third-generation bisphosphonate having distinctive profile of high potency as well as prolonged duration of action. Intravenous zoledronate is the recently approved bisphosphonate for the treatment of osteoporosis and has an attractive once-yearly regimen for the treatment of osteoporosis. Here we report, for the first time, a case of acute delirium following zoledronate administration for osteoporosis. An 86-year-old female patient presented to orthopedics out-patient department (OPD with complaints of pain and unable to bear weight on left thigh with history of fall from bed 2 months back. She was diagnosed as fracture neck of femur with severe osteoporosis and treated conservatively. She was given zoledronate IV 5 mg infusion over 30 min. After 10-12 h of zoledronate infusion, patient became confused, disorientated, and agitated. A septic work-up was negative. Electrolyte disturbances were excluded with normal sodium, potassium, calcium, and magnesium levels. Computed tomography of the brain was unremarkable. A metabolic cause could not be found for the change in her mental state. Patient was referred to medicine department where she was diagnosed as drug-induced acute delirium probably due to zoledronate. Patient was advised injections haloperidol and torsemide. In the following 48 h, her confusion got cleared and mental status was improved. According to the Naranjo′s scale, the effect of zoledronate in our patient was scored 6 indicating a probable likelihood of causing delirium. It was a probable cause of acute delirium according to World Health Organization (WHO causality scale.

  14. Effect of Probiotic Administration on Acute Inflammatory Pain

    Directory of Open Access Journals (Sweden)

    Shadnoush

    2016-11-01

    Full Text Available Background Acute inflammatory pain causes by direct stimulation of nociceptors and release of inflammatory mediators and cytokines. Probiotics are capable to modulate the immune system, down regulate the inflammatory mediators, and increase regulatory and anti-inflammatory cytokines. Objectives The aim of this study was to examine the effect of oral administration of probiotics on behavioral, cellular and molecular aspects of acute inflammatory pain in male rats. Methods Adult male Wistar rats (200 - 220 g were selected and randomly divided into 7 experimental groups (CFA, CFA control, CFA + vehicle (distilled water, CFA + 3 doses of probiotics, CFA + indomethacin and each group was divided into 3 subgroups based on different time points (days 0, 3, and 7 (n = 6 rats, each group. Complete Freund’s adjuvant (CFA-induced arthritis (AA was caused by a single subcutaneous injection of CFA into the rats’ left hind paw on day 0. Different doses of probiotics (1/250, 1/500 and 1/1000 (109 CFU/g was administered daily (gavage after the CFA injection. Blood samples were taken from the vessel retro-orbital corners of rat’s eyes. After behavioral and inflammatory tests, the lumbar segments of rat’s spinal cord (L1 - L5 were removed. Hyperalgesia, edema, serum TNF-α and IL-1β levels and NF-κB expression were assessed on days 0, 3, and 7 of the study. Results The results of this study showed the role of effective dose of probiotics (1/500 in reducing edema (P = 0.0009, hyperalgesia (P = 0.0002, serum levels of TNF-α (P = 0.0004 and IL-1β (P = 0.0004 and NF-κB expression (P = 0.0007 during the acute phase of inflammatory pain caused by CFA. Conclusions It seems that an effective dose of probiotics due to its direct effects on inhibition of intracellular signaling pathways and pro-inflammatory cytokines can alleviate inflammatory symptoms and pain in the acute phase.

  15. Effects of beer administration in mice on acute toxicities induced by X rays and carbon ions

    Energy Technology Data Exchange (ETDEWEB)

    Monobe, Manami [Chiba Univ. (Japan). Graduate School of Science and Technology; Koike, Sachiko; Uzawa, Akiko; Ando, Koichi [National Inst. of Radiological Sciences, Chiba (Japan)

    2003-03-01

    We have investigated the tissue specificity of radioprotection by beer, which was previously found for human lymphocytes. C3H/He female mice, aged 14 weeks, received an oral administration of beer, ethanol or saline at a dose of 1 ml/mouse 30 min before whole-body irradiation with {sup 137}Cs {gamma} rays or 50 keV/{mu}m carbon ions. The dicentrics of chromosome aberrations in spleen cells were significantly (p<0.05) reduced by beer and ethanol-administration for {gamma}-ray irradiation, but not for carbon-ion irradiation. The number of jejunal crypts plotted against the dose showed that both beer and ethanol significantly increased D{sub 0} (slope of a dose-survival curve) for {gamma} rays and carbon ions as well. Beer administration significantly (p<0.05) increased LD{sub 50/30} (radiation dose required to kill 50% of mice within 30 days) for {gamma} rays and carbon ions. Ethanol-administration also significantly (p<0.05) increased the LD{sub 50/30} value for {gamma} rays, but not for carbon ions. It is concluded that beer administration reduces the radiation injury caused by photons and carbon ions, depending on the tissue type. Radioprotection by beer administration is not solely due to OH radical-scavenging action by the ethanol contained in beer. (author)

  16. Acute oral toxicity study of ethanol extract of Ceiba pentandra leaves as a glucose lowering agent in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Hadiza Lami Muhammad; Adamu Yusuf Kabiru; Musa Bola Busari; Abdullah Mann; Abubakar Siddique Abdullah; Abdulrazaq Taye Usman; Usman Adamu

    2016-01-01

    Objective: To evaluate the use of Ceiba pentandra (C. pentandra) as a glucose lowering agent and the attendant physiological changes in albino rats. Methods: Acute oral toxicity study of the extract was carried out by the administration of 10, 100, 1 000, 1 600, 2 900, and 5 000 mg/kg body weight of C. pentandra to rats in their respective groups. Twenty healthy albino rats weighing between 140 and 150 g were randomly allotted to five groups of four rats each. 100 mg/kg body weight of alloxan monohydrate was i.p. administered to rats and rats with blood glucose ? 200 mg/dL were considered diabetic. 5 mg/kg body weight of standard drug, 200 and 400 mg/kg body weight of ethanol extract of C. pentandra were orally administered to diabetic rats in their respective groups once daily for 12 days while the control groups received 0.1 mL of normal saline for the same period. The blood glucose was checked after every 4 days and the experiment was terminated on the 17th day. Results: The safe dose (LD50) of the extract was greater than 5 000 mg/kg body weight. The extract treated groups exhibited a remarkable reduction in blood glucose [(87.72 ± 7.67) mg/dL for 200 mg/kg body weight dose and (86.33 ± 4.54) mg/dL for 400 mg/kg body weight dose] competitively with the normoglycemic group [(88.71 ± 4.56) mg/dL]. The body weight of the extract and standard drug treated groups appreciated significantly (P Conclusions: Ethanol extract of C. pentandra has glucose lowering effect and can ameliorate the biochemical abnormalities associated with diabetes mellitus.

  17. Using monosodium glutamate to initiate ethanol self-administration in inbred mouse strains.

    Science.gov (United States)

    McCool, Brian A; Chappell, Ann M

    2012-01-01

    Voluntary oral ethanol consumption in rodents is generally limited by strong taste-aversion in these species. Historically, this has been overcome by combining ethanol with a sweetener, typically sucrose or saccharine, and then slowly 'fading' away the sweetener. While useful in most instances, this approach has not proven as successful for some inbred strains of mice (e.g. DBA/2J) despite consistent evidence in the literature that these same strains express strong conditioned place preference for intraperitoneal- or intragastric-administered ethanol. Importantly, DBA/2J mice express a polymorphism in a 'sweet' taste receptor subunit gene that reduces the potency of sweet substances in these mice. We hypothesized that the presence of this polymorphism might help explain the contrasting behavioral findings of weak voluntary oral ethanol consumption following sucrose-fade yet robust conditioned place preference for ethanol in this strain. To test this, we compared ethanol consumption initiated by either a 'traditional' sucrose-fade or a fade from an alternative tastant, monosodium glutamate (MSG). We found that in both C57BL/6J and DBA/2J mice, the MSG-fade produced robust increases in home cage ethanol consumption relative to the traditional sucrose-fade. This increased ethanol intake following MSG-fade was evident across a range of ethanol concentrations. Our findings suggest the potential utility of the MSG-fade to establish stable voluntary oral ethanol consumption in mice, particularly ethanol 'non-preferring' strains such as DBA/2J and lend additional support to the notion that ethanol consumption in DBA/2J mice is limited by pronounced taste aversion.

  18. Model studies for evaluating the acute neurobehavioral effects of complex hydrocarbon solvents. I. Validation of methods with ethanol

    NARCIS (Netherlands)

    McKee, R.H.; Lammers, J.H.C.M.; Hoogendijk, E.M.G.; Emmen, H.H.; Muijser, H.; Barsotti, D.A.; Owen, D.E.; Kulig, B.M.

    2006-01-01

    As a preliminary step to evaluating the acute neurobehavioral effects of hydrocarbon solvents and to establish a working model for extrapolating animal test data to humans, joint neurobehavioral/toxicokinetic studies were conducted which involved administering ethanol to rats and volunteers. The spe

  19. Acute Inhalation Exposure to Titanium Ethanolate as a Possible Cause of Metal Fume Fever

    Directory of Open Access Journals (Sweden)

    M Ahmadimanesh

    2014-04-01

    Full Text Available Occupational inhalation exposure to noxious agents is not uncommon. Herein, we present a 26-year-old male student who had accidental acute inhalation exposure to a large quantity of titanium ethanolate and hydrogen chloride in chemistry lab. He was referred to the emergency department of our hospital with low-grade fever, dyspnea, headache, fatigue and myalgia. After 24 hrs of symptomatic treatment (oxygen therapy and acetaminophen, the fever was subsided and the patient discharged home in a good clinical condition. The presented symptoms could be interpreted as a form of metal fume fever. It can therefore be concluded that organo-metallic compound of titanium metal may have the potential to produce metal fume fever in human.

  20. Large-scale analysis of acute ethanol exposure in zebrafish development: a critical time window and resilience.

    Directory of Open Access Journals (Sweden)

    Shaukat Ali

    Full Text Available BACKGROUND: In humans, ethanol exposure during pregnancy causes a spectrum of developmental defects (fetal alcohol syndrome or FAS. Individuals vary in phenotypic expression. Zebrafish embryos develop FAS-like features after ethanol exposure. In this study, we ask whether stage-specific effects of ethanol can be identified in the zebrafish, and if so, whether they allow the pinpointing of sensitive developmental mechanisms. We have therefore conducted the first large-scale (>1500 embryos analysis of acute, stage-specific drug effects on zebrafish development, with a large panel of readouts. METHODOLOGY/PRINCIPAL FINDINGS: Zebrafish embryos were raised in 96-well plates. Range-finding indicated that 10% ethanol for 1 h was suitable for an acute exposure regime. High-resolution magic-angle spinning proton magnetic resonance spectroscopy showed that this produced a transient pulse of 0.86% concentration of ethanol in the embryo within the chorion. Survivors at 5 days postfertilisation were analysed. Phenotypes ranged from normal (resilient to severely malformed. Ethanol exposure at early stages caused high mortality (≥88%. At later stages of exposure, mortality declined and malformations developed. Pharyngeal arch hypoplasia and behavioral impairment were most common after prim-6 and prim-16 exposure. By contrast, microphthalmia and growth retardation were stage-independent. CONCLUSIONS: Our findings show that some ethanol effects are strongly stage-dependent. The phenotypes mimic key aspects of FAS including craniofacial abnormality, microphthalmia, growth retardation and behavioral impairment. We also identify a critical time window (prim-6 and prim-16 for ethanol sensitivity. Finally, our identification of a wide phenotypic spectrum is reminiscent of human FAS, and may provide a useful model for studying disease resilience.

  1. Tolerance to Ethanol or Nicotine Results in Increased Ethanol Self-Administration and Long-Term Depression in the Dorsolateral Striatum

    OpenAIRE

    Abburi, Chandrika; Wolfman, Shannon L.; Metz, Ryan A. E.; Kamber, Rinya; McGehee, Daniel S.; McDaid, John

    2016-01-01

    Abstract Ethanol (EtOH) and nicotine are the most widely coabused drugs. Tolerance to EtOH intoxication, including motor impairment, results in greater EtOH consumption and may result in a greater likelihood of addiction. Previous studies suggest that cross-tolerance between EtOH and nicotine may contribute to the abuse potential of these drugs. Here we demonstrate that repeated intermittent administration of either EtOH or nicotine in adult male Sprague Dawley rats results in tolerance to Et...

  2. Three months of chronic ethanol administration and the behavioral outcome of rats after lateral fluid percussion brain injury.

    Science.gov (United States)

    Masse, J; Billings, B; Dhillon, H S; Mace, D; Hicks, R; Barron, S; Kraemer, P J; Dendle, P; Prasad, R M

    2000-05-01

    This study examined the effects of 3 months of chronic ethanol administration (CEAn) on the behavioral outcome in rats after lateral fluid percussion (FP) brain injury. Rats were given either an ethanol liquid diet (ethanol diet groups) or a pair-fed isocaloric sucrose control diet (control diet groups) for 3 months. Then, rats from both diet groups were subjected to either lateral FP brain injury of moderate severity (1.8 atm) or to sham operation. Postinjury behavioral measurements revealed that brain injury caused significant spatial learning disability in both diet groups. There were no significant differences in spatial learning ability in the sham or brain-injured animals between the control and ethanol diets. However, a trend towards cognitive impairment in the sham animals and a trend towards reduced deficits in the brain-injured animals were observed in the ethanol diet group. Histologic analysis of injured animals from both diet groups revealed similar extents of ipsilateral cortical and hippocampal CA3 damage. These results, in general, suggest that 3 months of CEAn does not significantly alter the behavioral and morphologic outcome of experimental brain injury.

  3. CYP2E1-dependent hepatotoxicity and oxidative damage after ethanol administration in human primary hepatocytes

    Institute of Scientific and Technical Information of China (English)

    Lie-Gang Liu; Hong Yan; Ping Yao; Wen Zhang; Li-Jun Zou; Fang-Fang Song; Ke Li; Xiu-Fa Sun

    2005-01-01

    AIM: To observe the relationship between ethanol-induced oxidative damage in human primary cultured hepatocytes and cytochrome P450 2E1 (CYP2E1) activity, in order to address if inhibition of CYP2E1 could attenuate ethanol-induced cellular damage.METHODS: The dose-dependent (25-100 mmol/L) and time-dependent (0-24 h) exposures of primary human cultured hepatocytes to ethanol were carried out. CYP2E1 activity and protein expression were detected by spectrophotometer and Western blot analysis respectively.Hepatotoxicity was investigated by determination of lactate dehydrogenase (LDH) and aspartate transaminase (AST) level in hepatocyte culture supernatants, as well as the intracellular formation of malondialdehyde (MDA).RESULTS: A dose-and time-dependent response between ethanol exposure and CYP2E1 activity in human hepatocytes was demonstrated. Moreover, there was a time-dependent increase of CYP2E1 protein after 100 mmol/L ethanol exposure. Meanwhile, ethanol exposure of hepatocytes caused a time-dependent increase of ceilular MDA level, LDH, and AST activities in supernatants.Furthermore, the inhibitor of CYP2E1, diallyl sulfide (DAS) could partly attenuate the increases of MDA, LDH, and AST in human hepatocytes.CONCLUSION: A positive relationship between ethanol-induced oxidative aamage in human primary cultured hepatocytes and CYP2E1 activity was exhibited, and the inhibition of CYP2E1 could partly attenuate ethanol-induced oxidative damage.

  4. Cytokine Changes following Acute Ethanol Intoxication in Healthy Men: A Crossover Study

    Directory of Open Access Journals (Sweden)

    Sudan Prasad Neupane

    2016-01-01

    Full Text Available Alcohol is a known modulator of the innate immune system. Owing to the absence of human studies, alcohol’s effect on circulating cytokine profile remains unclear. We investigated the effect of acute high dose alcohol consumption on systemic cytokine release. After an overnight fasting, alcohol-experienced healthy male volunteers (N=20 aged 25–45 years were given oral ethanol in the form of vodka (4.28 mL/kg which they drank over a period of 30 minutes reaching peak blood alcohol concentration of 0.12% (SD 0.028. Blood samples were obtained prior to alcohol intake as well as 2, 7, and 12 hours thereafter. Serum levels of the inflammatory cytokines IL-1β, IL-1Ra, IL-6, IL-10, IL-17, IFN-γ, MCP-1, and TNF-α were determined by the multibead-based assay. Baseline cytokine levels were not related to BMI, hepatic parameters, electrolytes, glucose, or morning cortisol levels. Within 2 hours of alcohol intake, levels of IL-1Ra were elevated and remained so throughout the assessment period (p for trend = 0.015. In contrast, the levels of the chemokine MCP-1 dropped acutely followed by steadily increasing levels during the observation period (p<0.001. The impact of sustained elevated levels of MCP-1 even after the clearance of blood alcohol content deserves attention.

  5. Ginger extract protects rat's kidneys against oxidative damage after chronic ethanol administration.

    Science.gov (United States)

    Shirpoor, Aireza; Rezaei, Farzaneh; Fard, Amin Abdollahzade; Afshari, Ali Taghizadeh; Gharalari, Farzaneh Hosseini; Rasmi, Yousef

    2016-12-01

    Chronic alcohol ingestion is associated with pronounced detrimental effects on the renal system. In the current study, the protective effect of ginger extract on ethanol-induced damage was evaluated through determining 8-OHdG, cystatin C, glomerular filtration rate, and pathological changes such as cell proliferation and fibrosis in rats' kidneys. Male wistar rats were randomly divided into three groups and were treated as follows: (1) control, (2) ethanol and (3) ginger extract treated ethanolic (GETE) groups. After a six weeks period of treatment, the results revealed proliferation of glomerular and tubular cells, fibrosis in glomerular and peritubular and a significant rise in the level of 8-OHdG, cystatin C, plasma urea and creatinine. Moreover, compared to the control group, the ethanol group showed a significant decrease in the urine creatinine and creatinine clearance. In addition, significant amelioration of changes in the structure of kidneys, along with restoration of the biochemical alterations were found in the ginger extract treated ethanolic group, compared to the ethanol group. These findings indicate that ethanol induces kidneys abnormality by oxidative DNA damage and oxidative stress, and that these effects can be alleviated using ginger as an antioxidant and anti-inflammatory agent.

  6. Short-term and long-term ethanol administration inhibits the placental uptake and transport of valine in rats

    Energy Technology Data Exchange (ETDEWEB)

    Patwardhan, R.V.; Schenker, S.; Henderson, G.I.; Abou-Mourad, N.N.; Hoyumpa, A.M. Jr.

    1981-08-01

    Ethanol ingestion during pregnancy causes a pattern of fetal/neonatal dysfunction called the FAS. The effects of short- and long-term ethanol ingestion on the placental uptake and maternal-fetal transfer of valine were studied in rats. The in vivo placental uptake and fetal uptake were estimated after injection of 0.04 micromol of /sub 14/C-valine intravenously on day 20 of gestation in Sprague-Dawley rats. Short-term ethanol ingestion (4 gm/kg) caused a significant reduction in the placental uptake of /sub 14/C-valine by 33%, 60%, and 30%, and 31% at 2.5, 5, 10, and 15 min after valine administration, respectively (p less than 0.01), and a similar significant reduction occurred in the fetal uptake of /sub 14/C-valine (p less than 0.01). Long-term ethanol ingestion prior to and throughout gestation resulted in a 47% reduction in placental valine uptake (p less than 0.01) and a 46% reduction in fetal valine uptake (p less than 0.01). Long-term ethanol feeding from day 4 to day 20 of gestation caused a 32% reduction in placental valine uptake (p less than 0.01) and a 26% reduction in fetal valine uptake (p less than 0.01). We conclude that both short- and long-term ingestion of ethanol inhibit the placental uptake and maternal-fetal transfer of an essential amino acid--valine. An alteration of placental function may contribute to the pathogenesis of the FAS.

  7. Role of interleukin-10 (IL-10) in regulation of GABAergic transmission and acute response to ethanol.

    Science.gov (United States)

    Suryanarayanan, A; Carter, J M; Landin, J D; Morrow, A L; Werner, D F; Spigelman, I

    2016-08-01

    Mounting evidence indicates that ethanol (EtOH) exposure activates neuroimmune signaling. Alterations in pro-inflammatory cytokines after acute and chronic EtOH exposure have been heavily investigated. In contrast, little is known about the regulation of neurotransmission and/or modulation by anti-inflammatory cytokines in the brain after an acute EtOH exposure. Recent evidence suggests that interleukin-10 (IL-10), an anti-inflammatory cytokine, is upregulated during withdrawal from chronic EtOH exposure. In the present study, we show that IL-10 is increased early (1 h) after a single intoxicating dose of EtOH (5 g/kg, intragastric) in Sprague Dawley rats. We also show that IL-10 rapidly regulates GABAergic transmission in dentate gyrus neurons. In brain slice recordings, IL-10 application dose-dependently decreases miniature inhibitory postsynaptic current (mIPSC) area and frequency, and decreases the magnitude of the picrotoxin sensitive tonic current (Itonic), indicating both pre- and postsynaptic mechanisms. A PI3K inhibitor LY294002 (but not the negative control LY303511) ablated the inhibitory effects of IL-10 on mIPSC area and Itonic, but not on mIPSC frequency, indicating the involvement of PI3K in postsynaptic effects of IL-10 on GABAergic transmission. Lastly, we also identify a novel neurobehavioral regulation of EtOH sensitivity by IL-10, whereby IL-10 attenuates acute EtOH-induced hypnosis. These results suggest that EtOH causes an early release of IL-10 in the brain, which may contribute to neuronal hyperexcitability as well as disturbed sleep seen after binge exposure to EtOH. These results also identify IL-10 signaling as a potential therapeutic target in alcohol-use disorders and other CNS disorders where GABAergic transmission is altered.

  8. Alternative Splicing of AMPA subunits in Prefrontal Cortical Fields of Cynomolgus Monkeys following Chronic Ethanol Self-Administration

    Directory of Open Access Journals (Sweden)

    Glen eAcosta

    2012-01-01

    Full Text Available Functional impairment of the orbital and medial prefrontal cortex underlies deficits in executive control that characterize addictive disorders, including alcohol addiction. Previous studies indicate that alcohol alters glutamate neurotransmission and one substrate of these effects may be through the reconfiguration of the subunits constituting ionotropic glutamate receptor (iGluR complexes. Glutamatergic transmission is integral to cortico-cortical and cortico-subcortical communication and alcohol-induced changes in the abundance of the receptor subunits and/or their splice variants may result in critical functional impairments of prefrontal cortex in alcohol dependence. To this end, the effects of chronic ethanol self-administration on glutamate receptor ionotropic AMPA (GRIA subunit variant and kainate (GRIK subunit mRNA expression were studied in the orbitofrontal cortex (OFC, dorsolateral prefrontal cortex (DLPFC and anterior cingulate cortex (ACC of male cynomolgus monkeys. In DLPFC, total AMPA splice variant expression and total kainate receptor subunit expression were significantly decreased in alcohol drinking monkeys. Expression levels of GRIA3 flip and flop and GRIA4 flop mRNAs in this region were positively correlated with daily ethanol intake and blood ethanol concentrations averaged over the six months prior to necropsy. In OFC, AMPA subunit splice variant expression was reduced in the alcohol treated group. GRIA2 flop mRNA levels in this region were positively correlated with daily ethanol intake and blood ethanol concentrations averaged over the six months prior to necropsy. Results from these studies provide further evidence of transcriptional regulation of iGluR subunits in the primate brain following chronic alcohol self-administration. Additional studies examining the cellular localization of such effects in the framework of primate prefrontal cortical circuitry are warranted.

  9. Reversing gastric mucosal alterations during ethanol-induced chronic gastritis in rats by oral administration of Opuntia ficus- indica mucilage

    Institute of Scientific and Technical Information of China (English)

    Ricardo Vázquez-Ramírez; Marisela Olguín-Martínez; Carlos Kubli-Garfias; Rolando Hernández-Mu(n)oz

    2006-01-01

    AIM: To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica (Cactaceae) on the healing of ethanol-induced gastritis in rats.METHODS: Chronic gastric mucosa injury was treated with mucilage (5 mg/kg per day) after it was induced by ethanol. Lipid composition, activity of 5'-nucleotidase (a membrane-associated ectoenzyme) and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined.Histological studies of gastric samples from the experimental groups were included.RESULTS: Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes.Phosphatidylcholine (PC) decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect.The activity of 5'-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes.CONCLUSION: The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids,mainly PC and phosphatidylethanolamine (PE), may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage.

  10. Glutamatergic Mechanisms of Comorbidity Between Acute Stress and Cocaine Self-administration

    Science.gov (United States)

    Garcia-Keller, Constanza; Kupchik, Yonatan; Gipson, Cassandra D; Brown, Robyn M; Spencer, Sade; Bollati, Flavia; Esparza, Maria A; Roberts-Wolfe, Doug; Heinsbroek, Jasper; Bobadilla, Ana-Clara; Cancela, Liliana M; Kalivas, Peter W

    2015-01-01

    There is substantial comorbidity between stress disorders and substance use disorders (SUDs), and acute stress augments the locomotor stimulant effect of cocaine in animal models. Here we endeavor to understand the neural underpinnings of comorbid stress disorders and drug use by determining if the glutamatergic neuroadaptations that characterize cocaine self-administration are induced by acute stress. Rats were exposed to acute (2 h) immobilization stress and 3 weeks later the nucleus accumbens core was examined for changes in glutamate transport, glutamate mediated synaptic currents, and dendritic spine morphology. We also determined if acute stress potentiated the acquisition of cocaine self-administration. Acute stress produced an enduring reduction in glutamate transport, and potentiated excitatory synapses on medium spiny neurons. Acute stress also augmented the acquisition of cocaine self-administration. Importantly, by restoring glutamate transport in the accumbens core with ceftriaxone the capacity of acute stress to augment the acquisition of cocaine self-administration was abolished. Similarly, ceftriaxone treatment prevented stress-induced potentiation of cocaine-induced locomotor activity. However, ceftriaxone did not reverse stress-induced synaptic potentiation, indicating that this effect of stress exposure did not underpin the increased acquisition of cocaine self-administration. Reversing acute stress-induced vulnerability to self-administer cocaine by normalizing glutamate transport poses a novel treatment possibility for reducing comorbid SUDs in stress disorders. PMID:26821978

  11. Evaluation of the Acute and Subchronic Toxicities of Ethanol Leaf Extract of Spathodea campanulata P. Beauv.

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    E E Ilodigwe

    2010-06-01

    Full Text Available Summary: The acute and subchronic toxicities of the ethanol leaf extract of Spathodea campanulata, a popular Nigerian traditional anti-convulsant remedy was investigated. For the acute toxicity study, 1000-5000 mg/kg of the ethanol leaf extract were administered to rats and obvious toxic symptoms and mortality 24 hours post-adminstration of the extract were determined. The median lethal dose (LD50 of the extract was determined. In the subchronic study, 750-3000 mg/kg of the extract were administered daily for 90 days. The food and water consumption, body weight changes, as well as heamatological and biochemical parameters were determined periodically. The phytotochemical constituents of the extract were also investigated. Phytochemical analysis revealed the presence of tannins, saponins, anthraquinone glycosides, and flavonoids.. The estimated LD50 of the extract was 4466.84 mg/kg. There was no mortality during the period of study but the animals showed signs of anorexia, weakness, sluggishness and significant (p<0.05 reduction in food and water intake and body weight. The effects on haemoglobin concentration, PCV, RBC and WBC counts were non significant (P>0.05. The extract caused significant (p<0.05 increases in serum liver enzymes, AST, ALP and ALT. These changes showed recovery after 28 days post-treatment. These results suggest that the leaf extract of S. campanulata is safe in the treatment of epilepsy. Industrial relevance: Epilepsy is a chronic disorder that requires life-long management. The available anti-epileptic drugs (AEDs are not only limited by adverse effects, but are not readily accessible in resource poor communities where this disease appears more prevalent. The use of medicinal plants especially Spathodea campanulata in the treatment of epilepsy is very popular in Nigeria. Compared to AEDs, it is very cheap, readily available and relatively free from adverse effects. The results of the present study will enable the industry

  12. Evaluation of the antidepressant-like effects of acute and sub-acute administration of crocin and crocetin in mice

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    Bahareh Amin

    2015-08-01

    Full Text Available Objective: The present study was designed to investigate the putative antidepressant effects of crocin and crocetin, two major active ingredients of Crocus sativus L. (saffron using mice in two different regimens of acute and sub-acute administration. Material and Methods: In acute treatment, antidepressant-like activities of crocin and crocetin (10, 20 and 40 mg/kg, i.p. were evaluated using forced swim test (FST. In sub-acute study (21 times with 24-h intervals, antidepressant-like effects of oral administration of drugs were examined using FST and tail suspension test (TST. Locomotor activity and motor coordination were studied using open field and rotarod tests, respectively. Results: Acute treatment with crocin (40 mg/kg and crocetin (20 and 40 mg/kg produced antidepressant-like effect in FST without affecting the baseline locomotion in mice. Sub-acute oral administration of crocin significantly decreased immobility time only at the highest dose (100 mg/kg. Crocetin (12.5, 25 and 50 mg/kg was able to decrease immobility time in FST and TST. Locomotor activity and coordination of mice were not affected by crocin or crocetin. Conclusion: Since higher doses of crocin was required to show antidepressant effects, more efficacy of crocetin may be concluded. This observation provides further support for metabolism of crocin to crocetin following oral administration.

  13. Mode of ethanol administration influences the severity of hemorrhage-induced lactic acidemia in conscious guinea pigs.

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    McDonough, Kathleen H; Swafford, Albert N; Giaimo, Mary E; Adamson, Trinka W; Miller, Harvey I

    2010-09-01

    Mechanisms that limit metabolic acidemia during shock are limited by ethanol (EtOH). This may be due to (1) loss of respiratory compensation, (2) a greater fall in cardiac output, (3) altered removal of plasma lactate by the liver, and (4) alterations in central nervous system orchestration of compensatory responses. We have previously shown that loss of metabolic compensation during hemorrhage is correlated with plasma EtOH concentrations. The present study determines if the mode of ethanol administration influences compensation during hemorrhage. Male guinea pigs were administered EtOH (1 g/kg, 30% wt/vol) via intraperitoneal (IP) or intragastric (IG) routes. After 30 minutes, 60% of the estimated blood volume was removed. Animals remained in shock for 30 minutes were resuscitated with lactated Ringer solution and monitored for 3 hours. Plasma EtOH levels were similar in the 2 groups at the initiation of, and during, hemorrhage and resuscitation. Animals given EtOH IP exhibited more severe acidemia. The mode of EtOH administration may affect hepatic ethanol and lactate metabolism, thus exacerbating acidemia. An altered central nervous system response may impact compensatory responses during shock. Our results indicate that the "history" of the EtOH episode may be an important determinant in the compensation for hemorrhage and resuscitation.

  14. Ethylphenidate formation in human subjects after the administration of a single dose of methylphenidate and ethanol.

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    Markowitz, J S; DeVane, C L; Boulton, D W; Nahas, Z; Risch, S C; Diamond, F; Patrick, K S

    2000-06-01

    Ethylphenidate was recently reported as a novel drug metabolite in two overdose fatalities where there was evidence of methylphenidate and ethanol coingestion. This study explores the pharmacokinetics of ethylphenidate relative to methylphenidate and the major metabolite ritalinic acid, in six healthy subjects who received methylphenidate and ethanol under controlled conditions. Subjects (three males, three females) received a single oral dose of methylphenidate (20 mg; two 10-mg tablets) followed by consumption of ethanol (0.6 g/kg) 30 min later. Methylphenidate, ritalinic acid, and ethylphenidate were quantified using liquid chromatography-tandem mass spectrometry. Ethylphenidate was detectable in the plasma and urine of all subjects after ethanol ingestion. The mean (+/-S.D.) area under the concentration versus time curve for ethylphenidate was 1.2 +/- 0.7 ng/ml/h, representing 2.3 +/- 1.3% that of methylphenidate (48 +/- 12 ng/ml/h). A significant correlation was observed between the area under the concentration versus time curve of methylphenidate and that of ethylphenidate. In view of the known dopaminergic activity of racemic ethylphenidate, it remains possible that under certain circumstances of higher level dosing, e.g., in the abuse of methylphenidate and ethanol, the metabolite ethylphenidate may contribute to drug effects.

  15. Acute immune-mediated thrombocytopenia due to oxaliplatin administration: a case report.

    Science.gov (United States)

    Pietrantonio, Filippo; Di Bartolomeo, Maria; Buzzoni, Roberto; Bajetta, Emilio

    2010-01-01

    Drug-induced acute thrombocytopenia is an extremely rare side effect that may occur immediately after oxaliplatin infusion. This potentially fatal reaction is immune mediated and can be anticipated by mild hemorrhagic signs during previous administrations. This is the first report of acute thrombocytopenia occurring during adjuvant treatment of colorectal cancer with oxaliplatin. Clinicians should be aware of this adverse event in order to prevent possible serious consequences and stop further oxaliplatin administration.

  16. Adolescent rats are resistant to the development of ethanol-induced chronic tolerance and ethanol-induced conditioned aversion.

    Science.gov (United States)

    Pautassi, Ricardo Marcos; Godoy, Juan Carlos; Molina, Juan Carlos

    2015-11-01

    The analysis of chronic tolerance to ethanol in adult and adolescent rats has yielded mixed results. Tolerance to some effects of ethanol has been reported in adolescents, yet other studies found adults to exhibit greater tolerance than adolescents or comparable expression of the phenomena at both ages. Another unanswered question is how chronic ethanol exposure affects subsequent ethanol-mediated motivational learning at these ages. The present study examined the development of chronic tolerance to ethanol's hypothermic and motor stimulating effects, and subsequent acquisition of ethanol-mediated odor conditioning, in adolescent and adult male Wistar rats given every-other-day intragastric administrations of ethanol. Adolescent and adult rats exhibited lack of tolerance to the hypothermic effects of ethanol during an induction phase; whereas adults, but not adolescents, exhibited a trend towards a reduction in hypothermia at a challenge phase (Experiment 1). Adolescents, unlike adults, exhibited ethanol-induced motor activation after the first ethanol administration. Adults, but not adolescents, exhibited conditioned odor aversion by ethanol. Subsequent experiments conducted only in adolescents (Experiment 2, Experiment 3 and Experiment 4) manipulated the context, length and predictability of ethanol administration. These manipulations did not promote the expression of ethanol-induced tolerance. This study indicated that, when moderate ethanol doses are given every-other day for a relatively short period, adolescents are less likely than adults to develop chronic tolerance to ethanol-induced hypothermia. This resistance to tolerance development could limit long-term maintenance of ethanol intake. Adolescents, however, exhibited greater sensitivity than adults to the acute motor stimulating effects of ethanol and a blunted response to the aversive effects of ethanol. This pattern of response may put adolescents at risk for early initiation of ethanol intake.

  17. Influences of acute ethanol exposure on locomotor activities of zebrafish larvae under different illumination.

    Science.gov (United States)

    Guo, Ning; Lin, Jia; Peng, Xiaolan; Chen, Haojun; Zhang, Yinglan; Liu, Xiuyun; Li, Qiang

    2015-11-01

    Larval zebrafish present unique opportunities to study the behavioral responses of a model organism to environmental challenges during early developmental stages. The purpose of the current study was to investigate the locomotor activities of AB strain zebrafish larvae at 5 and 7 days post-fertilization (dpf) in response to light changes under the influence of ethanol, and to explore potential neurological mechanisms that are involved in ethanol intoxication. AB strain zebrafish larvae at both 5 and 7 dpf were treated with ethanol at 0% (control), 0.1%, 0.25%, 0.5%, 1%, and 2% (v/v%). The locomotor activities of the larvae during alternating light-dark challenges, as well as the locomotor responses immediately following the light transitions, were investigated. The levels of various neurotransmitters were also measured in selected ethanol-treated groups. The larvae at 5 and 7 dpf demonstrated similar patterns of locomotor responses to ethanol treatment. Ethanol treatment at 1% increased the swimming distances of the zebrafish larvae in the dark periods, but had no effect on the swimming distances in the light periods. In contrast, ethanol treatment at 2% increased the swimming distances in the light periods, but did not potentiate the swimming activity in the dark periods, compared to controls. Differences in the levels of neurotransmitters that are involved in norepinephrine, dopamine, and serotonin pathways were also observed in groups with different ethanol treatments. These results indicated the behavioral studies concerning the ethanol effects on locomotor activities of zebrafish larvae could be carried out as early as 5 dpf. The 1% and 2% ethanol-treated zebrafish larvae modeled ethanol effects at different intoxication states, and the differences in neurotransmitter levels suggested the involvement of various neurotransmitter pathways in different ethanol intoxication states.

  18. Ethanol extracts of Scutellaria baicalensis protect against lipopolysaccharide-induced acute liver injury in mice

    OpenAIRE

    Hai Nguyen Thanh; Hue Pham Thi Minh; Tuan Anh Le; Huong Duong Thi Ly; Tung Nguyen Huu; Loi Vu Duc; Thu Dang Kim; Tung Bui Thanh

    2015-01-01

    Objective: To investigated the protective potential of ethanol extracts of Scutellaria baicalensis (S. baicalensis) against lipopolysaccharide (LPS)-induced liver injury. Methods: Dried roots of S. baicalensis were extracted with ethanol and concentrated to yield a dry residue. Mice were administered 200 mg/kg of the ethanol extracts orally once daily for one week. Animals were subsequently administered a single dose of LPS (5 mg/kg of body weight, intraperitoneal injection). Both protein ...

  19. Roux-en-Y gastric bypass increases intravenous ethanol self-administration in dietary obese rats.

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    James E Polston

    Full Text Available Roux-en-Y gastric bypass surgery (RYGB is an effective treatment for severe obesity. Clinical studies however have reported susceptibility to increased alcohol use after RYGB, and preclinical studies have shown increased alcohol intake in obese rats after RYGB. This could reflect a direct enhancement of alcohol's rewarding effects in the brain or an indirect effect due to increased alcohol absorption after RGYB. To rule out the contribution that changes in alcohol absorption have on its rewarding effects, here we assessed the effects of RYGB on intravenously (IV administered ethanol (1%. For this purpose, high fat (60% kcal from fat diet-induced obese male Sprague Dawley rats were tested ~2 months after RYGB or sham surgery (SHAM using both fixed and progressive ratio schedules of reinforcement to evaluate if RGYB modified the reinforcing effects of IV ethanol. Compared to SHAM, RYGB rats made significantly more active spout responses to earn IV ethanol during the fixed ratio schedule, and achieved higher breakpoints during the progressive ratio schedule. Although additional studies are needed, our results provide preliminary evidence that RYGB increases the rewarding effects of alcohol independent of its effects on alcohol absorption.

  20. Self-administration of ethanol, cocaine, or nicotine does not decrease the soma size of ventral tegmental area dopamine neurons.

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    Michelle S Mazei-Robison

    Full Text Available Our previous observations show that chronic opiate administration, including self-administration, decrease the soma size of dopamine (DA neurons in the ventral tegmental area (VTA of rodents and humans, a morphological change correlated with increased firing rate and reward tolerance. Given that a general hallmark of drugs of abuse is to increase activity of the mesolimbic DA circuit, we sought to determine whether additional drug classes produced a similar morphological change. Sections containing VTA were obtained from rats that self-administered cocaine or ethanol and from mice that consumed nicotine. In contrast to opiates, we found no change in VTA DA soma size induced by any of these other drugs. These data suggest that VTA morphological changes are induced in a drug-specific manner and reinforce recent findings that some changes in mesolimbic signaling and neuroplasticity are drug-class dependent.

  1. Ethanol regulation of serum glucocorticoid kinase 1 expression in DBA2/J mouse prefrontal cortex.

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    Blair N Costin

    Full Text Available BACKGROUND: We previously identified a group of glucocorticoid-responsive genes, including Serum Glucocorticoid kinase 1 (Sgk1, regulated by acute ethanol in prefrontal cortex of DBA2/J mice. Acute ethanol activates the hypothalamic pituitary adrenal axis (HPA causing release of glucocorticoids. Chronic ethanol dysregulates the HPA response in both humans and rodents, possibly contributing to important interactions between stress and alcoholism. Because Sgk1 regulates ion channels and learning and memory, we hypothesized that Sgk1 contributes to HPA-dependent acute and adaptive neuronal responses to ethanol. These studies characterized acute and chronic ethanol regulation of Sgk1 mRNA and protein and their relationship with ethanol actions on the HPA axis. RESULTS: Acute ethanol increased Sgk1 mRNA expression in a dose and time dependent manner. Three separate results suggested that ethanol regulated Sgk1 via circulating glucocorticoids: acute ethanol increased glucocorticoid receptor binding to the Sgk1 promoter; adrenalectomy blocked ethanol induction of Sgk1 mRNA; and chronic ethanol exposure during locomotor sensitization down-regulated HPA axis activation and Sgk1 induction by acute ethanol. SGK1 protein had complex temporal responses to acute ethanol with rapid and transient increases in Ser422 phosphorylation at 15 min. following ethanol administration. This activating phosphorylation had functional consequences, as suggested by increased phosphorylation of the known SGK1 target, N-myc downstream-regulated gene 1 (NDRG1. After repeated ethanol administration during locomotor sensitization, basal SGK1 protein phosphorylation increased despite blunting of Sgk1 mRNA induction by ethanol. CONCLUSIONS: These results suggest that HPA axis and glucocorticoid receptor signaling mediate acute ethanol induction of Sgk1 transcription in mouse prefrontal cortex. However, acute ethanol also causes complex changes in SGK1 protein expression and

  2. Short Communication: Is Ethanol-Based Hand Sanitizer Involved in Acute Pancreatitis after Excessive Disinfection?—An Evaluation with the Use of PBPK Model

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    Céline Huynh-Delerme

    2012-01-01

    Full Text Available An occupational physician reported to the French Health Products Safety Agency (Afssaps a case of adverse effect of acute pancreatitis (AP in a teaching nurse, after multiple demonstrations with ethanol-based hand sanitizers (EBHSs used in a classroom with defective mechanical ventilation. It was suggested by the occupational physician that the exposure to ethanol may have produced a significant blood ethanol concentration and subsequently the AP. In order to verify if the confinement situation due to defective mechanical ventilation could increase the systemic exposure to ethanol via inhalation route, a physiologically based pharmacokinetic (PBPK modeling was used to predict ethanol blood levels. Under the worst case scenario, the simulation by PBPK modeling showed that the maximum blood ethanol concentration which can be predicted of 5.9 mg/l is of the same order of magnitude to endogenous ethanol concentration (mean = 1.1 mg/L; median = 0.4 mg/L; range = 0–35 mg/L in nondrinker humans (Al-Awadhi et al., 2004. The present study does not support the likelihood that EBHS leads to an increase in systemic ethanol concentration high enough to provoke an acute pancreatitis.

  3. Short Communication: Is Ethanol-Based Hand Sanitizer Involved in Acute Pancreatitis after Excessive Disinfection?-An Evaluation with the Use of PBPK Model.

    Science.gov (United States)

    Huynh-Delerme, Céline; Artigou, Catherine; Bodin, Laurent; Tardif, Robert; Charest-Tardif, Ginette; Verdier, Cécile; Sater, Nessryne; Ould-Elhkim, Mostafa; Desmares, Catherine

    2012-01-01

    An occupational physician reported to the French Health Products Safety Agency (Afssaps) a case of adverse effect of acute pancreatitis (AP) in a teaching nurse, after multiple demonstrations with ethanol-based hand sanitizers (EBHSs) used in a classroom with defective mechanical ventilation. It was suggested by the occupational physician that the exposure to ethanol may have produced a significant blood ethanol concentration and subsequently the AP. In order to verify if the confinement situation due to defective mechanical ventilation could increase the systemic exposure to ethanol via inhalation route, a physiologically based pharmacokinetic (PBPK) modeling was used to predict ethanol blood levels. Under the worst case scenario, the simulation by PBPK modeling showed that the maximum blood ethanol concentration which can be predicted of 5.9 mg/l is of the same order of magnitude to endogenous ethanol concentration (mean = 1.1 mg/L; median = 0.4 mg/L; range = 0-35 mg/L) in nondrinker humans (Al-Awadhi et al., 2004). The present study does not support the likelihood that EBHS leads to an increase in systemic ethanol concentration high enough to provoke an acute pancreatitis.

  4. Amelioration of alcohol-induced hepatotoxicity by the administration of ethanolic extract of Sida cordifolia Linn.

    Science.gov (United States)

    Rejitha, S; Prathibha, P; Indira, M

    2012-10-01

    Sida cordifolia Linn. (Malvaceae) is a plant used in folk medicine for the treatment of the inflammation of oral mucosa, asthmatic bronchitis, nasal congestion and rheumatism. We studied the hepatoprotective activity of 50 % ethanolic extract of S. cordifolia Linn. against alcohol intoxication. The duration of the experiment was 90 d. The substantially elevated levels of toxicity markers such as alanine aminotransferase, aspartate aminotransferase and γ-glutamyl transferase due to the alcohol treatment were significantly lowered in the extract-treated groups. The activity of antioxidant enzymes and glutathione content, which was lowered due to alcohol toxicity, was increased to a near-normal level in the co-administered group. Lipid peroxidation products, protein carbonyls, total collagen and hydroxyproline, which were increased in the alcohol-treated group, were reduced in the co-administered group. The mRNA levels of cytochrome P450 2E1, NF-κB, TNF-α and transforming growth factor-β1 were found to be increased in the alcohol-treated rats, and their expressions were found to be decreased in the co-administered group. These observations were reinforced by histopathological analysis. Thus, the present study clearly indicates that 50 % ethanolic extract of the roots of S. cordifolia Linn. has a potent hepatoprotective action against alcohol-induced toxicity, which was mediated by lowering oxidative stress and by down-regulating the transcription factors.

  5. Coorection Of Lipid Peroxydation And Antioxydant Protective System By Mexidol And Glycine In Patients With Acute Ethanol Intoxication

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    R.S. Farshatov

    2009-12-01

    Full Text Available The research goal is to study lipid peroxydation and ferments of antioxidant protection in group of patients with an acute alcohol intoxication and their correction by medicaments with antioxidant activity (mexidol, glycine and their combination. Patients with diagnosis of ethanol toxic action of moderate severity degree were under study. There were 4 groups - receiving standard therapy, standard therapy and glycine, standard therapy and mexidol, patients receiving standard therapy with combination of mexidol and glycine. Clinical condition and changes in system "lipid peroxidation - antioxidant protection» were estimated. The expressed improvement was revealed applying standard therapy with combination of mexidol and glycine

  6. Acute administration of l-tyrosine alters energetic metabolism of hippocampus and striatum of infant rats.

    Science.gov (United States)

    Ramos, Andrea C; Ferreira, Gabriela K; Carvalho-Silva, Milena; Furlanetto, Camila B; Gonçalves, Cinara L; Ferreira, Gustavo C; Schuck, Patrícia F; Streck, Emilio L

    2013-08-01

    Tyrosinemia type II is an inborn error of metabolism caused by mutations in the gene that encodes tyrosine aminotransferase, which leads to increased blood tyrosine levels. Considering that tyrosine levels are highly elevated in fluids of patients with tyrosinemia type II, and that previous studies demonstrated significant alterations in brain energy metabolism of young rats caused by l-tyrosine, the present study aimed to evaluate the effect of acute administration of l-tyrosine on the activities of citrate synthase, malate dehydrogenase, succinate dehydrogenase, and mitochondrial respiratory chain complexes I, II, II-III, and IV in posterior cortex, hippocampus, and striatum of infant rats. Wistar rats (10 days old) were killed 1h after a single intraperitoneal injection of tyrosine (500 mg/kg) or saline. The activities of energy metabolism enzymes were evaluated in brain of rats. Our results demonstrated that acute administration of l-tyrosine inhibited the activity of citrate synthase activity in striatum and increased the activities of malate dehydrogenase and succinate dehydrogenase in hippocampus. On the other hand, these enzymes were not affected in posterior cortex. The activities of complex I and complex II were inhibited by acute administration of l-tyrosine in striatum. On the other hand, the acute administration of l-tyrosine increased the activity of activity of complex II-III in hippocampus. Complex IV was not affected by acute administration of l-tyrosine in infant rats. Our results indicate an alteration in the energy metabolism in hippocampus and striatum of infant rats after acute administration of l-tyrosine. If the same effects occur in the brain of the patients, it is possible that energy metabolism impairment may be contribute to possible damage in memory and cognitive processes in patients with tyrosinemia type II.

  7. The novelty-seeking phenotype modulates the long-lasting effects of intermittent ethanol administration during adolescence.

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    Sandra Montagud-Romero

    Full Text Available The aim of the present study was to investigate if a novelty-seeking phenotype mediates the long-lasting consequences of intermittent EtOH intoxication during adolescence. The hole board test was employed to classify adolescent mice as High- or Low-Novelty Seekers. Subsequently, animals were administered ethanol (1.25 or 2.5 g/kg on two consecutive days at 48-h intervals over a 14-day period. Anxiety levels--measured using the elevated plus maze- spontaneous motor activity and social interaction test were studied 3 weeks later. A different set of mice underwent the same procedure, but received only the 2.5 g/kg dose of ethanol. Three weeks later, in order to induce CPP, the same animals were administered 1 or 6 mg/kg of cocaine or 1 or 2.5 mg/kg MDMA. The results revealed a decrease in aggressive behaviors and an anxiolytic profile in HNS mice and longer latency to explore the novel object by LNS mice. Ethanol exposure enhanced the reinforcing effects of cocaine and MDMA in both groups when CPP was induced with a sub-threshold dose of the drugs. The extinguished cocaine-induced CPP (1 and 6 mg/kg was reinstated after a priming dose in HNS animals only. Our results confirm that intermittent EtOH administration during adolescence induces long-lasting effects that are manifested in adult life, and that there is an association between these effects and the novelty-seeking phenotype.

  8. Protective Effects of Garlic Oil against Liver Damage Induced by Combined Administration of Ethanol and Carbon Tetrachloride in Rats

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    Ashraf B. Abdel-Naim a, Amani E. Khalifaa, Sherif H. Ahmed b

    2002-03-01

    Full Text Available Herbs are known to play a vital role in the management of various liver diseases. Garlic oil (GO contains numerous organosulfur compounds with potential hepatoprotective effects. The present work was planned to evaluate the possible preventive role of GO on biochemical and histopathological alterations induced by combined administration of ethanol (EOH and carbon tetrachloride (CCl4 in rat liver. Two dose levels of GO (5 or 10 mg/kg/day were administered orally to rats for 7 consecutive days with EOH + CCl4-induced liver damage. Activity of GO against liver damage was compared with that of silymarin (25 mg/kg/day, p.o. for 7 consecutive days. Biochemical parameters including serum aspartate aminotransferase (AST, alanine aminotransferase (ALT, gamma glutamyl transpeptidase (­GT, alkaline phophatase (ALP and bilirubin were estimated to assess the liver function. In addition, the level of total proteins, triglycerides, total cholesterol, glutathione (GSH, and thiobarbituric acid reactive substances (TBARS, in liver tissues were estimated. Liver damage was evidenced by an increase in the activity/level of AST, ALT, -GT, ALP and bilirubin in sera of rats after the combined administration of EOH and CCl4 compared to normal animals. Pretreatment of rats with GO reduced the EOH + CCl4-induced elevated levels of the above indices. Similarly, GO significantly prevented the decline in total proteins and the increase in triglycerides and total cholesterol resulted after EOH + CCl4 administration in rat liver homogenates. In addition, GO pretreatment restored liver GSH levels decreased due to EOH + CCl4 administration. The elevation in liver TBARS level due to EOH + CCl4 administration was also prevented by pretreatment with both low and high doses of GO. Histopathological examination indicated that GO exhibited an obvious preventive effect against the centrilobular necrosis and nodule formation induced by EOH + CCl4 administration. In conclusion, GO

  9. Mechanistic Studies of the Anti-Ulcerogenic Activity and Acute Toxicity Evaluation of Dichlorido-Copper(II-4-(2-5-Bromo-benzylideneaminoethyl Piperazin-1-ium Phenolate Complex against Ethanol-Induced Gastric Injury in Rats

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    A. Hamid A. Hadi

    2011-10-01

    Full Text Available The compound dichlorido-copper(II-4-(2-5-bromobenzylideneaminoethyl piperazin-1-ium phenolate (CuLBS was synthesized, characterized and screened for acute toxicity and protective activity against ethanol-induced gastric mucosal injury in rats. Gross microscopic lesions, biochemical and immunological parameters and histochemcial staining of glycogen storage were taken into consideration. Oral administration of CuLBS (30 and 60 mg/Kg for two weeks dose-dependently flattened gastric mucosa, significantly increased gastric mucus and total acidity, compared with control group (P < 0.01. Serum levels of liver enzymes aspartate (AST and alanine transaminases (ALT, pro-inflammatory (IL-6 and TNF-α and anti-inflammatory (IL-10 cytokines in the rats exposed to ethanol induced ulceration have been altered. Administration of CuLBS showed considerable (P < 0.05 protection against ulceration by modulating the acute alterations of cytokines AST, ALT and stomach glycogen. Interestingly, CuLBS did not interfere with the natural release of nitric oxide. CuLBS alone (60 mg/Kg did not exhibit any ulcerogenic effect as assessed using Adami’s scoring scale. An acute toxicity study showed that rats treated with CuLBS (1,000 and 2,000 mg/Kg manifested no abnormal signs. These findings therefore, suggested that the gastroprotective activity of CuLBS might contribute in modulating the inflammatory cytokine-mediated oxidative damage to gastric mucosa.

  10. Neuropeptide Y Administration into the Amygdala Suppresses Ethanol Drinking in Alcohol-Preferring (P) Rats Following Multiple Deprivations

    Science.gov (United States)

    Gilpin, Nicholas W.; Stewart, Robert B.; Badia-Elder, Nancy E.

    2008-01-01

    The present experiment examines the effects of NPY administered into the amygdala on ethanol drinking by alcohol-preferring P rats following long-term continuous ethanol access, with and without multiple periods of imposed ethanol abstinence. P rats had access to 15% (v/v) ethanol and water for 11 weeks followed by 2 weeks of ethanol abstinence, re-exposure to ethanol for 2 weeks, 2 more weeks of ethanol abstinence, and a final ethanol re-exposure. Immediately prior to the second ethanol re-exposure, 4 groups of rats received bilateral infusions NPY (0.25, 0.5, 1.0 μg) or artificial cerebrospinal fluid (aCSF) into the amygdala. Two additional groups were given uninterrupted ethanol access and were infused with a single NPY dose (1.0 μg) or aCSF. The highest NPY dose (1.0 μg) suppressed ethanol intake for 24 hrs in rats with a history of ethanol abstinence (i.e. deprivation) periods, but had no effect in rats with a history of continuous ethanol access. Water and food intakes were not altered. These results suggest that the amygdala mediates the suppressive effects of centrally administered NPY on ethanol drinking, and that NPY may block relapse-like drinking by opposing the anxiogenic effects of ethanol abstinence. PMID:18499241

  11. Acute nicotine administration in Alzheimer's disease: an exploratory EEG study.

    Science.gov (United States)

    Knott, V; Engeland, C; Mohr, E; Mahoney, C; Ilivitsky, V

    2000-01-01

    Previous findings of cognitive deficits and EEG slowing in Alzheimer's patients, together with independent reports of the performance enhancing and electrocortical activating properties of nicotine in normal adults, stimulated this study to examine the acute effects of nicotine on spectrum-analyzed EEG in patients with dementia of the Alzheimer type (DAT). Thirteen patients, 6 currently receiving cholinesterase inhibitor treatment and the remaining being medication free, were administered 2 mg of nicotine polacrilex under randomized, placebo-controlled conditions. Compared to age-regressed EEG norms, the pretreatment EEG spectrums of patients in general were characterized by excessive slow (delta and theta)-wave power, diminished fast (alpha and beta)-wave power and slow mean alpha and total band frequencies. Although postnicotine EEG indices remained within the abnormal range, nicotine, compared to placebo, significantly shifted EEG towards normal values by reducing slow wave (relative delta and theta) power and augmenting fast (relative alpha-1, alpha-2, beta-1) wave power. No differences were observed between treated and nontreated patients in response to nicotine. The results are discussed in relation to cholinergic and brain arousal systems and their relationship to cognitive processes.

  12. Acute anti-inflammatory activity of ethanolic extract of leaves of Leucas indica by carrageenan induced paw oedema in wistar albino rats

    Directory of Open Access Journals (Sweden)

    Chandrashekar R.

    2013-06-01

    Full Text Available Background: Inflammation is basically a defense phenomenon but can lead to serious pathological conditions. It is treated by various agents with good to moderate success because of both considerable toxicity and side effects. There are various mediators to cause an inflammatory reaction that can contribute to the associated symptoms and tissue injury. Even though non steroidal anti-inflammatory drugs are the most commonly prescribed drugs in the world, their use as anti-inflammatory agents continues to be principally limited by their undesired side effects. Hence, the traditional medical practitioners and scientists are turning towards Indian System of Medicine (ISM. Methods: Dried powdered leaves of Leucas indica were subjected to solvent extraction by using 90 % ethanol. Based on acute oral toxicity study according to Organization for Economic Cooperation and Development (OECD guidelines No. 423, three doses of the test drug 75, 150 & 300mg/kg were selected and subjected to preclinical anti-inflammatory screening by carrageenin induced paw oedema in Wistar Albino rats. Results : Oral administration of Ethanolic Extract Of Leaves of Leucas Indica (EELLI at doses of 150 mg/kg and 300mg/kg showed significant anti-inflammatory activity 52.58% (p<0.01 and 36.87% (p<0.05 respectively compared to control. Conclusion: Even though oral administration of EELLI has shown significant anti-inflammatory activity, further studies are required to evaluate its comprehensive analysis including quantitative / semi quantitative analysis, characterize its chemical structure and assess its pharmacotherapeutic activities with exact mechanism of action as an anti-inflammatory agent. [Int J Basic Clin Pharmacol 2013; 2(3.000: 302-305

  13. Effect of acute thioacetamide administration on rat brain phospholipid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Osada, J.; Aylagas, H.; Miro-Obradors, M.J.; Arce, C.; Palacios-Alaiz, E.; Cascales, M. (Tufs Univ., Boston, MA (USA))

    1990-09-01

    Brain phospholipid composition and the ({sup 32}P)orthophosphate incorporation into brain phospholipids of control and rats treated for 3 days with thioacetamide were studied. Brain phospholipid content, phosphatidylcholine, phosphatidylethanolamine, lysolecithin and phosphatidic acid did not show any significant change by the effect of thioacetamide. In contrast, thioacetamide induced a significant decrease in the levels of phosphatidylserine, sphingomyelin, phosphatidylinositol and diphosphatidylglycerol. After 75 minutes of intraperitoneal label injection, specific radioactivity of all the above phospholipids with the exception of phosphatidylethanolamine and phosphatidylcholine significantly increased. After 13 hours of isotope administration the specific radioactivity of almost all studied phospholipid classes was elevated, except for phosphatidic acid, the specific radioactivity of which did not change and for diphosphatidylglycerol which showed a decrease in specific radioactivity. These results suggest that under thioacetamide treatment brain phospholipids undergo metabolic transformations that may contribute to the hepatic encephalopathy induced by thioacetamide.

  14. Neurocognitive performance following acute mephedrone administration, with and without alcohol.

    Science.gov (United States)

    de Sousa Fernandes Perna, E B; Papaseit, E; Pérez-Mañá, C; Mateus, J; Theunissen, E L; Kuypers, Kpc; de la Torre, R; Farré, M; Ramaekers, J G

    2016-12-01

    Recreational use of mephedrone, alone and in combination with alcohol, has increased over the past years. Pharmacological properties of mephedrone share similarities with methylenedioxymethamphetamine (MDMA), but its effect on neurocognitive function has not been well established in humans. The present study assessed the effect of mephedrone alone and after co-administration with alcohol on neurocognitive function. It was hypothesised that mephedrone would improve psychomotor performance but impair memory performance, when administered alone. Neurocognitive performance was expected to be impaired following mephedrone when combined with alcohol. Eleven participants received single doses of 200 mg mephedrone or placebo combined with 0.8 g/kg alcohol or placebo. Neurocognitive performance was assessed at baseline (T0), at one hour (T1) and four hours after (T2) mephedrone administration, by means of the Divided Attention Task (DAT), Critical Tracking Task (CTT), and the Spatial Memory Test (SMT). Mephedrone intoxication impaired short-term spatial memory at T1 and improved critical tracking performance at T2 Mephedrone alone did not affect divided attention, but did show an interaction with alcohol on reaction time at T2 Reaction time decreased when mephedrone was combined with alcohol as compared to alcohol alone. Alcohol intoxication impaired both short- and long-term spatial memory at T1 and divided attention at T1 and T2 Critical tracking performance was not affected by alcohol intoxication. The current findings support the hypothesis that mephedrone improves psychomotor performance, impairs spatial memory and does not affect divided attention performance. Stimulatory effects of mephedrone were not sufficient to compensate for the impairing effects of alcohol on most performance parameters.

  15. Concomitant stress potentiates the preference for, and consumption of, ethanol induced by chronic pre-exposure to ethanol

    Directory of Open Access Journals (Sweden)

    G. Morais-Silva

    2016-01-01

    Full Text Available Ethanol abuse is linked to several acute and chronic injuries that can lead to health problems. Ethanol addiction is one of the most severe diseases linked to the abuse of this drug. Symptoms of ethanol addiction include compulsive substance intake and withdrawal syndrome. Stress exposure has an important role in addictive behavior for many drugs of abuse (including ethanol, but the consequences of stress and ethanol in the organism when these factors are concomitant results in a complex interaction. We investigated the effects of concomitant, chronic administration of ethanol and stress exposure on the withdrawal and consumption of, as well as the preference for, ethanol in mice. Male Swiss mice (30–35 g, 8-10 per group were exposed to an ethanol liquid diet as the only source of food for 15 days. In the final 5 days, they were exposed to forced swimming stress. Twelve hours after removal of the ethanol liquid diet, animals were evaluated for ethanol withdrawal by measuring anxiety-related behaviors and locomotor activity. Twenty-four hours after evaluation of ethanol withdrawal, they were evaluated for voluntary consumption of ethanol in a “three-bottle choice” paradigm. Mice exposed to chronic consumption of ethanol had decreased locomotor activity during withdrawal. Contrary to our expectations, a concomitant forced swimming stress did not aggravate ethanol withdrawal. Nevertheless, simultaneous ethanol administration and stress exposure increased voluntary consumption of ethanol, mainly solutions containing high concentrations of ethanol. These results showed that stressful situations during ethanol intake may aggravate specific addiction-related behaviors.

  16. Concomitant stress potentiates the preference for, and consumption of, ethanol induced by chronic pre-exposure to ethanol.

    Science.gov (United States)

    Morais-Silva, G; Fernandes-Santos, J; Moreira-Silva, D; Marin, M T

    2016-01-01

    Ethanol abuse is linked to several acute and chronic injuries that can lead to health problems. Ethanol addiction is one of the most severe diseases linked to the abuse of this drug. Symptoms of ethanol addiction include compulsive substance intake and withdrawal syndrome. Stress exposure has an important role in addictive behavior for many drugs of abuse (including ethanol), but the consequences of stress and ethanol in the organism when these factors are concomitant results in a complex interaction. We investigated the effects of concomitant, chronic administration of ethanol and stress exposure on the withdrawal and consumption of, as well as the preference for, ethanol in mice. Male Swiss mice (30-35 g, 8-10 per group) were exposed to an ethanol liquid diet as the only source of food for 15 days. In the final 5 days, they were exposed to forced swimming stress. Twelve hours after removal of the ethanol liquid diet, animals were evaluated for ethanol withdrawal by measuring anxiety-related behaviors and locomotor activity. Twenty-four hours after evaluation of ethanol withdrawal, they were evaluated for voluntary consumption of ethanol in a "three-bottle choice" paradigm. Mice exposed to chronic consumption of ethanol had decreased locomotor activity during withdrawal. Contrary to our expectations, a concomitant forced swimming stress did not aggravate ethanol withdrawal. Nevertheless, simultaneous ethanol administration and stress exposure increased voluntary consumption of ethanol, mainly solutions containing high concentrations of ethanol. These results showed that stressful situations during ethanol intake may aggravate specific addiction-related behaviors.

  17. Effects of age and acute ethanol on glutamatergic neurotransmission in the medial prefrontal cortex of freely moving rats using enzyme-based microelectrode amperometry.

    Science.gov (United States)

    Mishra, Devesh; Harrison, Nicholas R; Gonzales, Carolina B; Schilström, Björn; Konradsson-Geuken, Åsa

    2015-01-01

    Ethanol abuse during adolescence may significantly alter development of the prefrontal cortex which continues to undergo structural remodeling into adulthood. Glutamatergic neurotransmission plays an important role during these brain maturation processes and is modulated by ethanol. In this study, we investigated glutamate dynamics in the medial prefrontal cortex of freely moving rats, using enzyme-based microelectrode amperometry. We analyzed the effects of an intraperitoneal ethanol injection (1 g/kg) on cortical glutamate levels in adolescent and adult rats. Notably, basal glutamate levels decreased with age and these levels were found to be significantly different between postnatal day (PND) 28-38 vs PND 44-55 (pprefrontal cortex and suggest that acute ethanol injections have both inhibitory and excitatory effects in adolescent rats. These effects of ethanol on the prefrontal cortex may disturb its maturation and possibly limiting individuals´ control over addictive behaviors.

  18. Adolescent and adult rats differ in the amnesic effects of acute ethanol in two hippocampus-dependent tasks: Trace and contextual fear conditioning.

    Science.gov (United States)

    Hunt, Pamela S; Barnet, Robert C

    2016-02-01

    Experience-produced deficits in trace conditioning and context conditioning have been useful tools for examining the role of the hippocampus in learning. It has also been suggested that learning in these tasks is especially vulnerable to neurotoxic effects of alcohol during key developmental periods such as adolescence. In five experiments we systematically examined the presence and source of age-dependent vulnerability to the memory-disrupting effects of acute ethanol in trace conditioning and contextual fear conditioning. In Experiment 1a pre-training ethanol disrupted trace conditioning more strongly in adolescent (postnatal day, PD30-35) than adult rats (PD65-75). In Experiment 1b when pre-training ethanol was accompanied by pre-test ethanol no deficit in trace conditioning was observed in adolescents, suggesting that state-dependent retrieval failure mediated ethanol's disruption of trace conditioning at this age. Experiment 2a and b examined the effect of ethanol pretreatment on context conditioning. Here, adult but not adolescent rats were impaired in conditioned freezing to context cues. Experiment 2c explored state-dependency of this effect. Pre-training ethanol continued to disrupt context conditioning in adults even when ethanol was also administered prior to test. Collectively these findings reveal clear age-dependent and task-dependent vulnerabilities in ethanol's disruptive effects on hippocampus-dependent memory. Adolescents were more disrupted by ethanol in trace conditioning than adults, and adults were more disrupted by ethanol in context conditioning than adolescents. We suggest that adolescents may be more susceptible to changes in internal state (state-dependent retrieval failure) than adults and that ethanol disrupted performance in trace and context conditioning through different mechanisms. Relevance of these findings to theories of hippocampus function is discussed.

  19. EFFECTS OF ADMINISTRATION OF ETHANOLIC ROOT EXTRACT OF JATROPHA GOSSYPIFOLIA AND PREDNISOLONE ON THE KIDNEYS OF WISTAR RATS

    Directory of Open Access Journals (Sweden)

    Medubi L.J

    2010-01-01

    Full Text Available The effect of oral administration of ethanolic root extract of Jatropha gossypifolia and prednisolone on the kidney histology and renal function of albino rats was studied to assess the safety and toxicity of the plant as an herbal remedy.The rats were divided into four groups I, II, III and IV. Group I served as control and was given feed and water only. Group II, III, and IV were subdivided into Group IIa, IIb, IIIa, IIIb, IVa and IVb. Groups IIa, IIIa, and IVa received 10 mg, 20 mg and 30 mg/kg b.w of the extract while Group IIb, IIIb and IVb received 10 mg ,20 mg and 30 mg/kg b.w of the extract respectively plus 10 mg/kg b.w of prednisolone per day. The animals were sacrificed on day 7, 10 and 14 and their kidneys harvested and processed for histological studies. Their blood was also collected for serum urea measurement.Photomicrographs of the histological sections of Groups II, III and IV rats revealed changes compared to the control group and serum urea levels were significantly higher in these groups. Histological changes observed are consistent with glomerulonephritis and include increased urinary (Bowman's space, shrinkage and distortion of the glomerular tuft as well as scarring of the glomeruli. Changes appear to be both dosage and time dependent and the administration of prednisolone as an adjunct did not exert any ameliorative effect.We conclude that ethanolic root extract of Jatropha gossypifolia is toxic to the kidney and causes increased urea retention in the blood.

  20. Effect of Acute Administration of loganin on Spatial Memory in Diabetic Male Rats

    OpenAIRE

    Gisou Mohaddes; Saeideh Hasani Azami; Shirin Babri

    2013-01-01

    Purpose: Diabetes is associated with memory and learning disorder. The purpose of this study is to determine the effect of acute oral administration of loganin on memory in diabetic male rats. Methods: 42 male Wistar rats (250-300 g) were divided into six groups: Control, Diabetic (1 week), Diabetic (12 weeks), Loganin, Diabetic (1 week) + Loganin, Diabetic (12 weeks) + Loganin. Diabetes was induced by IP injection of Streptozotocin (60 mg/kg). Loganin (40 mg/kg, po) was administrate...

  1. [Acute neurological disclosure of B12 avitaminosis induced by folic acid administration].

    Science.gov (United States)

    Ammar, N; Martinez Almoyna, L; Husson, H; De Broucker, T

    2005-04-01

    A paradigmatic case of acute combined spinal cord degeneration and delirium due to inappropriate administration of folic acid in the context of chronic cobalamin deficiency is described. Rapid improvement was obtained with immediate cessation of folate administration and parenteral cobalamin supplementation. Folic acid and cobalamin prescription rules are recalled. Pathophysiological hypotheses tentatively explaining the neurotoxicity of folic acid in case of vitamin B12 deficiency are summarized.

  2. Brain and muscle redox imbalance elicited by acute ethylmalonic acid administration.

    Directory of Open Access Journals (Sweden)

    Patrícia Fernanda Schuck

    Full Text Available Ethylmalonic acid (EMA accumulates in tissues and biological fluids of patients affected by short-chain acyl-CoA dehydrogenase deficiency (SCADD and ethylmalonic encephalopathy, illnesses characterized by neurological and muscular symptoms. Considering that the mechanisms responsible for the brain and skeletal muscle damage in these diseases are poorly known, in the present work we investigated the effects of acute EMA administration on redox status parameters in cerebral cortex and skeletal muscle from 30-day-old rats. Animals received three subcutaneous injections of EMA (6 μmol/g; 90 min interval between injections and were killed 1 h after the last administration. Control animals received saline in the same volumes. EMA administration significantly increased thiobarbituric acid-reactive substances levels in cerebral cortex and skeletal muscle, indicating increased lipid peroxidation. In addition, carbonyl content was increased in EMA-treated animal skeletal muscle when compared to the saline group. EMA administration also significantly increased 2',7'-dihydrodichlorofluorescein oxidation and superoxide production (reactive species markers, and decreased glutathione peroxidase activity in cerebral cortex, while glutathione levels were decreased only in skeletal muscle. On the other hand, respiratory chain complex I-III activity was altered by acute EMA administration neither in cerebral cortex nor in skeletal muscle. The present results show that acute EMA administration elicits oxidative stress in rat brain and skeletal muscle, suggesting that oxidative damage may be involved in the pathophysiology of the brain and muscle symptoms found in patients affected by SCADD and ethylmalonic encephalopathy.

  3. Brain and muscle redox imbalance elicited by acute ethylmalonic acid administration.

    Science.gov (United States)

    Schuck, Patrícia Fernanda; Milanez, Ana Paula; Felisberto, Francine; Galant, Leticia Selinger; Machado, Jéssica Luca; Furlanetto, Camila Brulezi; Petronilho, Fabricia; Dal-Pizzol, Felipe; Streck, Emilio Luiz; Ferreira, Gustavo Costa

    2015-01-01

    Ethylmalonic acid (EMA) accumulates in tissues and biological fluids of patients affected by short-chain acyl-CoA dehydrogenase deficiency (SCADD) and ethylmalonic encephalopathy, illnesses characterized by neurological and muscular symptoms. Considering that the mechanisms responsible for the brain and skeletal muscle damage in these diseases are poorly known, in the present work we investigated the effects of acute EMA administration on redox status parameters in cerebral cortex and skeletal muscle from 30-day-old rats. Animals received three subcutaneous injections of EMA (6 μmol/g; 90 min interval between injections) and were killed 1 h after the last administration. Control animals received saline in the same volumes. EMA administration significantly increased thiobarbituric acid-reactive substances levels in cerebral cortex and skeletal muscle, indicating increased lipid peroxidation. In addition, carbonyl content was increased in EMA-treated animal skeletal muscle when compared to the saline group. EMA administration also significantly increased 2',7'-dihydrodichlorofluorescein oxidation and superoxide production (reactive species markers), and decreased glutathione peroxidase activity in cerebral cortex, while glutathione levels were decreased only in skeletal muscle. On the other hand, respiratory chain complex I-III activity was altered by acute EMA administration neither in cerebral cortex nor in skeletal muscle. The present results show that acute EMA administration elicits oxidative stress in rat brain and skeletal muscle, suggesting that oxidative damage may be involved in the pathophysiology of the brain and muscle symptoms found in patients affected by SCADD and ethylmalonic encephalopathy.

  4. Antidepressant Effect of Aminophylline After Ethanol Exposure

    Science.gov (United States)

    Escudeiro, Sarah Souza; Soares, Paula Matias; Almeida, Anália Barbosa; de Freitas Guimarães Lobato, Rodrigo; de Araujo, Dayane Pessoa; Macedo, Danielle Silveira; Sousa, Francisca Cléa Florenço; Patrocínio, Manoel Cláudio Azevedo; Vasconcelos, Silvânia Maria Mendes

    2013-01-01

    This work investigated the association of acute ethanol and aminophylline administration on behavioral models of depression and prefrontal monoamine levels (i.e. norepinephrine and dopamine) in mice. The animals received a single dose of ethanol (2 g/kg) or aminophylline (5 or 10 mg/kg) alone or in association. Thirty minutes after the last drug administration, the animals were assessed in behavioral models by the forced swimming and tail suspension tests. After these tests, the animals were sacrificed and the prefrontal cortices dissected to measure monoamine content. Results showed that ethanol presented depression-like activity in the forced swimming and tail suspension tests. These effects were reversed by the association with aminophylline in all tests. Norepinephrine and dopamine levels decreased, while an increase in the dopamine metabolite, (4-hydroxy-3-methoxyphenyl)acetic acid (DOPAC), after ethanol administration was observed. On the contrary, the association of ethanol and aminophylline increased the norepinephrine and dopamine content, while it decreased DOPAC when compared to the ethanol group, confirming the alterations observed in the behavioral tests. These data reinforce the involvement of the adenosinergic system on ethanol effects, highlighting the importance of the norepinephrine and dopamine pathways in the prefrontal cortex to the effects of ethanol. PMID:23641339

  5. Effects of acute prenatal exposure to ethanol on microRNA expression are ameliorated by social enrichment

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    Cherry eIgnacio

    2014-09-01

    Full Text Available Fetal alcohol spectrum disorders (FASDs are associated with abnormal social behavior. These behavioral changes may resemble those seen in autism. Rats acutely exposed to ethanol on gestational day 12 show decreased social motivation at postnatal day 42. We previously showed that housing these ethanol-exposed rats with non-exposed controls normalized this deficit. The amygdala is critical for social behavior and regulates it, in part, through connections with the basal ganglia, particularly the ventral striatum. MicroRNAs (miRNAs are short, hairpin-derived RNAs that repress mRNA expression. Many brain disorders, including FASD, show dysregulation of miRNAs. In this study, we tested if miRNA and mRNA networks are altered in the amygdala and ventral striatum as a consequence of prenatal ethanol exposure and show any evidence of reversal as a result of Social Enrichment. RNA samples from two different brain regions in 72 male and female adolescent rats were analyzed by RNA-Seq and microarray analysis. Several miRNAs showed significant changes due to prenatal ethanol exposure and/or Social Enrichment in one or both brain regions. The top predicted gene targets of these miRNAs were mapped and subjected to pathway enrichment analysis. Several miRNA changes caused by ethanol were reversed by Social Enrichment, including mir-204, mir-299a, miR-384-5p, miR-222-3p, miR-301b-3p and mir-6239. Moreover, enriched gene networks incorporating the targets of these miRNAs also showed reversal. We also extended our previously published mRNA expression analysis by directly examining all annotated brain-related canonical pathways. The additional pathways that were most strongly affected at the mRNA level included p53, CREB, Glutamate and GABA signaling. Together, our data suggest a number of novel epigenetic mechanisms for Social Enrichment to reverse the effects of ethanol exposure through widespread influences on gene expression.

  6. Acute cortisol administration modulates EEG alpha asymmetry in volunteers : relevance to depression

    NARCIS (Netherlands)

    Tops, M; Wijers, AA; van Staveren, ASJ; Bruin, KJ; Den Boer, JA; Meijman, TF; Korf, J

    2005-01-01

    The acute effects of cortisol (35 mg) administration in 11 healthy male volunteers on resting frontal EEG asymmetry measured in the alpha band were investigated, using a within-subjects double-blind design. Results were indicative of a relative increase of right frontal activity with cortisol. This

  7. Oral Administration of Escin Inhibits Acute Inflammation and Reduces Intestinal Mucosal Injury in Animal Models

    Directory of Open Access Journals (Sweden)

    Minmin Li

    2015-01-01

    Full Text Available The present study aimed to investigate the effects of oral administration of escin on acute inflammation and intestinal mucosal injury in animal models. The effects of escin on carrageenan-induced paw edema in a rat model of acute inflammation, cecal ligation and puncture (CLP induced intestinal mucosal injury in a mouse model, were observed. It was shown that oral administration of escin inhibits carrageenan-induced paw edema and decreases the production of prostaglandin E2 (PGE2 and cyclooxygenase- (COX- 2. In CLP model, low dose of escin ameliorates endotoxin induced liver injury and intestinal mucosal injury and increases the expression of tight junction protein claudin-5 in mice. These findings suggest that escin effectively inhibits acute inflammation and reduces intestinal mucosal injury in animal models.

  8. Acute ethanol exposure inhibits silencing of cerebellar Golgi cell firing induced by granule cell axon input

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    Paolo eBotta

    2014-02-01

    Full Text Available Golgi cells (GoCs are specialized interneurons that provide inhibitory input to granule cells in the cerebellar cortex. GoCs are pacemaker neurons that spontaneously fire action potentials, triggering spontaneous inhibitory postsynaptic currents in granule cells and also contributing to the generation tonic GABAA receptor-mediated currents in granule cells. In turn, granule cell axons provide feedback glutamatergic input to GoCs. It has been shown that high frequency stimulation of granule cell axons induces a transient pause in GoC firing in a type 2-metabotropic glutamate receptor (mGluR2-dependent manner. Here, we investigated the effect ethanol on the pause of GoC firing induced by high frequency stimulation of granule cell axons. GoC electrophysiological recordings were performed in parasagittal cerebellar vermis slices from postnatal day 23 to 26 rats. Loose-patch cell-attached recordings revealed that ethanol (40 mM reversibly decreases the pause duration. An antagonist of mGluR2 reduced the pause duration but did not affect the effect of ethanol. Whole-cell voltage-clamp recordings showed that currents evoked by an mGluR2 agonist were not significantly affected by ethanol. Perforated-patch experiments in which hyperpolarizing and depolarizing currents were injected into GoCs demonstrated that there is an inverse relationship between spontaneous firing and pause duration. Slight inhibition of the Na+/K+ pump mimicked the effect of ethanol on pause duration. In conclusion, ethanol reduces the granule cell axon-mediated feedback mechanism by reducing the input responsiveness of GoCs. This would result in a transient increase of GABAA receptor-mediated inhibition of granule cells, limiting information flow at the input stage of the cerebellar cortex.

  9. Both acute and prolonged administration of EPO reduce cerebral and systemic vascular conductance in humans

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Kim, Yu-Sok; Krogh-Madsen, Rikke;

    2012-01-01

    Administration of erythropoietin (EPO) has been linked to cerebrovascular events. EPO reduces vascular conductance, possibly because of the increase in hematocrit. Whether EPO in itself affects the vasculature remains unknown; here it was evaluated in healthy males by determining systemic...... and cerebrovascular variables following acute (30,000 IU/d for 3 d; n=8) and chronic (5000 IU/week for 13 wk; n=8) administration of EPO, while the responsiveness of the vasculature was challenged during cycling exercise, with and without hypoxia. Prolonged administration of EPO increased hematocrit from 42.5 ± 3...

  10. Ethanol extracts of Scutellaria baicalensis protect against lipopolysaccharide-induced acute liver injury in mice

    Institute of Scientific and Technical Information of China (English)

    Hai Nguyen Thanh; Hue Pham Thi Minh; Tuan Anh Le; Huong Duong Thi Ly; Tung Nguyen Huu; Loi Vu Duc; Thu Dang Kim; Tung Bui Thanh

    2015-01-01

    To investigated the protective potential of ethanol extracts of Scutellaria baicalensis (S. baicalensis ) against lipopolysaccharide (LPS)-induced liver injury. Methods: Dried roots of S. baicalensis were extracted with ethanol and concentrated to yield a dry residue. Mice were administered 200 mg/kg of the ethanol extracts orally once daily for one week. Animals were subsequently administered a single dose of LPS (5 mg/kg of body weight, intraperitoneal injection). Both protein and mRNA levels of cytokines, such as tumor necrosis factor alpha, interleukin-1β, and interleukin-6 in liver tissues were evaluated by ELISA assay and quantitative PCR. Cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor-κB protein levels in liver tissues were analyzed by western blotting. Results: Liver injury induced by LPS significantly increased necrosis factor alpha, interleukin-1β, interleukin-6, cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor-κB in liver tissues. Treatment with ethanol extracts of S. baicalensis prevented all of these observed changes associated with LPS-induced injury in liver mice. Conclusions: Our study showed that S. baicalensis is potentially protective against LPS-induced liver injury in mice.

  11. Ethanol extracts of Scutellaria baicalensis protect against lipopolysaccharide-induced acute liver injury in mice

    Institute of Scientific and Technical Information of China (English)

    Hai; Nguyen; Thanh; Hue; Pham; Thi; Minh; Tuan; Anh; Le; Huong; Duong; Thi; Ly; Tung; Nguyen; Huu; Loi; Vu; Duc; Thu; Dang; Kim; Tung; Bui; Thanh

    2015-01-01

    Objective: To investigated the protective potential of ethanol extracts of Scutellaria baicalensis(S. baicalensis) against lipopolysaccharide(LPS)-induced liver injury. Methods: Dried roots of S. baicalensis were extracted with ethanol and concentrated to yield a dry residue. Mice were administered 200 mg/kg of the ethanol extracts orally once daily for one week. Animals were subsequently administered a single dose of LPS(5 mg/kg of body weight, intraperitoneal injection). Both protein and m RNA levels of cytokines, such as tumor necrosis factor alpha, interleukin-1β, and interleukin-6 in liver tissues were evaluated by ELISA assay and quantitative PCR. C yclooxygenase-2, inducible nitric oxide synthase, and nuclear factor-κB protein levels in liver tissues were analyzed by western blotting. Results: Liver injury induced by LPS signifi cantly increased necrosis factor alpha, interleukin-1β, interleukin-6, cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor-κB in liver tissues. Treatment with ethanol extracts of S. baicalensis prevented all of these observed changes associated with LPS-induced injury in liver mice.Conclusions: Our study showed that S. baicalensis is potentially protective against LPS-induced liver injury in mice.

  12. RAB GTPASES ASSOCIATE WITH ISOLATED LIPID DROPLETS (LDS) AND SHOW ALTERED CONTENT AFTER ETHANOL ADMINISTRATION: POTENTIAL ROLE IN ALCOHOL-IMPAIRED LD METABOLISM

    Science.gov (United States)

    Rasineni, Karuna; McVicker, Benita L.; Tuma, Dean J.; McNiven, Mark A.; Casey, Carol A.

    2013-01-01

    Background Alcoholic liver disease is manifested by the presence of fatty liver, primarily due to accumulation of hepatocellular lipid droplets (LDs). The presence of membrane-trafficking proteins (e.g. Rab GTPases) with LDs indicates that LDs may be involved in trafficking pathways known to be altered in ethanol damaged hepatocytes. Since these Rab GTPases are crucial regulators of protein trafficking, we examined the effect ethanol administration has on hepatic Rab protein content and association with LDs. Methods Male Wistar rats were pair-fed Lieber-DeCarli diets for 5 to 8 weeks. Whole liver and isolated LD fractions were analyzed. Identification of LDs and associated Rab proteins was performed in frozen liver or paraffin-embedded sections followed by immunohistochemical analysis. Results Lipid accumulation was characterized by larger LD vacuoles and increased total triglyceride content in ethanol-fed rats. Rabs 1, 2, 3d, 5, 7 and 18 were analyzed in post-nuclear supernatant (PNS) as well as LDs. All of the Rabs were found in the PNS, and Rabs 1, 2, 5 and 7 did not show alcohol-altered content, while Rab 3d content was reduced by over 80%, and Rab 18 also showed ethanol-induced reduction in content. Rab 3d was not found to associate with LDs, while all other Rabs were found in the LD fractions, and several showed an ethanol-related decrease (Rabs 2, 5, 7, 18). Immunohistochemical analysis revealed the enhanced content of a LD-associated protein, perilipin 2 (PLIN2) that was paralleled with an associated decrease of Rab 18 in ethanol-fed rat sections. Conclusion Chronic ethanol feeding was associated with increased PLIN2 and altered Rab GTPase content in enriched LD fractions. Although mechanisms driving these changes are not established, further studies on intracellular protein trafficking and LD biology after alcohol administration will likely contribute to our understanding of fatty liver disease. PMID:24117505

  13. Protective effect of Matricaria chamomilla on ethanol-induced acute gastric mucosal injury in rats.

    Science.gov (United States)

    Cemek, Mustafa; Yilmaz, Ezgi; Büyükokuroğlu, Mehmet Emin

    2010-07-01

    The antiulcerogenic and antioxidant properties of Matricaria chamomilla L. (Compositae) hydroalcoholic extract (MCE) on ethanol-induced gastric mucosal injury were investigated in rats. After the induction of gastric mucosal injury, all groups were sacrificed; the gastric ulcer index was calculated, and malondialdehyde (MDA) and reduced glutathione (GSH) in whole blood and gastric tissue, and serum ascorbic acid, retinol, and beta-carotene levels were measured in all groups. Pretreatment with MCE at some doses significantly reduced gastric lesions. Again, some doses of MCE significantly reduced the MDA, and significantly increased GSH levels in gastric tissue or whole blood. Serum beta-carotene and retinol levels were significantly higher in the 200 mg/kg MCE-administered group with respect to control. As a result, MCE clearly has a protective effect against ethanol-induced gastric mucosal lesions, and this effect, at least in part, depends upon the reduction in lipid peroxidation and augmentation in antioxidant activity.

  14. A Standardized Composition from Extracts of Myristica Fragrans, Astragalus Membranaceus, and Poria Cocos Protects Liver from Acute Ethanol Insult.

    Science.gov (United States)

    Yimam, Mesfin; Jiao, Ping; Hong, Mei; Jia, Qi

    2016-08-01

    Despite the promising advances in therapeutic discovery, there still is a major challenge in the development of a safe, effective, and economical intervention for managing alcohol-related liver disorders. In this study, we describe the potential use of "MAP," a standardized composition comprising three extracts from Myristica fragrans, Astragalus membranaceus, and Poria cocos, in ameliorating alcohol-induced acute liver toxicity. Ethanol-induced acute hepatotoxicity as an animal model of binge drinking was utilized. Mice received oral doses of MAP at 300 mg/kg for four consecutive days. Mice were orally gavaged with 50% ethanol in 12 mL/kg dosing volume following the third dose of MAP every 12 h thereafter for a total of three doses. Hepatic functional tests from serum collected at T12, and hepatic glutathione (GSH), superoxide dismutases (SODs), and triglyceride from liver homogenates were evaluated. Histopathology analysis and alcoholic steatohepatitis (ASH) scoring were also determined. Excessive increases of serum alanine aminotransferase and aspartate aminotransferase were significantly inhibited at 46.3% and 43.6%, respectively, when mice were treated with MAP. MAP replenished the depleted SOD by more than 60%, while causing significant stimulation of GSH productions. MAP showed statistically significant reduction in ballooning degeneration, vascular steatosis, cytoplasmic or nuclear condensation, and shrinkage, as well as inflammations when compared to vehicle-treated alcohol-induced liver toxicity model. Mice treated with MAP showed statistically significant reduction in ASH scoring when compared to vehicle control. Therefore, the composition MAP could be potentially utilized as an effective hepatic-detoxifying agent for the protection of liver damage caused by alcohol consumptions.

  15. Antihyperglycemic Effect on Chronic Administration of Butanol Fraction of Ethanol Extract of Moringa Stenopetala Leaves in Alloxan Induced Diabetic Mice

    Institute of Scientific and Technical Information of China (English)

    Alemayehu Toma; Eyasu Makonnen; Asfaw Debella; Birhanu Tesfaye

    2012-01-01

    Objective: The present study was conducted to evaluate the antihyperglycemic activity on chronic administration of the butanol fraction of the ethanol extract of Moringa Stenopetala leaves in alloxan induced diabetic mice. Methods: The mice were grouped in four groups; Normal control, Diabetic control, Butanol fraction treated and standard drug treated groups. The Diabetic mice received the butanol fraction of Moringa stenopetala daily for 28 days. Results: The butanol fraction of Moringastenopetala treatment resulted in significant reduction of fasting blood glucose level, serum total cholesterol and triglycerides level. This fraction also showed a tendency to improve body weight gain in diabetic mice. Its oral LD50 was found to be greater than 5000mg/Kg indicating its safety in mice. Conclusions: Though the mechanism of action of Moringa stenopetala seems to be similar to that of sulfonylureas, further studies should be done to confirm its mechanism of antidiabetic action. Furthermore the active principle(s) responsible for the antidabetic effects should also be identified.

  16. Acute Toxicity and Cytotoxicity Effect of Ethanolic Extract of Spondias tuberosa Arruda Bark: Hematological, Biochemical and Histopathological Evaluation

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    HUMBERTO M. BARBOSA

    Full Text Available ABSTRACT Spondias tuberosa Arruda, popularly named as umbu, is native from savanna-like vegetation and widely used for medicinal purposes, however, the toxicological profile is not available yet. This study evaluated the phytochemical profile and acute toxicity and citoxicity of Ethanolic Extract of Spondias tuberosa Arruda Bark (EEStb in hematological, biochemical and histopathological parameters. Female Wistar rats were divided into: control (C and animal treated single doses of 300mg/Kg (EEStb300 or 2.000mg/kg body weight (ESStb2.000 of the EEStb. After 24 hours and 14 days from gavage, the behavior, hematological, biochemical and histopathological parameters were assayed. Cytotoxicity effect was evaluated on HEp-2 cell lines. Neither EEStb300 nor EEStb2.000 produced mortality nor changes in body weight during the 14-days of observation, but EEStb2.000 reduced quietly the food and water intake as well as locomotor activity at first day. There were no changes in macroscopic, histopathological, biochemical and hematological parameters. EEStb in concentrations of 6.25- 50μg ml−1 on HEp-2 cell did not produce cytotoxic effect. These results suggest that EEStb did not cause acute toxicity and cytotoxic, suggesting a good safety rate for Spondias tuberosa Arruda.

  17. Acute Toxicity and Cytotoxicity Effect of Ethanolic Extract of Spondias tuberosa Arruda Bark: Hematological, Biochemical and Histopathological Evaluation.

    Science.gov (United States)

    Barbosa, Humberto M; Nascimento, Jailson N DO; Araújo, Thiago A S; Duarte, Filipe S; Albuquerque, Ulysses P; Vieira, Jeymesson R C; Santana, Edson R B DE; Yara, Ricardo; Lima, Cláudia S A; Gomes, Dayane A; Lira, Eduardo C

    2016-01-01

    Spondias tuberosa Arruda, popularly named as umbu, is native from savanna-like vegetation and widely used for medicinal purposes, however, the toxicological profile is not available yet. This study evaluated the phytochemical profile and acute toxicity and citoxicity of Ethanolic Extract of Spondias tuberosa Arruda Bark (EEStb) in hematological, biochemical and histopathological parameters. Female Wistar rats were divided into: control (C) and animal treated single doses of 300mg/Kg (EEStb300) or 2.000mg/kg body weight (ESStb2.000) of the EEStb. After 24 hours and 14 days from gavage, the behavior, hematological, biochemical and histopathological parameters were assayed. Cytotoxicity effect was evaluated on HEp-2 cell lines. Neither EEStb300 nor EEStb2.000 produced mortality nor changes in body weight during the 14-days of observation, but EEStb2.000 reduced quietly the food and water intake as well as locomotor activity at first day. There were no changes in macroscopic, histopathological, biochemical and hematological parameters. EEStb in concentrations of 6.25- 50μg ml-1 on HEp-2 cell did not produce cytotoxic effect. These results suggest that EEStb did not cause acute toxicity and cytotoxic, suggesting a good safety rate for Spondias tuberosa Arruda.

  18. Effects of chronic ethanol administration on expression of BDNF and trkB mRNAs in rat hippocampus after experimental brain injury.

    Science.gov (United States)

    Zhang, L; Dhillon, H S; Barron, S; Hicks1, R R; Prasad, R M; Seroogy, K B

    2000-06-23

    Previous evidence indicates that both chronic alcohol treatment and traumatic brain injury modulate expression of certain neurotrophins and neurotrophin receptors in cortical tissue. However, the combined effects of chronic alcohol and brain trauma on expression of neurotrophins and their receptors have not been investigated. In the present study, we examined the effects of 6 weeks of chronic ethanol administration on lateral fluid percussion (FP) brain injury-induced alterations in expression of mRNAs for the neurotrophin brain-derived neurotrophic factor (BDNF) and its high affinity receptor, trkB, in rat hippocampus. In both the control- (pair-fed isocaloric sucrose) diet and the chronic ethanol-diet groups, unilateral FP brain injury induced a bilateral increase in levels of both BDNF and trkB mRNAs in the dentate gyrus granule cell layer, and of BDNF mRNA in hippocampal region CA3. However, no significant differences in expression were found between the control-diet and ethanol-diet groups, in either the sham-injured or FP-injured animals. These findings suggest that 6 weeks of chronic ethanol administration does not alter the plasticity of hippocampal BDNF/trkB expression in response to experimental brain injury.

  19. Effect of Acute Administration of loganin on Spatial Memory in Diabetic Male Rats

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    Gisou Mohaddes

    2013-02-01

    Full Text Available Purpose: Diabetes is associated with memory and learning disorder. The purpose of this study is to determine the effect of acute oral administration of loganin on memory in diabetic male rats. Methods: 42 male Wistar rats (250-300 g were divided into six groups: Control, Diabetic (1 week, Diabetic (12 weeks, Loganin, Diabetic (1 week + Loganin, Diabetic (12 weeks + Loganin. Diabetes was induced by IP injection of Streptozotocin (60 mg/kg. Loganin (40 mg/kg, po was administrated 1 hour before test. Then, spatial memory was compared between groups with Morris Water Maze tests. Results: Administration of loganin during acquisition, significantly (p<0.05 decreased both escape latency and traveled distance to find hidden platform in 1 and 12 weeks diabetic rats. In evaluation of recall phase of memory, loganin significantly (p<0.05 increased time and distance spent in the target quadrant in 1 and 12 weeks diabetic rats. Conclusion: Acute administration of loganin could improve spatial memory in diabetic rats.

  20. Effects of inhaled L-arginine administration in a murine model of acute asthma.

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    Zeynep Arikan-Ayyildiz

    2014-10-01

    Full Text Available Increased arginase activity in the airways decreases L-arginine and causes deficiency of bronchodilating and anti-inflammatory nitric oxide (NO in asthma. As, it is suggested that L-arginine may have therapeutic potential in asthma treatment, we aimed to investigate the effects of inhaled L-arginine on oxygen saturation (SaO₂ and airway histology in a murine model of acute asthma. Twenty eight BALB/c mice were divided into four groups; I, II, III and IV (control. All groups except the control were sensitized and challenged with ovalbumin. After establishement of acute asthma attack by metacholine administration, the mice were treated with inhaled L-arginine (Group I, saline (Group II and budesonide (Group III, respectively. SaO₂was measured by pulse oximeter just before and 5 min after methacholine. A third measurement of SaO₂was also obtained 15 min after drug administration in these study groups. Inflammation in the lung tissues of the sacrificed animals were scored to determine the effects of the study drugs. The number of eosinophils in bronchoalveolar lavage (BAL was determined. The results indicated that inflammatory scores significantly improved in groups receiving study drugs when compared with placebo and L-arginine was similar in decreasing scores when compared with budesonide. SaO₂had a tendency to increase after L-arginine administration after acute asthma attack and this increase was statistically significant (p=0.043. Eosinophilia in BAL significantly reduced in group receiving L-arginine when compared with placebo (p<0.05. Thus in this study we demonstrated that L-arginine improved SaO₂and inflammatory scores in an acute model of asthma.

  1. Acute aortic rupture in a dog with spirocercosis following the administration of medetomidine : clinical communication

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    K.E. Joubert

    2005-06-01

    Full Text Available Spirocercosis is an emerging disease in veterinary medicine. A strong suspicion of spirocercosis is usually evident after a thorough clinical examination and radiography of the chest has been performed. Lesions seen on radiography include an oesophageal mass, spondylitis and oesophageal air. Unfortunately, radiography is not diagnostic and additional diagnostic procedures are required to confirm the diagnosis. Endoscopy is commonly performed to diagnose the condition. The dog presented in this study had radiographic and clinical signs consistent with spirocercosis and definitive diagnosis was required. Shortly after sedation with medetomidine, the dog went into cardiac arrest and failed to respond to resuscitative measures. On post mortem, the diagnosis of spirocercosis was confirmed and the cause of death was identified as acute aortic rupture. Aortic aneurysms are not an uncommon finding and cause of acute death in dogs with spirocercosis. The acute rupture of the aorta in this case is most probably the result of cardiovascular changes associated with the administration of medetomidine. Medetomidine causes an acute rise in systemic vascular resistance with hypertension. The increase in shear stress across the weakened aortic wall resulted in rupture. Caution with the use of medetomidine in patients with spirocercosis is advised.

  2. The role of oestradiol in sexually dimorphic hypothalamic-pituitary-adrena axis responses to intracerebroventricular ethanol administration in the rat.

    Science.gov (United States)

    Larkin, J W; Binks, S L; Li, Y; Selvage, D

    2010-01-01

    Systemic ethanol (EtOH) administration activates the hypothalamic-pituitary-adrenal (HPA) axis of rats in a sexually dimorphic manner. The present studies tested the role played by the central nervous system (CNS) in this phenomenon. To localise the effects of the drug to the brain, we utilised an experimental paradigm whereby a small, nontoxic amount of the drug was delivered via intracerebroventricular (i.c.v.) injection. EtoH administered i.c.v. rapidly diffuses throughout the cerebrospinal fluid and brain, and does not cause neuronal damage or have any long-term physiological or behavioural effects. Experimental groups included intact males, intact cycling females, and ovariectomised (OVX) animals with or without replacement oestradiol (E(2)). Intracerebroventricular EtOH-induced HPA hormonal activation was determined by measuring plasma adrenocorticotrophin (ACTH) levels. Activation of brain areas that both regulate HPA function and are responsive to gonadal hormones was determined using expression of the transcription factor c-fos (Fos) as a marker of neuronal activity. We observed sex- and oestrous cycle- dependent differences in HPA activation by EtOH as measured by both these parameters. ACTH secretion was highest in females in pro-oestrus or oestrus, just prior to or after the endogenous peak of E(2), as was Fos expression in the paraventricular nucleus of the hypothalamus (PVN) and the locus coreuleus (LC) of the brainstem. In OVX animals, E(2) replacement caused an increase in PVN and LC Fos expression in response to i.c.v. EtOH compared to OVX controls, but a decrease in ACTH secretion. Taken together, these results indicate that at the level of the CNS, EtOH stimulates HPA activity more robustly at times when the effects of E(2) are high, but that E(2) alone is not responsible for this effect. The data further suggest that the LC plays an important role in the circuitry, which appears to be different from that activated following the systemic

  3. Acute administration of fenproporex increased acetylcholinesterase activity in brain of young rats

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    BRENA P. TEODORAK

    2015-08-01

    Full Text Available Fenproporex is the second most commonly amphetamine-based anorectic consumed worldwide; this drug is rapidly converted into amphetamine, in vivo, and acts by increasing dopamine levels in the synaptic cleft. Considering that fenproporex effects on the central nervous system are still poorly known and that acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine, the present study investigated the effects of acute administration of fenproporex on acetylcholinesterase activity in brain of young rats. Young male Wistar rats received a single injection of fenproporex (6.25, 12.5 or 25mg/kg i.p. or vehicle (2% Tween 80. Two hours after the injection, the rats were killed by decapitation and the brain was removed for evaluation of acetylcholinesterase activity. Results showed that fenproporex administration increased acetylcholinesterase activity in the hippocampus and posterior cortex, whereas in the prefrontal cortex, striatum and cerebellum the enzyme activity was not altered. In conclusion, in the present study we demonstrated that acute administration of fenproporex exerts an effect in the cholinergic system causing an increase in the activity of acetylcholinesterase in a dose-dependent manner in the hippocampus and posterior cortex. Thus, we suggest that the imbalance in cholinergic homeostasis could be considered as an important pathophysiological mechanism underlying the brain damage observed in patients who use amphetamines such as fenproporex.

  4. Acute effects of nicotine administration during prospective memory, an event related fMRI study.

    Science.gov (United States)

    Rusted, Jennifer; Ruest, Torsten; Gray, Marcus A

    2011-07-01

    We previously demonstrated that stimulating neuronal nicotinic acetylcholine receptors modulates prospective memory (PM), the ability to remember and implement a prior intention. Here we used fMRI to explore the neuronal correlates of acute nicotinic (1mg) modulation during PM, employing a double blind, valence-matched placebo-controlled design, and a solely event-related analysis. Eight healthy adults completed on two occasions (1 week washout) a simple attentional task containing infrequent PM trials. PM activated bilateral parietal, prefrontal (BA10) and anterior cingulate, and deactivated genual cingulate and medial prefrontal regions. Further, acute nicotine administration decreased activity within a largely overlapping right parietal region. This data validates a purely event-related approach to exploring PM, and suggests procholinergic modulation of PM by parietal rather than BA10/frontal regions.

  5. [A case of acute ethanol intoxication with remarkable hyperglycemia by "ume-shu", a Japanese apricot liquor made with a large amount of sugar].

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    Sugano, Takayuki; Kojima, Naoki; Kaneko, Susumu; Ishida, Junro; Terada, Taizo; Inagawa, Hiroshi; Okada, Yasusei

    2002-07-01

    A 19-year-old woman ingested 2.2 L of "umeshu", a Japanese apricot liquor made with a large amount of sugar. She was unconscious and in shock. The estimated blood ethanol concentration was 607 mg/dl, and the blood glucose level was 576 mg/dl. Because her respiration and circulation was highly suppressed, blood purification was indicated. Continuous hemodiafiltration (CHDF) was performed instead of hemodialysis because her hemodynamics was unstable. After CHDF was instituted, her blood glucose level reduced to normal range, and her consciousness became alert. CHDF was effective in eliminating ethanol and stabilizing her hemodynamics within an early stage. Though acute ethanol intoxication is known to inhibit glucogenesis, leading to hypoglycemia, marked hyperglycemia was seen in this case. Ingestion of a large amount of glucose-rich liquor and being in shock seemed to be the causes of hyperglycemia.

  6. Maternal ethanol administration inhibits 5-hydroxytryptamine synthesis and tryptophan hydroxylase expression in the dorsal raphe of rat offspring.

    Science.gov (United States)

    Kim, Eun-Kyung; Lee, Myoung-Hwa; Kim, Hong; Sim, Young-Je; Shin, Mal-Soon; Lee, Sam-Jun; Yang, Hye-Young; Chang, Hyun-Kyung; Lee, Taeck-Hyun; Jang, Mi-Hyeon; Shin, Min-Chul; Lee, Hee-Hyuk; Kim, Chang-Ju

    2005-10-01

    Maternal ethanol consumption during pregnancy has a detrimental effect on the central nervous system (CNS) development of fetus. 5-Hydroxytryptamine (5-HT) is an important neurotransmitter and/or neuromodulator in the mammalian CNS. Tryptophan hydroxylase (TPH) is the rate limiting enzyme of 5-HT synthesis. Ethanol is known to induce neuropsychiatric disorders by alteration of the central serotonergic system. In the present study, the effects of maternal ethanol intake on the 5-HT synthesis and the TPH expression in the dorsal raphe of rat offspring were investigated. The present results show that the synthesis of 5-HT and the expression of TPH in the dorsal raphe of rat offspring were suppressed by maternal ethanol intake and that the suppressive effect of alcohol was more potent in the 5 weeks old rat pups compared to the 3 weeks old rat pups. Based on the present study, it can be suggested that the pathogenesis of ethanol-induced neuropsychological disorders involves ethanol-induced suppression on the 5-HT synthesis and the TPH expression in the dorsal raphe of offspring.

  7. Retrobulbar blood flow and visual field alterations after acute ethanol ingestion

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    Weber A

    2013-08-01

    Full Text Available Anke Weber, Andreas Remky, Marion Bienert, Klaudia Huber-van der Velden, Thomas Kirschkamp, Corinna Rennings, Gernot Roessler, Niklas Plange Department of Ophthalmology, RWTH Aachen University, Aachen, Germany Background: The purpose of this study was to test the effect of ethyl alcohol on the koniocellular and magnocellular pathway of visual function and to investigate the relationship between such visual field changes and retrobulbar blood flow in healthy subjects. Methods: In 12 healthy subjects (mean age 32 ± 4 years, color Doppler imaging, short-wavelength automated perimetry, and frequency doubling perimetry was performed before and 60 minutes after oral intake of 80 mL of 40 vol% ethanol. Mean and pattern standard deviations for short-wavelength automated and frequency doubling perimetry were assessed. End diastolic velocity (EDV and peak systolic velocity (PSV were measured in the central retinal and ophthalmic arteries using color Doppler imaging. Systemic blood pressure, heart rate, intraocular pressure, and blood alcohol concentration were determined. Results: Mean PSV and EDV in the central retinal artery showed a significant increase after alcohol intake (P = 0.03 and P = 0.02, respectively. Similarly, we found a significant acceleration of blood flow velocity in the ophthalmic artery (P = 0.02 for PSV; P = 0.04 for EDV. Mean intraocular pressure decreased by 1.0 mmHg after alcohol ingestion (P = 0.01. Retinal sensitivity in short-wavelength automated perimetry did not alter, whereas in frequency doubling perimetry, the mean deviation decreased significantly. Systolic and diastolic blood pressure did not change significantly. Mean blood alcohol concentration was 0.38 ± 0.16 g/L. Conclusion: Although ethanol is known to cause peripheral vasodilation, our subjects had no significant drop in systemic blood pressure. However, a significant increase of blood flow velocity was seen in the retrobulbar vessels. Regarding visual function

  8. Acute Cerebral Infarction after FK 506 Administration in a Kidney Transplantation Recipient: A Case Report

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    Lim, Ji Kyung; Byun, Woo Mok; Kim, Jae Woon [Yeungnam University College of Medicine, Daegu (Korea, Republic of)

    2011-02-15

    FK506 is widely used as a potent immunosuppressive agent following organ transplantation. However, the use of FK506 is associated with a wide spectrum of neurotoxicity. FK506-induced cerebral infarctions have rarely been reported. We report here on a case of the acute cerebral infarction caused by vasospasm after FK506 administration in a kidney transplantation recipient. There were areas with increased signal intensity on the diffusion-weighted image. The areas showing increased signal intensity on the diffusion- and T2-weighted images demonstrated decreased signal intensity on the apparent diffusion coefficient mapping. MR angiography showed diffuse stenosis in both the anterior and middle cerebral arteries

  9. Reversing gastric mucosal alterations during ethanol-induced chronic gastritis in rats by oral administration of Opuntia ficus-indica mucilage

    Science.gov (United States)

    Vázquez-Ramírez, Ricardo; Olguín-Martínez, Marisela; Kubli-Garfias, Carlos; Hernández-Muñoz, Rolando

    2006-01-01

    AIM: To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica (Cactaceae) on the healing of ethanol-induced gastritis in rats. METHODS: Chronic gastric mucosa injury was treated with mucilage (5 mg/kg per day) after it was induced by ethanol. Lipid composition, activity of 5’-nucleotidase (a membrane-associated ectoenzyme) and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined. Histological studies of gastric samples from the experimental groups were included. RESULTS: Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes. Phosphatidylcholine (PC) decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect. The activity of 5’-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes. CONCLUSION: The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids, mainly PC and phosphatidylethanolamine (PE), may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage. PMID:16865772

  10. Antinociceptive, anti-inflammatory effects and acute toxicity of aqueous and ethanolic extracts of Myrtus communis L. Aerial parts in mice.

    Science.gov (United States)

    Hosseinzadeh, Hossein; Khoshdel, Mohammad; Ghorbani, Maryam

    2011-12-01

    Myrtus communis L. aerial parts have been used in traditional medicine for the treatment of inflammatory disease. In this study 350 mice were divided into three main groups: negative (saline), positive (morphine or diclofenac) controls, and test groups. The acute toxicity was assessed for 2 days. Antinociceptive activity was performed using hot plate and writhing tests. The anti-inflammatory effect was investigated using xylene-induced ear edema and a cotton pellet test. According to phytochemical screening, the extracts contained tannins, alkaloids, and flavonoids. The LD50 values of the aqueous and ethanolic extracts were 0.473 and 0.79 g/kg, respectively. In hot plate test, the aqueous and ethanolic extracts showed significant antinociceptive activity that was inhibited by naloxone. The extracts exhibited antinociceptive activity against acetic acid-induced writhing and also showed significant activity against acute inflammation which was dose dependent for aqueous extract. The ethanolic (0.05 g/kg) and aqueous extracts (0.005, 0.015, and 0.03 g/kg) demonstrated anti-inflammatory effects against chronic inflammation. The aqueous and ethanolic extracts of the aerial parts of M communis L. showed antinociceptive effects and these may be mediated by opioid receptors.

  11. The sigma-receptor antagonist BD-1063 decreases ethanol intake and reinforcement in animal models of excessive drinking.

    Science.gov (United States)

    Sabino, Valentina; Cottone, Pietro; Zhao, Yu; Iyer, Malliga R; Steardo, Luca; Steardo, Luca; Rice, Kenner C; Conti, Bruno; Koob, George F; Zorrilla, Eric P

    2009-05-01

    Sigma-Receptors (SigRs) have been implicated in behavioral and appetitive effects of psychostimulants and may also modulate the motivating properties of ethanol. This study tested the hypothesis that SigRs modulate ethanol reinforcement and contribute to excessive ethanol intake. The effects of subcutaneous treatment with the potent, selective Sig-1R antagonist BD-1063 on operant ethanol self-administration were studied in two models of excessive drinking-Sardinian alcohol-preferring (sP) rats and acutely withdrawn ethanol-dependent Wistar rats-and compared to ethanol self-administration in nondependent Wistar controls. To assess the specificity of action, the effects of BD-1063 on self-administration of an equally reinforcing saccharin solution were determined in Wistar and sP rats. Gene expression of Sig-1R in reward-related brain areas implicated in ethanol reinforcement was compared between ethanol-naive sP and Wistar rats and withdrawn ethanol-dependent Wistar rats. BD-1063 dose dependently reduced ethanol self-administration in sP rats (3.3-11 mg/kg) and withdrawn, dependent Wistar rats (4-11 mg/kg) at doses that did not modify mean ethanol self-administration in nondependent Wistar controls. BD-1063 did not reduce concurrent water self-administration and did not comparably suppress saccharin self-administration, suggesting selectivity of action. BD-1063 also reduced the breakpoints of sP rats to work for ethanol under a progressive-ratio reinforcement schedule. Ethanol-naive sP rats and 24-h withdrawn, dependent Wistar rats showed reduced Sig-1R mRNA expression in the nucleus accumbens. The results suggest that SigR systems may contribute to innate or ethanol-induced increases in susceptibility to self-administer high ethanol levels, identifying a potential neuroadaptive mechanism contributing to excessive drinking and a therapeutic target for alcohol abuse and dependence.

  12. DARPP-32 and Akt regulation in ethanol-preferring AA and ethanol-avoiding ANA rats.

    Science.gov (United States)

    Nuutinen, Saara; Kiianmaa, Kalervo; Panula, Pertti

    2011-09-26

    Ethanol and other addictive drugs affect many intracellular phosphorylation and dephosphorylation cascades. These cascades are thought to be highly important in the regulation of neuronal activity. The present experiments characterized the regulation of three key signaling molecules, DARPP-32 (dopamine and cAMP regulated phosphoprotein, 32kDa), Akt kinase and ERK1/2 (extracellular signal-regulated kinase 1 and 2) in ethanol-preferring AA (Alko, alcohol) and ethanol-avoiding ANA (Alko, non-alcohol) rat lines. Radioactive in situ hybridization was used in drug naïve animals and Western blotting after acute ethanol administration in striatum, hippocampus and prefrontal cortex. The mRNA levels of DARPP-32 in striatal areas were higher in ANA rats than in AA rats. There was no difference in the striatal enriched phosphatase (STEP61), the downstream target of DARPP-32 expression between the rat lines. Ethanol (1.5g/kg) increased phosphorylation of DARPP-32 at threonine 34 in both AA and in ANA rats indicating that acute ethanol activates DARPP-32 similarly in these rat lines. The expression of Akt kinase was higher in the CA1 of hippocampus in ANA than in AA rats and acute ethanol activated Akt in hippocampus in ANA but not in AA rats. No significant alterations in the regulation of ERK1/2 were found in either rat line. Our findings suggest that DARPP-32 and Akt are regulated by ethanol and differences in the regulation of these molecules might contribute to the dramatically different ethanol drinking patterns seen in AA and ANA rats.

  13. Acute Sodium Arsenite-Induced Hematological and Biochemical Changes in Wistar Rats: Protective Effects of Ethanol Extract of Ageratum conyzoides

    Science.gov (United States)

    Ola-Davies, Olufunke Eunice; Akinrinde, Akinleye Stephen

    2016-01-01

    Background: Ageratum conyzoides L. (Asteraceae) is an annual herbaceous plant used in folklore medicine for the treatment of a wide range of diseases. Objective: To investigate the protective effect of the ethanol leaf extract of A. conyzoides (EEAC) against hematological, serum biochemical and histological alterations induced by Sodium arsenite administration to Wistar rats. Materials and Methods: Twenty male Wistar rats were randomly assigned into four groups of five rats each. Group I received propylene glycol and Group II rats were given the (EEAC, 100 mg/kg b.w.) orally for 7 days. Group III were given a single oral dose of sodium arsenite (NaAsO2, 2.5 mg/kg b.w.). Animals in Group IV were pretreated with 100 mg/kg EEAC for 7 days followed by a single oral dose of sodium arsenite. Results: Arsenic exposure resulted in significant reductions (P produced significant reversal of the reduction in the erythrocytic indices (packed cell volume, red blood cell, and Hb) caused by sodium arseniteSodium arsenite-induced slight elevations in serum aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP), correlating with the histopathological lesions observedAgeratum conyzoides produced only slight reductions in AST, ALT, and ALP compared to the sodium arsenite group, but significantly reduced the severity of histopathological lesions. Abbreviations Used: EEAC: Ethanol extract of Ageratum conyzoides; RBC: Red blood cell; WBC: White blood cell; Hb: Hemoglobin; ALT: Alanine transaminase; AST: Aspartate transaminase or Aspartate aminotransferase; ALP: Alkaline phosphatase; GGT: Gamma glutamyl transferase. PMID:27114688

  14. Influence of acute ethanol intoxication on neuronal apoptosis and Bcl-2 protein expression after severe traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    HE Min; LIU Wei-guo; WEN Liang; DU Hang-gen; YIN Li-chun; CHEN Li

    2013-01-01

    To study the influence and mechanism of acute ethanol intoxication (AEI) on rat neuronal apoptosis after severe traumatic brain injury (TBI).Methods:Ninety-six Sprague-Dawley rats were randomly divided into four groups:normal control,AEI-only,TBI-only and TBI+AEI (n=24 for each).Severe TBI model was developed according to Feeney's method.Rats in TBI+AEI group were firstly subjected to AEI,and then suffered head trauma.In each group,animals were sacrificed at 6 h,24 h,72 h,and 168 h after TBI.The level of neuronal apoptosis and the expression of Bcl-2 protein were determined by TUNEL assay and immunohistochemical method,respectively.Results:Apoptotic cells mainly distributed in the cortex and white matter around the damaged area.Neuronal apoptosis significantly increased at 6 h after trauma and peaked at 72 h.Both the level of neuronal apoptosis and expression of Bcl-2 protein in TBI-only group and TBI+AEI group were higher than those in control group (P<0.05).Compared with TBI-only group,the two indexes were much higher in TBI+AEI group at all time points (P<0.05).Conclusion:Our findings suggest that AEI can increase neuronal apoptosis after severe TBI.

  15. Dose-dependent increase and decrease in active glucose uptake in jejunal epithelium of broilers after acute exposure to ethanol.

    Science.gov (United States)

    Yunus, Agha Waqar; Awad, Wageha A; Kröger, Susan; Zentek, Jürgen; Böhm, Josef

    2011-06-01

    Little is known about the effects of ethanol on gastrointestinal tract of chicken. In this study, we investigated the effects of low levels of ethanol on electrophysiological variables of jejunal epithelium of commercial broilers. Jejunal tissues from 35- to 39-day-old broilers were exposed to either 0 or 0.1% ethanol in Ussing chambers, and electrophysiological variables were monitored for 40 min. After 40 and 60 min of incubation, glucose (20 mM) and carbamoylcholine (200 μM), respectively, were introduced into the chambers. The absolute and percent increase in short-circuit current (Isc) and potential difference (Vt) induced by glucose were increased significantly with 0.1% ethanol. There was no significant effect of 0.1% ethanol on carbamoylcholine-induced electrophysiological variables. To investigate if higher levels of ethanol have similar effects, we tested the effects of 0, 0.33, and 0.66% ethanol under similar experimental conditions until the glucose-addition step. Contrary to 0.1% ethanol, both the 0.33 and 0.66% ethanol levels significantly decreased the basal and glucose-induced Isc and Vt. Tissue conductivity remained unaffected in all cases. These results indicate that intestinal epithelia of chicken may be more sensitive to the effects of ethanol as compared with other species. This is the first report indicating dose-dependent increase and decrease in active glucose absorption in intestinal epithelia in the presence of ethanol.

  16. Both acute and prolonged administration of EPO reduce cerebral and systemic vascular conductance in humans.

    Science.gov (United States)

    Rasmussen, Peter; Kim, Yu-Sok; Krogh-Madsen, Rikke; Lundby, Carsten; Olsen, Niels V; Secher, Niels H; van Lieshout, Johannes J

    2012-03-01

    Administration of erythropoietin (EPO) has been linked to cerebrovascular events. EPO reduces vascular conductance, possibly because of the increase in hematocrit. Whether EPO in itself affects the vasculature remains unknown; here it was evaluated in healthy males by determining systemic and cerebrovascular variables following acute (30,000 IU/d for 3 d; n=8) and chronic (5000 IU/week for 13 wk; n=8) administration of EPO, while the responsiveness of the vasculature was challenged during cycling exercise, with and without hypoxia. Prolonged administration of EPO increased hematocrit from 42.5 ± 3.7 to 47.6 ± 4.1% (PEPO administration. Yet, the two EPO regimes increased arterial pressure similarly (by 8±4 and 7±3 mmHg, respectively; P=0.01) through reduced vascular conductance (by 7±3 and 5±2%; PEPO regimes widened the arterial-to-jugular O(2) differences at rest as well as during normoxic and hypoxic exercise (PEPO to healthy humans lowers systemic and cerebral conductance independent of its effect on hematocrit.

  17. Anticataleptic activity of cathinone and MDMA (Ecstasy) upon acute and subchronic administration in rat.

    Science.gov (United States)

    Banjaw, Mehret Yerdaw; Mayerhofer, Andreas; Schmidt, Werner J

    2003-09-15

    It was recently demonstrated that acute administration of 3,4-methylenedioxymethamphet-amine (MDMA, "Ecstasy") is capable of counteracting haloperidol-induced catalepsy in rats. The present study was done with another psychostimulant, S-(-)-cathinone. In these experiments, 32 male Sprague-Dawley rats, 225 +/- 25 g, were used. They were divided into three groups. All groups received 0.5 mg/kg haloperidol in normal saline (s.c.) as a first injection. Then 30 min later each group received either isotonic phosphate-buffered saline, 1 mg/kg S-(-)-cathinone, or 2.5 mg/kg (RS)-MDMA (s.c.) as a second injection. The results of descent latency on both the horizontal bar and vertical grid showed that S-(-)-cathinone or (RS)-MDMA upon acute administration induces a strong anticataleptic activity (P mechanism of the observed strong anticataleptic activity of S-(-)-cathinone (which is considered a potent dopamine releaser) requires further investigation.

  18. Oral Administration of Astrovirus Capsid Protein Is Sufficient To Induce Acute Diarrhea In Vivo

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    Victoria A. Meliopoulos

    2016-11-01

    Full Text Available The disease mechanisms associated with the onset of astrovirus diarrhea are unknown. Unlike other enteric virus infections, astrovirus infection is not associated with an inflammatory response or cellular damage. In vitro studies in differentiated Caco-2 cells demonstrated that human astrovirus serotype 1 (HAstV-1 capsid protein alone disrupts the actin cytoskeleton and tight junction complex, leading to increased epithelial barrier permeability. In this study, we show that oral administration of purified recombinant turkey astrovirus 2 (TAstV-2 capsid protein results in acute diarrhea in a dose- and time-dependent manner in turkey poults. Similarly to that induced by infectious virus, TAstV-2 capsid-induced diarrhea was independent of inflammation or histological changes but was associated with increased intestinal barrier permeability, as well as redistribution of sodium hydrogen exchanger 3 (NHE3 from the membrane to the cytoplasm of the intestinal epithelium. Unlike other viral enterotoxins that have been identified, astrovirus capsid induces diarrhea after oral administration, reproducing the natural route of infection and demonstrating that ingestion of intact noninfectious capsid protein may be sufficient to provoke acute diarrhea. Based on these data, we hypothesize that the astrovirus capsid acts like an enterotoxin and induces intestinal epithelial barrier dysfunction.

  19. Administration of reconstituted polyphenol oil bodies efficiently suppresses dendritic cell inflammatory pathways and acute intestinal inflammation.

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    Elisabetta Cavalcanti

    Full Text Available Polyphenols are natural compounds capable of interfering with the inflammatory pathways of several in vitro model systems. In this study, we developed a stable and effective strategy to administer polyphenols to treat in vivo models of acute intestinal inflammation. The in vitro suppressive properties of several polyphenols were first tested and compared for dendritic cells (DCs production of inflammatory cytokines. A combination of the polyphenols, quercetin and piperine, were then encapsulated into reconstituted oil bodies (OBs in order to increase their stability. Our results showed that administration of low dose reconstituted polyphenol OBs inhibited LPS-mediated inflammatory cytokine secretion, including IL-6, IL-23, and IL-12, while increasing IL-10 and IL-1Rα production. Mice treated with the polyphenol-containing reconstituted OBs (ROBs were partially protected from dextran sodium sulfate (DSS-induced colitis and associated weight loss, while mortality and inflammatory scores revealed an overall anti-inflammatory effect that was likely mediated by impaired DC immune responses. Our study indicates that the administration of reconstituted quercetin and piperine-containing OBs may represent an effective and potent anti-inflammatory strategy to treat acute intestinal inflammation.

  20. Effects of acute or chronic administration of substituted benzamides in experimental models of depression in rats.

    Science.gov (United States)

    Drago, F; Arezzi, A; Virzì, A

    2000-12-01

    The effects of substituted benzamides, sulpiride and raclopride on experimental models of depression were studied in male rats after acute or chronic administration in comparison to those of the classical antidepressant, clomipramine. In contrast to clomipramine (50 mg/kg), acute doses of sulpiride or raclopride (1 or 5 mg/kg) failed to change the behavioral response of animals tested in the despair (constrained swim) test or in the model of reserpine-induced changes in the open field behavior. These doses also did not modify the grooming response of rats exposed to a novel environment. Sulpiride or raclopride 10 mg/kg increased the immobility time in the despair test and reduced novelty-induced grooming. The repeated injection for 21 days of sulpiride or raclopride (1 or 5 mg/kg, but not 10 mg/kg) induced a reduction of the immobility period during the constrained swim test similar to that following the chronic treatment with clomipramine 50 mg/kg. This appeared to be a clear-cut reversed dose-response relationship for both substituted benzamides, being the dose potency 1 mg/kg>5 mg/kg>10 mg/kg. Raclopride was more potent than sulpiride in this respect. Furthermore, like clomipramine, sulpiride (1 or 5 mg/kg) and raclopride (1 mg/kg) antagonized reserpine-induced changes in the open field behavior and enhanced novelty-induced grooming. These results indicate that, in contrast to acute injection, repeated administration of small doses of the substituted benzamides, sulpiride or raclopride induce an effect similar to that of the classical antidepressant, clomipramine. The reverse dose-response relationship suggests that these drugs in small doses act on presynaptic dopamine D(2) receptors. This may be consistent with a postsynaptic action of greater doses that exert sedative effects and increase immobility time in the despair test.

  1. 17β-Estradiol administration attenuates seawater aspiration-induced acute lung injury in rats.

    Science.gov (United States)

    Fan, Qixin; Zhao, Pengtao; Li, Jiahuan; Xie, Xiaoyan; Xu, Min; Zhang, Yong; Mu, Deguang; Li, Wangping; Sun, Ruilin; Liu, Wei; Nan, Yandong; Zhang, Bo; Jin, Faguang; Li, Zhichao

    2011-12-01

    There is very little evidence on the value of administering estrogen in cases of seawater drowning which can induce acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Therefore, this study aimed to investigate whether 17β-estradiol (E2) treatment can attenuate seawater aspiration-induced ALI in rats. In the experiment, ALI was induced by endotracheal instillation of seawater (4mL/kg) and the rats were then given intraperitoneal injection of E2 (5mg/kg) 20min after seawater instillation. Finally, the changes of arterial blood gases which contained hydrogen ion concentration (pH), arterial oxygen tension (PaO(2)) and arterial carbon dioxide tension (PaCO(2)) were measured and the measurement of extravascular lung water (EVLW) was observed. The pulmonary histological changes were evaluated by hematoxylin-eosin stain. The expression of aquaporins (AQPs) 1, AQP5, and estrogen receptor-β (ERβ) was measured by western blotting and immunohistochemical methods. The results showed that compared with normal saline water, seawater aspiration induced more serious ALI in rats which was markedly alleviated by E2 treatment. Meanwhile, the ERβ in lung tissues was activated after E2 administration. The seawater aspiration group also presented with severe pulmonary edema which was paralleled with over expressed AQP1 and AQP5. However, the up-regulation of AQP1 and AQP5 was suppressed by the administration of E2, resulting in an attenuation of lung edema. In conclusion, E2 treatment could effectively attenuate seawater aspiration-induced acute lung injury in rats by the down-regulation of AQP1 and AQP5.

  2. Coronary flow and hemorrhagic complications after alteplase and streptokinase administration in patients with acute myocardial infarction

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    Kostić Tomislav

    2009-01-01

    Full Text Available Background/Aim. Up-to-date treatment of acute myocardial infarction (AIM has been based on as early as possible establishment of circulation in ischemic myocardium whether by the use of fibrinolythic therapy and/or urgent coronary intervention which significantly changes the destiny of patients with AMI, but also increases the risk of bleeding. The aim of this study was to compare coronary flow and bleeding complications in patients with acute myocardial infarction with ST-elevation (STEMI after administration of alteplase or streptokinase. Methods. The study included 254 patients with STEMI. The group I (n = 174 received streptokinase, and the group II (n = 80 received alteplase. We followed frequency of complications such as bleeding and hypotension in the investigated groups of patients, based on the TIMI classification of bleeding, as well as the transience of infarction artery in accordance with TIMI flow. Results. The patients with myocardial infarction after administration of alteplase had statistically significantly higher coronary flow (TIMI- 3, 72.5% as compared to the patients who received streptokinase, 39.2%. Hypotension as complication of fibrynolythic therapy administration occurred in a significantly higher percentage in the group of patients who received streptokinase. There was no statistically significant difference in the appearance of major bleeding in the groups of patients who received streptokinasis and alteplase (6.9% and 7.5%, respectively. Also, there was no difference in the appearance of minor and minimal bleeding among the investigated groups of patients. Conclusion. It was shown that alteplase in a higher number of patients provided TIMI-3 coronary flow as compared to streptokinese. In comparison with streptokinase, a combination of alteplase, enoxaparin and double antiplatelet therapy enabled earlier achievement of coronary flow through previously blocked coronary artery that was more complete (higher frequency of

  3. Delayed administration of darbepoetin or erythropoietin protects against ischemic acute renal injury and failure.

    Science.gov (United States)

    Johnson, D W; Pat, B; Vesey, D A; Guan, Z; Endre, Z; Gobe, G C

    2006-05-01

    Administration of human recombinant erythropoietin (EPO) at time of acute ischemic renal injury (IRI) inhibits apoptosis, enhances tubular epithelial regeneration, and promotes renal functional recovery. The present study aimed to determine whether darbepoetin-alfa (DPO) exhibits comparable renoprotection to that afforded by EPO, whether pro or antiapoptotic Bcl-2 proteins are involved, and whether delayed administration of EPO or DPO 6 h following IRI ameliorates renal dysfunction. The model of IRI involved bilateral renal artery occlusion for 45 min in rats (N = 4 per group), followed by reperfusion for 1-7 days. Controls were sham-operated. Rats were treated at time of ischemia or sham operation (T0), or post-treated (6 h after the onset of reperfusion, T6) with EPO (5000 IU/kg), DPO (25 mug/kg), or appropriate vehicle by intraperitoneal injection. Renal function, structure, and immunohistochemistry for Bcl-2, Bcl-XL, and Bax were analyzed. DPO or EPO at T0 significantly abrogated renal dysfunction in IRI animals (serum creatinine for IRI 0.17 +/- 0.05 mmol/l vs DPO-IRI 0.08 +/- 0.03 mmol/l vs EPO-IRI 0.04 +/- 0.01 mmol/l, P = 0.01). Delayed administration of DPO or EPO (T6) also significantly abrogated subsequent renal dysfunction (serum creatinine for IRI 0.17 +/- 0.05 mmol/l vs DPO-IRI 0.06 +/- 0.01 mmol/l vs EPO-IRI 0.03 +/- 0.03 mmol/l, P = 0.01). There was also significantly decreased tissue injury (apoptosis, P EPO at T0 or T6. These results reaffirm the potential clinical application of DPO and EPO as novel renoprotective agents for patients at risk of ischemic acute renal failure or after having sustained an ischemic renal insult.

  4. Acute caffeine administration effect on brain activation patterns in mild cognitive impairment.

    Science.gov (United States)

    Haller, Sven; Montandon, Marie-Louise; Rodriguez, Cristelle; Moser, Dominik; Toma, Simona; Hofmeister, Jeremy; Sinanaj, Indrit; Lovblad, Karl-Olof; Giannakopoulos, Panteleimon

    2014-01-01

    Previous studies showed that acute caffeine administration enhances task-related brain activation in elderly individuals with preserved cognition. To explore the effects of this widely used agent on cognition and brain activation in early phases of cognitive decline, we performed a double-blinded, placebo-controlled functional magnetic resonance imaging (fMRI) study during an n-back working memory task in 17 individuals with mild cognitive impairment (MCI) compared to 17 age-matched healthy controls (HC). All individuals were regular caffeine consumers with an overnight abstinence and given 200 mg caffeine versus placebo tablets 30 minutes before testing. Analyses included assessment of task-related activation (general linear model), functional connectivity (tensorial-independent component analysis, TICA), baseline perfusion (arterial spin labeling, ASL), grey matter density (voxel-based morphometry, VBM), and white matter microstructure (tract-based spatial statistics, TBSS). Acute caffeine administration induced a focal activation of the prefrontal areas in HC with a more diffuse and posteromedial activation pattern in MCI individuals. In MCI, TICA documented a significant caffeine-related enhancement in the prefrontal cortex, supplementary motor area, ventral premotor and parietal cortex as well as the basal ganglia and cerebellum. The absence of significant group differences in baseline ASL perfusion patterns supports a neuronal rather than a purely vascular origin of these differences. The VBM and TBSS analyses excluded potentially confounding differences in grey matter density and white matter microstructure between MCI and HC. The present findings suggest a posterior displacement of working memory-related brain activation patterns after caffeine administration in MCI that may represent a compensatory mechanism to counterbalance a frontal lobe dysfunction.

  5. The impact of intravenous fat emulsion administration in acute lung injury.

    Science.gov (United States)

    Lekka, Marilena E; Liokatis, Stamatis; Nathanail, Christos; Galani, Vasiliki; Nakos, George

    2004-03-01

    The aim of this study was to evaluate the effect of parenteral nutrition containing medium- and long-chain triglycerides on the function of the respiratory system and to investigate mechanisms involved in this process. We studied 13 patients with acute respiratory distress syndrome (ARDS), 8 receiving lipid and 5 placebo, and 6 without ARDS, receiving lipid. Bronchoalveolar lavage (BAL) was performed before and 1 hour after administration of lipid or placebo. In patients with ARDS, lipid administration resulted in deterioration of oxygenation (Pa(O(2))/FI(O(2)): from 129 +/- 37 to 95 +/- 42), compliance of respiratory system (from 39.2 +/- 12 to 33.1 +/- 9.2 ml/cm H(2)O), and pulmonary vascular resistance (from 258 +/- 47 to 321 +/- 58 dyne x s x cm(-5)). In the BAL fluid of the same group, an increase in total protein and phospholipid concentrations, phospholipase activities, platelet-activating factor and neutrophils, as well as alterations in BAL lipid profile were observed. No significant changes were observed in the control or in the ARDS-Placebo groups. In conclusion, this study indicates that administration of medium- and long-chain triglycerides in patients with ARDS causes alterations in lung function and hemodynamics. Inflammatory cells, possibly activated by lipids, release phospholipase A(2) and platelet-activating factor, enhancing edema formation, inflammation, and surfactant alterations.

  6. Lateral/Basolateral Amygdala Serotonin Type-2 Receptors Modulate Operant Self-administration of a Sweetened Ethanol Solution via Inhibition of Principal Neuron Activity

    Directory of Open Access Journals (Sweden)

    Brian eMccool

    2014-01-01

    Full Text Available The lateral/basolateral amygdala (BLA forms an integral part of the neural circuitry controlling innate anxiety and learned fear. More recently, BLA dependent modulation of self-administration behaviors suggests a much broader role in the regulation of reward evaluation. To test this, we employed a self-administration paradigm that procedurally segregates ‘seeking’ (exemplified as lever-press behaviors from consumption (drinking directed at a sweetened ethanol solution. Microinjection of the nonselective serotonin type-2 receptor agonist, alpha-methyl-5-hydroxytryptamine (-m5HT into the BLA reduced lever pressing behaviors in a dose-dependent fashion. This was associated with a significant reduction in the number of response-bouts expressed during non-reinforced sessions without altering the size of a bout or the rate of responding. Conversely, intra-BLA -m5HT only modestly effected consumption-related behaviors; the highest dose reduced the total time spent consuming a sweetened ethanol solution but did not inhibit the total number of licks, number of lick bouts, or amount of solution consumed during a session. In vitro neurophysiological characterization of BLA synaptic responses showed that -m5HT significantly reduced extracellular field potentials. This was blocked by the 5-HT2A/C antagonist ketanserin suggesting that 5-HT2-like receptors mediate the behavioral effect of -m5HT. During whole-cell patch current-clamp recordings, we subsequently found that -m5HT increased action potential threshold and hyperpolarized the resting membrane potential of BLA pyramidal neurons. Together, our findings show that the activation of BLA 5-HT2A/C receptors inhibits behaviors related to reward-seeking by suppressing BLA principal neuron activity. These data are consistent with the hypothesis that the BLA modulates reward-related behaviors and provides specific insight into BLA contributions during operant self-administration of a

  7. Effects of biliverdin administration on acute lung injury induced by hemorrhagic shock and resuscitation in rats.

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    Junko Kosaka

    Full Text Available Hemorrhagic shock and resuscitation induces pulmonary inflammation that leads to acute lung injury. Biliverdin, a metabolite of heme catabolism, has been shown to have potent cytoprotective, anti-inflammatory, and anti-oxidant effects. This study aimed to examine the effects of intravenous biliverdin administration on lung injury induced by hemorrhagic shock and resuscitation in rats. Biliverdin or vehicle was administered to the rats 1 h before sham or hemorrhagic shock-inducing surgery. The sham-operated rats underwent all surgical procedures except bleeding. To induce hemorrhagic shock, rats were bled to achieve a mean arterial pressure of 30 mmHg that was maintained for 60 min, followed by resuscitation with shed blood. Histopathological changes in the lungs were evaluated by histopathological scoring analysis. Inflammatory gene expression was determined by Northern blot analysis, and oxidative DNA damage was assessed by measuring 8-hydroxy-2' deoxyguanosine levels in the lungs. Hemorrhagic shock and resuscitation resulted in prominent histopathological damage, including congestion, edema, cellular infiltration, and hemorrhage. Biliverdin administration prior to hemorrhagic shock and resuscitation significantly ameliorated these lung injuries as judged by histopathological improvement. After hemorrhagic shock and resuscitation, inflammatory gene expression of tumor necrosis factor-α and inducible nitric oxide synthase were increased by 18- and 8-fold, respectively. Inflammatory gene expression significantly decreased when biliverdin was administered prior to hemorrhagic shock and resuscitation. Moreover, after hemorrhagic shock and resuscitation, lung 8-hydroxy-2' deoxyguanosine levels in mitochondrial DNA expressed in the pulmonary interstitium increased by 1.5-fold. Biliverdin administration prior to hemorrhagic shock and resuscitation decreased mitochondrial 8-hydroxy-2' deoxyguanosine levels to almost the same level as that in the

  8. Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity

    Energy Technology Data Exchange (ETDEWEB)

    Tiradentes, R.V. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Centro Universitário do Espírito Santo, Colatina, ES (Brazil); Pires, J.G.P. [Centro Universitário do Espírito Santo, Colatina, ES (Brazil); Escola de Medicina da Empresa Brasileira de Ensino, Vitória, ES (Brazil); Silva, N.F. [Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Ramage, A.G. [Department of Neuroscience, Physiology and Pharmacology, University College London, London (United Kingdom); Santuzzi, C.H. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Centro Universitário do Espírito Santo, Colatina, ES (Brazil); Futuro, H.A. Neto [Escola de Medicina da Empresa Brasileira de Ensino, Vitória, ES (Brazil); Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Escola Superior de Ciências da Saúde, Santa Casa de Misericórdia de Vitória, Vitória, ES (Brazil)

    2014-05-30

    Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33±4.7 and -31±5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35±5.4 and -31±5.5%, respectively, with an increase in blood pressure +26.3±2.5; 3 mg/kg sertraline reduced RSNA by -59.4±8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central.

  9. Central nervous insulin administration does not potentiate the acute glucoregulatory impact of concurrent mild hyperinsulinemia.

    Science.gov (United States)

    Ott, Volker; Lehnert, Hendrik; Staub, Josefine; Wönne, Kathrin; Born, Jan; Hallschmid, Manfred

    2015-03-01

    Experiments in rodents suggest that hypothalamic insulin signaling essentially contributes to the acute control of peripheral glucose homeostasis. Against this background, we investigated in healthy humans whether intranasal (IN) insulin, which is known to effectively reach the brain compartment, impacts systemic glucose metabolism. Twenty overnight-fasted healthy, normal-weight men were IN administered 210 and 420 international units [IU] (10 and 20 IU every 15 min) of the insulin analog aspart (ins-asp) and placebo, respectively, during experimental sessions lasting 6 h. The use of ins-asp rather than human insulin enabled us to disentangle exogenous and endogenous insulin kinetics. IN insulin dose-dependently decreased plasma glucose concentrations while reducing C-peptide and attenuating endogenous insulin levels. However, we also observed a slight dose-dependent permeation of ins-asp into the circulation. In control experiments mimicking the systemic but not the central nervous uptake of the IN 210 IU dose via intravenous infusion of ins-asp at a dose of 0.12 IU/kg/24 h (n = 10), we obtained essentially identical effects on fasting plasma glucose concentrations. This pattern indicates that sustained IN insulin administration to the human brain to enhance central nervous insulin signaling does not acutely alter systemic glucose homeostasis beyond effects accounted for by concurrent mild hyperinsulinemia.

  10. GABAergic modulation of human social interaction in a prisoner's dilemma model by acute administration of alprazolam.

    Science.gov (United States)

    Lane, Scott D; Gowin, Joshua L

    2009-10-01

    Recent work in neuroeconomics has used game theory paradigms to examine neural systems that subserve human social interaction and decision making. Attempts to modify social interaction through pharmacological manipulation have been less common. Here we show dose-dependent modification of human social behavior in a prisoner's dilemma model after acute administration of the γ-aminobutyric acid (GABA)-A modulating benzodiazepine alprazolam. Nine healthy adults received doses of placebo, 0.5, 1.0, and 2.0 mg alprazolam in a counterbalanced within-subject design, while completing multiple test blocks per day on an iterated prisoner's dilemma game. During test blocks in which peak subjective effects of alprazolam were reported, cooperative choices were significantly decreased as a function of dose. Consistent with previous reports showing that high acute doses of GABA-modulating drugs are associated with violence and other antisocial behavior, our data suggest that at sufficiently high doses, alprazolam can decrease cooperation. These behavioral changes may be facilitated by changes in inhibitory control facilitated by GABA. Game theory paradigms may prove useful in behavioral pharmacology studies seeking to measure social interaction, and may help inform the emerging field of neuroeconomics.

  11. Peningkatan Produktivitas Ayam Petelur Melalui Pemberian Ekstrak Etanol Daun Kemangi (INCREASED LAYING HENS PRODUCTIVITY THROUGH THE ADMINISTRATION OF ETHANOL EXTRACT OF KEMANGI LEAVES

    Directory of Open Access Journals (Sweden)

    Andriyanto .

    2014-08-01

    Full Text Available Empirically, kemangi leaves reported to increase health quality in human and livestock. Thepreliminary study was designed to explore the potency of ethanol extract of kemangi leaves to increaselaying hens performance. Sixteen laying hens (pullet were divided into 4 groups and repeated 4 times.Control group was laying hen administered aquadest orally, treated group was laying hen administeredextract of kemangi leaves orally at a dose of 1, 2, and 3 mg/kg BW, respectively. Every day, the experimentallaying hens were fed for 3 times and drinking water was provided ad libitum. Variables observed were thenumber of eggs, egg weight, time of first laying, egg laying intervals, egg quality ( water content, crudeprotein, and crude fat, and liver function (SGPT and SGOT values . Results of this research showed thatadministration of kemangi leaves extract at a dose of 3 mg/kg BW significantly increased the number ofegg production and egg weight (p<0.05. Time of first laying and laying interval did not show any significantdifference among treatments. Examination of moisture, crude protein, and crude fat content of the eggindicated that the administration of kemangi leaves extract did not affect egg quality. Extract of kemangileaves decreased SGPT and SGOT values that indicated improvement of liver function. It was concludedthat administration of ethanol extract of kemangi leaves could increase laying hens productivity byimprovement of liver function that is critical in vitellogenesis.

  12. Latent inhibition is disrupted by acute and repeated administration of corticosterone.

    Science.gov (United States)

    Shalev, U.; Feldon, J.; Weiner, I.

    1998-12-01

    Latent inhibition (LI), namely, a retardation in conditioning to a stimulus, as a consequence of its prior non- reinforced pre-exposure, is disrupted in amphetamine-treated rats and humans and in some subsets of schizophrenic patients. One factor that has been repeatedly implicated in precipitating and/or exacerbating psychotic episodes is stress. Since a principal biological response to stress is the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis, leading, as its end product, to the secretion of corticosterone, the present experiments tested whether increase in corticosterone levels following exogenous corticosterone administration would disrupt LI. Both repeated (Experiment 1) and acute (Experiment 2) administration of corticosterone led to LI disruption, providing evidence for the involvement of the HPA axis alterations in LI and further supporting the viability of disrupted LI as an animal model of psychosis. Both regimens also increased amphetamine-induced activity. We suggest that disrupted LI may reflect a cognitive mechanism whereby prolonged periods of increased corticosterone levels can lead to 'sensory flooding' characteristic of psychosis.

  13. Ginseng administration protects skeletal muscle from oxidative stress induced by acute exercise in rats

    Directory of Open Access Journals (Sweden)

    J. Voces

    2004-12-01

    Full Text Available Enzymatic activity was analyzed in the soleus, gastrocnemius (red and white and plantaris muscles of acutely exercised rats after long-term administration of Panax ginseng extract in order to evaluate the protective role of ginseng against skeletal muscle oxidation. Ginseng extract (3, 10, 100, or 500 mg/kg was administered orally for three months to male Wistar rats weighing 200 ± 50 g before exercise and to non-exercised rats (N = 8/group. The results showed a membrane stabilizing capacity of the extract since mitochondrial function measured on the basis of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase activities was reduced, on average, by 20% (P < 0.05 after exercise but the activities remained unchanged in animals treated with a ginseng dose of 100 mg/kg. Glutathione status did not show significant changes after exercise or treatment. Lipid peroxidation, measured on the basis of malondialdehyde levels, was significantly higher in all muscles after exercise, and again was reduced by about 74% (P < 0.05 by the use of ginseng extract. The administration of ginseng extract was able to protect muscle from exercise-induced oxidative stress irrespective of fiber type.

  14. Administration

    DEFF Research Database (Denmark)

    Bogen handler om den praksis, vi kalder administration. Vi er i den offentlige sektor i Danmark hos kontorfolkene med deres sagsmapper, computere, telefoner,, lovsamlinger,, retningslinier og regneark. I bogen udfoldes en mangfoldighed af konkrete historier om det administrative arbejde fra...... forskellige områder i den offentlige sektor. Hensigten er at forstå den praksis og faglighed der knytter sig til det administrative arbejde...

  15. Ethanol-Induced Neurodegeneration and Glial Activation in the Developing Brain

    Directory of Open Access Journals (Sweden)

    Mariko Saito

    2016-08-01

    Full Text Available Ethanol induces neurodegeneration in the developing brain, which may partially explain the long-lasting adverse effects of prenatal ethanol exposure in fetal alcohol spectrum disorders (FASD. While animal models of FASD show that ethanol-induced neurodegeneration is associated with glial activation, the relationship between glial activation and neurodegeneration has not been clarified. This review focuses on the roles of activated microglia and astrocytes in neurodegeneration triggered by ethanol in rodents during the early postnatal period (equivalent to the third trimester of human pregnancy. Previous literature indicates that acute binge-like ethanol exposure in postnatal day 7 (P7 mice induces apoptotic neurodegeneration, transient activation of microglia resulting in phagocytosis of degenerating neurons, and a prolonged increase in glial fibrillary acidic protein-positive astrocytes. In our present study, systemic administration of a moderate dose of lipopolysaccharides, which causes glial activation, attenuates ethanol-induced neurodegeneration. These studies suggest that activation of microglia and astrocytes by acute ethanol in the neonatal brain may provide neuroprotection. However, repeated or chronic ethanol can induce significant proinflammatory glial reaction and neurotoxicity. Further studies are necessary to elucidate whether acute or sustained glial activation caused by ethanol exposure in the developing brain can affect long-lasting cellular and behavioral abnormalities observed in the adult brain.

  16. Inflammation and Oxidative Stress in Young and Aged Rats after Acute Homocysteine Administration

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    Cristina-Sorina CĂTANĂ

    2011-06-01

    Full Text Available Introduction: Hyperhomocysteinemia plays an etiologic role in homocystinuria, neurodegenerative and cardiovascular diseases. Potential mechanisms involved in the degenerative diseases of aging include: oxidative stress, endothelial dysfunction and inflammation. Aim: In the present study we evaluated the effect of acute administration of homocysteine (Hcy, at a level similar to that found in homocystinuria, on biochemical markers of inflammation (such as IL-6 and of oxidative stress (such as gluthathione peroxidase - GPx. Material and Method: The study was performed on 40 young and older Wistar rats. IL-6 serum level was quantified by a high-sensitivity enzyme-linked immunoabsorbent assay (ELISA method and the activity of whole blood GPx was measured using a commercially available Randox kit. Results: Our results showed that Hcy administration increased the pro-inflammatory cytokine IL-6 in young rats (p<0.3 and decreased IL-6 level in older rats (p<0.008, when compared to the control group. GPx activity was found to increase with age (587.07 U/gHb versus 847.5 U/gHb, p<0.001. Two hours after Hcy administration, GPx activity was found to decrease, but not in a statistically significant manner. The difference between GPx activities in Hcy treated groups remains statistically significant (p<0.01 in the younger group, compared to older group (556.62 U/gHb versus 748.38 U/gHb. Conclusion: Our results indicate the existence of a correlation between hyperhomocysteinemia, proinflammatory state and oxidative stress, illustrated by the direct dependence of whole blood GPx activities on the increasing age.

  17. Efficacy of Acute Pain Control Protocol in Triage Department on Analgesics Administration Time and Patients' Satisfaction

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    Seyedhossein Seyyedhoseini Davaraani

    2014-07-01

    Full Text Available Objective: Current study was conducted to develop a pain control protocol by Morphine Sulfate (MS Suppository in triage ward with the main primary outcomes of first analgesic administration time, patients' satisfaction and also the changes in pain intensity.Methods: In this randomized clinical trial, 318 consecutive patients attending to an academic tertiary health care center in Tehran, Iran in 2011 and 2012 were enrolled. The patients were randomly assigned to receive either routine pain control by emergency medicine residents in emergency department (n=132 or pain control protocol in triage level by nurses (n=186. Those with pain in control group were treated with conventional pain control program and those in intervention group with pain intensities higher than four were treated with suppository stat 10 mg dose of MS administered by nurses in triage ward.Results: The mean change in pain intensity was significantly (P<0.0001 higher in intervention group (4.2 versus 0.2 and the first analgesic administration time was significantly different between groups (P<0.05 being less in the intervention group (43.1 versus 4.6. Also the patients' satisfaction was significantly higher in the intervention group (P<0.0001. No drug adverse effects were seen.Conclusions: Totally, according to the obtained results, it may be concluded that acute pain control protocol in triage department by suppository of MS would result in reduced analgesics administration time and higher patients' satisfaction. Keywords: Analgesia; Emergency Department; Pain Control

  18. Acute psychomotor, memory and subjective effects of MDMA and THC co-administration over time in healthy volunteers

    NARCIS (Netherlands)

    Dumont, G.J.H.; Van Hasselt, J.G.C.; De Kam, M.; Van Gerven, J.M.A.; Touw, D.J.; Buitelaar, J.K.; Verkes, R.J.

    2011-01-01

    In Western societies a considerable percentage of young people expose themselves to the combination of 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') and cannabis. The aim of the present study was to assess the acute effects of co-administration of MDMA and THC (the main psychoactive compound

  19. Cytoplasmic Phospholipase A2 Modulation of Adolescent Rat Ethanol-Induced Protein Kinase C Translocation and Behavior

    Science.gov (United States)

    Santerre, J. L.; Kolitz, E. B.; Pal, R.; Rogow, J. A.; Werner, D. F.

    2015-01-01

    Ethanol consumption typically begins during adolescence, a developmental period which exhibits many age-dependent differences in ethanol behavioral sensitivity. Protein kinase C (PKC) activity is largely implicated in ethanol-behaviors, and our previous work indicates that regulation of novel PKC isoforms likely contributes to decreased high-dose ethanol sensitivity during adolescence. The cytoplasmic Phospholipase A2 (cPLA2) signaling cascade selectivity modulates novel and atypical PKC isoform activity, as well as adolescent ethanol hypnotic sensitivity. Therefore, the current study was designed to ascertain adolescent cPLA2 activity both basally and in response to ethanol, as well as it's involvement in ethanol-induced PKC isoform translocation patterns. cPLA2 expression was elevated during adolescence, and activity was increased only in adolescents following high-dose ethanol administration. Novel, but not atypical PKC isoforms translocate to cytosolic regions following high-dose ethanol administration. Inhibiting cPLA2 with AACOCF3 blocked ethanol-induced PKC cytosolic translocation. Finally, inhibition of novel, but not atypical, PKC isoforms when cPLA2 activity was elevated, modulated adolescent high-dose ethanol-sensitivity. These data suggest that the cPLA2/PKC pathway contributes to the acute behavioral effects of ethanol during adolescence. PMID:25791059

  20. Acute and chronic administration of gold nanoparticles cause DNA damage in the cerebral cortex of adult rats.

    Science.gov (United States)

    Cardoso, Eria; Rezin, Gislaine Tezza; Zanoni, Elton Torres; de Souza Notoya, Frederico; Leffa, Daniela Dimer; Damiani, Adriani Paganini; Daumann, Francine; Rodriguez, Juan Carlos Ortiz; Benavides, Roberto; da Silva, Luciano; Andrade, Vanessa M; da Silva Paula, Marcos Marques

    2014-01-01

    The use of gold nanoparticles is increasing in medicine; however, their toxic effects remain to be elucidated. Studies show that gold nanoparticles can cross the blood-brain barrier, as well as accumulate in the brain. Therefore, this study was undertaken to better understand the effects of gold nanoparticles on rat brains. DNA damage parameters were evaluated in the cerebral cortex of adult rats submitted to acute and chronic administration of gold nanoparticles of two different diameters: 10 and 30nm. During acute administration, adult rats received a single intraperitoneal injection of either gold nanoparticles or saline solution. During chronic administration, adult rats received a daily single injection for 28 days of the same gold nanoparticles or saline solution. Twenty-four hours after either single (acute) or last injection (chronic), the rats were euthanized by decapitation, their brains removed, and the cerebral cortices isolated for evaluation of DNA damage parameters. Our study showed that acute administration of gold nanoparticles in adult rats presented higher levels of damage frequency and damage index in their DNA compared to the control group. It was also observed that gold nanoparticles of 30nm presented higher levels of damage frequency and damage index in the DNA compared to the 10nm ones. When comparing the effects of chronic administration of gold nanoparticles of 10 and 30nm, we observed that occurred significant different index and frequency damage, comparing with control group. However, there is no difference between the 10 and 30nm groups in the levels of DNA damage for both parameters of the Comet assay. Results suggest that gold nanoparticles for both sizes cause DNA damage for chronic as well as acute treatments, although a higher damage was observed for the chronic one.

  1. Adolescent alcohol exposure reduces behavioral flexibility, promotes disinhibition, and increases resistance to extinction of ethanol self-administration in adulthood.

    Science.gov (United States)

    Gass, Justin T; Glen, William Bailey; McGonigal, Justin T; Trantham-Davidson, Heather; Lopez, Marcelo F; Randall, Patrick K; Yaxley, Richard; Floresco, Stan B; Chandler, L Judson

    2014-10-01

    The prefrontal cortex (PFC) is a brain region that is critically involved in cognitive function and inhibitory control of behavior, and adolescence represents an important period of continued PFC development that parallels the maturation of these functions. Evidence suggests that this period of continued development of the PFC may render it especially vulnerable to environmental insults that impact PFC function in adulthood. Experimentation with alcohol typically begins during adolescence when binge-like consumption of large quantities is common. In the present study, we investigated the effects of repeated cycles of adolescent intermittent ethanol (AIE) exposure (postnatal days 28-42) by vapor inhalation on different aspects of executive functioning in the adult rat. In an operant set-shifting task, AIE-exposed rats exhibited deficits in their ability to shift their response strategy when the rules of the task changed, indicating reduced behavioral flexibility. There were no differences in progressive ratio response for the reinforcer suggesting that AIE did not alter reinforcer motivation. Examination of performance on the elevated plus maze under conditions designed to minimize stress revealed that AIE exposure enhanced the number of entries into the open arms, which may reflect either reduced anxiety and/or disinhibition of exploratory-like behavior. In rats that trained to self-administer ethanol in an operant paradigm, AIE increased resistance to extinction of ethanol-seeking behavior. This resistance to extinction was reversed by positive allosteric modulation of mGluR5 during extinction training, an effect that is thought to reflect promotion of extinction learning mechanisms within the medial PFC. Consistent with this, CDPPB was also observed to reverse the deficits in behavioral flexibility. Finally, diffusion tensor imaging with multivariate analysis of 32 brain areas revealed that while there were no differences in the total brain volume, the volume of

  2. The effects of acute L-carnitine administration on ventilatory breakpoint and exercise performanceduring incremental exercise

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    Mojtaba Kaviani

    2009-01-01

    Full Text Available (Received 31 October, 2009 ; Accepted 10 March, 2010AbstractBackground and purpose: Many athletes adopt nutritional manipulations to improve their performance. Among the substances generally consumed is carnitine (L-trimethyl-3-hydroxy-ammoniobutanoate which has been used by athletes as an ergogenic aid, due to its role in the transport of long-chain fatty acids across mitochondrial membranes. Nutritional supplements containing carbohydrates, proteins, vitamins, and minerals have been widely used in various sporting fields to provide a boost to the recommended daily allowance. The aim of this study is to investigate the effects of acute L-carnitine administration on ventilatory breakpoint, an exercise performance during incremental exercise.Materials and methods: This study was double-blind, randomized and crossover in design. The subjects were 12 randomly selected active male physical education students, 21.75±0.64 years old, with a mean body mass index (BMI of 23.7±0.94kg/m2, divided into 2 groups. They received orally either 2g of L-carnitine dissolved in 200 ml of water, plus 6 drops of lemon juice or a placebo (6 ml lemon juice dissolved in 200 ml of water 90 minutes before they began to exercise on a treadmill. They performed a modified protocol of Conconi test to exhaustion. One-way analysis of variance with repeated measurements was used for data analysis.Results: The results showed that exercise performance improved in LC group (2980±155 meter compared with placebo group (2331±51 meter. Furthermore, no significant difference was found in ventilatory breakpoint between the two groups.Conclusion: This finding indicates that administration of L- Carnitine, 90 minutes prior to exercise may improve performance; despite the ventilatory breakpoint as one of the anaerobic system indices that had no effect. J Mazand Univ Med Sci 2009; 19(73: 43-50 (Persian.

  3. Acute administration of benzodiazepines as part of treatment strategies for epilepsy.

    Science.gov (United States)

    Wolf, Peter

    2011-08-01

    Ad-hoc administration of benzodiazepines (BZD) is well established in status epilepticus, but intermittent BZD use in the treatment of chronic epilepsy is little known beyond catamenial epilepsy. We aim to assess the use of acute drug administration (ADA) in the treatment of 24 patients with epilepsy (9 idiopathic generalized, 14 focal symptomatic/cryptogenic, 1 migraine-epilepsy) receiving ADA for (1) prevention of generalized tonic-clonic seizures (GTCS) after minor seizures, (2) prevention of seizures at perceived risk, (3) prevention of seizure clusters. Standard ADA was 10 mg oral clobazam (CLB); one patient received 10 mg rectal diazepam. Concomitant antiepileptic drugs (AED) remained unchanged whenever possible. Ten patients used ADA always correctly, 7 mostly, 7 sporadically or not. Outcome considering seizure control was positive in 44% of all patients (59% of those who actually used ADA): 5 patients seizure free, 1 free of disabling seizures, 4 with >50% reduction in seizure frequency. Eleven had minor or no improvement, 3 patients could not be rated. Thirteen (of 19 possible) patients attempted prevention of seizures or clusters, 10 with full or >50% success (52.6 resp. 76.9%). Prevention of clusters sometimes required higher or repetitive CLB dosing. Self rating of patients who did use ADA was positive or very positive in 88.2%. Retention rate was 66.7% of all patients, and 88.2% of those using ADA. The best results were obtained in idiopathic generalized epilepsy (IGE) patients with seizures habitually triggered by typical factors (sleep deprival, alcohol) but also some others were successful. The only adverse effect was gait ataxia in a multiple-handicapped patient. ADA is an elegant and often successful but underused treatment option for selected patient groups where it can make the difference between becoming seizure free or not. Depending on the individual case it can be applied as monotherapy or in combination with a basis AED. A controlled

  4. Acute oral administration of low doses of methylphenidate targets calretinin neurons in the rat septal area.

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    Alvaro eGarcía-Aviles

    2015-03-01

    Full Text Available Methylphenidate (MPD is a commonly administered drug to treat children suffering from attention deficit hyperactivity disorder (ADHD. Alterations in septal driven hippocampal theta rhythm may underlie attention deficits observed in these patients. Amongst others, the septo-hippocampal connections have long been acknowledged to be important in preserving hippocampal function. Thus, we wanted to ascertain if methylphenidate administration, which improves attention in patients, could affect septal areas connecting with hippocampus. We used low and orally administered methylphenidate doses (1.3; 2.7 and 5mg/Kg to rats what mimics the dosage range in humans. In our model, we observed no effect when using 1.3mg/Kg methylphenidate; whereas 2.7 and 5 mg/Kg induced a significant increase in c-fos expression specifically in the medial septum, an area intimately connected to the hippocampus. We analyzed dopaminergic areas such as nucleus accumbens and striatum, and found that only 5mg/Kg induced c-fos levels increase. In these areas tyrosine hydroxylase correlated well with c-fos staining, whereas in the medial septum the sparse tyrosine hydroxylase fibres did not overlap with c-fos positive neurons. Double immunofluorescence of c-fos with neuronal markers in the septal area revealed that co-localization with choline acethyl transferase, parvalbumin, and calbindin with c-fos did not change with MPD treatment; whereas, calretinin and c-fos double labeled neurons increased after MPD administration. Altogether, these results suggest that low and acute doses of methylphenidate primary target specific populations of caltretinin medial septal neurons.

  5. Alpha and beta EEG power reflects L-dopa acute administration in parkinsonian patients

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    Jean-Marc eMelgari

    2014-11-01

    Full Text Available Aim. To evaluate the effect of an acute L-dopa administration on eye-closed resting state electroencephalographic (EEG activity of cognitively preserved Parkinsonian patients. Methods. We examined 24 right-handed patients diagnosed as uncomplicated probable Parkinson’s disease (PD. Each patient underwent UPDRS-part-III evaluation before and 60 minutes after an oral load of L-dopa-methyl-ester/carbidopa 250/25 mg. Resting condition eyes-closed EEG data were recorded both pre- and post L-dopa load. Absolute EEG power values were calculated at each scalp derivation for Delta, Theta, Alpha and Beta frequency bands. UPDRS scores (both global and subscale scores and EEG data (power values of different frequency bands for each scalp derivation were submitted to a statistical analysis to compare Pre e Post L-Dopa conditions. Finally, a correlation analysis was carried out between EEG spectral content and UPDRS scores. Results. Considering EEG power spectral analysis, no statistically significant differences arose on Delta and Theta bands after L-dopa intake. Conversely, Alpha and Beta rhythms significantly increased on centro-parietal scalp derivations, as a function of L-dopa administration. Correlation analysis indicated a significant negative correlation between Beta power increase on centro-parietal areas and UPDRS subscores (Rigidity of arms and Bradykinesia. A minor significant negative correlation was also found between Alpha band increase and resting tremor. Conclusions. Assuming that a significant change in EEG power spectrum after L-dopa intake may be related to dopaminergic mechanisms, our findings are consistent with the hypothesis that dopaminergic defective networks are implicated in cortical oscillatory abnormalities at rest in non-demented PD patients.

  6. Effects of acute cortisol administration on perceptual priming of trauma-related material.

    Science.gov (United States)

    Holz, Elena; Lass-Hennemann, Johanna; Streb, Markus; Pfaltz, Monique; Michael, Tanja

    2014-01-01

    Intrusive memories are a hallmark symptom of posttraumatic stress disorder (PTSD). They reflect excessive and uncontrolled retrieval of the traumatic memory. Acute elevations of cortisol are known to impair the retrieval of already stored memory information. Thus, continuous cortisol administration might help in reducing intrusive memories in PTSD. Strong perceptual priming for neutral stimuli associated with a "traumatic" context has been shown to be one important learning mechanism that leads to intrusive memories. However, the memory modulating effects of cortisol have only been shown for explicit declarative memory processes. Thus, in our double blind, placebo controlled study we aimed to investigate whether cortisol influences perceptual priming of neutral stimuli that appeared in a "traumatic" context. Two groups of healthy volunteers (N = 160) watched either neutral or "traumatic" picture stories on a computer screen. Neutral objects were presented in between the pictures. Memory for these neutral objects was tested after 24 hours with a perceptual priming task and an explicit memory task. Prior to memory testing half of the participants in each group received 25 mg of cortisol, the other half received placebo. In the placebo group participants in the "traumatic" stories condition showed more perceptual priming for the neutral objects than participants in the neutral stories condition, indicating a strong perceptual priming effect for neutral stimuli presented in a "traumatic" context. In the cortisol group this effect was not present: Participants in the neutral stories and participants in the "traumatic" stories condition in the cortisol group showed comparable priming effects for the neutral objects. Our findings show that cortisol inhibits perceptual priming for neutral stimuli that appeared in a "traumatic" context. These findings indicate that cortisol influences PTSD-relevant memory processes and thus further support the idea that administration

  7. Effects of acute cortisol administration on perceptual priming of trauma-related material.

    Directory of Open Access Journals (Sweden)

    Elena Holz

    Full Text Available Intrusive memories are a hallmark symptom of posttraumatic stress disorder (PTSD. They reflect excessive and uncontrolled retrieval of the traumatic memory. Acute elevations of cortisol are known to impair the retrieval of already stored memory information. Thus, continuous cortisol administration might help in reducing intrusive memories in PTSD. Strong perceptual priming for neutral stimuli associated with a "traumatic" context has been shown to be one important learning mechanism that leads to intrusive memories. However, the memory modulating effects of cortisol have only been shown for explicit declarative memory processes. Thus, in our double blind, placebo controlled study we aimed to investigate whether cortisol influences perceptual priming of neutral stimuli that appeared in a "traumatic" context. Two groups of healthy volunteers (N = 160 watched either neutral or "traumatic" picture stories on a computer screen. Neutral objects were presented in between the pictures. Memory for these neutral objects was tested after 24 hours with a perceptual priming task and an explicit memory task. Prior to memory testing half of the participants in each group received 25 mg of cortisol, the other half received placebo. In the placebo group participants in the "traumatic" stories condition showed more perceptual priming for the neutral objects than participants in the neutral stories condition, indicating a strong perceptual priming effect for neutral stimuli presented in a "traumatic" context. In the cortisol group this effect was not present: Participants in the neutral stories and participants in the "traumatic" stories condition in the cortisol group showed comparable priming effects for the neutral objects. Our findings show that cortisol inhibits perceptual priming for neutral stimuli that appeared in a "traumatic" context. These findings indicate that cortisol influences PTSD-relevant memory processes and thus further support the idea

  8. Effects of acute and 2-week administration of oral salbutamol on exercise performance and muscle strength in athletes

    DEFF Research Database (Denmark)

    Hostrup, Morten; Kalsen, Anders; Auchenberg, Michael

    2016-01-01

    included in a randomized, double-blinded and placebo-controlled parallel study. At baseline, after acute administration, and again after 2-week administration of the study drugs (8 mg salbutamol or placebo), subjects' maximal voluntary contraction (MVC) of m. quadriceps and isometric endurance of m.......05) peak power during first and second Wingate test by 6.4 ± 2.0 and 4.2 ± 1.0%. Neither acute nor 2-week administration of salbutamol had any effect on MVC, exercise performance at 110% of VO2max or on isometric endurance. No differences were observed in the placebo group. In conclusion, salbutamol...

  9. Antibiotic treatment for acute haematogenous osteomyelitis of childhood: moving towards shorter courses and oral administration.

    Science.gov (United States)

    Pääkkönen, M; Peltola, H

    2011-10-01

    Acute haematogenous osteomyelitis (AHOM) of childhood usually affects the long bones of the lower limbs. Although almost any agent may cause AHOM, Staphylococcus aureus is the most common bacterium, followed by Streptococcus pneumoniae and, in some countries, Salmonella spp. and Kingella kingae. Magnetic resonance imaging (MRI) has improved the diagnostic accuracy of traditional radiography and scintigraphy. Except for the pre-treatment diagnostic sample from bone before the institution of antibiotic therapy, no other surgery is usually required. Traditionally, non-neonatal AHOM has been treated with a 1-3-month course of antibiotics, including an intravenous (i.v.) phase for the first weeks, but recent prospective randomised studies challenge this approach. For most uncomplicated cases, a course of 20 days including an i.v. period of 2-4 days suffices, provided large enough doses of a well-absorbed agent (clindamycin or a first-generation cephalosporin, local resistance permitting) are used, administration is four times daily and most symptoms and signs subside within a few days. Serum C-reactive protein (CRP) is a good guide in monitoring the course of illness, and the antimicrobial can usually be discontinued if CRP has decreased to <20 mg/L. Newer and costly agents, such as linezolid, should be reserved for cases due to resistant S. aureus strains. AHOM in neonates and immunocompromised patients probably requires a different approach. Because sequelae may develop slowly, follow-up for at least 1 year post hospitalisation is recommended.

  10. Acute toxicity, histopathology, and coagulopathy in American kestrels (Falco sparverius) following administration of the rodenticie diphacinone

    Science.gov (United States)

    Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Day, Daniel D.; Meteyer, Carol U.; Voler, Steven F.; Eisemann, John D.; Johnston, John J.

    2011-01-01

    The acute oral toxicity of the anticoagulant rodenticide diphacinone was found to be over 20 times greater in American kestrels (Falco sparverius; median lethal dose 96.8 mg/kg body weight) compared with Northern bobwhite (Colinus virginianus) and mallards (Anas platyrhynchos). Modest evidence of internal bleeding was observed at necropsy, although histological examination of heart, liver, kidney, lung, intestine, and skeletal muscle revealed hemorrhage over a wide range of doses (35.1-675 mg/kg). Residue analysis suggests that the half-life of diphacinone in the liver of kestrels that survived was relatively short, with the majority of the dose cleared within 7 d of exposure. Several precise and sensitive clotting assays (prothrombin time, Russell's viper venom time, thrombin clotting time) were adapted for use in this species, and oral administration of diphacinone at 50 mg/kg increased prothrombin time and Russell?s viper venom time at 48 and 96 h postdose compared with controls. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and generally corresponded with the onset of overt signs of toxicity and lethality. In view of the toxicity and risk evaluation data derived from American kestrels, the involvement of diphacinone in some raptor mortality events, and the paucity of threshold effects data following short-term dietary exposure for birds of prey, additional feeding trials with captive raptors are warranted to characterize more fully the risk of secondary poisoning.

  11. Bidirectional Tachycardia after an Acute Intravenous Administration of Digitalis for a Suicidal Gesture

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    Diletta Sabatini

    2014-01-01

    Full Text Available Acute digoxin intoxication is a life-threating condition associated with severe cardiotoxicity. Female gender, age, low lean body mass, hypertension, and renal insufficiency may worsen the prognosis. Arrhythmias caused by digitalis glycosides are characterized by an increased automaticity coupled with concomitant conduction delay. Bidirectional tachycardia is pathognomonic of digoxin intoxication, but it is rarely observed. An 83-year-old woman was admitted to the Emergency Department after self-administration of 5 mg of digoxin i.v. for suicidal purpose. Her digoxin serum concentration was 17.4 ng/mL. The patient developed a bidirectional tachycardia and the Poison Control Center of the hospital provided digoxin immune fab. Bidirectional tachycardia quickly reversed and the patient remained stable throughout the hospital stay. This case shows that a multiple disciplinary approach, involving cardiologists and toxicologists, is essential for the management of digoxin intoxication. The optimal treatment of this rare event depends on the clinical conditions and on the serum drug concentration of the patient. Digoxin immune fab represents a safe, effective, and specific method for rapidly reversing digitalis cardiotoxicity and should be started as soon as the diagnosis is defined.

  12. Effects of acute and chronic administration of venlafaxine and desipramine on extracellular monoamine levels in the mouse prefrontal cortex and striatum.

    Science.gov (United States)

    Higashino, Kosuke; Ago, Yukio; Umehara, Masato; Kita, Yuki; Fujita, Kazumi; Takuma, Kazuhiro; Matsuda, Toshio

    2014-04-15

    Prefrontal catecholamine neurotransmission plays a key role in the therapeutic actions of drugs for attention-deficit/hyperactivity disorder (ADHD). We have recently shown that serotonin/noradrenaline reuptake inhibitors and the noradrenaline reuptake inhibitor desipramine attenuated horizontal hyperactivity in spontaneously hypertensive rats, an animal model of ADHD, and that these drugs are potential pharmacotherapeutics for ADHD. In this study, we used in vivo microdialysis to study the effects of acute and chronic (once daily for 3 weeks) administration of the serotonin/noradrenaline reuptake inhibitor venlafaxine and the noradrenaline reuptake inhibitor desipramine on noradrenaline, dopamine, and serotonin levels, and the expression of the neuronal activity marker c-Fos in the mouse prefrontal cortex and striatum. Both acute and chronic venlafaxine administration increased prefrontal noradrenaline, dopamine, and serotonin levels and striatal noradrenaline and serotonin levels. Both acute and chronic desipramine administration increased prefrontal noradrenaline and dopamine levels and striatal noradrenaline levels, with chronic administration yielding stronger increase. Chronic desipramine did not affect striatal dopamine and serotonin levels. Both acute and chronic venlafaxine administration increased the expression of c-Fos in the prefrontal cortex, whereas chronic, but not acute, desipramine administration increased the expression of c-Fos in the prefrontal cortex. Both acute and chronic venlafaxine administration increased the striatal c-Fos expression to some degree, whereas desipramine administration did not. These results suggest that acute and chronic venlafaxine and chronic desipramine administration maximally activate the prefrontal adrenergic and dopaminergic systems without affecting striatal dopaminergic systems in mice.

  13. Acute Toxicity and Gastroprotective Role of M. pruriens in Ethanol-Induced Gastric Mucosal Injuries in Rats

    Science.gov (United States)

    Hassandarvish, Pouya; Abdul Majid, Nazia; Hadi, A. Hamid A.; Nordin, Noraziah; Abdulla, Mahmood A.

    2013-01-01

    The investigation was to evaluate gastroprotective effects of ethanolic extract of M. pruriens leaves on ethanol-induced gastric mucosal injuries in rats. Forty-eight rats were divided into 8 groups: negative control, extract control, ulcer control, reference control, and four experimental groups. As a pretreatment, the negative control and the ulcer control groups were orally administered carboxymethylcellulose (CMC). The reference control was administered omeprazole orally (20 mg/kg). The ethanolic extract of M. pruriens leaves was given orally to the extract control group (500 mg/kg) and the experimental groups (62.5, 125, 250, and 500 mg/kg). After 1 h, CMC was given orally to the negative and the extract control groups. The other groups received absolute ethanol. The rats were sacrificed after 1 h. The ulcer control group exhibited significant mucosal injuries with decreased gastric wall mucus and severe damage to the gastric mucosa. The extract caused upregulation of Hsp70 protein, downregulation of Bax protein, and intense periodic acid schiff uptake of glandular portion of stomach. Gastric mucosal homogenate showed significant antioxidant properties with increase in synthesis of PGE2, while MDA was significantly decreased. The ethanolic extract of M. pruriens leaves was nontoxic (<5 g/kg) and could enhance defensive mechanisms against hemorrhagic mucosal lesions. PMID:23781513

  14. Acute Toxicity and Gastroprotective Role of M. pruriens in Ethanol-Induced Gastric Mucosal Injuries in Rats

    Directory of Open Access Journals (Sweden)

    Shahram Golbabapour

    2013-01-01

    Full Text Available The investigation was to evaluate gastroprotective effects of ethanolic extract of M. pruriens leaves on ethanol-induced gastric mucosal injuries in rats. Forty-eight rats were divided into 8 groups: negative control, extract control, ulcer control, reference control, and four experimental groups. As a pretreatment, the negative control and the ulcer control groups were orally administered carboxymethylcellulose (CMC. The reference control was administered omeprazole orally (20 mg/kg. The ethanolic extract of M. pruriens leaves was given orally to the extract control group (500 mg/kg and the experimental groups (62.5, 125, 250, and 500 mg/kg. After 1 h, CMC was given orally to the negative and the extract control groups. The other groups received absolute ethanol. The rats were sacrificed after 1 h. The ulcer control group exhibited significant mucosal injuries with decreased gastric wall mucus and severe damage to the gastric mucosa. The extract caused upregulation of Hsp70 protein, downregulation of Bax protein, and intense periodic acid schiff uptake of glandular portion of stomach. Gastric mucosal homogenate showed significant antioxidant properties with increase in synthesis of PGE2, while MDA was significantly decreased. The ethanolic extract of M. pruriens leaves was nontoxic (<5 g/kg and could enhance defensive mechanisms against hemorrhagic mucosal lesions.

  15. Oral administration of lactulose: a novel therapy for acute carbon monoxide poisoning via increasing intestinal hydrogen production.

    Science.gov (United States)

    Fan, Dan-Feng; Hu, Hui-Jun; Sun, Xue-Jun; Meng, Xiang-En; Zhang, Yu; Pan, Shu-Yi

    2016-01-01

    It has been known that the pathophysiology of carbon monoxide (CO) poisoning is related to hypoxia, the increased production of reactive oxygen species (ROS) and oxidative stress. Studies have shown that the novel, safe and effective free radical scavenger, hydrogen, has neuroprotective effects in both acute CO poisoning and delayed neuropsychological sequelae in CO poisoning. Orally administered lactulose, which may be used by some intestinal bacteria as a food source to produce endogenous hydrogen, can ameliorate oxidative stress. Based on the available findings, we hypothesize that oral administration of lactulose may be a novel therapy for acute CO poisoning via increasing intestinal hydrogen production.

  16. Effect of acute administration of L-tyrosine on oxidative stress parameters in brain of young rats.

    Science.gov (United States)

    Macêdo, Livia G R P; Carvalho-Silva, Milena; Ferreira, Gabriela K; Vieira, Júlia S; Olegário, Natália; Gonçalves, Renata C; Vuolo, Francieli S; Ferreira, Gustavo C; Schuck, Patrícia F; Dal-Pizzol, Felipe; Streck, Emilio L

    2013-12-01

    Tyrosinemia type II, also known as Richner-Hanhart syndrome, is an autosomal recessive inborn error of metabolism caused by a deficiency of hepatic cytosolic tyrosine aminotransferase, and is associated with neurologic and development difficulties in numerous patients. Considering that the mechanisms underlying the neurological dysfunction in hypertyrosinemic patients are poorly known and that studies demonstrated that high concentrations of tyrosine provoke oxidative stress in vitro and in vivo in the cerebral cortex of rats, in the present study we investigate the oxidative stress parameters (enzymatic antioxidant defenses, thiobarbituric acid-reactive substances and protein carbonyl content) in cerebellum, hippocampus and striatum of 30-old-day rats after acute administration of L-tyrosine. Our results demonstrated that the acute administration of L-tyrosine increased the thiobarbituric acid reactive species levels in hippocampus and the carbonyl levels in cerebellum, hippocampus and striatum. In addition, acute administration of L-tyrosine significantly decreased superoxide dismutase activity in cerebellum, hippocampus and striatum, while catalase was increased in striatum. In conclusion, the oxidative stress may contribute, along with other mechanisms, to the neurological dysfunction characteristic of hypertyrosinemia and the administration of antioxidants may be considered as a potential adjuvant therapy for tyrosinemia, especially type II.

  17. Effects of acute and 2-week administration of oral salbutamol on exercise performance and muscle strength in athletes.

    Science.gov (United States)

    Hostrup, M; Kalsen, A; Auchenberg, M; Bangsbo, J; Backer, V

    2016-01-01

    Our objective was to investigate effects of acute and 2-week administration of oral salbutamol on repeated sprint ability, exercise performance, and muscle strength in elite endurance athletes. Twenty male elite athletes [VO2max: 69.4 ± 1.8 (Mean ± SE) mL/min/kg], aged 25.9 ± 1.4 years, were included in a randomized, double-blinded and placebo-controlled parallel study. At baseline, after acute administration, and again after 2-week administration of the study drugs (8 mg salbutamol or placebo), subjects' maximal voluntary contraction (MVC) of m. quadriceps and isometric endurance of m. deltoideus were measured, followed by three repeated Wingate tests. Exercise performance at 110% of VO2max was determined on a bike ergometer. Acute administration of salbutamol increased peak power during first Wingate test by 4.1 ± 1.7% (P salbutamol increased (P salbutamol had any effect on MVC, exercise performance at 110% of VO2max or on isometric endurance. No differences were observed in the placebo group. In conclusion, salbutamol benefits athletes' sprint ability. Thus, the present study supports the restriction of oral salbutamol in competitive sports.

  18. Acute administration of high dose trimetazidine inhibits pentylenetetrazol-induced seizures in rats

    Directory of Open Access Journals (Sweden)

    Serkan GURGUL

    2017-03-01

    Full Text Available Objective: Resistant epilepsy is widely seen in clinical settings manipulate the researchers to pursuit novel anti-epileptic treatments. Although trimetazidine (TMZ is commonly used in the treatment of angina and ischemic diseases, it is considered that the drug may be beneficial in the treatment of epileptic seizures and convulsions. We aimed to evaluate electrophysiologically the protective effects of high dose acute TMZ on epileptic seizures and convulsions in a rat model of epilepsy induced by pentilentetrazol (PTZ. Method: Forty-eight male Sprague-Dawley rats were used for the EEG evaluation (Group-A; n=24 and behavioral assessment (Group-B; n=24. Grup-A1 and Grup-B1 were determined as control group and given no medication. 35 mg/kg (Group-A2, -A3 and -A4 and 70 mg/kg (Group-B2, -B3 and -B4 of PTZ were administered intraperitoneally (ip. so as to generate seizures and convulsions. Group-A2 and Group-B2 were treated with saline. 40 mg/kg (Grup-A3 and Grup-B3 and 80 mg/kg of TMZ (Group-A4 and Group-B4 were administered to the treatment groups by ip. Brain malondialdehyde (MDA levels, spike-percentage values, Racine’s Convulsion Scale (RCS scores and "first myoclonic jerk (FMJ" latencies of each rat were determined. Results: Brain MDA levels, spike-percentage values, RCS scores, and FMJ latencies of Group-A2 and Group-B2 were significantly increased compared to those of the control’s (Grup-A1 and Grup-B1 (P<0.05 for all comparisons. However, in TMZ treated groups (Group-A3 and -A4; Group-B3 and -B4 the elevated values of these parameters were found to be significantly decreased (P<0.05 for all comparisons. Conclusions: This study has demonstrated that the high dose acute TMZ administration may prevent PTZ-induced seizures and convulsions in rats. Furthermore, it can be also said that TMZ has a neuroprotective effects on oxidative stress associated with PTZ. Therefore, it may be considered for use with therapeutic purposes of TMZ in

  19. Acute cadmium administration to rats exerts both immunosuppressive and proinflammatory effects in spleen.

    Science.gov (United States)

    Demenesku, Jelena; Mirkov, Ivana; Ninkov, Marina; Popov Aleksandrov, Aleksandra; Zolotarevski, Lidija; Kataranovski, Dragan; Kataranovski, Milena

    2014-12-04

    Conflicting data (both suppression and augmentation as well as lack of the effect) exist in respect to cadmium (Cd) and splenic T cell-based immune cell activity. Spleen is also the site of innate immune responses but impact of Cd on this type of immunity has been less explored. In the present study the effects of acute Cd administration on basic aspects of both T cell-based and innate immune spleen cell activity were examined in rats. Intraperitoneal injection of 1mg of Cd/kg resulted in decrease in concanavalin A (ConA) induced proliferation which seems to be more related to altered spleen cells responsiveness to IL-2 than to apoptosis. Differential effects on proinflammatory T cell derived cytokines were observed (decreases of IFN-γ gene expression and ConA-stimulated production, but increases in IL-17 mRNA levels with no effect on concentrations of protein product). Reduction of IFN-γ production seemed not to rely on IL-4 and IL-10, but at least partly on nitric oxide (NO). Increased activity relevant for innate immunity (granulocyte and CD11b(+) cell accumulation in the spleen, inducible nitric oxide synthase/iNOS expression and NO production by spleen cells) was observed, but there was a decrease in respiratory burst (dihydrorhodamine/DHR oxidation and nitroblue tetrazolium/NBT reduction). Increases of TNF-α and IL-1β gene expression and IL-1β protein product were noted as well. Administration of 0.5mg Cd/kg resulted in less pronounced (ConA-induced proliferation) or lack of the effect (IFN-γ production) on spleen T cell activities and on innate activities (granulocyte accumulation, NO production) as well. However, increases of spleen cell respiratory burst activity and IL-1β production were observed. Effects of lower cadmium doses (5ppm and 50ppm) on several aspects of spleen cell immune activity were observed in intermediate period of exposure (30 days, oral intake) as well. Differential effects of Cd on immune activities of spleen cells might

  20. Anti-Ulcerogenic Properties of Lycium chinense Mill Extracts against Ethanol-Induced Acute Gastric Lesion in Animal Models and Its Active Constituents

    Directory of Open Access Journals (Sweden)

    Opeyemi J. Olatunji

    2015-12-01

    Full Text Available The objective of this study was to explore the gastroprotective properties of the aerial part of Lycium chinense Mill (LCA against ethanol-induced gastric mucosa lesions in mice models. Administration of LCA at doses of 50, 100, 200 and 400 mg/kg body weight prior to ethanol consumption dose dependently inhibited gastric ulcers. The gastric mucosal injury was analyzed by gastric juice acidity, glutathione (GSH, superoxide dismutase (SOD, malondialdehyde (MDA, myeloperoxidase (MPO activities. Furthermore, the levels of the inflammatory mediators, tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6 and interleukin-1β (IL-1β in serum were also analyzed using ELISA. Pathological changes were also observed with the aid of hematoxylin-eosin (HE staining. Our results indicated that LCA significantly reduced the levels of MPO, MDA and increased SOD and GSH activities. Furthermore, LCA also significantly inhibited the levels of TNF-α, IL-6, and IL-1β in the serum of ulcerated mice in a dose dependent manner. Immunohistological analysis indicated that LCA also significantly attenuated the overexpression of nuclear factor-κB in pretreated mice models. This findings suggests Lycium chinense Mill possesses gastroprotective properties against ethanol-induced gastric injury and could be a possible therapeutic intervention in the treatment and management of gastric ulcers.

  1. An example of US Food and Drug Administration device regulation: medical devices indicated for use in acute ischemic stroke.

    Science.gov (United States)

    Peña, Carlos; Li, Khan; Felten, Richard; Ogden, Neil; Melkerson, Mark

    2007-06-01

    The Food and Drug Administration has established requirements for protecting the public health by assuring the safety and effectiveness of a variety of medical products including drugs, devices, and biological products, and for promoting public health by expediting the approval of treatments that are safe and effective. The Center for Devices and Radiological Health is the center within the agency that is responsible for pre- and postmarket regulation of medical devices. In this article, we review current regulation of medical devices, research and development programs, pre- and postmarket perspectives, and future considerations of medical devices, particularly as they relate to devices targeting acute ischemic stroke as an example of the process. We also review the Center for Devices and Radiological Health's historical perspective of acute ischemic stroke trials and clinical trial design considerations used in prior studies that have led to US market clearance as they are related to currently marketed devices indicated for acute ischemic stroke.

  2. Noribogaine, but not 18-MC, exhibits similar actions as ibogaine on GDNF expression and ethanol self-administration.

    OpenAIRE

    2010-01-01

    Carnicella S present adress: Grenoble Institut des Neurosciences, Inserm U836; International audience; Ibogaine is a naturally occurring alkaloid that has been reported to decrease various adverse phenotypes associated with exposure to drugs of abuse and alcohol in human and rodent models. Unfortunately, ibogaine cannot be used as a medication to treat addiction because of severe side effects. Previously, we reported that the desirable actions of ibogaine to reduce self-administration of, and...

  3. Evaluation of Acute and Sub-chronic Toxicities of Aqueous Ethanol Root Extract of Raphia hookeri Palmaceae on Swiss Albino Rats

    Directory of Open Access Journals (Sweden)

    G.O. Mbaka

    2014-08-01

    Full Text Available This study evaluated the acute and sub-chronic toxicities of treatment with aqueous ethanol root extract of Raphia hookri (Palmaceae on rats. In acute toxicity study, the root extract in a graded doses of 125-2000 mg/kg bwt administered Intra-Peritoneal (IP produced dose dependent mortality with median acute toxicity (LD50 of approximately 562.3 mg/kg bwt. The animals fed with the extract by gavages tolerated up to 4000 mg/kg body weight (bwt with no sign of physical/behavioural changes hence 1/20th of the dose (200 mg/kg was used as the highest therapeutic dose. In sub-chronic toxicity study, significant increase (p0.05 decrease in Red Blood Cell (RBC count and haemoglobin (Hb level while White Blood Cell (WBC showed increase. In tissue analysis, the extract caused marked deleterious effect on the testes leading to drastic reduction in sperm cells whereas tissues of liver, kidney and heart however showed normal appearance.

  4. Turning Rate Dynamics of Zebrafish Exposed to Ethanol

    Science.gov (United States)

    Mwaffo, Violet; Porfiri, Maurizio

    2015-06-01

    Zebrafish is emerging as a species of choice in alcohol-related pharmacological studies. In these studies, zebrafish are often exposed to acute ethanol treatments and their activity scored during behavioral assays. Computational modeling of zebrafish behavior is expected to positively impact these efforts by offering a predictive toolbox to plan hypothesis-driven studies, reduce the number of subjects, perform pilot trials, and refine behavioral screening. In this work, we demonstrate the use of the recently proposed jump persistent turning walker to model the turning rate dynamics of zebrafish exposed to acute ethanol administration. This modeling framework is based on a stochastic mean reverting jump process to capture the sudden and large changes in orientation of swimming zebrafish. The model is calibrated on an available experimental dataset of 40 subjects, tested at different ethanol concentrations. We demonstrate that model parameters are modulated by ethanol administration, whereby both the relaxation rate and jump frequency of the turning rate dynamics are influenced by ethanol concentration. This effort offers a first evidence for the possibility of complementing zebrafish pharmacological research with computational modeling of animal behavior.

  5. Noribogaine, but not 18-MC, exhibits similar actions as ibogaine on GDNF expression and ethanol self-administration.

    Science.gov (United States)

    Carnicella, Sebastien; He, Dao-Yao; Yowell, Quinn V; Glick, Stanley D; Ron, Dorit

    2010-10-01

    Ibogaine is a naturally occurring alkaloid that has been reported to decrease various adverse phenotypes associated with exposure to drugs of abuse and alcohol in human and rodent models. Unfortunately, ibogaine cannot be used as a medication to treat addiction because of severe side effects. Previously, we reported that the desirable actions of ibogaine to reduce self-administration of, and relapse to, alcohol consumption are mediated via the upregulation of the expression of the glial cell line-derived neurotrophic factor (GDNF) in the midbrain ventral tegmental area (VTA), and the consequent activation of the GDNF pathway. The ibogaine metabolite, noribogaine, and a synthetic derivative of ibogaine, 18-Methoxycoronaridine (18-MC), possess a similar anti-addictive profile as ibogaine in rodent models, but without some of its adverse side effects. Here, we determined whether noribogaine and/or 18-MC, like ibogaine, increase GDNF expression, and whether their site of action to reduce alcohol consumption is the VTA. We used SH-SY5Y cells as a cell culture model and found that noribogaine, like ibogaine, but not 18-MC, induces a robust increase in GDNF mRNA levels. Next, we tested the effect of intra-VTA infusion of noribogaine and 18-MC on rat operant alcohol self-administration and found that noribogaine, but not 18-MC, in the VTA decreases responding for alcohol. Together, our results suggest that noribogaine and 18-MC have different mechanisms and sites of action.

  6. Opposite effects of acute ethanol exposure on GAP-43 and BDNF expression in the hippocampus versus the cerebellum of juvenile rats.

    Science.gov (United States)

    Kulkarny, V V; Wiest, N E; Marquez, C P; Nixon, S C; Valenzuela, C F; Perrone-Bizzozero, N I

    2011-08-01

    The adolescent brain is particularly vulnerable to the effects of alcohol, with intoxications at this developmental age often producing long-lasting effects. The present study addresses the effects of a single acute ethanol exposure on growth-associated protein-43 (GAP-43) and brain-derived neurotrophic factor (BDNF) gene expression in neurons in the cerebellum and hippocampus of adolescent rats. Male postnatal day 23 (P23) Sprague-Dawley rats were exposed to ethanol vapors for 2h and after a recovery period of 2h, the cerebellum and hippocampus were harvested and samples were taken for blood alcohol concentration (BAC) determinations. We found that this exposure resulted in a mean BAC of 174 mg/dL, which resembles levels in human adolescents after binge drinking. Analyses of total RNA and protein by quantitative reverse transcription PCR and western blotting, respectively, revealed that this single ethanol exposure significantly decreased the levels of GAP-43 mRNA and protein in the cerebellum but increased the levels of mRNA and protein in the hippocampus. BDNF mRNA and protein levels were also increased in the hippocampus but not in the cerebellum of these animals. In situ hybridizations revealed that GAP-43 and BDNF mRNA levels were primarily increased by alcohol exposure in hippocampal dentate granule cells and CA3 neurons. Overall, the reported alterations in the expression of the plasticity-associated genes GAP-43 and BDNF in juvenile rats are consistent with the known deleterious effects of binge drinking on motor coordination and cognitive function.

  7. The acute effects of MDMA and ethanol administration on electrophysiological correlates of performance monitoring in healthy volunteers

    NARCIS (Netherlands)

    Spronk, D.B.; Dumont, G.J.H.; Verkes, R.J.; Bruijn, E.R. de

    2014-01-01

    RATIONALE: Knowing how commonly used drugs affect performance monitoring is of great importance, because drug use is often associated with compromised behavioral control. Two of the most commonly used recreational drugs in the western world, 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") and

  8. Suppressive effect of astaxanthin isolated from the Xanthophyllomyces dendrorhous mutant on ethanol-induced gastric mucosal injury in rats.

    Science.gov (United States)

    Kim, Jeong-Hwan; Choi, Seok-Keun; Choi, Sang-Yun; Kim, Han-Kyeom; Chang, Hyo-Ihl

    2005-07-01

    Ethanol has been found to induce ulcerative gastric lesion in humans. The present study investigated the in vivo protective effect of astaxanthin isolated from the Xanthophyllomyces dendrorhous mutant against ethanol-induced gastric mucosal injury in rats. The rats were treated with 80% ethanol for 3 d after pretreatment with two doses of astaxanthin (5 and 25 mg/kg of body weight respectively) for 3 d, while the control rats received only 80% ethanol for 3 d. The oral administration of astaxanthin (5 and 25 mg/kg of body weight) showed significant protection against ethanol-induced gastric lesion and inhibited elevation of the lipid peroxide level in gastric mucosa. In addition, pretreatment with astaxanthin resulted in a significant increase in the activities of radical scavenging enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. A histologic examination clearly indicated that the acute gastric mucosal lesion induced by ethanol nearly disappeared after pretreatment with astaxanthin.

  9. Acute Carnosine Administration Increases Respiratory Chain Complexes and Citric Acid Cycle Enzyme Activities in Cerebral Cortex of Young Rats.

    Science.gov (United States)

    Macedo, Levy W; Cararo, José H; Maravai, Soliany G; Gonçalves, Cinara L; Oliveira, Giovanna M T; Kist, Luiza W; Guerra Martinez, Camila; Kurtenbach, Eleonora; Bogo, Maurício R; Hipkiss, Alan R; Streck, Emilio L; Schuck, Patrícia F; Ferreira, Gustavo C

    2016-10-01

    Carnosine (β-alanyl-L-histidine) is an imidazole dipeptide synthesized in excitable tissues of many animals, whose biochemical properties include carbonyl scavenger, anti-oxidant, bivalent metal ion chelator, proton buffer, and immunomodulating agent, although its precise physiological role(s) in skeletal muscle and brain tissues in vivo remain unclear. The aim of the present study was to investigate the in vivo effects of acute carnosine administration on various aspects of brain bioenergetics of young Wistar rats. The activity of mitochondrial enzymes in cerebral cortex was assessed using a spectrophotometer, and it was found that there was an increase in the activities of complexes I-III and II-III and succinate dehydrogenase in carnosine-treated rats, as compared to vehicle-treated animals. However, quantitative real-time RT-PCR (RT-qPCR) data on mRNA levels of mitochondrial biogenesis-related proteins (nuclear respiratory factor 1 (Nrf1), peroxisome proliferator-activated receptor-γ coactivator 1-α (Ppargc1α), and mitochondrial transcription factor A (Tfam)) were not altered significantly and therefore suggest that short-term carnosine administration does not affect mitochondrial biogenesis. It was in agreement with the finding that immunocontent of respiratory chain complexes was not altered in animals receiving carnosine. These observations indicate that acute carnosine administration increases the respiratory chain and citric acid cycle enzyme activities in cerebral cortex of young rats, substantiating, at least in part, a neuroprotector effect assigned to carnosine against oxidative-driven disorders.

  10. Acute Morphine Administration Reduces Cell-Mediated Immunity and Induces Reactivation of Latent Herpes Simplex Virus Type 1 in BALB/c Mice

    Institute of Scientific and Technical Information of China (English)

    Shafi Mojadadi; Abbas Jamali; Behzad Khansarinejad; Hoorieh Soleimanjahi; Taravat Bamdad

    2009-01-01

    Acute morphine administration is known to alter the course of herpes simplex virus infection. In this study, the effect of acute morphine administration on the reactivation of latent herpes was investigated in a mouse model. Because of the important role of cytolytic T lymphocyte (CTL) activity in the inhibition of herpes simplex virus type 1 (HSV-1) reactivation, the effect of acute morphine administration on CTL responses was also evaluated. Furthermore, lymphocyte proliferation and IFN-γ production were evaluated for their roles in the induction of the CTL response. The findings showed that acute morphine administration significantly reduced CTL responses, lymphocyte proliferation, and IFN-γ production. Furthermore, acute morphine administration has been shown to reactivate latent HSV-1. Previous studies have shown that cellular immune responses have important roles in the inhibition of HSV reactivation. These findings suggest that suppression of a portion of the cellular immune response after acute morphine administration may constitute one part of the mechanism that induces HSV reactivation. Cellular & Molecular Immunology.

  11. Induction of Heat Shock Protein 72 in RGCs of Rat Acute Glaucoma Model after Heat Stress or Zinc Administration

    Institute of Scientific and Technical Information of China (English)

    Guoping Qing; Xuanchu Duan; Youqin Jiang

    2004-01-01

    Purpose :To investigate the dynamics of heat shock protein 72 (HSP72) expression in retinal ganglion cells (RGCs) in rat model of acute glaucoma treated with heat stress or intraperitoneal injection of zinc sulfate.Methods: Twenty-seven male Wistar rats were used to make acute glaucoma models. Five others served as normal control. Acute glaucoma models were made by intracameral irrigation in the right eyes with balanced salt saline (BSS) at 102 mmHg for 2 hours. Nine model rats were killed at different intervals after intracameral irrigation without treatment, which served as damage control. Ten were treated with heat stress 40℃~42℃, and 8 were used for zinc sulfate administration 2 days posterior to intracameral irrigation.Treated model rats were sacrificed at designed intervals after treatment. Right eyes were enucleated immediately, and the retinas were dissected for Western blot.Results: No HSP72 was found in RGCs of normal Wistar rats. In damage control group,slight HSP72 was detected during 6~36 hours posterior to intracameral irrigation. HSP72was detected significantly expressed in RGCs of both heat shock group and zinc sulfate group. But the dynamics of HSP72 production were quite different in these two treated groups. In heat shock group, HSP72 appeared at the sixth hour after treatment, and increased gradually until its peak production emerged at the 48th hour. HSP72 vanished 8days later after treatment. In zinc sulfate group, HSP72 expression began 24 hours later after zinc administration, and reached its highest level at the 72th hour posterior to treatment. HSP72 expression then decreased slowly, and disappeared 21 days later after treatment.Conclusion:HSP72 can be induced in RGCs of rat acute glaucoma models with heat stress or zinc sulfate adddministration. But the dynamics of the HSP72 induction in those two groups were quite different. Eye Science 2004;20:30-33.

  12. Nanostructured lipid carriers-based flurbiprofen gel after topical administration: acute skin irritation, pharmacodynamics, and percutaneous absorption mechanism.

    Science.gov (United States)

    Song, Aihua; Su, Zhen; Li, Sanming; Han, Fei

    2015-01-01

    In order to assess the preliminary safety and effectiveness of nanostructured lipid carriers-based flurbiprofen gel (FP NLC-gel), the acute irritation test, in vivo pharmacodynamics evaluation and pharmacokinetic study were investigated after topical application. No dropsy and erythema were observed after continuous dosing 7 d of FP NLC-gel on the rabbit skin, and the xylene-induced ear drossy could be inhibited by FP NLC-gel at different dosages. The maximum concentration of FP in rats muscle was 2.03 μg/g and 1.55 μg/g after oral and topical administration, respectively. While the peak concentration in untreated muscle after topical administration was only 0.37 μg/mL. And at any time, following topical administration the mean muscle-plasma concentration ratio Cmuscle/CPlasma was obviously higher than that following oral administration. Results indicated that FP could directly penetrate into the subcutaneous muscle tissue from the administration site. Thus, the developed FP NLC-gel could be a safe and effective vehicle for topical delivery of FP.

  13. Complete recovery following intra-arterial tenecteplase administration in a woman with acute ischemic stroke.

    Science.gov (United States)

    Meenakshi-Sundaram, S; Periakaruppan, A; Karuppiah, S N K P; Karthik, S N; Roopakumar, L; Thembavani, I

    2013-12-01

    A 23-year-old woman, who underwent a percutaneous transluminal mitral commissurotomy for a tight mitral stenosis, developed an acute ischemic stroke involving the proximal right middle cerebral artery territory. She had a dense left hemiplegia with a National Institutes of Health Stroke Scale score of 12. She was emergently treated within 1 hour with intra-arterial tenecteplase and made a dramatic recovery. Intra-arterial tenecteplase is an attractive option for treating acute ischemic stroke with proximal or major vessel occlusion.

  14. Inhibitory Effect of the Hexane Fraction of the Ethanolic Extract of the Fruits of Pterodon pubescens Benth in Acute and Chronic Inflammation

    Directory of Open Access Journals (Sweden)

    Jaqueline Hoscheid

    2013-01-01

    Full Text Available Fruits of Pterodon pubescens Benth have been used traditionally for the treatment of rheumatism, sore throat, and respiratory disorders, and also as anti-inflammatory, analgesic, depurative, tonic, and hypoglycemic agent. The study was aimed at evaluating the anti-inflammatory activity of the hexane fraction of an ethanolic extract of P. pubescens fruits. The oil from P. pubescens fruits was extracted with ethanol and partitioned with hexane. The anti-inflammatory activity was measured with increasing doses of the hexane fraction (FHPp by using a carrageenan-induced rat model of pleurisy and a rat model of complete Freund's adjuvant-induced arthritis by using an FHPp dose of 250 mg/kg for 21 days. Treatment with an FHPp resulted in anti-inflammatory activity in both models. The results of biochemical, hematological, and histological analyses indicated a significant decrease in glucose, cholesterol, and triglycerides levels (18.32%, 34.20%, and 41.70%, resp. and reduction in the numbers of total leukocytes and mononuclear cells. The FHPp dose of 1000 mg/kg induced no changes in behavioral parameters, and no animal died. The results of this study extend the findings of previous reports that have shown that administration of extracts and fractions obtained from species of the genus Pterodon exhibits anti-inflammatory activity and lacks toxicity.

  15. Prophylactic Administration of Silybin Ameliorates L-Arginine-Induced Acute Pancreatitis

    Science.gov (United States)

    Uçmak, Feyzullah; Ekin, Nazım; İbiloğlu, İbrahim; Arslan, Serkan; Kaplan, İbrahim; Şenateş, Ebubekir

    2016-01-01

    Background Oxidative stress have been shown to play a role in the pathogenesis of acute pancreatitis. The aim of this study was to investigate the potential effect of silybin, a potent antioxidant, on L-arginine-induced acute pancreatitis in an experimental rat model. Material/Methods Forty female Wistar Albino rats were divided into 5 groups as follows: Group 1 (C): control group (n=8), Group 2 (SL): silybin group (n=8), Group 3 (LA): acute pancreatitis group (n=8), Group 4 (SLLA): prophylaxis group (n=8), and Group 5 (LASL): treatment group (n=8). Group C (control) received 2 intraperitoneal (i.p.) injections of physiological saline at an interval of 1 h. Group SL received only a single i.p. injection of silybin. The SLLA group received a single i.p. injection of silybin before the induction of acute pancreatitis with L-arginine, whereas the LASL group received the same injection after the induction of acute pancreatitis with L-arginine. Pancreatic tissues were histopathologically examined. Levels of amylase and oxidative stress markers (total oxidant status and total anti-oxidant status) were determined in the blood samples. Oxidative stress index was calculated. Results In comparison to the LA, the prophylaxis and treatment groups showed significant improvements in serum oxidative stress parameters (p=0.001 and p=0.005, respectively). Histopathological analysis showed that the treatment group had significant improvements in edema scores only (p=0.006), whereas the prophylaxis group had the same improvements in inflammation and necrosis scores as well as in total scores (p=0.004, 0.006, and 0.004, respectively). Conclusions When used for prophylactic rather than therapeutic purposes, silybin ameliorates serum oxidative stress parameters and improves histopathological results via its antioxidant and anti-inflammatory properties. PMID:27725627

  16. Evaluation of the acute and sub-acute toxicity of the ethanolic extract of Pericampylus glaucus (Lam. Merr. in BALB/c mice

    Directory of Open Access Journals (Sweden)

    Muhammad Kifayatullah

    2015-10-01

    Conclusions: The result indicates that the oral administration of Pericampylus glaucus (Lam. Merr. extract did not produce any significant toxic effect in BALB/c mice. Hence, the extract can be utilized safely for therapeutic use in pharmaceutical formulations.

  17. AMPA receptor potentiation can prevent ethanol-induced intoxication.

    Science.gov (United States)

    Jones, Nicholas; Messenger, Marcus J; O'Neill, Michael J; Oldershaw, Anna; Gilmour, Gary; Simmons, Rosa M A; Iyengar, Smriti; Libri, Vincenzo; Tricklebank, Mark; Williams, Steve C R

    2008-06-01

    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.

  18. HIGH ETHANOL DOSE DURING EARLY ADOLESCENCE INDUCES LOCOMOTOR ACTIVATION AND INCREASES SUBSEQUENT ETHANOL INTAKE DURING LATE ADOLESCENCE

    OpenAIRE

    Acevedo, María Belén; Molina, Juan Carlos; Nizhnikov, Michael E.; Spear, Norman E.; Pautassi, Ricardo Marcos

    2010-01-01

    Adolescent initiation of ethanol consumption is associated with subsequent heightened probability of ethanol-use disorders. The present study examined the relationship between motivational sensitivity to ethanol initiation in adolescent rats and later ethanol intake. Experiment 1 determined that ethanol induces locomotor activation shortly after administration but not if tested at a later post-administration interval. In Experiment 2, adolescents were assessed for ethanol-induced locomotor ac...

  19. Ethanol Metabolism and Osmolarity Modify Behavioral Responses to Ethanol in C. elegans

    Science.gov (United States)

    Alaimo, Joseph T.; Davis, Scott J.; Song, Sam S.; Burnette, Christopher R.; Grotewiel, Mike; Shelton, Keith L.; Pierce-Shimomura, Jonathan T.; Davies, Andrew G.; Bettinger, Jill C.

    2012-01-01

    Background Ethanol is metabolized by a two-step process in which alcohol dehydrogenase (ADH) oxidizes ethanol to acetaldehyde, which is further oxidized to acetate by aldehyde dehydrogenase (ALDH). Although variation in ethanol metabolism in humans strongly influences the propensity to chronically abuse alcohol, few data exist on the behavioral effects of altered ethanol metabolism. Here, we used the nematode C. elegans to directly examine how changes in ethanol metabolism alter behavioral responses to alcohol during an acute exposure. Additionally, we investigated ethanol solution osmolarity as a potential explanation for contrasting published data on C. elegans ethanol sensitivity. Methods We developed a gas chromatography assay and validated a spectrophotometric method to measure internal ethanol in ethanol-exposed worms. Further, we tested the effects of mutations in ADH and ALDH genes on ethanol tissue accumulation and behavioral sensitivity to the drug. Finally, we tested the effects of ethanol solution osmolarity on behavioral responses and tissue ethanol accumulation. Results Only a small amount of exogenously applied ethanol accumulated in the tissues of C. elegans and consequently their tissue concentrations were similar to those that intoxicate humans. Independent inactivation of an ADH-encoding gene (sodh-1) or an ALDH-encoding gene (alh-6 or alh-13) increased the ethanol concentration in worms and caused hypersensitivity to the acute sedative effects of ethanol on locomotion. We also found that the sensitivity to the depressive effects of ethanol on locomotion is strongly influenced by the osmolarity of the exogenous ethanol solution. Conclusions Our results indicate that ethanol metabolism via ADH and ALDH has a statistically discernable but surprisingly minor influence on ethanol sedation and internal ethanol accumulation in worms. In contrast, the osmolarity of the medium in which ethanol is delivered to the animals has a more substantial effect on

  20. Acute pulmonary edema after intravenous administration of nonionic contrast media: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Cheon, Jung Eun; Im, Jung Gi; Chung, Jin Wook; Park, Jae Hyung; Han, Man Chung [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    1997-02-01

    We describe high-resolution CT findings of pulmonary edema following the administration of intravenous nonionic contrast media in a patient who had no previous history of cardiovascular disease; areas of ground glass opacity and interlobular septal thickenings which partly disappeared on scans obtained 90 minutes after the initial scans. The proposed mechanisms of pulmonary edema are briefly discussed.

  1. Acute phenobarbital administration induces hyperalgesia: pharmacological evidence for the involvement of supraspinal GABA-A receptors

    Directory of Open Access Journals (Sweden)

    C.M. Yokoro

    2001-03-01

    Full Text Available The aim of the present study was to determine if phenobarbital affects the nociception threshold. Systemic (1-20 mg/kg phenobarbital administration dose dependently induced hyperalgesia in the tail-flick, hot-plate and formalin tests in rats and in the abdominal constriction test in mice. Formalin and abdominal constriction tests were the most sensitive procedures for the detection of hyperalgesia in response to phenobarbital compared with the tail-flick and hot-plate tests. The hyperalgesia induced by systemic phenobarbital was blocked by previous administration of 1 mg/kg ip picrotoxin or either 1-2 mg/kg sc or 10 ng icv bicuculline. Intracerebroventricular phenobarbital administration (5 µg induced hyperalgesia in the tail-flick test. In contrast, intrathecal phenobarbital administration (5 µg induced antinociception and blocked systemic-induced hyperalgesia in this test. We suggest that phenobarbital may mediate hyperalgesia through GABA-A receptors at supraspinal levels and antinociception through the same kind of receptors at spinal levels.

  2. 小鼠急性乙醇性胃黏膜损伤模型的制备%Establishment of animal model of ethanol-induced acute gastric mucosal lesions in mice

    Institute of Scientific and Technical Information of China (English)

    叶惠惠; 刘河霞; 张咏梅; 吴克俭

    2011-01-01

    Objective To investigate the optimal ethanol concentration and capacity contributing to ethanol -induced acute gastric mucosal injury and to establish the stable model of ethanol - induced acute gastric mucosal injury in mice. Methods Eighty Kunming mice were randomly divided into control group, normal saline gavage group, 75% ethanol gavage group, and 99.5% ethanol gavage group, followed by sacrifice of animals at 1 h and 4 h for removal of their stomachs and observation of the gastric mucosal lesions. Results The gastric mucosal lesions were evident following gavage of ethanol at the time point of 1 h in mice and 99.5% ethanol at 0.2 ml/10 g gavage induced much sever damage. The gastric mucosal lesions at 1 h were attenuated as compared to 4 h following 99.5% ethanol at 0.2 ml/10 g gavage. There wasn't significant change of survival rates with the concentration and duration of ethanol gavage in mice. Conclusion Ethanol gavage can induce acute gastric mucosal injury in mice, with 99.5% ethanol at 0.2 ml/10 g as the optimal choice to establish the model of acute gastric mucosal injury.%目的 研究引起小鼠急性乙醇性胃黏膜损伤的最佳乙醇浓度与容量,以建立稳定的小鼠急性乙醇性胃黏膜损伤模型.方法 80只昆明小鼠随机分成正常对照组、生理盐水灌胃组、75%乙醇灌胃组、99.5%乙醇灌胃组,然后分别在1 h、4 h处死小鼠取胃,观察小鼠胃黏膜损伤情况.结果 乙醇灌胃1 h后,胃黏膜出现不同程度的损伤,其中99.5%乙醇0.2 ml/10 g对小鼠胃黏膜的损伤较重.99.5%乙醇0.2 ml/10 g灌胃4 h与1 h相比,胃黏膜损伤指数有所下降.随着乙醇浓度的增加与乙醇灌胃时间的延长小鼠的生存率并无显著变化.结论 乙醇灌胃可致小鼠急性胃黏膜损伤,且以99.5%乙醇0.2 ml/10 g灌胃用来制备小鼠急性乙醇性胃黏膜损伤模型最佳.

  3. The Effects of Combined Adiponectin-Metformin on Glucose and Lipids Levels in Mice and Acute Toxicity and Anti-Ulcerogenic Activity of Adiponectin Against Ethanol-Induced Gastric Mucosal Injuries in Rat

    Directory of Open Access Journals (Sweden)

    Mohammed A. Alshawsh

    2011-11-01

    Full Text Available Adiponectin is a protein hormone secreted entirely by abdominal fat tissue. It exhibits various biological activities. The present study was performed to evaluate the effects of metformin alone or in combination with adiponectin on blood glucose, TG (triglyceride, CHOL (Total cholesterol, LDL (Low density lipoprotein and HDL (High density lipoprotein levels in mice and also to evaluate the anti-ulcerogenic activity of adiponectin against ethanol induced gastric mucosal injury in rats. Three groups of mice were gavaged with 1% volume/body weight high fat-sucrose. Metformin at a dosage of 250 mg/kg was added to the feed and a dosage of 2.5 mg/kg adiponectin was injected intraperitoneally (i.p. Blood glucose was measured at one hour intervals for five hours. Blood concentrations of TG, CHOL, LDL and HDL were also measured at the end of the fifth hour of the experiment. On the other hand, four groups of adult healthy rats were i.p. injected with distilled water, omeprazole 20 mg/kg, 2.5 mg/kg and 5 mg/kg adiponectin one hour before oral administration of absolute ethanol to generate gastric mucosal injury. After an additional hour the rats were sacrificed and the ulcer areas of the gastric walls were determined. Furthermore, an acute toxicity study has indicated no mortality with 5 mg/kg dose of adiponectin injected i.p in rats and no major clinical signs of toxicity were observed. The results indicate that the effect of a combination of metformin and adiponectin on blood glucose and HDL is quite effective. Histology of the gastric wall of negative control rats revealed severe damage of gastric mucosa, along with edema and leucocyte infiltration of the submucosal layer compared to rats pre-treated with either omeprazole or adiponectin extract where there was marked gastric protection along with reduction or inhibition of edema and leucocytes infiltration. The results suggest that combination of metfomin and adiponectin give a promising antidiabetic

  4. Impairment of Electron Transfer Chain Induced by Acute Carnosine Administration in Skeletal Muscle of Young Rats

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    José Roberto Macarini

    2014-01-01

    Full Text Available Serum carnosinase deficiency is an inherited disorder that leads to an accumulation of carnosine in the brain tissue, cerebrospinal fluid, skeletal muscle, and other tissues of affected patients. Considering that high levels of carnosine are associated with neurological dysfunction and that the pathophysiological mechanisms involved in serum carnosinase deficiency remain poorly understood, we investigated the in vivo effects of carnosine on bioenergetics parameters, namely, respiratory chain complexes (I–III, II, and II-III, malate dehydrogenase, succinate dehydrogenase, and creatine kinase activities and the expression of mitochondrial-specific transcription factors (NRF-1, PGC-1α, and TFAM in skeletal muscle of young Wistar rats. We observed a significant decrease of complexes I–III and II activities in animals receiving carnosine acutely, as compared to control group. However, no significant alterations in respiratory chain complexes, citric acid cycle enzymes, and creatine kinase activities were found between rats receiving carnosine chronically and control group animals. As compared to control group, mRNA levels of NRF-1, PGC-1α, and TFAM were unchanged. The present findings indicate that electron transfer through the respiratory chain is impaired in skeletal muscle of rats receiving carnosine acutely. In case these findings are confirmed by further studies and ATP depletion is also observed, impairment of bioenergetics could be considered a putative mechanism responsible for the muscle damage observed in serum carnosinase-deficient patients.

  5. Time-course of changes in the social interaction test of anxiety following acute and chronic administration of nicotine.

    Science.gov (United States)

    Irvine, E E; Cheeta, S; File, S E

    1999-11-01

    The purpose of these experiments was to explore the hypothesis that the effects of nicotine on anxiety depend on the time since administration and the duration of treatment. In the social interaction test of anxiety, acute nicotine administration (0.1 mg/kg, subcutaneously) decreased social interaction when rats were tested 5 min after injection, but increased it when they were tested 30 min after injection. Social interaction was also decreased 1 h post-injection, but levels returned to baseline between 3 and 30 h. As these changes were independent of any changes in locomotor activity, nicotine seemed to be having both anxiogenic and anxiolytic effects at different times after injection. An anxiolytic effect was also observed 30 min after the second nicotine injection, and the anxiogenic effect observed 5 min after injection remained after 4 days of nicotine administration. However, after 7 days of nicotine treatment, tolerance was observed to both these effects. When rats were tested 72 h after the last of 7 or 14 days of nicotine treatment, an anxiogenic withdrawal response was observed. Thus, an oppositional mechanism may underlie tolerance to the anxiolytic effects, whereas there is as yet no evidence for this type of mechanism mediating tolerance to the anxiogenic effects.

  6. Ethanol Basics

    Energy Technology Data Exchange (ETDEWEB)

    None

    2015-01-30

    Ethanol is a widely-used, domestically-produced renewable fuel made from corn and other plant materials. More than 96% of gasoline sold in the United States contains ethanol. Learn more about this alternative fuel in the Ethanol Basics Fact Sheet, produced by the U.S. Department of Energy's Clean Cities program.

  7. Conessine, an H3 receptor antagonist, alters behavioral and neurochemical effects of ethanol in mice.

    Science.gov (United States)

    Morais-Silva, Gessynger; Ferreira-Santos, Mariane; Marin, Marcelo T

    2016-05-15

    Ethanol abuse potential is mainly due to its reinforcing properties, crucial in the transition from the recreational to pathological use. These properties are mediated by mesocorticolimbic and nigrostriatal dopaminergic pathways and neuroadaptations in these pathways seem to be responsible for addiction. Both pathways are modulated by other neurotransmitters systems, including neuronal histaminergic system. Among the histamine receptors, H3 receptor stands out due to its role in modulation of histamine and other neurotransmitters release. Thus, histaminergic system, through H3 receptors, may have an important role in ethanol addiction development. Aiming to understand these interactions, conessine, an H3 receptor antagonist, was given to mice subjected to the evaluation of ethanol-induced psychostimulation, ethanol CPP and quantification of norepinephrine, dopamine, serotonin and their metabolites in mesocorticolimbic and nigrostriatal pathways following acute ethanol treatment. Systemic conessine administration exacerbated ethanol effects on locomotor activity. Despite of conessine reinforcing effect on CPP, this drug did not alter acquisition of ethanol CPP. Ethanol treatment affects the serotoninergic neurotransmission in the ventral tegmental area, the dopaminergic neurotransmission in the pre-frontal cortex (PFC) and caudate-putamen nucleus (CPu) and the noradrenergic neurotransmission in the CPu. In the PFC, conessine blocked ethanol effects on dopaminergic and noradrenergic neurotransmission. The blockade of H3 receptors and ethanol seem to interact in the modulation of dopaminergic neurotransmission of nigrostriatal pathway, decreasing dopamine metabolites in substantia nigra. In conclusion, conessine was able to change psychostimulant effect of ethanol, without altering its reinforcing properties. This exacerbation of ethanol-induced psychostimulation would be related to alterations in dopaminergic neurotransmission in the nigrostriatal pathway.

  8. Two cases of "cannabis acute psychosis" following the administration of oral cannabis

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    Pin Marie

    2005-04-01

    Full Text Available Abstract Background Cannabis is the most commonly used illegal drug and its therapeutic aspects have a growing interest. Short-term psychotic reactions have been described but not clearly with synthetic oral THC, especially in occasional users. Case presentations We report two cases of healthy subjects who were occasional but regular cannabis users without psychiatric history who developed transient psychotic symptoms (depersonalization, paranoid feelings and derealisation following oral administration of cannabis. In contrast to most other case reports where circumstances and blood concentrations are unknown, the two cases reported here happened under experimental conditions with all subjects negative for cannabis, opiates, amphetamines, cocaine, benzodiazepines and alcohol, and therefore the ingested dose, the time-events of effects on behavior and performance as well as the cannabinoid blood levels were documented. Conclusion While the oral route of administration achieves only limited blood concentrations, significant psychotic reactions may occur.

  9. Sequential Administration of Methotrexate and Asparaginase in Relapsed or Refractory Pediatric Acute Myeloid Leukemia

    Science.gov (United States)

    Buaboonnam, Jassada; Cao, Xueyuan; Pauley, Jennifer L.; Pui, Ching-Hon; Ribeiro, Raul C.; Rubnitz, Jeffrey E.; Inaba, Hiroto

    2014-01-01

    Background The efficacy of combination chemotherapy with methotrexate (MTX) and asparaginase is not well known in relapsed and refractory acute leukemia after contemporary therapy. Procedure A retrospective study of pediatric patients with relapsed or refractory acute myeloid leukemia (AML) who received MTX and asparaginase as a salvage therapy at St. Jude Children Research Hospital was performed. MTX was given intravenously followed by a dose of asparaginase intramuscularly or intravenously 24 hours later. The chemotherapy cycle was repeated every 7-10 days. Response, survival, and toxicities were evaluated. Results Fifteen patients, median age 10.5 years (range, 1.1-18.5 years), were treated. Median number of previous therapeutic regimens was 3 (range, 1-4). Six patients responded to treatment (3 had morphologic complete remission with incomplete blood count recovery, 2 had partial remission, and 1 had stable disease for 16 months), and 4 are still alive. Three of 6 responders had monoblastic leukemia, and also developed tumor lysis syndrome. The 1- and 2-year overall survival rates are 35.6% and 17.8%, respectively. The most common adverse event was transient elevation of transaminases (9 patients). Two patients developed pancreatitis. Episodes of febrile neutropenia were rare (2 patients), and most courses (75 out of 93 total courses) were given in an outpatient setting. Conclusions Combination chemotherapy with MTX and asparaginase appears to be an effective salvage therapy and well tolerated in patients with relapsed or refractory childhood AML, even in those heavily pretreated with contemporary frontline or salvage therapy. PMID:23335430

  10. Effects of inhaled CO administration on acute lung injury in baboons with pneumococcal pneumonia

    Science.gov (United States)

    Kraft, Bryan D.; Hess, Dean R.; Harris, R. Scott; Wolf, Monroe A.; Suliman, Hagir B.; Roggli, Victor L.; Davies, John D.; Winkler, Tilo; Stenzler, Alex; Baron, Rebecca M.; Thompson, B. Taylor; Choi, Augustine M.; Welty-Wolf, Karen E.; Piantadosi, Claude A.

    2015-01-01

    Inhaled carbon monoxide (CO) gas has therapeutic potential for patients with acute respiratory distress syndrome if a safe, evidence-based dosing strategy and a ventilator-compatible CO delivery system can be developed. In this study, we used a clinically relevant baboon model of Streptococcus pneumoniae pneumonia to 1) test a novel, ventilator-compatible CO delivery system; 2) establish a safe and effective CO dosing regimen; and 3) investigate the local and systemic effects of CO therapy on inflammation and acute lung injury (ALI). Animals were inoculated with S. pneumoniae (108-109 CFU) (n = 14) or saline vehicle (n = 5); in a subset with pneumonia (n = 5), we administered low-dose, inhaled CO gas (100–300 ppm × 60–90 min) at 0, 6, 24, and/or 48 h postinoculation and serially measured blood carboxyhemoglobin (COHb) levels. We found that CO inhalation at 200 ppm for 60 min is well tolerated and achieves a COHb of 6–8% with ambient CO levels ≤ 1 ppm. The COHb level measured at 20 min predicted the 60-min COHb level by the Coburn-Forster-Kane equation with high accuracy. Animals given inhaled CO + antibiotics displayed significantly less ALI at 8 days postinoculation compared with antibiotics alone. Inhaled CO was associated with activation of mitochondrial biogenesis in the lung and with augmentation of renal antioxidative programs. These data support the feasibility of safely delivering inhaled CO gas during mechanical ventilation and provide preliminary evidence that CO may accelerate the resolution of ALI in a clinically relevant nonhuman primate pneumonia model. PMID:26320156

  11. Efficacy comparison of combined intracoronary administration of high-dose adenosine and tirofiban versus intracoronary tirofiban during primary percutaneous coronary intervention in patients with acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    佟子川

    2013-01-01

    Objective To compare the efficacy of intracoronary administration of combined high-dose adenosine and tirofiban versus intracoronary tirofiban during primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction.Methods Consecutive 258 patients with acute ST-segment elevation myocardial infarction (STEMI) underwent primary PCI,treated with thrombus aspiration and then intracoronary tirofiban,and were randomly divided into adenosine group (n=130) and con-

  12. PS-022 Complex automated medication systems reduce medication administration error rates in an acute medical ward

    DEFF Research Database (Denmark)

    Risør, Bettina Wulff; Lisby, Marianne; Sørensen, Jan

    2017-01-01

    Background Medication errors have received extensive attention in recent decades and are of significant concern to healthcare organisations globally. Medication errors occur frequently, and adverse events associated with medications are one of the largest causes of harm to hospitalised patients....... Reviews have suggested that up to 50% of the adverse events in the medication process may be preventable. Thus the medication process is an important means to improve safety. Purpose The objective of this study was to evaluate the effectiveness of two automated medication systems in reducing...... the medication administration error rate in comparison with current practice. Material and methods This was a controlled before and after study with follow-up after 7 and 14 months. The study was conducted in two acute medical hospital wards. Two automated medication systems were tested: (1) automated dispensing...

  13. N-Methyl-3,4-methylenedioxyamphetamine-induced hepatotoxicity in rats: Oxidative stress after acute and chronic administration

    Directory of Open Access Journals (Sweden)

    Ninković Milica

    2004-01-01

    Full Text Available Background. The underlying mechanisms of N-Methyl-3,4-methylenedioxyamphetamine-MDMA-induced hepatotoxicity are still unknown. The aim of this study was to evaluate hepatic oxido-reductive status in the rats liver after the single and repeated administration of MDMA. Methods. MDMA was dissolved in distilled water and administered in the doses of 5 mg, 10 mg, 20 mg, and 40 mg/kg. The animals from the acute experiment were treated per os with the single dose of the appropriate solution, through the orogastric tube. The animals from the chronic experiment were treated per os, with the doses of 5, 10, or 20 mg/kg of MDMA every day during 14 days. The control groups were treated with water only. Eight hours after the last dose, the animals were sacrificed, dissected their livers were rapidly removed, frozen and stored at -70°C until the moment of analysis. The parameters of oxidative stress in the crude mitochondrial fractions of the livers were analyzed. Results. Superoxide dismutase (SOD activity increased in the livers of the animals that were treated with single doses of MDMA. Chronically treated animals showed the increased SOD activity only after the highest dose (20 mg/kg. The content of reduced glutathione decreased in both groups, but the depletion was much more expressed after the single administration. Lipid peroxidation index increased in dose-dependent manner in both groups, being much higher after the single administration. Conclusion. The increased index of lipid peroxidation and the decreased reduced glutathione levels suggested that MDMA application induced the state of oxidative stress in the liver. These changes were much more expressed after the single administration of MDMA.

  14. Exogenous glucose administration impairs glucose tolerance and pancreatic insulin secretion during acute sepsis in non-diabetic mice.

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    Yoshio Watanabe

    Full Text Available OBJECTIVES: The development of hyperglycemia and the use of early parenteral feeding are associated with poor outcomes in critically ill patients. We therefore examined the impact of exogenous glucose administration on the integrated metabolic function of endotoxemic mice using our recently developed frequently sampled intravenous glucose tolerance test (FSIVGTT. We next extended our findings using a cecal ligation and puncture (CLP sepsis model administered early parenteral glucose support. METHODS: Male C57BL/6J mice, 8-12 weeks, were instrumented with chronic indwelling arterial and venous catheters. Endotoxemia was initiated with intra-arterial lipopolysaccharide (LPS; 1 mg/kg in the presence of saline or glucose infusion (100 µL/hr, and an FSIVGTT was performed after five hours. In a second experiment, catheterized mice underwent CLP and the impact of early parenteral glucose administration on glucose homeostasis and mortality was assessed over 24 hrs. MEASUREMENTS: AND MAIN RESULTS: Administration of LPS alone did not impair metabolic function, whereas glucose administration alone induced an insulin sensitive state. In contrast, LPS and glucose combined caused marked glucose intolerance and insulin resistance and significantly impaired pancreatic insulin secretion. Similarly, CLP mice receiving parenteral glucose developed fulminant hyperglycemia within 18 hrs (all > 600 mg/dl associated with increased systemic cytokine release and 40% mortality, whereas CLP alone (85 ± 2 mg/dL or sham mice receiving parenteral glucose (113 ± 3 mg/dL all survived and were not hyperglycemic. Despite profound hyperglycemia, plasma insulin in the CLP glucose-infused mice (3.7 ± 1.2 ng/ml was not higher than sham glucose infused mice (2.1 ± 0.3 ng/ml. CONCLUSIONS: The combination of parenteral glucose support and the systemic inflammatory response in the acute phase of sepsis induces profound insulin resistance and impairs compensatory pancreatic insulin

  15. A Study of Intravenous Administration of Vitamin C in the Treatment of Acute Herpetic Pain and Postherpetic Neuralgia

    Science.gov (United States)

    Kim, Min Sung; Kim, Dong Jin; Na, Chan Ho

    2016-01-01

    Background Although there are several available management strategies for treatment of both acute pain of herpes zoster (HZ) and postherpetic neuralgia (PHN), it is difficult to treat them adequately. Objective The aim of this study was to evaluate the efficacy of intravenously administrated vitamin C on acute pain and its preventive effects on PHN in patients with HZ. Methods Between September 2011 and May 2013 eighty-seven patients who were admitted for HZ were assessed according to age, sex, underlying diseases, duration of pain and skin lesion, dermatomal distribution, and PHN. It was a randomized controlled study, in which 87 patients were randomly allocated into the ascorbic acid group and control group. Each patient received normal saline infusion with or without 5 g of ascorbic acid on days 1, 3, and 5 then answered questionnaires that included side effects and pain severity using visual analogue scale on days 1, 2, 3, 4, and 5. After discharge, the severity of pain was obtained at out-patient clinic or by telephone on weeks 2, 4, 8, and 16. Results There was no differences in severity of pain on patients' age, sex, underlying diseases, duration of pain and skin lesion and dermatomal distribution between two groups (p>0.05). Since 8th week, pain score in ascorbic acid treatment group was significantly lower than control group (p <0.05). The incidence of PHN was significantly lower in the treatment group compared to control group (p=0.014). The changes of overall pain score was significantly different between the two groups (p<0.05). Conclusion Intravenously administered ascorbic acid did not relieve acute HZ pain; but is effective for reducing the incidence of PHN. PMID:27904265

  16. Acute administration of unacylated ghrelin has no effect on Basal or stimulated insulin secretion in healthy humans.

    Science.gov (United States)

    Tong, Jenny; Davis, Harold W; Summer, Suzanne; Benoit, Stephen C; Haque, Ahrar; Bidlingmaier, Martin; Tschöp, Matthias H; D'Alessio, David

    2014-07-01

    Unacylated ghrelin (UAG) is the predominant ghrelin isoform in the circulation. Despite its inability to activate the classical ghrelin receptor, preclinical studies suggest that UAG may promote β-cell function. We hypothesized that UAG would oppose the effects of acylated ghrelin (AG) on insulin secretion and glucose tolerance. AG (1 µg/kg/h), UAG (4 µg/kg/h), combined AG+UAG, or saline were infused to 17 healthy subjects (9 men and 8 women) on four occasions in randomized order. Ghrelin was infused for 30 min to achieve steady-state levels and continued through a 3-h intravenous glucose tolerance test. The acute insulin response to glucose (AIRg), insulin sensitivity index (SI), disposition index (DI), and intravenous glucose tolerance (kg) were compared for each subject during the four infusions. AG infusion raised fasting glucose levels but had no effect on fasting plasma insulin. Compared with the saline control, AG and AG+UAG both decreased AIRg, but UAG alone had no effect. SI did not differ among the treatments. AG, but not UAG, reduced DI and kg and increased plasma growth hormone. UAG did not alter growth hormone, cortisol, glucagon, or free fatty acid levels. UAG selectively decreased glucose and fructose consumption compared with the other treatments. In contrast to previous reports, acute administration of UAG does not have independent effects on glucose tolerance or β-cell function and neither augments nor antagonizes the effects of AG.

  17. Acute oral administration of a tyrosine and phenylalanine-free amino acid mixture reduces exercise capacity in the heat.

    Science.gov (United States)

    Tumilty, Les; Davison, Glen; Beckmann, Manfred; Thatcher, Rhys

    2013-06-01

    Acute tyrosine administration is associated with increased exercise capacity in the heat. To explore whether reduced plasma tyrosine and phenylalanine (tyrosine precursor) is associated with impaired exercise capacity in the heat, eight healthy, moderately trained male volunteers, unacclimated to exercise in the heat, performed two tests in a crossover design separated by at least 7 days. In a randomised, double-blind fashion, subjects ingested 500 mL flavoured, sugar-free water containing amino acids [(TYR-free; isoleucine 15 g, leucine 22.5 g, valine 17.5 g, lysine 17.5 g, methionine 5 g, threonine 10 g, tryptophan 2.5 g)] to lower the ratio of plasma tyrosine plus phenylalanine:amino acids competing for blood-brain barrier uptake (CAA), a key determinant of brain uptake, or a balanced mixture (BAL; TYR-free plus 12.5 g tyrosine and 12.5 g phenylalanine). One hour later, subjects cycled to exhaustion at 63 ± 5 % [Formula: see text]O2peak in 30 °C and 60 % relative humidity. Pre-exercise ratio of plasma tyrosine plus phenylalanine:ΣCAA declined 75 ± 5 % from rest in TYR-free (P 0.05) and thermal sensation (P > 0.05) were similar at exhaustion in both trials. These data indicate that acutely depleting plasma catecholamine precursors:ΣCAA is associated with reduced submaximal exercise capacity in the heat.

  18. TRAIL administration down-modulated the acute systemic inflammatory response induced in a mouse model by muramyldipeptide or lipopolysaccharide.

    Science.gov (United States)

    Marcuzzi, Annalisa; Secchiero, Paola; Crovella, Sergio; Zauli, Giorgio

    2012-10-01

    The potent inducer of apoptosis TRAIL/Apo2 ligand is now under considerations in clinical trials for the treatment of different types of cancer. Since the natural history of cancer is often characterized by microbial infections, we have investigated the effect of recombinant human TRAIL in a mouse model of systemic acute inflammation of microbial origin represented by BALB/c mice treated with either bacterial muramyldipeptide (MDP) or lipopolysaccharide (LPS). When administered intraperitoneally (i.p.), these inflammatory bacterial compounds triggered a severe systemic inflammatory response within 2h, represented by body temperature elevation, increase of circulating serum amyloid-A (SAA) and of the number of leukocytes in the peritoneal cavity. Moreover, both MDP and LPS induced a significant elevation of the circulating levels of several inflammatory cytokines and chemokines. Noteworthy, pre-treatment with recombinant human TRAIL 48 and 72 h before administration of either MDP or LPS, significantly counteracted all acute inflammatory responses, including the elevation of key pro-inflammatory cytokines/chemokines such as IL-1α, IL-6, G-CSF, MCP-1. These data demonstrate for the first time that TRAIL has a potent anti-inflammatory activity, which might be beneficial for the anti-tumoral activity of TRAIL.

  19. Study on acute toxicological evaluation of ethanol extracts from fusty tea%莓茶乙醇提取物的急性毒性研究

    Institute of Scientific and Technical Information of China (English)

    谭平; 姚茂君; 辛益妹; 马美湖

    2011-01-01

    The acute toxicological evaluation was studied of ethanol extracts from fusty tea (Ampelopsis grossedentata). The rats were given the ethanol extracts from fusty tea with the maximum concentration and capacity by gastric perfusion. Twice a day, for 14 days. The result showed that compared with Wistar control group, there were no abnormal reactions during the observation period on skin, mucosa, coat color, eyes, breath, circulation, locomotor activity, central nervous system, behavior etc. In Wistar sample group, without rats' death, and the maximum tolerance was 10. Og/kg by gastric perfusion. There were no change in the tissues and organs on volume, color and texture, which showed the extracts were low toxic and are better safe to eat.%对莓荼乙醇提取物的急性毒性进行研究.取Wistar大鼠40只,清洁级,随机分为2组,每组20只,雌雄各半,以最大耐受量法灌胃给予受试样品组大鼠最大使用浓度和最大灌胃容量的莓茶乙醇提取物,1天2次(相隔4h),连续观察14d.结果表明,受试样品组大鼠毛色,皮肤,粘膜,眼睛,呼吸,循环,自主活动及中枢神经系统、行为表现等均与阴性对照组大鼠无明显差别,整个试验期内无大鼠死亡,莓茶乙醇提取物大鼠口服灌胃的最大耐受量为10.0g/kg大鼠体重;对所有试验大鼠进行大体解剖,组织器官未见有颜色、体积、质地等改变,说明莓荼乙醇提取物的毒性很小,具有较好的食用安全性.

  20. Paradoxical Glucose-Sensitizing yet Proinflammatory Effects of Acute ASP Administration in Mice

    Directory of Open Access Journals (Sweden)

    Alexandre Fisette

    2013-01-01

    Full Text Available Acylation stimulating protein (ASP is an adipokine derived from the immune complement system, which stimulates fat storage and is typically increased in obesity, type 2 diabetes, and cardiovascular disease. Using a diet-induced obesity (DIO mouse model, the acute effects of ASP on energy metabolism and inflammatory processes in vivo were evaluated. We hypothesized that ASP would specifically exert proinflammatory effects. C57Bl/6 wild-type mice were put on a high-fat-high-sucrose diet for 12 weeks. Mice were then subjected to both glucose and insulin tolerance tests, each manipulation being preceded by recombinant ASP or vehicle (control bolus injection. ASP supplementation increased whole-body glucose excursion, and this was accomplished with reduced concomitant insulin levels. However, ASP did not directly alter insulin sensitivity. ASP supplementation induced a proinflammatory phenotype, with higher levels of cytokines including IL-6 and TNF-α in plasma and in adipose tissue, liver, and skeletal muscle mRNA. Additionally, ASP increased M1 macrophage content of these tissues. ASP exerted a direct concentration-dependent role in the migration and M1 activation of cultured macrophages. Altogether, the in vivo and in vitro experiments demonstrate that ASP plays a role in both energy metabolism and inflammation, with paradoxical whole-body glucose-sensitizing yet proinflammatory effects.

  1. Differential effects of acute morphine administrations on polymorphonuclear cell metabolism in various mouse strains.

    Science.gov (United States)

    Di Francesco, P; Tavazzi, B; Gaziano, R; Lazzarino, G; Casalinuovo, I A; Di Pierro, D; Garaci, E

    1998-01-01

    This paper shows that an acute morphine treatment dose-dependently alters the energetic and oxidative metabolism of polymorphonuclear leukocytes obtained from BALB/c and DBA/2 mice, while phagocytic cells from C57BL/6 were not affected. In sensitive mouse strains, i.e. BALB/c and DBA/2, morphine decreased both ATP concentration and energy charge potential. At the same time, ATP catabolic products, i.e. nucleosides (inosine+adenosine) and oxypurines (hypoxanthine+xanthine+uric acid), significantly increased, indicating an imbalance between energy production and consumption. Morphine treatment also induced malondialdehyde and superoxide anions production in leukocyte cells from sensitive mice. The opiate antagonist naloxone blocked morphine-induced modifications by the lower morphine dose. The same parameters in cells from C57BL/6 mice were not affected. These findings confirm that: i) the phagocytic cells are an important target for the in vivo effects of morphine, and ii) the genotype-dependent variation influences the immunological responsiveness to opiates.

  2. Cycling efficiency and time to exhaustion are reduced after acute passive stretching administration.

    Science.gov (United States)

    Esposito, F; Cè, E; Limonta, E

    2012-12-01

    The aim of this study was to assess the effects of acute passive stretching on cycling efficiency during an exercise of heavy intensity. After maximum aerobic power (VO(2max)) assessment, nine active males (24 ± 5 years; stature 1.71 ± 0.09 m; body mass 69 ± 7 kg; mean ± standard deviation) performed tests at 85% of VO(2max) (W(85)) until exhaustion, with and without pre-exercise stretching. During the tests, we determined the gas exchange, metabolic and cardiorespiratory parameters. With stretching, no differences in VO(2max) occurred (3.64 ± 0.14 vs 3.66 ± 0.07 L/min for stretching and control, respectively). During W(85), pre-exercise stretching (i) decreased time to exhaustion (t(lim)) by 26% (Pstretching and control, respectively; Pstretching and control, respectively; Pstretching did not have an effect on VO(2max), t(lim) and e(net) during heavy constant load exercise were significantly affected. These results are suggestive of an impairment in cycling efficiency due to changes in muscle neural activation and viscoelastic characteristics induced by stretching.

  3. Weight-based contrast administration in the computerized tomography evaluation of acute pulmonary embolism

    Science.gov (United States)

    Laurent, Lisa; Zamfirova, Ina; Sulo, Suela; Baral, Pesach

    2017-01-01

    Abstract Compare individualized contrast protocol, or weight-based protocol, to standard methodology in evaluating acute pulmonary embolism. Retrospective chart review was performed on patients undergoing computed tomography angiography with standard contrast protocol (n = 50) or individualized protocol (n = 50). Computerized tomography images were assessed for vascular enhancement and image quality. Demographics were comparable, however, more patients in the individualized group were admitted to intensive care unit (48% vs 16%, P = 0.004). Vascular enhancement and image quality were also comparable, although individualized protocol had significantly fewer contrast and motion artifact limitations (28% vs 48%, P = 0.039). Fifteen percent decrease in intravenous contrast volume was identified in individualized group with no compromise in image quality. Individualized contrast protocol provided comparable vascular enhancement and image quality to the standard, yet with fewer limitations and lower intravenous contrast volume. Catheter-gauge flow rate restrictions resulting in inconsistent technologist exam execution were identified, supporting the need for further investigation of this regimen. PMID:28151887

  4. Innate BDNF expression is associated with ethanol intake in alcohol-preferring AA and alcohol-avoiding ANA rats.

    Science.gov (United States)

    Raivio, Noora; Miettinen, Pekka; Kiianmaa, Kalervo

    2014-09-04

    We have shown recently that acute administration of ethanol modulates the expression of brain-derived neurotrophic factor (BDNF) in several rat brain areas known to be involved in the development of addiction to ethanol and other drugs of abuse, suggesting that BDNF may be a factor contributing to the neuroadaptive changes set in motion by ethanol exposure. The purpose of the present study was to further clarify the role of BDNF in reinforcement from ethanol and in the development of addiction to ethanol by specifying the effect of acute administration of ethanol (1.5 or 3.0 g/kg i.p.) on the expression profile of BDNF mRNA in the ventral tegmental area and in the terminal areas of the mesolimbic dopamine pathway in the brain of alcohol-preferring AA and alcohol-avoiding ANA rats, selected for high and low voluntary ethanol intake, respectively. The level of BDNF mRNA expression was higher in the amygdala and ventral tegmental area of AA than in those of ANA rats, and there was a trend for a higher level in the nucleus accumbens. In the amygdala and hippocampus, a biphasic change in the BDNF mRNA levels was detected: the levels were decreased at 3 and 6h but increased above the basal levels at 24h. Furthermore, there was a difference between the AA and ANA lines in the effect of ethanol, the ANA rats showing an increase in BDNF mRNA levels while such a change was not seen in AA rats. These findings suggest that the innate levels of BDNF expression may play a role in the mediation of the reinforcing effects of ethanol and in the control of ethanol intake.

  5. Lycopene treatment prevents hematological, reproductive and histopathological damage induced by acute zearalenone administration in male Swiss mice.

    Science.gov (United States)

    Boeira, Silvana Peterini; Filho, Carlos Borges; Del'Fabbro, Lucian; Roman, Silvane Souza; Royes, Luiz Fernando Freire; Fighera, Michele Rechia; Jessé, Cristiano Ricardo; Oliveira, Mauro Schneider; Furian, Ana Flávia

    2014-07-01

    Zearalenone (ZEA) is a mycotoxin commonly found as a contaminant in cereals. ZEA toxicity targets mainly the reproductive system, and oxidative stress plays an etiological role in its toxic effects. Therefore, the present study aimed to investigate the effect of lycopene, a potent carotenoid antioxidant, on markers of oxidative stress in liver, kidney and testes, and on reproductive, hematological and histopathological parameters after ZEA administration. Adult Swiss albino male mice received lycopene (20mg/kg, p.o.) for ten days before a single oral administration of ZEA (40mg/kg, p.o.), and 48h thereafter tissues (liver, kidney, testes and blood) were collected for biochemical, hematological and histological analyses. Lycopene prevented ZEA-induced changes in hematological parameters (increased number of leukocytes, segmented neutrophils, sticks, eosinophils and monocytes and decreased number of red blood cells (RBC), number of lymphocytes and platelets). Moreover, lycopene prevented the reduction in the number and motility of spermatozoa and the testicular tissue damage induced by ZEA. In addition, lycopene prevented the decrease in glutathione-S-transferase activity in kidney and testes and increased glutathione-S-transferase activity per se in the liver, kidneys and testes as well as superoxide dismutase activity in the liver. In summary, lycopene was able to prevent ZEA-induced acute toxic effects in male mice, suggesting that this antioxidant carotenoid may represent a promising prophylactic strategy against ZEA toxicity.

  6. Acute-Onset Type 1 Diabetes that Developed During the Administration of Olanzapine

    Science.gov (United States)

    Iwaku, Kenji; Otuka, Fumiko; Taniyama, Matsuo

    2017-01-01

    The patient was 32-year-old man, who received olanzapine for schizophrenia and developed polyuria and thirst without drinking soft-drinks after 4 months. Five months after the initiation of treatment, he developed diabetic ketoacidosis (blood glucose: 490 mg/dL, HbA1c: 15.5%). He was diagnosed with type 1 diabetes (glutamic acid decarboxylase (GAD)-Ab: 5.6 U/mL, IA-2 Ab: 5.9 U/mL, fasting C-peptide: 0.12 ng/mL) and was put on intensive insulin therapy. At four months after the onset of 1A diabetes, he experienced a honeymoon phase that was sustained until the 40th month of treatment. We hypothesize that the administration of olanzapine to a patient with pre-type 1A diabetes induced marked hyperglycemia and accelerated the onset of type 1A diabetes. PMID:28154279

  7. Acute effect of hydralazine administration on pulmonary artery hemodynamics in dogs with chronic heartworm disease.

    Science.gov (United States)

    Atkins, C E; Keene, B W; McGuirk, S M; Sato, T

    1994-02-01

    In an effort to better understand the role of vasodilators in the management of pulmonary hypertension associated with chronic heartworm disease (HWD), pulmonary hemodynamic measurements were obtained from 7 experimentally infected, anesthetized dogs before and after hydralazine administration (mean dose, 1.96 mg/kg of body weight). Five dogs were maintained on room air, while 2 were maintained on 100% oxygen during the hydralazine study. The hemodynamic effect of hydralazine in dogs with HWD was evaluated, using heart rate, cardiac index, mean pulmonary artery pressure, mean arterial pressure, total pulmonary resistance, total systemic resistance, total systemic resistance/total pulmonary resistance, left ventricular dP/dtmax, left ventricular end diastolic pressure, and left and right ventricular double products ([mean arterial pressure x heart rate] and [mean pulmonary artery pressure x heart rate], respectively). Responders were defined as those in which total pulmonary resistance decreased > or = 20% without an increase in mean pulmonary arterial pressure and in which heart rate increase was < or = 10%. Comparison was also made between maximal hemodynamic effect of hydralazine with that after 100% oxygen administration for 15 minutes to previously normoxemic dogs (n = 5). Significance was determined if P < 0.05, using the paired t-test. Hydralazine induced significant reductions in mean pulmonary and systemic arterial pressures and total pulmonary resistance, with no significant change in heart rate, cardiac index, total systemic resistance, left ventricular dP/dtmax, left ventricular end diastolic pressure, or right and left ventricular double products. Four (57%) of the 7 dogs studied were considered responders. Pretreatment cardiac index, mean pulmonary artery pressure, and total pulmonary resistance did not allow differentiation of responders from nonresponders.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Acute liver failure in a term neonate after repeated paracetamol administration

    Directory of Open Access Journals (Sweden)

    Fabio Bucaretchi

    2014-03-01

    Full Text Available Objective: Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate. Case description: A 26-day-old boy was admitted with intestinal bleeding, shock signs, slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate: 7.1mEq/L, hypoglycemia (18mg/dL, increased serum aminotransferase activity (AST=4,039IU/L; ALT=1,087IU/L and hyperbilirubinemia (total: 9.57mg/dL; direct: 6.18mg/dL after receiving oral paracetamol (10mg/kg/dose every 4 hours for three consecutive days (total dose around 180mg/kg; serum concentration 36-48 hours after the last dose of 77µg/ mL. Apart from supportive measures, the patient was successfully treated with intravenous N-acetylcysteine infusion during 11 consecutive days, and was discharged on day 34. The follow-up revealed full recovery of clinical and of laboratory findings of hepatic function. Comments: The paracetamol pharmacokinetics and pharmacodynamics in neonates and infants differ substantially from those in older children and adults. Despite the reduced rates of metabolism by the P-450 CYP2E1 enzyme system and the increased ability to synthesize glutathione - which provides greater resistance after overdoses -, it is possible to produce hepatotoxic metabolites (N-acetyl-p-benzoquinone that cause hepatocellular damage, if glutathione sources are depleted. Paracetamol clearance is reduced and the half-life of elimination is prolonged. Therefore, a particular dosing regimen should be followed due to the toxicity risk of cumulative doses. This report highlights the risk for severe hepatotoxicity in neonates after paracetamol multiple doses for more than two to three days.

  9. Acute nicotine administration effects on fractional anisotropy of cerebral white matter and associated attention performance

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    Peter eKochunov

    2013-09-01

    Full Text Available Introduction.Nicotinic acetylcholine receptors are present in the cerebral white matter (WM. We hypothesized that WM response to nicotine can be detected by diffusion tensor imaging (DTI; and that such responses may be associated with nicotine-led cognitive enhancement in sustained attention. MethodsA randomized, nicotine-placebo patch, crossover, double-blind clinical trial in two non-overlapping cohorts of smokers was used to test the hypothesis. The discovery cohort consisted of 39 subjects (N=20/19 controls/schizophrenic patients, age=36.8±10.1years and the replication cohorts consisted of 38 healthy smokers (31.7±10.5years. WM integrity was measured by fractional anisotropy (FA values for the whole brain and nine preselected WM tracts using tract-based-spatial-statistics. Results.Nicotine significantly enhanced FA values for the genu of corpus callosum compared with placebo (FAgenu (p=0.01 in smokers with low recent smoking exposure as measured by low average cotinine level. This finding was replicated in the second cohort (p=0.02. FAgenu values explained 22% of variance in performance of a sustained attention task during the nicotine session (p=0.006. However, this effect was limited to schizophrenia patients (r= 0.62 and 0.09; p=0.003 and 0.7 for patients and controls, respectively.Conclusion. Acute pharmacological influence of nicotine patch on WM integrity appeared present, but was dependent on nicotine intake from recent smoking. Change in the WM integrity in the genu of corpus callosum was assocatied with a significant proportion of variability of nicotine-led changes in sustained attention/working memory of the smokers. Further studies will be necessary to understand biophysical underpinning of the nicotine-related changes in FA.

  10. [Ethanol metabolism and pathobiochemistry of organ damage--1992. IV. Ethanol in relation to the cardiovascular system. Hematologic, immunologic, endocrine disorders and muscle and bone damage caused by ethanol. Fetal alcohol syndrome].

    Science.gov (United States)

    Zima, T

    1993-01-01

    Peripheral vasodilatation with increased cardiac output, tachycardia and increased blood pressure are described after alcohol administration. An increased HDL-cholesterol is found in moderate drinkers (both HDL-2 and HDL-3 fractions), with diminishing risk of coronary heart diseases. Acute ethanol intake causes an increased the level of triglycerides without changes in HDL-cholesterol level. This may be put into correlation with higher incidence of cardiovascular diseases in so-called "week-end" drinkers. Alcohol abuse may result in central diabetes insipidus. An increased elimination of lactate diminishes tubular secretion of uric acid with subsequent secondary hyperuricemia. Ethanol reduced the number of lymphocytes, reduces phagocytosis by macrophages and diminishes the activity of NK-cells. Bone marrow cellulity diminishes with the subsequent reduction in erythropoiesis, trombopoiesis and leukopoiesis. Alcohol may cause sideropenic and megaloblastic anemia. There are two forms of alcohol muscle injury: the acute one, with myonecrosis and inflammatory reaction, and chronic one, with muscle weakness and atrophy. Alcohol is one of etiologic factors of osteoporosis. An acute intoxication result in transitory hypoparatthyreoidism, while chronic ethanol intake make grow the PTH level and decreases the level of D vitamin metabolises. Stimulation of cortisol secretion, decrease of testosterone level and a reversible decrease of T3 and T4 levels have been described following ethanol administration. Hypothalamic-pituitary-adrenal axis suffers alteration in alcoholics, and secondary amenorrhea is observed in female alcoholics. Ethanol behaves as an agonist on GABA receptor. Fetal alcohol syndrome together with Down's syndrome and spina bifida are the most frequent reasons of mental retardation in developed countries. Toxicity of ethanol affects the whole pregnancy period.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Antidiabetic and antihyperlipidaemic activity of ethanol extract of Melastoma malabathricum Linn. leaf in alloxan induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Karuppasamy Balamurugan; Antony Nishanthini; Veerabahu Ramasamy Mohan

    2014-01-01

    Objective: To evaluate the antidiabetic and antihyperlipidaemic effect of ethanol extract ofMelastoma malabathricum (M. malabathricum) Linn. leaf in alloxan induced diabetic rats. Methods: Diabetes was induced in albino rats by administration of alloxan monohydrate (150 mg/kg i.p). the ethanol extracts of M. malabathricum at a dose of 150 and 300 mg/kg of body weight were administrated at a single dose per day to diabetes induced rats for a period of 14 d. The effect of ethanol extract of M. malabathricum leaf extract on blood glucose, plasma insulin, creatinine, glycosylated haemoglobin, urea serum lipid profile [total cholesterol, triglycerides, low density lipoprotein-cholesterol, very low density lipoprotein-cholesterol, high density lipoprotein-cholesterol and phospholipid, serum protein, albumin, globulin, serum enzymes (serum glutamate pyruvate transaminases), serum glutamate oxaloacetate transaminases, and alkaline phosphatase] were measured in the diabetic rats.Results:In the acute toxicity study, ethanol extract of M. malabathricum leaf was non-toxic at 2 000 mg/kg in rats. The increased body weight, decreased blood glucose, glycosylated haemoglobin and other biochemical parameters level were observed in diabetic rats treated with both doses of ethanol extract of M. malabathricum leaf compared to diabetic control rats. In diabetic rats, ethanol extract of M. malabathricum leaf administration, altered lipid profiles were reversed to near normal than diabetic control rats.Conclusions:Ethanol extract of M. malabathricum leaf possesses significant antidiabetic and antihyperlipidaemic activity in diabetic rats.

  12. The Effects of Acute Arginine Vasopressin Administration on Social Cognition in Healthy Males

    Directory of Open Access Journals (Sweden)

    Amanda R. Kenyon

    2013-01-01

    Full Text Available The structurally similar neuropeptides and hormones oxytocin (OT and arginine vasopressin (AVP play significant and complex roles in modulating a range of social behaviours, including social recognition and bond formation. Although OT has well-known roles in facilitating prosocial behaviors and enhancing emotion recognition, AVP has received increasing interest for diverging effects on social cognition behaviour most notably in males. The current study aimed to determine whether AVP also modulates the ability to understand emotion. Using a randomised double blind procedure, 45 healthy young males received either an AVP or placebo nasal spray and completed the Reading the Mind in the Eyes Test (RMET. In contrast to previous findings, there were no significant differences observed in performance on the RMET between AVP and placebo groups, even after examining items separated by task difficulty, emotional valence, and gender. This study provides diverging evidence from previous findings and adds to the growing body of research exploring the influence of neuropeptide hormones in social behaviour. It demonstrates that in this sample of participants, AVP does not enhance the ability to understand higher order emotion from others. Implications and suggestions for future AVP administration studies are discussed.

  13. Effects of L-carnitine administration on left ventricular remodeling after acute anterior myocardial infarction: The L-carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) trial

    NARCIS (Netherlands)

    S. Iliceto (Sabino); D. Scrutinio (Domenico); P. Bruzzi (P.); G. D'Ambrosio (Gaetano); A. Boni (Alejandro); M. Di Biase (Matteo); G. Biasco (Giuseppina); P.G. Hugenholtz (Paul); P. Rizzon (Paolo)

    1995-01-01

    textabstractObjectives. This study was performed to evaluate the effects of l-carnitine administration on long-term left ventricular dilation in patients with acute anterior myocardial infarction. Background. Carnitine is a physiologic compound that performs an essential role in myocardial energy p

  14. Acute Central Neuropeptide Y Administration Increases Food Intake but Does Not Affect Hepatic Very Low-Density Lipoprotein (Vldl) Production in Mice

    NARCIS (Netherlands)

    Geerling, J.J.; Wang, Y.; Havekes, L.M.; Romijn, J.A.; Rensen, P.C.N.

    2013-01-01

    Objective: Central neuropeptide Y (NPY) administration stimulates food intake in rodents. In addition, acute modulation of central NPY signaling increases hepatic production of very low-density lipoprotein (VLDL)-triglyceride (TG) in rats. As hypertriglyceridemia is an important risk factor for athe

  15. Downstream signaling pathways in mouse adipose tissues following acute in vivo administration of fibroblast growth factor 21.

    Science.gov (United States)

    Muise, Eric S; Souza, Sandra; Chi, An; Tan, Yejun; Zhao, Xuemei; Liu, Franklin; Dallas-Yang, Qing; Wu, Margaret; Sarr, Tim; Zhu, Lan; Guo, Hongbo; Li, Zhihua; Li, Wenyu; Hu, Weiwen; Jiang, Guoqiang; Paweletz, Cloud P; Hendrickson, Ronald C; Thompson, John R; Mu, James; Berger, Joel P; Mehmet, Huseyin

    2013-01-01

    FGF21 is a novel secreted protein with robust anti-diabetic, anti-obesity, and anti-atherogenic activities in preclinical species. In the current study, we investigated the signal transduction pathways downstream of FGF21 following acute administration of the growth factor to mice. Focusing on adipose tissues, we identified FGF21-mediated downstream signaling events and target engagement biomarkers. Specifically, RNA profiling of adipose tissues and phosphoproteomic profiling of adipocytes, following FGF21 treatment revealed several specific changes in gene expression and post-translational modifications, specifically phosphorylation, in several relevant proteins. Affymetrix microarray analysis of white adipose tissues isolated from both C57BL/6 (fed either regular chow or HFD) and db/db mice identified over 150 robust potential RNA transcripts and over 50 potential secreted proteins that were changed greater than 1.5 fold by FGF21 acutely. Phosphoprofiling analysis identified over 130 phosphoproteins that were modulated greater than 1.5 fold by FGF21 in 3T3-L1 adipocytes. Bioinformatic analysis of the combined gene and phosphoprotein profiling data identified a number of known metabolic pathways such as glucose uptake, insulin receptor signaling, Erk/Mapk signaling cascades, and lipid metabolism. Moreover, a number of novel events with hitherto unknown links to FGF21 signaling were observed at both the transcription and protein phosphorylation levels following treatment. We conclude that such a combined "omics" approach can be used not only to identify robust biomarkers for novel therapeutics but can also enhance our understanding of downstream signaling pathways; in the example presented here, novel FGF21-mediated signaling events in adipose tissue have been revealed that warrant further investigation.

  16. Effects of acute nicotine administration on behavioral and neural (EEG) correlates of working memory in non-smokers.

    Science.gov (United States)

    Fisher, Derek J; Daniels, Richelle; Jaworska, Natalia; Knobelsdorf, Amy; Knott, Verner J

    2012-01-06

    Enhancements in working memory (WM) performance have been previously reported following acute smoking/nicotine. Neuroimaging and behavioral assessments of nicotine's effects on WM have yielded inconsistent findings. Few studies, however, have examined the effects of nicotine on WM-related neural activity in non-smokers. The present study examined the effect of acute nicotine gum administration (6 mg) on electroencephalographic (EEG) activity (alpha(1), alpha(2) and theta bands) and performance on the parametrically manipulated N-back task of WM in 20 non-smoking adults. EEG activity varied with WM load (e.g. alpha(1) decreasing and theta increasing). Performance on the N-back was also load-sensitive, with slower reaction times and decreased accuracy associated with increasing memory load. Neither response speed nor accuracy measures were affected by nicotine but EEG was, with the effects varying by load and brain region. Nicotine-induced increases in alpha(2) and theta were observed under lower (0-, 1-back) memory load conditions Additionally, nicotine significantly reduced signal detection sensitivity values and altered response bias toward being more conservative at all levels of the N-back. Taken together, these findings suggest that while nicotine may boost WM neural processes at lower levels of WM load in non-smokers, it also may activate concurrent behavioral inhibition networks that negate any effects on behavioral performance. Additionally, nicotine appears to have no impact, or perhaps a negative impact, on these processes under more demanding (2-back, 3-back) conditions in non-smokers.

  17. Psychomotor performance in relation to acute oral administration of Delta9-tetrahydrocannabinol and standardized cannabis extract in healthy human subjects.

    Science.gov (United States)

    Roser, Patrik; Gallinat, Jürgen; Weinberg, Gordon; Juckel, Georg; Gorynia, Inge; Stadelmann, Andreas M

    2009-08-01

    Abnormalities in psychomotor performance are a consistent finding in schizophrenic patients as well as in chronic cannabis users. The high levels of central cannabinoid (CB(1)) receptors in the basal ganglia, the cerebral cortex and the cerebellum indicate their implication in the regulation of motor activity. Based on the close relationship between cannabis use, the endogenous cannabinoid system and motor disturbances found in schizophrenia, we expected that administration of cannabinoids may change pattern of psychomotor activity like in schizophrenic patients. This prospective, double-blind, placebo-controlled cross-over study investigated the acute effects of cannabinoids on psychomotor performance in 24 healthy right-handed volunteers (age 27.9 +/- 2.9 years, 12 male) by comparing Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and standardized cannabis extract containing Delta(9)-THC and cannabidiol. Psychomotor performance was assessed by using a finger tapping test series. Cannabis extract, but not Delta(9)-THC, revealed a significant reduction of right-hand tapping frequencies that was also found in schizophrenia. As to the pure Delta(9)-THC condition, left-hand tapping frequencies were correlated with the plasma concentrations of the Delta(9)-THC metabolite 11-OH-THC. These effects are thought to be related to cannabinoid actions on CB(1) receptors in the basal ganglia, the cerebral cortex and the cerebellum. Our data further demonstrate that acute CB(1) receptor activation under the cannabis extract condition may also affect intermanual coordination (IMC) as an index of interhemispheric transfer. AIR-Scale scores as a measure of subjective perception of intoxication were dose-dependently related to IMC which was shown by an inverted U-curve. This result may be due to functional changes involving GABAergic and glutamatergic neurotransmission within the corpus callosum.

  18. Effects of acute and chronic administration of MK-801 on c-Fos protein expression in mice brain regions implicated in schizophrenia and antagonistic action of clozapine

    Institute of Scientific and Technical Information of China (English)

    ZUO Dai-ying; CAO Yue; ZHANG Lan; WANG Hai-feng; WU Ying-liang

    2008-01-01

    Objective To investigate the effects of acute and chronic administration of the non-competitive NMDA receptor antagonists MK-801 on c-Fos protein expression in different brain regions of mice and antagonistic action of clozapine. Methods Immunohistochemistry was used to detect the expression of c-Fos protein. Results MK-801 (0.6 mg·kg-1) acute administration produced a significant increase in the expression of c-Fos protein in the layers Ⅲ-Ⅳ of posterior cingulate and retrosplenial (PC/RS) cortex, which was consistent with the previous reports. Moreover, we presented a new finding that MK-801 (0.6 mg·kg-1) chronic administration for 8 days produced a significant increase of c-Fos protein expression in the PC/RS cortex, prefrontal cortex (PFC) and hypothalamus of mice. Among that, c-Fos protein expression in the PC/ RS cortex of mice was most significant. Compared acute administration with chronic administration, we found that MK-801 chronic administration significantly increased the expression of c-Fos protein in the PC/ RS cortex, PFC and hypothalamus. Furthermore, pretreatment of mice with clozapine significantly decreased the expression of c-Fos protein induced by MK-801 acute and chronic administration. Conclusions Marked expression of c-Fos protein induced by MK-801 is associated with neurotransmitters' change noted in our previous studies, and c-Fos protein, the marker of neuronal activation, might play an important role in the chronic pathophysiological process of schizophrenic model induced by NMDA receptor antagonist.

  19. Anti-ulcer activity of Ficus religiosa leaf ethanolic extract

    Institute of Scientific and Technical Information of China (English)

    Marslin Gregory; B Divya; Revina Ann Mary; M M Hipolith Viji; V K Kalaichelvan; V Palanivel

    2013-01-01

    Objective:To evaluate the anti-ulcer activity and acute toxicity of Ficus religiosa (F. religiosa) leaf ethanolic extract in animal models. Methods:Anti-ulcer activity of F. religiosa ethanolic extract (250 and 500 mg/kg body weight) was studied on stress induced ulcer animal models. Ranitidine was used as standard. The anti-ulcer activity of F. religiosa was evaluated with the help of ulcer area and histopatholgical examination. Preliminary phyto-chemical screening and acute toxicity studies of F. religiosa also carried out. Results: Results showed that the extract treatments prevented ulcer area and gastric secretion in a dose-dependent manner. Administration of 2 000 mg/kg extract did not show any acute toxicity in albino mice. Preliminary phytochemical analysis identified the presence of flavonoids in the ethanolic extract of F. religiosa. Conclusions: The extract is non-toxic even at relatively high concentrations. The anti-ulcer activity is probably due to the presence of flavanoids.

  20. Acute Coronary Syndromes, Gastrointestinal Protection, and Recommendations Regarding Concomitant Administration of Proton-Pump Inhibitors (Omeprazol/Esomeprazole) and Clopidogrel.

    Science.gov (United States)

    Lozano, Iñigo; Sanchez-Insa, Esther; de Leiras, Sergio Rodríguez; Carrillo, Pilar; Ruiz-Quevedo, Valeriano; Pinar, Eduardo; Gopar-Gopar, Silvia; Bayon, Jeremías; Mañas, Pilar; Lasa, Garikoitz; CruzGonzalez, Ignacio; Hernandez, Felipe; Fernandez-Portales, Javier; Fernandez-Fernandez, Javier; Pérez-Serradilla, Ana; de la Torre Hernandez, José M; Gomez-Jaume, Alfredo

    2016-02-01

    The Food and Drug Administration and the European Medicines Agency sent a warning in 2010 discouraging the concomitant use of clopidogrel with omeprazole or esomeprazole. The purpose is to know the gastroprotective approach in patients with acute coronary syndrome (ACS) and the level of follow-up of the alert. In 17 hospitals with catheterization laboratory in Spain, 1 per region, we studied 25 consecutive patients per hospital whose diagnosis of discharge since October 1, 2013, had been any type of ACS. We analyzed their baseline clinical profile, the gatroprotective agents at admission and discharge and the antiplatelet therapy at discharge. The number of patients included was 425: age 67.2 ± 12.5 years, women 29.8%, diabetes 36.5%. The patients presented unstable angina in 21.6%, non-ST-elevation myocardial infarction in 35.3% and ST-elevation myocardial infarction in 43.1%. Conservative approach was chosen in 17.9%, bare-metal stents 32.2%, ≥ 1 drug-eluting stent 48.5%, and surgery 1.4%. Aspirin was indicated in 1.9%, aspirin + clopidogrel 73.6%, aspirin + prasugrel 17.6%, and aspririn + ticagrelor 6.8%. Gastroprotective agents were present in 40.2% patients at admission and this percentage increased to 93.7% at discharge. Of the 313 (73.6%) on clopidogrel in 96 (30.6%) was combined with omeprazole and 3 (0.95%) with esomeprazole, whereas the most commonly used was pantoprazole with 190 patients (44.7%). In conclusion, almost the totality of the patients with an ACS receive gastroprotective agents at the moment of discharge, most of them with proton-pump inhibitors. In one every 3 cases of the patients who are on clopidogrel, the recommendation of the Food and Drug Administration and the European Medicines Agency is not followed.

  1. The influence of the time of antidotal treatment administration on the potency of newly developed oximes to counteract acute toxic effects of tabun in mice.

    Science.gov (United States)

    Kassa, Jirí

    2005-01-01

    (1) The influence of the time of administration of antidotal treatment consisting of anticholinergic drug (atropine) and newly developed oxime (K027 or K048) on its effectiveness to eliminate tabun-induced lethal toxic effects was studied in mice. (2) The therapeutic efficacy of antidotal treatment of tabun-induced acute poisoning depends on the time of its administration regardless of the choice of the oxime. (3) Our results show that both oximes studied (K027, K048) are able to sufficiently eliminate lethal effects of tabun. Nevertheless, their efficacy significantly decreases when they were administered 5 min after tabun poisoning. (4) The findings support the hypothesis that both newly developed oximes appear to be suitable oximes to counteract acute toxicity of tabun although their ability to eliminate lethal toxic effects of tabun significantly decreases with prolonged time interval between tabun challenge and antidotal treatment administration.

  2. Neuroimmunomodulatory effects of transcranial laser therapy combined with intravenous tPA administration for acute cerebral ischemic injury

    Institute of Scientific and Technical Information of China (English)

    Philip V. Peplow

    2015-01-01

    At present, the only FDA approved treatment for ischemic strokes is intravenous administration of tissue plasminogen activator within 4.5 hours of stroke onset. Owing to this brief window only a small percentage of patients receive tissue plasminogen activator. Transcranial laser therapy has been shown to be effective in animal models of acute ischemic stroke, resulting in signiifcant improvement in neurological score and function. NEST-1 and NEST-2 clinical trials in human patients have demonstrated the safety and positive trends in efifcacy of transcranial laser therapy for the treatment of ischemic stroke when initiated close to the time of stroke onset. Combining intravenous tissue plasminogen activator treatment with transcranial laser therapy may provide better functional outcomes. Statins given within 4 weeks of stroke onset improve stroke out-comes at 90 days compared to patients not given statins, and giving statins following transcranial laser therapy may provide an effective treatment for patients not able to be given tissue plasmin-ogen activator due to time constraints.

  3. Brain plasticity and cognitive functions after ethanol consumption in C57BL/6J mice

    Science.gov (United States)

    Stragier, E; Martin, V; Davenas, E; Poilbout, C; Mongeau, R; Corradetti, R; Lanfumey, L

    2015-01-01

    Acute or chronic administrations of high doses of ethanol in mice are known to produce severe cognitive deficits linked to hippocampal damage. However, we recently reported that chronic and moderate ethanol intake in C57BL/6J mice induced chromatin remodeling within the Bdnf promoters, leading to both enhanced brain-derived neurotrophic factor (BDNF) expression and hippocampal neurogenesis under free-choice protocol. We performed here a series of cellular and behavioral studies to analyze the consequences of these modifications. We showed that a 3-week chronic free-choice ethanol consumption in C57BL/6J mice led to a decrease in DNA methylation of the Bdnf gene within the CA1 and CA3 subfields of the hippocampus, and upregulated hippocampal BDNF signaling pathways mediated by ERK, AKT and CREB. However, this activation did not affect long-term potentiation in the CA1. Conversely, ethanol intake impaired learning and memory capacities analyzed in the contextual fear conditioning test and the novel object recognition task. In addition, ethanol increased behavioral perseveration in the Barnes maze test but did not alter the mouse overall spatial capacities. These data suggested that in conditions of chronic and moderate ethanol intake, the chromatin remodeling leading to BDNF signaling upregulation is probably an adaptive process, engaged via epigenetic regulations, to counteract the cognitive deficits induced by ethanol. PMID:26670281

  4. Inhibitory effect on key enzymes relevant to acute type-2 diabetes and antioxidative activity of ethanolic extract of Artocarpus heterophyllus stem bark

    Institute of Scientific and Technical Information of China (English)

    Basiru Olaitan Ajiboye; Oluwafemi Adeleke Ojo; Oluwatosin Adeyonu; Oluwatosin Imiere; Isreal Olayide; Adewale Fadaka; Babatunji Emmanuel Oyinloye

    2016-01-01

    Objective: To investigate the in vitro antioxidant activity of ethanolic extract of Arto-carpus heterophyllus (A. heterophyllus) stem bark and its inhibitory effect on a-amylase and a-glucosidase. Methods: The A. heterophyllus stem bark was extracted using methanol and tested for antioxidative activity. Results: The results revealed that the ethanolic extract has polyphenolics and free radical scavenging compounds which were significantly higher (P Conclusions: Therefore, it can be inferred from this study that ethanolic extract of A. heterophyllus stem bark may be useful in the management of diabetes mellitus probably due to bioactive compounds observed in the extract.

  5. Chronic Voluntary Ethanol Consumption Induces Favorable Ceramide Profiles in Selectively Bred Alcohol-Preferring (P Rats.

    Directory of Open Access Journals (Sweden)

    Jessica Godfrey

    Full Text Available Heavy alcohol consumption has detrimental neurologic effects, inducing widespread neuronal loss in both fetuses and adults. One proposed mechanism of ethanol-induced cell loss with sufficient exposure is an elevation in concentrations of bioactive lipids that mediate apoptosis, including the membrane sphingolipid metabolites ceramide and sphingosine. While these naturally-occurring lipids serve as important modulators of normal neuronal development, elevated levels resulting from various extracellular insults have been implicated in pathological apoptosis of neurons and oligodendrocytes in several neuroinflammatory and neurodegenerative disorders. Prior work has shown that acute administration of ethanol to developing mice increases levels of ceramide in multiple brain regions, hypothesized to be a mediator of fetal alcohol-induced neuronal loss. Elevated ceramide levels have also been implicated in ethanol-mediated neurodegeneration in adult animals and humans. Here, we determined the effect of chronic voluntary ethanol consumption on lipid profiles in brain and peripheral tissues from adult alcohol-preferring (P rats to further examine alterations in lipid composition as a potential contributor to ethanol-induced cellular damage. P rats were exposed for 13 weeks to a 20% ethanol intermittent-access drinking paradigm (45 ethanol sessions total or were given access only to water (control. Following the final session, tissues were collected for subsequent chromatographic analysis of lipid content and enzymatic gene expression. Contrary to expectations, ethanol-exposed rats displayed substantial reductions in concentrations of ceramides in forebrain and heart relative to non-exposed controls, and modest but significant decreases in liver cholesterol. qRT-PCR analysis showed a reduction in the expression of sphingolipid delta(4-desaturase (Degs2, an enzyme involved in de novo ceramide synthesis. These findings indicate that ethanol intake levels

  6. Chronic Voluntary Ethanol Consumption Induces Favorable Ceramide Profiles in Selectively Bred Alcohol-Preferring (P) Rats.

    Science.gov (United States)

    Godfrey, Jessica; Jeanguenin, Lisa; Castro, Norma; Olney, Jeffrey J; Dudley, Jason; Pipkin, Joseph; Walls, Stanley M; Wang, Wei; Herr, Deron R; Harris, Greg L; Brasser, Susan M

    2015-01-01

    Heavy alcohol consumption has detrimental neurologic effects, inducing widespread neuronal loss in both fetuses and adults. One proposed mechanism of ethanol-induced cell loss with sufficient exposure is an elevation in concentrations of bioactive lipids that mediate apoptosis, including the membrane sphingolipid metabolites ceramide and sphingosine. While these naturally-occurring lipids serve as important modulators of normal neuronal development, elevated levels resulting from various extracellular insults have been implicated in pathological apoptosis of neurons and oligodendrocytes in several neuroinflammatory and neurodegenerative disorders. Prior work has shown that acute administration of ethanol to developing mice increases levels of ceramide in multiple brain regions, hypothesized to be a mediator of fetal alcohol-induced neuronal loss. Elevated ceramide levels have also been implicated in ethanol-mediated neurodegeneration in adult animals and humans. Here, we determined the effect of chronic voluntary ethanol consumption on lipid profiles in brain and peripheral tissues from adult alcohol-preferring (P) rats to further examine alterations in lipid composition as a potential contributor to ethanol-induced cellular damage. P rats were exposed for 13 weeks to a 20% ethanol intermittent-access drinking paradigm (45 ethanol sessions total) or were given access only to water (control). Following the final session, tissues were collected for subsequent chromatographic analysis of lipid content and enzymatic gene expression. Contrary to expectations, ethanol-exposed rats displayed substantial reductions in concentrations of ceramides in forebrain and heart relative to non-exposed controls, and modest but significant decreases in liver cholesterol. qRT-PCR analysis showed a reduction in the expression of sphingolipid delta(4)-desaturase (Degs2), an enzyme involved in de novo ceramide synthesis. These findings indicate that ethanol intake levels achieved by

  7. Characteristic of endocrine cells of rat small intestine after administration of cryopreserved placenta on the background of acute aseptic peritoneal inflammation

    Directory of Open Access Journals (Sweden)

    Shepitko K.V.

    2015-06-01

    Full Text Available Background. Modern conceptions about mechanisms of inflammation of the small intestine could not be formed without an understanding of intercellular relationships that are realized by biologically active signaling molecules produced by endocrine cells. Methods. The experimental study has been carried out on the small intestine extracted from 140 adult male rats. Electron and light microscopy methods were used. Acute aseptic inflammation was modeled by intraperitoneal carrageenan injection; influence of subcutaneously cryopreserved placenta injection was analyzed. Results. After modeling of the acute aseptic peritoneal inflammation the maximal increase of ECL-cells was noted on the 21st day. The slowest restoration of endocrine cells number occurred on all measured parameters and was observed on day 30th of the observation. In case of administration of cryopreserved placenta at the early stages (days 3rd – 7th the increase of average number of EC- and ECL-cells promoted the enhanced permeability of vessels in the lamina propria. The decrease in number of P-cells prevented the development of hyperacid gastritis. Reduction in the average number of D1- cells prevented the excessive vasodilatation and facilitated the excretion of excess fluid from the foci of inflammation. In simultaneous subcutaneous administration of cryopreserved placenta and modeling of acute aseptic peritoneal inflammation the number of ЕС- and ЕСL-cells increased, accelerating the vascular response to inflammation. Conclusion. Active appearance of low-differentiated cells including those with “shapes of mitosis” on the day 14th indicates restoration of structural components of the small intestine mucosa and processes of absorption and parietal digestion after placenta administration during acute aseptic inflammation. Citation: Shepitko KV. [Characteristic of endocrine cells of rat small intestine after administration of cryopreserved placenta on the background of

  8. Protective Effects of Manassantin A against Ethanol-Induced Gastric Injury in Rats.

    Science.gov (United States)

    Song, Ji-Won; Seo, Chang-Seob; Kim, Tae-In; Moon, Og-Sung; Won, Young-Suk; Son, Hwa-Young; Son, Jong-Keun; Kwon, Hyo-Jung

    2016-01-01

    Manassantin A, a neolignan isolated from Saururus chinensis, is a major phytochemical compound that has various biological activities, including anti-inflammatory, neuroleptic, and human acyl-CoA : cholesterol acyltransferase (ACAT) inhibitory activities. In this study, we investigated the protective effects of manassantin A against ethanol-induced acute gastric injury in rats. Gastric injury was induced by intragastric administration of 5 mL/kg body weight of absolute ethanol to each rat. The positive control group and the manassantin A group were given oral doses of omeprazole (20 mg/kg) or manassantin A (15 mg/kg), respectively, 1 h prior to the administration of absolute ethanol. Our examinations revealed that manassantin A pretreatment reduced ethanol-induced hemorrhage, hyperemia, and epithelial cell loss in the gastric mucosa. Manassantin A pretreatment also attenuated the increased lipid peroxidation associated with ethanol-induced acute gastric lesions, increased the mucosal glutathione (GSH) content, and enhanced the activities of antioxidant enzymes. The levels of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β were clearly decreased in the manassantin A-pretreated group. In addition, manassantin A pretreatment enhanced the levels of cyclooxygenase (COX)-1, COX-2, and prostaglandin E2 (PGE2) and reduced the inducible nitric oxide synthase (iNOS) overproduction and nuclear factor kappa B (NF-κB) phosphorylation. Collectively, these results indicate that manassantin A protects the gastric mucosa from ethanol-induced acute gastric injury, and suggest that these protective effects might be associated with COX/PGE2 stimulation, inhibition of iNOS production and NF-κB activation, and improvements in the antioxidant and anti-inflammatory status.

  9. Protective effects of diallyl sulfide against acute ethanol-induced liver injury%二烯丙基一硫化物对小鼠急性酒精性肝损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    朱振平; 曾涛; 邵晓颖; 于丽华; 谢克勤

    2012-01-01

    目的 研究二烯丙基一硫化物(DAS)对急性酒精性肝损伤的保护作用.方法 将40只健康SPF级雄性昆明小鼠随机分为4组,分别为对照组、模型组、DAS干预组和DAS对照组,每组10只.DAS干预组和DAS对照组小鼠经口灌胃给予50 mg/kg的DAS溶液,每天1次,连续7d;对照组和模型组小鼠给予等体积的玉米油.末次给药2h后,模型组和DAS干预组小鼠经口灌胃给予5g/kg乙醇诱导肝损伤,连续3次,每次间隔12h;对照组和DAS对照组小鼠给予等体积等热量的麦芽糖糊精.测定血清丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)的活力以及肝组织匀浆中谷胱甘肽(GSH)、丙二醛(MDA)含量和超氧化物歧化酶(SOD)、谷胱甘肽还原酶(GR)、谷胱甘肽过氧化物酶(GPx)活力.结果 与模型组比较,对照组、DAS干预组和DAS对照组小鼠血清ALT、AST活力和肝组织匀浆中MDA含量均较低,肝组织匀浆中GSH含量和SOD、GPx、GR活力均较高,差异有统计学意义(P<0.05或P<0.01).结论 DAS对小鼠急性酒精性肝损伤有保护作用,机制可能与其具有的抗氧化活性有关.%Objective To study the protective effects of diallyl sulfide(DAS) against acute ethanol-induced liver injury in mice. Methods A total of 40 SPF male Kunming mice were randomly divided into four groups, control group, ethanol group, DAS plus ethanol group, and DAS group (re=10). The mice in DAS plus ethanol group and DAS group were pretreated with DAS (50 mg/kg body weight, I.g., 10 ml/kg) for seven consecutive days, while the mice in the other groups were treated with the same volume of corn oil. Two hours after the last treatment, the mice in ethanol group and DAS plus ethanol group were treated with 5 g/kg body weight ethanol (20 ml/kg bodyweight, I.g.) for total of three doses with an interval of 12 h,while the other mice were treated with isocaloric and isovolumetric maltose—dextrin. The serum aminotransferase (ALT, AST

  10. Prenatal ethanol exposure leads to greater ethanol-induced appetitive reinforcement.

    Science.gov (United States)

    Pautassi, Ricardo M; Nizhnikov, Michael E; Spear, Norman E; Molina, Juan C

    2012-09-01

    Prenatal ethanol significantly heightens later alcohol consumption, but the mechanisms that underlie this phenomenon are poorly understood. Little is known about the basis of 'this effect of prenatal ethanol on the sensitivity to ethanol's reinforcing effects. One possibility is that prenatal ethanol exposure makes subjects more sensitive to the appetitive effects of ethanol or less sensitive to ethanol's aversive consequences. The present study assessed ethanol-induced second-order conditioned place preference (CPP) and aversion and ethanol-induced conditioned taste aversion (CTA) in infant rats prenatally exposed to ethanol (2.0 g/kg) or vehicle (water) or left untreated. The involvement of the κ opioid receptor system in ethanol-induced CTA was also explored. When place conditioning occurred during the ascending limb of the blood-ethanol curve (Experiment 1), the pups exposed to ethanol in utero exhibited greater CPP than untreated controls, with a shift to the right of the dose-response curve. Conditioning during a later phase of intoxication (30-45 min post-administration; Experiment 2) resulted in place aversion in control pups exposed to vehicle during late gestation but not in pups that were exposed to ethanol in utero. Ethanol induced a reliable and similar CTA (Experiment 3) in the pups treated with vehicle or ethanol during gestation, and CTA was insensitive to κ antagonism. These results suggest that brief exposure to a moderate ethanol dose during late gestation promotes ethanol-mediated reinforcement and alters the expression of conditioned aversion by ethanol. This shift in the motivational reactivity to ethanol may be an underlying basis of the effect of prenatal ethanol on later ethanol acceptance.

  11. Ethanol-induced effects on sting extension response and punishment learning in the western honey bee (Apis mellifera.

    Directory of Open Access Journals (Sweden)

    Manuel A Giannoni-Guzmán

    Full Text Available Acute ethanol administration is associated with sedation and analgesia as well as behavioral disinhibition and memory loss but the mechanisms underlying these effects remain to be elucidated. During the past decade, insects have emerged as important model systems to understand the neural and genetic bases of alcohol effects. However, novel assays to assess ethanol's effects on complex behaviors in social or isolated contexts are necessary. Here we used the honey bee as an especially relevant model system since bees are typically exposed to ethanol in nature when collecting standing nectar crop of flowers, and there is recent evidence for independent biological significance of this exposure for social behavior. Bee's inhibitory control of the sting extension response (SER and a conditioned-place aversion assay were used to study ethanol effects on analgesia, behavioral disinhibition, and associative learning. Our findings indicate that although ethanol, in a dose-dependent manner, increases SER thresholds (analgesic effects, it disrupts the ability of honey bees to inhibit SER and to associate aversive stimuli with their environment. These results suggest that ethanol's effects on analgesia, behavioral disinhibition and associative learning are common across vertebrates and invertebrates. These results add to the use of honey bees as an ethanol model to understand ethanol's effects on complex, socially relevant behaviors.

  12. Simultaneous Determination of Four Tanshinones by UPLC-TQ/MS and Their Pharmacokinetic Application after Administration of Single Ethanol Extract of Danshen Combined with Water Extract in Normal and Adenine-Induced Chronic Renal Failure Rats

    Directory of Open Access Journals (Sweden)

    Hong-Die Cai

    2016-11-01

    Full Text Available Salvia miltiorrhiza, one of the major traditional Chinese medicines, is commonly used and the main active ingredients—tanshinones—possess the ability to improve renal function. In this paper, the UPLC-TQ/MS method of simultaneously determining four tanshinones—tanshinone IIA, dihydrotanshinone I, tanshinone I, and cryptotanshinone—was established and applied to assess the pharmacokinetics in normal and chronic renal failure (CRF rat plasma. The pharmacokinetics of tanshinones in rats were studied after separately intragastric administration of Salvia miltiorrhiza ethanol extract (SMEE (0.65 g/kg, SMEE (0.65 g/kg combined with Salvia miltiorrhiza water extract (SMWE (1.55 g/kg. The results showed Cmax and AUC0–t of tanshinone IIA, tanshinone I, cryptotanshinone reduced by 50%~80% and CLz/F increased by 2~4 times (p < 0.05 in model group after administrated with SMEE. Nevertheless, after intragastric administration of a combination of SMWE and SMEE, the Cmax and AUC0–t of four tanshinones were upregulated and CLz/F was downregulated, which undulated similarity from the model group to the normal group with compatibility of SMEE and SMWE. These results hinted that SMWE could improve the bioavailability of tanshinones in CRF rats, which provides scientific information for further exploration the mechanism of the combination of SMWE and SMEE and offers a reference for clinical administration of Salvia miltiorrhiza.

  13. Improving Effect of the Acute Administration of Dietary Fiber-Enriched Cereals on Blood Glucose Levels and Gut Hormone Secretion.

    Science.gov (United States)

    Kim, Eun Ky; Oh, Tae Jung; Kim, Lee-Kyung; Cho, Young Min

    2016-02-01

    Dietary fiber improves hyperglycemia in patients with type 2 diabetes through its physicochemical properties and possible modulation of gut hormone secretion, such as glucagon-like peptide 1 (GLP-1). We assessed the effect of dietary fiber-enriched cereal flakes (DC) on postprandial hyperglycemia and gut hormone secretion in patients with type 2 diabetes. Thirteen participants ate isocaloric meals based on either DC or conventional cereal flakes (CC) in a crossover design. DC or CC was provided for dinner, night snack on day 1 and breakfast on day 2, followed by a high-fat lunch. On day 2, the levels of plasma glucose, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and insulin were measured. Compared to CC, DC intake exhibited a lower post-breakfast 2-hours glucose level (198.5±12.8 vs. 245.9±15.2 mg/dL, P<0.05) and a lower incremental peak of glucose from baseline (101.8±9.1 vs. 140.3±14.3 mg/dL, P<0.001). The incremental area under the curve (iAUC) of glucose after breakfast was lower with DC than with CC (P<0.001). However, there were no differences in the plasma insulin, glucagon, GLP-1, and GIP levels. In conclusion, acute administration of DC attenuates postprandial hyperglycemia without any significant change in the representative glucose-regulating hormones in patients with type 2 diabetes (ClinicalTrials.gov. NCT 01997281).

  14. Effect of acute lindane and alcohol intoxication on serum concentration of enzymes and fatty acids in rats.

    Science.gov (United States)

    Radosavljević, T; Mladenović, D; Vucević, D; Petrović, J; Hrncić, D; Djuric, D; Loncar-Stevanović, H; Stanojlović, O

    2008-05-01

    This study examines possible synergistic effects of lindane and ethanol on inducing liver injury and serum fatty acid derangement in adult male Wistar rats. When administered together, ethanol and lindane-induced even more pronounced increase of alanine aminotransferase (165 +/- 10 U/L) and gamma-glutamyltranspeptidase activity (10.3 +/- 0.6 U/L) than after isolated administration of either substance. In addition, separate administration of lindane and ethanol was followed by a significant decrease of linoleic acid level in the serum (301 +/- 38 mg/L, 276 +/- 35 mg/L vs. 416 +/- 48 mg/L). However, when ethanol administration was followed by lindane injection, serum linoleic acid was at the similar level found in the control group (516 +/- 62 mg/L). Ethanol-treated rats that received lindane 30 min after ethanol administration have shown a marked increase of palmitic (421 +/- 27 mg/L) and linolic acid level (43 +/- 5 mg/L) in comparison with rats that have been treated only with ethanol (316+/-26 mg/L for palmitic and 32 +/- 2 mg/L for linolic acid) or lindane (295 +/- 26 mg/L for palmitic and 301 +/- 38 mg/L for linolic acid). Linolic acid level was significantly greater in comparison with control group (29 +/- 1 mg/L). In conclusion, this study found enough evidence to support the hypothesis that acute ethanol intoxication potentiates lindane-induced liver injury and enhances lipid derangement.

  15. Effects of acute and chronic aripiprazole treatment on choice between cocaine self-administration and food under a concurrent schedule of reinforcement in rats

    DEFF Research Database (Denmark)

    Thomsen, Morgane; Fink-Jensen, Anders; Woldbye, David

    2008-01-01

    the hypothesis that aripiprazole, both as acute and as chronic treatment, would preferentially decrease cocaine self-administration while sparing behavior maintained by a natural reinforcer, resulting in a shift in the allocation of behavior from cocaine-taking towards the alternative reinforcer. MATERIALS...... AND METHODS: Rats were trained to self-administer intravenous cocaine in a concurrent choice procedure, with a palatable food as the competing reinforcer, under a fixed ratio (FR) 1 FR 5 chain schedule. Aripiprazole was then administered as continuous infusion by osmotic minipumps for 5 days, during which...... performance in the choice procedure was assessed daily. RESULTS: An intermediate dose of aripiprazole decreased cocaine self-administration and shifted the cocaine choice curve to the right as an acute treatment. However, as a chronic treatment, aripiprazole failed to decrease cocaine self...

  16. A Naturalistic, Single-blind Comparison of Rapid Dose Administration of Divalproex ER Versus Quetiapine in Patients with Acute Bipolar Mania

    Science.gov (United States)

    Galangue, Barbara; MacDonald, Kai; Cobb, Patrice; Dinca, Ana; Becker, Olga; Cooper, J.; Hadley, Allison

    2011-01-01

    Objective: When treating acute bipolar mania, the speed of onset of anti-manic effects is crucial. Quetiapine and divalproex ER are widely used agents to treat acute mania. Rapid dose administration regimens for divalproex ER and for quetiapine have been described. We conducted a naturalistic, head-to-head, pilot study comparing the efficacy and safety of rapidly titrated divalproex ER and quetiapine in acutely manic inpatients, with the primary outcome being improvement within the first seven days. Method: Thirty consenting bipolar patients with acute mania (Young Mania Rating Scale >17 ) needing hospitalization due to acute mania were randomized to receive rapidly loaded divalproex ER (30mg/kg/day) or rapidly titrated quetiapine (200mg Day 1, raised by 200mg/day up to 800mg as tolerated). Assessments were made on Day 1 (baseline), Day 3, Day 7, Day 14, and Day 21 and included Young Mania Rating Scale, Clinical Global Impressions-Severity, Clinical Global Impressions-Improvement, and Montgomery-Asberg Depression Rating Scale. Raters but not patients or treating physicians were blinded (single-blinded study). Results: Subjects in both treatment groups exhibited significant and rapid improvement in their mania starting at Day 3 with few significant adverse effects; however, there were no significant differences in the degree or rate of improvement between the two treatment groups in any of the efficacy or adverse effects scales. Conclusion: Results of this small study indicate that rapid-dose administration of both quetiapine and divalproex ER produce rapid improvement in acute mania within the first seven days and both seem to be well tolerated. PMID:21311705

  17. Inhibitor y effect on key enzymes relevant to acute type-2 diabetes and antioxidative activity of ethanolic extract of Artocarpus heterophyllus stem bark

    Directory of Open Access Journals (Sweden)

    Basiru Olaitan Ajiboye

    2016-09-01

    Full Text Available Objective: To investigate the in vitro antioxidant activity of ethanolic extract of Artocarpus heterophyllus (A. heterophyllus stem bark and its inhibitory effect on a-amylase and a-glucosidase. Methods: The A. heterophyllus stem bark was extracted using methanol and tested for antioxidative activity. Results: The results revealed that the ethanolic extract has polyphenolics and free radical scavenging compounds which were significantly higher (P < 0.05 than their respective standard, at concentration dependent manner. The ethanolic extract of A. heterophyllus stem bark was observed to show inhibitory activities on a-amylase and a-glucosidase with IC50 of (4.18 ± 0.01 and (3.53 ± 0.03 mg/mL, respectively. The Lineweaver-Burk plot revealed that ethanolic extract of A. heterophyllus stem bark exhibited non-competitive inhibition for a-amylase and uncompetitive inhibition for a-glucosidase activities. Also, gas chromatography–mass spectrometry showed the presence of different bioactive compounds in extract. Conclusions: Therefore, it can be inferred from this study that ethanolic extract of A. heterophyllus stem bark may be useful in the management of diabetes mellitus probably due to bioactive compounds observed in the extract.

  18. Long-term benefit of early pre-reperfusion metoprolol administration in patients with acute myocardial infarction: Results from the Metocard-CNIC trial (Effect of Metoprolol in Cardioprotection during an Acute Myocardial Infarction)

    OpenAIRE

    Pizarro, Gonzalo; García Lunar, Inés; Martínez de Vega, Vicente; Cabrera Rodríguez, José Ángel

    2014-01-01

    The goal of this trial was to study the long-term effects of intravenous (IV) metoprolol administration before reperfusion on left ventricular (LV) function and clinical events. Early IV metoprolol during ST-segment elevation myocardial infarction (STEMI) has been shown to reduce infarct size when used in conjunction with primary percutaneous coronary intervention (pPCI). The METOCARD-CNIC (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction) trial recruited 270 pat...

  19. Changes on metabolic parameters induced by acute cannabinoid administration (CBD, THC in a rat experimental model of nutritional vitamin A deficiency

    Directory of Open Access Journals (Sweden)

    Loubna El Amrani

    2013-06-01

    Full Text Available Introduction: Vitamin A deficiency can result from malnutrition, malabsorption of vitamin A, impaired vitamin metabolism associated with liver disease, or chronic debilitating diseases like HIV infection or cancer. Background & aims: Cannabis administration has been described as a palliative symptom management therapy in such pathological stages. Therefore, this research aimed to study the effects of acute administration of cannabidiol (CBD or thetrahydrocannabinol (THC on the levels of retinol in plasma and in the liver, and biochemical parameters related to lipid and glucose metabolism (cholesterolaemia, triglyceridemia and glycemia in a rat experimental model of vitamin A deficiency. Methods: The experimental animal model of Vitamin A deficiency was developed during a 50-day experimental period in which rats consumed a vitamin A-free diet. Cannabidiol (10 mg/kg body weight or thetrahydrocannabinol (5 mg/kg body weight were administered intraperitoneally 2 hours prior to sacrifice of the animals. Results: The nutritional deficiency caused a significant decrease in plasmatic and liver contents of retinol and biochemical parameters of glycemic, lipidic, and mineral metabolism. Acute intraperitoneal administration of Cannabidiol and thetrahydrocannabinol did not improve the indices of vitamin A status in either control or vitamin A-deficient rats. However, it had a significant effect on specific biochemical parameters such as glucose, triglycerides, and cholesterol. Conclusion: Under our experimental conditions, the reported effects of cannabinoid administration on certain signs of nutritional vitamin A deficiency appeared to be mediated through mechanisms other than changes in retinol metabolism or its mobilization after the acute administration of such compounds.

  20. Ethanol-Induced Cerebellar Ataxia: Cellular and Molecular Mechanisms.

    Science.gov (United States)

    Dar, M Saeed

    2015-08-01

    The cerebellum is an important target of ethanol toxicity given that cerebellar ataxia is the most consistent physical manifestation of acute ethanol consumption. Despite the significance of the cerebellum in ethanol-induced cerebellar ataxia (EICA), the cellular and molecular mechanisms underlying EICA are incompletely understood. However, two important findings have shed greater light on this phenomenon. First, ethanol-induced blockade of cerebellar adenosine uptake in rodent models points to a role for adenosinergic A1 modulation of EICA. Second, the consistent observation that intracerebellar administration of nicotine in mice leads to antagonism of EICA provides evidence for a critical role of cerebellar nitric oxide (NO) in EICA reversal. Based on these two important findings, this review discusses the potential molecular events at two key synaptic sites (mossy fiber-granule cell-Golgi cell (MGG synaptic site) and granule cell parallel fiber-Purkinje cell (GPP synaptic site) that lead to EICA. Specifically, ethanol-induced neuronal NOS inhibition at the MGG synaptic site acts as a critical trigger for Golgi cell activation which leads to granule cell deafferentation. Concurrently, ethanol-induced inhibition of adenosine uptake at the GPP synaptic site produces adenosine accumulation which decreases glutamate release and leads to the profound activation of Purkinje cells (PCs). These molecular events at the MGG and GPP synaptic sites are mutually reinforcing and lead to cerebellar dysfunction, decreased excitatory output of deep cerebellar nuclei, and EICA. The critical importance of PCs as the sole output of the cerebellar cortex suggests normalization of PC function could have important therapeutic implications.

  1. Effects of long-term acetyl-L-carnitine administration in rats: I. increased dopamine output in mesocorticolimbic areas and protection toward acute stress exposure.

    Science.gov (United States)

    Tolu, Pierluigi; Masi, Flavio; Leggio, Benedetta; Scheggi, Simona; Tagliamonte, Alessandro; De Montis, M Graziella; Gambarana, Carla

    2002-09-01

    Acetyl-L-carnitine (ALCAR) is the acetyl ester of carnitine that has been reported to be beneficial in depressive disorders and Alzheimer's disease. A 7-day administration of ALCAR in rats increased dopamine and serotonin output in the nucleus accumbens shell and it prevented the development of escape deficit produced by acute exposure to unavoidable stress. No tolerance developed to this protective effect, which appeared to be mediated by (1) the activation of 5-HT(1A) receptors, as it was antagonized by the administration of WAY100635 30 min before stress exposure; and (2) a process of neuronal plasticity dependent on NMDA receptor activity, as subcutaneous dizocilpine infusion during ALCAR treatment prevented the development of the protective effect on stress. Chronic stress exposure maintains an escape deficit condition that is reverted by a long-term treatment with antidepressants, but the same condition was not modified by long-term ALCAR administration. Thus, ALCAR cannot be defined as an antidepressant.

  2. Cellulosic ethanol

    DEFF Research Database (Denmark)

    Lindedam, Jane; Bruun, Sander; Jørgensen, Henning;

    2010-01-01

    Background Variations in sugar yield due to genotypic qualities of feedstock are largely undescribed for pilot-scale ethanol processing. Our objectives were to compare glucose and xylose yield (conversion and total sugar yield) from straw of five winter wheat cultivars at three enzyme loadings (2...

  3. Repeated episodes of chronic intermittent ethanol promote insensitivity to devaluation of the reinforcing effect of ethanol.

    Science.gov (United States)

    Lopez, M F; Becker, H C; Chandler, L J

    2014-11-01

    Studies in animal models have shown that repeated episodes of alcohol dependence and withdrawal promote escalation of drinking that is presumably associated with alterations in the addiction neurocircuitry. Using a lithium chloride-ethanol pairing procedure to devalue the reinforcing properties of ethanol, the present study determined whether multiple cycles of chronic intermittent ethanol (CIE) exposure by vapor inhalation also alters the sensitivity of drinking behavior to the devaluation of ethanol's reinforcing effects. The effect of devaluation on operant ethanol self-administration and extinction was examined in mice prior to initiation of CIE (short drinking history) and after repeated cycles of CIE or air control exposure (long drinking history). Devaluation significantly attenuated the recovery of baseline ethanol self-administration when tested either prior to CIE or in the air-exposed controls that had experienced repeated bouts of drinking but no CIE. In contrast, in mice that had undergone repeated cycles of CIE exposure that promoted escalation of ethanol drinking, self-administration was completely resistant to the effect of devaluation. Devaluation had no effect on the time course of extinction training in either pre-CIE or post-CIE mice. Taken together, these results are consistent with the suggestion that repeated cycles of ethanol dependence and withdrawal produce escalation of ethanol self-administration that is associated with a change in sensitivity to devaluation of the reinforcing properties of ethanol.

  4. Ethanol modulation of mammalian BK channels in excitable tissues: molecular targets and their possible contribution to alcohol-induced altered behavior

    Directory of Open Access Journals (Sweden)

    Alex M. Dopico

    2014-12-01

    Full Text Available In most tissues, the function of calcium- and voltage-gated potassium (BK channels is modified in response to ethanol concentrations reached in human blood during alcohol intoxication. In general, modification of BK current from ethanol-naïve preparations in response to brief ethanol exposure results from changes in channel open probability without modification of unitary conductance or change in BK protein levels in the membrane. Protracted and/or repeated ethanol exposure, however, may evoke changes in BK expression. The final ethanol effect on BK open probability leading to either BK current potentiation or BK current reduction is determined by an orchestration of molecular factors, including levels of activating ligand (cytosolic calcium, BK subunit composition and posttranslational modifications, and the channel’s lipid microenvironment. These factors seem to allosterically regulate a direct interaction between ethanol and a recognition pocket of discrete dimensions recently mapped to the channel-forming (slo1 subunit. Type of ethanol exposure also plays a role in the final BK response to the drug: in several central nervous system regions (e.g., striatum, primary sensory neurons, and supraoptic nucleus, acute exposure to ethanol reduces neuronal excitability by enhancing BK activity. In contrast, protracted or repetitive ethanol administration may alter BK subunit composition and membrane expression, rendering the BK complex insensitive to further ethanol exposure. In neurohypophysial axon terminals, ethanol potentiation of BK channel activity leads to a reduction in neuropeptide release. In vascular smooth muscle, however, ethanol inhibition of BK current leads to cell contraction and vascular constriction.

  5. Effects of acute intravenous administration of pentamidine, a typical hERG-trafficking inhibitor, on the cardiac repolarization process of halothane-anesthetized dogs.

    Science.gov (United States)

    Yokoyama, Hirofumi; Nakamura, Yuji; Iwasaki, Hiroshi; Nagayama, Yukitoshi; Hoshiai, Kiyotaka; Mitsumori, Yoshitaka; Sugiyama, Atsushi

    2009-08-01

    Although acute treatment of pentamidine does not directly modify any ionic channel function in the heart at clinically relevant concentrations, its continuous exposure can prolong QT interval. Recent in vitro studies have indicated that hERG trafficking inhibition may play an important role in the onset of pentamidine-induced long QT syndrome. In this study, we examined acute in vivo electropharmacological effects of pentamidine using the halothane-anesthetized canine model (n = 5). The clinically relevant total dose of 4 mg/kg of pentamidine (namely, 1 mg/kg, i.v. over 10 min followed by 3 mg/kg, i.v. over 10 min with a pause of 20 min) decreased the mean blood pressure, ventricular contraction, preload to the left ventricle, and peripheral vascular resistance. Pentamidine also enhanced the atrioventricular conduction in parallel with its cardiohemodynamic actions, but it gradually prolonged both the ventricular repolarization period and effective refractory period, whereas no significant change was detected in the intraventricular conduction. Thus, acute administration of a clinically relevant dose of pentamidine can suppress cardiac function and vascular tone with reflex-mediated increase of sympathetic activity, whereas it may delay the repolarization process, suggesting that inhibition of potassium-channel trafficking might be induced more acutely in vivo than those previously expected in vitro.

  6. ETHANOL-INDUCED LOCOMOTOR ACTIVITY IN ADOLESCENT RATS AND THE RELATIONSHIP WITH ETHANOL-INDUCED CONDITIONED PLACE PREFERENCE AND CONDITIONED TASTE AVERSION

    OpenAIRE

    Acevedo, María Belén; Nizhnikov, Michael E.; Spear, Norman E.; Molina, Juan C.; Pautassi, Ricardo Marcos

    2012-01-01

    Adolescent rats exhibit ethanol-induced locomotor activity (LMA), which is considered an index of ethanol’s motivational properties likely to predict ethanol self-administration, but few studies have reported or correlated ethanol-induced LMA with conditioned place preference by ethanol at this age. The present study assessed age-related differences in ethanol’s motor stimulating effects and analysed the association between ethanol-induced LMA and conventional measures of ethanol-induced rein...

  7. Protective effects of alginate-chitosan microspheres loaded with alkaloids from Coptis chinensis Franch. and Evodia rutaecarpa (Juss.) Benth. (Zuojin Pill) against ethanol-induced acute gastric mucosal injury in rats.

    Science.gov (United States)

    Wang, Qiang-Song; Zhu, Xiao-Ning; Jiang, Heng-Li; Wang, Gui-Fang; Cui, Yuan-Lu

    2015-01-01

    Zuojin Pill (ZJP), a traditional Chinese medicine formula, consists of Coptis chinensis Franch. and Evodia rutaecarpa (Juss.) Benth. in a ratio of 6:1 (w/w) and was first recorded in "Danxi's experiential therapy" for treating gastrointestinal disorders in the 15th century. However, the poor solubility of alkaloids from ZJP restricted the protective effect in treating gastritis and gastric ulcer. The aim of the study was to investigate the protective mechanism of mucoadhesive microspheres loaded with alkaloids from C. chinensis Franch. and E. rutaecarpa (Juss.) Benth. on ethanol-induced acute gastric mucosal injury in rats. Surface morphology, particle size, drug loading, encapsulation efficiency, in vitro drug release, mucoadhesiveness, and fluorescent imaging of the microspheres in gastrointestinal tract were studied. The results showed that the mucoadhesive microspheres loaded with alkaloids could sustain the release of drugs beyond 12 hours and had gastric mucoadhesive property with 82.63% retention rate in vitro. The fluorescence tracer indicated high retention of mucoadhesive microspheres within 12 hours in vivo. The mucoadhesive microspheres loaded with alkaloids could reduce the gastric injury by decreasing the mucosal lesion index, increasing the percentage of inhibition and increasing the amount of mucus in the gastric mucosa in an ethanol-induced gastric mucosal injury rat model. Moreover, the mucoadhesive microspheres loaded with alkaloids reduce the inflammatory response by decreasing the levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), downregulating the mRNA expression of inducible nitric oxide synthase, TNF-α, and IL-1β in gastric mucosa. All the results indicate that mucoadhesive microspheres loaded with alkaloids could not only increase the residence time of alkaloids in rat stomach, but also exert gastroprotective effects through reducing the inflammatory response on ethanol-induced gastric mucosal damage. Thus, these

  8. Moderate ingestion of alcohol is associated with acute ethanol-induced suppression of circulating CTX in a PTH-independent fashion.

    Science.gov (United States)

    Sripanyakorn, Supannee; Jugdaohsingh, Ravin; Mander, Adrian; Davidson, Sarah L; Thompson, Richard Ph; Powell, Jonathan J

    2009-08-01

    The "J shape" curve linking the risk of poor bone health to alcohol intake is now well recognized from epidemiological studies. Ethanol and nonethanol components of alcoholic beverages could influence bone remodeling. However, in the absence of a solid underlying mechanism, the positive association between moderate alcoholic intake and BMD remains questionable because of confounding associated social factors. The objective of this work was to characterize the short-term effects of moderate alcohol consumption on circulating bone markers, especially those involved in bone resorption. Two sequential blood-sampling studies were undertaken in fasted healthy volunteers (age, 20-47 yr) over a 6-h period using beer of different alcohol levels (2% ethanol; p 6 h). The early effect on bone resorption is well described after the intake of energy, mediated by glucagon-like peptide-2, but the late effect of moderate alcohol ingestion is novel, seems to be ethanol specific, and is mediated in a non-calcitonin- and a non-PTH-dependent fashion, thus providing a mechanism for the positive association between moderate alcohol ingestion and BMD.

  9. Adaptive cytoprotection through modulation of nitric oxide in ethanol-evoked gastritis

    Institute of Scientific and Technical Information of China (English)

    Joshua Ka-Shun Ko; Chi-Hin Cho; Shiu-Kum Lam

    2004-01-01

    AIM: To assess the mechanisms of protective action by different mild irritants through maintenance of gastric mucosal integrity and modulation of mucosal nitric oxide (NO) in experimental gastritis rats.METHODS: Either 200 ml/L ethanol, 50 g/L NaCl or 0.3 mol/LHCl was pretreated to normal or 800 mL/L ethanol-induced acute gastritis Sprague-Dawley rats before a subsequent challenge with 500 mL/L ethanol. Both macroscopic lesion areas and histological damage scores were determined in the gastric mucosa of each group of animals. Besides,gastric mucosal activities of NO synthase isoforms and of superoxide dismutase, along with mucosal level of leukotriene (LT)C4 were measured.RESULTS: Macroscopic mucosal damages were protected by 200 mL/L ethanol and 50 g/L NaCl in gastritis rats.However, although 200 mL/L ethanol could protect the surface layers of mucosal cells in normal animals (protection attenuated by NG-nitro-L-arginine methyl ester), no cytoprotection against deeper histological damages was found in gastritis rats. Besides, inducible NO synthase activity was increased in the mucosa of gastritis animals and unaltered by mild irritants. Nevertheless, the elevation in mucosal LTC4 level following 500 mL/L ethanol administration and under gastritis condition was significantly reduced by pretreatment of all three mild irritants in both normal and gastritis animals.CONCLUSION: These findings suggest that the aggravated 500 mL/L ethanol-evoked mucosal damages under gastritis condition could be due to increased inducible NO and LTC4 production in the gastric mucosa. Only 200 mL/L ethanol is truly "cytoprotective" at the surface glandular level of nongastritis mucosa. Furthermore, the macroscopic protection of the three mild irritants involves reduction of LTC4 level in both normal and gastritis mucosa, implicating preservation of the vasculature.

  10. Serotonin-2C receptors in the basolateral nucleus of the amygdala mediate the anxiogenic effect of acute imipramine and fluoxetine administration.

    Science.gov (United States)

    Vicente, Maria Adrielle; Zangrossi, Helio

    2012-04-01

    A growing body of evidence indicates that facilitation of serotonin-2C receptor (5-HT2CR)-mediated neurotransmission in the basolateral nucleus of the amygdala (BLA) is involved in anxiety generation. We investigated here whether BLA 5-HT2CRs exert a differential role in the regulation of defensive behaviours related to generalized anxiety (inhibitory avoidance) and panic (escape) disorders. We also evaluated whether activation of BLA 5-HT2CRs accounts for the anxiogenic effect caused by acute systemic administration of the antidepressants imipramine and fluoxetine. Male Wistar rats were tested in the elevated T-maze after intra-BLA injection of the endogenous agonist 5-HT, the 5-HT2CR agonist MK-212 or the 5-HT2CR antagonist SB-242084. This test allows the measurement of inhibitory avoidance acquisition and escape expression. We also investigated whether intra-BLA administration of SB-242084 interferes with the acute anxiogenic effect caused by imipramine and fluoxetine in the Vogel conflict test, and imipramine in the elevated T-maze. While intra-BLA administration of 5-HT and MK-212 facilitated inhibitory avoidance acquisition, suggesting an anxiogenic effect, SB-242084 had the opposite effect. None of these drugs affected escape performance. Intra-BLA injection of a sub-effective dose of SB-242084 fully blocked the anxiogenic effect caused either by the local microinjection of 5-HT or the systemic administration of imipramine and fluoxetine. Our findings indicate that 5-HT2CRs in BLA are selectively involved in the regulation of defensive behaviours associated with generalized anxiety, but not panic. The results also provide the first direct evidence that activation of BLA 5-HT2CRs accounts for the short-term aversive effect of antidepressants.

  11. Effect of Resveratrol Administration on the Element Metabolism in the Blood and Brain Tissues of Rats Subjected to Acute Swimming Exercise.

    Science.gov (United States)

    Baltaci, Abdulkerim Kasim; Arslangil, Dilek; Mogulkoc, Rasim; Patlar, Suleyman

    2017-02-01

    The aim of the present study is to examine how resveratrol administration affects the element metabolism in the blood and brain cortex tissues of rats subjected to an acute swimming exercise. The study was carried out on Wistar-Albino-type adult male rats supplied by the Center. Group 1 is the control group. Group 2 is the swimming control group. Group 3 is the resveratrol (10 mg/kg/day) + swimming group. Group 4 is the resveratrol (10 mg/kg/day) group. Blood and brain cortex tissues were analyzed for some elements. The acute swimming exercise led to increases in the rats' serum iron, selenium, lead, cobalt, and boron levels, while the resveratrol-swimming group has increases in copper, phosphorus, and calcium values. The brain cortex tissue of the resveratrol-swimming group had significantly higher molybdenum levels than others. The results obtained in the study indicate that acute swimming exercise altered the distribution of elements in the serum to a considerable extent; however, resveratrol's affect is limited. Especially, resveratrol supplementation may have a regulatory affect on serum iron and magnesium levels.

  12. Acute and chronic administration of cannabidiol increases mitochondrial complex and creatine kinase activity in the rat brain

    Directory of Open Access Journals (Sweden)

    Samira S. Valvassori

    2013-12-01

    Full Text Available Objective: To investigate the effects of cannabidiol (CBD on mitochondrial complex and creatine kinase (CK activity in the rat brain using spectrophotometry. Method: Male adult Wistar rats were given intraperitoneal injections of vehicle or CBD (15, 30, or 60 mg/kg in an acute (single dose or chronic (once daily for 14 consecutive days regimen. The activities of mitochondrial complexes and CK were measured in the hippocampus, striatum, and prefrontal cortex. Results: Both acute and chronic injection of CBD increased the activity of the mitochondrial complexes (I, II, II-III, and IV and CK in the rat brain. Conclusions: Considering that metabolism impairment is certainly involved in the pathophysiology of mood disorders, the modulation of energy metabolism (e.g., by increased mitochondrial complex and CK activity by CBD could be an important mechanism implicated in the action of CBD.

  13. Effects of Ketamine on Levels of Inflammatory Cytokines IL-6, IL-1β, and TNF-α in the Hippocampus of Mice Following Acute or Chronic Administration.

    Science.gov (United States)

    Li, Yanning; Shen, Ruipeng; Wen, Gehua; Ding, Runtao; Du, Ao; Zhou, Jichuan; Dong, Zhibin; Ren, Xinghua; Yao, Hui; Zhao, Rui; Zhang, Guohua; Lu, Yan; Wu, Xu

    2017-01-01

    Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neuroinflammation has been suggested to play an important role in neurodegeneration. Meanwhile, ketamine has been shown to modulate the levels of inflammatory cytokines. We hypothesized that the effects of ketamine on the central nervous system are associated with inflammatory cytokines. Therefore, we set out to establish acute and chronic ketamine administration models in C57BL/6 mice, to evaluate spatial recognition memory and emotional response, to analyze the changes in the levels of the inflammatory cytokines interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the mouse hippocampus, employing behavioral tests, Western blot, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and immunohistochemistry. Our results showed that ketamine at the dose of 60 mg/kg induced spatial recognition memory deficit and reduced anxiety-like behaviors in mice after chronic administration. Moreover, we found that ketamine increased the hippocampal levels of IL-6 and IL-1β after single, multiple and long-term administration in a dose-dependent manner. However, the expression level of TNF-α differed in the mouse hippocampus under different conditions. Single administration of ketamine increased the level of TNF-α, whereas multiple and long-term administration decreased it significantly. We considered that TNF-α expression could be controlled by a bi-directional regulatory pathway, which was associated with the dose and duration of ketamine administration. Our results suggest that the alterations in the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α may be involved in the neurotoxicity of ketamine.

  14. Inhibition of Carrageenan-Induced Acute Inflammation in Mice by Oral Administration of Anthocyanin Mixture from Wild Mulberry and Cyanidin-3-Glucoside

    Directory of Open Access Journals (Sweden)

    Neuza Mariko Aymoto Hassimotto

    2013-01-01

    Full Text Available Anthocyanins are flavonoids which demonstrated biological activities in in vivo and in vitro models. Here in the anti-inflammatory properties of an anthocyanin-enriched fraction (AF extracted from wild mulberry and the cyanidin-3-glucoside (C3G, the most abundant anthocyanin in diet, were studied in two acute inflammation experimental models, in the peritonitis and in the paw oedema assays, both of which were induced by carrageenan (cg in mice. In each trial, AF and C3G (4 mg/100 g/animal were orally administered in two distinct protocols: 30 min before and 1 h after cg stimulus. The administration of both AF and C3G suppresses the paw oedema in both administration times (P<0.05. In the peritonitis, AF and C3G reduced the polymorphonuclear leukocytes (PMN influx in the peritoneal exudates when administered 1 h after cg injection. AF was more efficient reducing the PMN when administered 30 min before cg. Both AF and C3G were found to suppress mRNA as well as protein levels of COX-2 upregulated by cg in both protocols, but the inhibitory effect on PGE2 production in the peritoneal exudates was observed when administered 30 min before cg (P<0.05. Our findings suggest that AF and C3G minimize acute inflammation and they present positive contributions as dietary supplements.

  15. Ethanol consumption as inductor of pancreatitis

    Institute of Scientific and Technical Information of China (English)

    José; A; Tapia; Ginés; M; Salido; Antonio; González

    2010-01-01

    Alcohol abuse is a major cause of pancreatitis, a condition that can manifest as both acute necroinflammation and chronic damage (acinar atrophy and f ibrosis). Pancreatic acinar cells can metabolize ethanol via the oxidative pathway, which generates acetaldehyde and involves the enzymes alcohol dehydrogenase and possibly cytochrome P4502E1. Additionally, ethanol can be metabolized via a nonoxidative pathway involving fatty acid ethyl ester synthases. Metabolism of ethanol by acinar and other pancreatic cells and the consequent generation of toxic metabolites, are postulated to play an important role in the development of alcohol-related acute and chronic pancreatic injury. This current work will review some recent advances in the knowledge about ethanol actions on the exocrine pancreas and its relationship to inflammatory disease and cancer.

  16. Loss of phenotype of parvalbumin interneurons in rat prefrontal cortex is involved in antidepressant- and propsychotic-like behaviors following acute and repeated ketamine administration.

    Science.gov (United States)

    Zhou, ZhiQiang; Zhang, GuangFen; Li, XiaoMin; Liu, XiaoYu; Wang, Nan; Qiu, LiLi; Liu, WenXue; Zuo, ZhiYi; Yang, JianJun

    2015-04-01

    Accumulating evidence has demonstrated that single subanesthetic dose of ketamine exerts rapid, robust, and lasting antidepressant-like effects. Nevertheless, repeated subanesthetic doses of ketamine produce psychosis-like effects with dysfunction of parvalbumin (PV) interneurons. We hypothesized that PV interneurons play an important role in the antidepressant-like actions of ketamine, and different changes in PV interneurons occur with the antidepressant-like and propsychotic-like effects of ketamine. To test this hypothesis, ketamine's antidepressant-like effects were evaluated by the forced swimming test. Ketamine-induced stereotyped behaviors and hyperactivity actions and the function of PV interneurons were also assessed. We demonstrated that an acute dose of 10 mg/kg ketamine induced significant antidepressant-like effects and reduced the levels of PV and the gamma-aminobutyric acid (GABA)-producing enzyme GAD67 in the rat prefrontal cortex. Moreover, inhibition of ketamine-induced loss of PV by apocynin blocked these antidepressant-like effects. Repeated administration of 30 mg/kg ketamine elicited stereotyped behaviors and hyperactivity actions as well as a longer duration of PV and GAD67 loss, higher brain glutamate levels, and lower brain GABA levels than acute single dose of ketamine. Our results reveal that the loss of phenotype of PV interneurons in the prefrontal cortex contributes to the antidepressant-like actions and is also involved in the propsychotic-like behaviors following acute and repeated ketamine administration, which may be partially mediated by the disinhibition of glutamate signaling. The different degrees and durations of the actions on PV interneurons produced by the two regimens of ketamine may partly underline the behavioral variance between the antidepressant- and propsychotic-like effects.

  17. Antiulcer Activity after Oral Administration of the Wormwood Ethanol Extract on Lesions due to Leishmania major Parasites in BALB/C Mice

    Directory of Open Access Journals (Sweden)

    Kourosh Azizi, Fatemeh Shahidi-Hakak Mohammad Djaefar Moemenbellah-Fard,\tQasem Asgari,\tSoliman Mohammadi-Samani

    2016-04-01

    Full Text Available Herbal extracts were used to investigate the in vivo efficacy of Artemisia absinthium on the treatment of cutaneous leishmaniasis in susceptible mice. A total of 40 BALB/c mice were subjected to assays. In each, 3-5×103 amastigotes of standard Leishmania major strain were inoculated subcutaneously into the tail base of mice. Groups of mice were assigned as: I-negative control, II-positive control, III-Glucantime®, IV-ointment twice a day, V-ointment with oral medicine, VI-oral medicine on parasite injection, VII-oral medicine once ulcer develops, and VIII-ointment-based crème on ulcer. The gold standard of clinical infection control was based on ulcer size measurement using a Vernier scale weekly during 4 weeks Post-Ulcer Development (PUD. The mean ulcer sizes in different groups were compared using the post hoc Dunnett's 3 statistical analyses. There was a significant difference between the two groups of ointment with medicine (V and medicine on parasite inoculation (VI (P ≤ 0.027. Antiulcer activity and healing was noted after oral treatment with aqueous extract on parasite injection. There was a significant difference between data from positive control group and local ointment with oral medicine (P ≤ 0.045 indicating that ointment use facilitated ulcer growth. There was also a significant difference between data from Glucantime® use and ointment with medicine group (P ≤ 0.039 which showed the deteriorating effect of oil-based ointment use. The oral administration of extract had an effect similar to Glucantime® use and led to the repair of ulcer. A. absinthium extract as oral feeder appeared to cause modulation of host responses, ulcer size reduction and tissue repair.

  18. Effects of Alcohol and Saccharin Deprivations on Concurrent Ethanol and Saccharin Operant Self-Administration by Alcohol-Preferring (P) Rats

    Science.gov (United States)

    Toalston, Jamie E.; Oster, Scott M.; Kuc, Kelly A.; Pommer, Tylene J.; Murphy, James M.; Lumeng, Lawrence; Bell, Richard L.; McBride, William J.; Rodd, Zachary A.

    2008-01-01

    Consumption of sweet solutions has been associated with a reduction in withdrawal symptoms and alcohol craving in humans. The objective of the present study was to determine the effects of EtOH and saccharin (SACC) deprivations on operant oral self-administration. P rats were allowed to lever press concurrently self-administer EtOH (15% v/v) and SACC (0.0125% g/v) for 8 weeks. Rats were then maintained on daily operant access (non-deprived), deprived of both fluids (2 weeks), deprived of SACC and given 2 ml of EtOH daily, or deprived of EtOH and given 2 ml of SACC daily. All groups were then given two weeks of daily operant access to EtOH and SACC, followed by an identical second deprivation period. P rats responded more for EtOH than SACC. All deprived groups increased responding on the EtOH lever, but not on the SACC lever. Daily consumption of 2 ml EtOH decreased the duration of the ADE. Home cage access to 2 ml SACC also decreased the ADE but to a lesser extent than access to EtOH. A second deprivation period further increased and prolonged the expression of an ADE. These results show EtOH is a more salient reinforcer than SACC. With concurrent access to EtOH and SACC, P rats do not display a saccharin deprivation effect. Depriving P rats of both EtOH and SACC had the most pronounced effect on the magnitude and duration of the ADE, suggesting that there may be some interactions between EtOH and SACC in their CNS reinforcing effects. PMID:18400451

  19. An evaluation of the effects of acute and chronic L-tyrosine administration on BDNF levels and BDNF mRNA expression in the rat brain.

    Science.gov (United States)

    Ferreira, Gabriela K; Scaini, Giselli; Jeremias, Isabela C; Carvalho-Silva, Milena; Gonçalves, Cinara L; Pereira, Talita C B; Oliveira, Giovanna M T; Kist, Luiza W; Bogo, Maurício R; Schuck, Patrícia F; Ferreira, Gustavo C; Streck, Emilio L

    2014-04-01

    Tyrosinemia type II, which is also known as Richner-Hanhart syndrome, is an inborn error of metabolism that is due to a block in the transamination reaction that converts tyrosine to p-hydroxyphenylpyruvate. Because the mechanisms of neurological dysfunction in hypertyrosinemic patients are poorly known and the symptoms of these patients are related to the central nervous system, the present study evaluated brain-derived neurotrophic factor (BDNF) levels and bdnf mRNA expression in young rats and during growth. In our acute protocol, Wistar rats (10 and 30 days old) were killed 1 h after a single intraperitoneal L-tyrosine injection (500 mg/kg) or saline. Chronic administration consisted of L-tyrosine (500 mg/kg) or saline injections 12 h apart for 24 days in Wistar rats (7 days old), and the rats were killed 12 h after the last injection. The brains were rapidly removed, and we evaluated the BDNF levels and bdnf mRNA expression. The present results showed that the acute administration of L-tyrosine decreased both BDNF and bdnf mRNA levels in the striatum of 10-day-old rats. In the 30-day-old rats, we observed decreased BDNF levels without modifications in bdnf transcript level in the hippocampus and striatum. Chronic administration of L-tyrosine increased the BDNF levels in the striatum of rats during their growth, whereas bdnf mRNA expression was not altered. We hypothesize that oxidative stress can interact with the BDNF system to modulate synaptic plasticity and cognitive function. The present results enhance our knowledge of the pathophysiology of hypertyrosinemia.

  20. Subcutaneous administration of granulocyte colony stimulating factor and stem cell factor ameliorates the outcome of acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    LIN Ling; ZHOU Sheng-hua; QI Shu-shan; SHEN Xiang-qian; LIU Qi-ming; FANG Zhen-fei

    2005-01-01

    @@ Orlic et al1 treated mice (splenectomized two weeks ago) with granulocyte colony stimulating factor (G-CSF) and stem cell factor (SCF) for five days before acute myocardium infarction (AMI) and three days after AMI.They found that those treatments could repair infarcted hearts,improve heart performance and decrease mortality.However,from the clinical standpoint,the work of Orlic and his co-workers has an obvious limitation.The strategy of delivering agents before infarction is not practicable because the onset of infarction is unpredictable.Therefore,we delivered the agents after infarction to modify its effect on rats closer to clinical reality.

  1. Acute and repeated intranasal oxytocin administration exerts anti-aggressive and pro-affiliative effects in male rats

    NARCIS (Netherlands)

    Calcagnoli, Federica; Kreutzmann, Judith C.; de Boer, Sietse F.; Althaus, Monika; Koolhaas, Jaap M.

    2015-01-01

    Socio-emotional deficits and impulsive/aggressive outbursts are prevalent symptoms of many neuropsychiatric disorders, and intranasal administration of oxytocin (OXT) is emerging as a putative novel therapeutic approach to curb these problems. Recently, we demonstrated potent anti-aggressive and pro

  2. Consequences of amygdala kindling and repeated withdrawal from ethanol on amphetamine-induced behaviours.

    Science.gov (United States)

    Ripley, Tamzin L; Dunworth, Sarah J; Stephens, David N

    2002-09-01

    relatively mild chronic ethanol treatment modulates neuronal systems that may also be involved in PTZ-induced kindling but not those involved in either the acute stimulant effects of amphetamine or behavioural sensitization or appetitive conditioning following repeated amphetamine administration. Behavioural changes following amygdala kindling differed from those following repeated ethanol withdrawal, suggesting that withdrawal kindling from a mild ethanol treatment differs in its effects from amygdala kindling.

  3. Acute central neuropeptide Y administration increases food intake but does not affect hepatic very low-density lipoprotein (VLDL production in mice.

    Directory of Open Access Journals (Sweden)

    Janine J Geerling

    Full Text Available OBJECTIVE: Central neuropeptide Y (NPY administration stimulates food intake in rodents. In addition, acute modulation of central NPY signaling increases hepatic production of very low-density lipoprotein (VLDL-triglyceride (TG in rats. As hypertriglyceridemia is an important risk factor for atherosclerosis, for which well-established mouse models are available, we set out to validate the effect of NPY on hepatic VLDL-TG production in mice, to ultimately investigate whether NPY, by increasing VLDL production, contributes to the development of atherosclerosis. RESEARCH DESIGN AND METHODS: Male C57Bl/6J mice received an intracerebroventricular (i.c.v. cannula into the lateral (LV or third (3V ventricle of the brain. One week later, after a 4 h fast, the animals received an intravenous (i.v. injection of Tran(35S (100 µCi followed by tyloxapol (500 mg/kg body weight; BW, enabling the study of hepatic VLDL-apoB and VLDL-TG production, respectively. Immediately after the i.v. injection of tyloxapol, the animals received either an i.c.v. injection of NPY (0.2 mg/kg BW in artificial cerebrospinal fluid; aCSF, synthetic Y1 receptor antagonist GR231118 (0.5 mg/kg BW in aCSF or vehicle (aCSF, or an i.v. injection of PYY3-36 (0.5 mg/kg BW in PBS or vehicle (PBS. RESULTS: Administration of NPY into both the LV and 3V increased food intake within one hour after injection (+164%, p<0.001 and +367%, p<0.001, respectively. NPY administration neither in the LV nor in the 3V affected hepatic VLDL-TG or VLDL-apoB production. Likewise, antagonizing central NPY signaling by either PYY3-36 or GR231118 administration did not affect hepatic VLDL production. CONCLUSION: In mice, as opposed to rats, acute central administration of NPY increases food intake without affecting hepatic VLDL production. These results are of great significance when extrapolating findings on the central regulation of hepatic VLDL production between species.

  4. Acute and Chronic Administrations of Rheum palmatum Reduced the Bioavailability of Phenytoin in Rats: A New Herb-Drug Interaction

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    Ying-Chang Chi

    2012-01-01

    Full Text Available The rhizome of Rheum palmatum (RP is a commonly used herb in clinical Chinese medicine. Phenytoin (PHT is an antiepileptic with narrow therapeutic window. This study investigated the acute and chronic effects of RP on the pharmacokinetics of PHT in rat. Rats were orally administered with PHT (200 mg/kg with and without RP decoction (single dose and seven doses of 2 g/kg in a crossover design. The serum concentrations of PHT, PHT glucuronide (PHT-G, 4-hydroxyphenytoin (HPPH, and HPPH glucuronide (HPPH-G were determined by HPLC method. Cell line models were used to identify the underlying mechanisms. The results showed that coadministration of single dose or multiple doses of RP significantly decreased the Cmax and AUC0-t as well as the K10 of PHT, PHT-G, HPPH, and HPPH-G. Cell line studies revealed that RP significantly induced the P-gp-mediated efflux of PHT and inhibited the MRP-2-medicated transport of PHT and HPPH. In conclusion, acute and chronic coadministrations of RP markedly decreased the oral bioavailability of PHT via activation of P-gp, although the MRP-2-mediated excretion of PHT was inhibited. It is recommended that caution should be exercised during concurrent use of RP and PHT.

  5. Acute and Chronic Administrations of Rheum palmatum Reduced the Bioavailability of Phenytoin in Rats: A New Herb-Drug Interaction

    Science.gov (United States)

    Chi, Ying-Chang; Juang, Shin-Hun; Chui, Wai Keung; Hou, Yu-Chi; Chao, Pei-Dawn Lee

    2012-01-01

    The rhizome of Rheum palmatum (RP) is a commonly used herb in clinical Chinese medicine. Phenytoin (PHT) is an antiepileptic with narrow therapeutic window. This study investigated the acute and chronic effects of RP on the pharmacokinetics of PHT in rat. Rats were orally administered with PHT (200 mg/kg) with and without RP decoction (single dose and seven doses of 2 g/kg) in a crossover design. The serum concentrations of PHT, PHT glucuronide (PHT-G), 4-hydroxyphenytoin (HPPH), and HPPH glucuronide (HPPH-G) were determined by HPLC method. Cell line models were used to identify the underlying mechanisms. The results showed that coadministration of single dose or multiple doses of RP significantly decreased the Cmax and AUC0-t as well as the K10 of PHT, PHT-G, HPPH, and HPPH-G. Cell line studies revealed that RP significantly induced the P-gp-mediated efflux of PHT and inhibited the MRP-2-medicated transport of PHT and HPPH. In conclusion, acute and chronic coadministrations of RP markedly decreased the oral bioavailability of PHT via activation of P-gp, although the MRP-2-mediated excretion of PHT was inhibited. It is recommended that caution should be exercised during concurrent use of RP and PHT. PMID:22829856

  6. The role of nitrergic system in antidepressant effects of acute administration of zinc, magnesium and thiamine on progesterone induced postpartum depression in mice

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    Nikseresht S

    2010-08-01

    Full Text Available "nBackground: Postpartum depression is a mood disorder that has harmful effects on mothers, infants, family and relationships. Acute decrease of progesterone after delivery has been proposed as a cause for postpartum depression. This hormone can affect neurotransmitters' function. Zinc (Zn and magnesium (Mg as trace elements exert their antidepressant effects through neurotransmitter pathways. On the other hand, thiamin (Vit B1 deficiency leads to depression in animal models. The aim of this study was to evaluate effects of combination of zinc, magnesium and thiamine on postpartum depression and role of nitrergic system. "n"nMethods: One hundred ten female mice in five groups were used. Postpartum depression was conducted using progesterone injections. Combinations of Zinc chloride, magnesium chloride and thiamine HCL were administered 30 minutes before open field and forced swimming test (FST. In order to investigate role of nitrergic system, L-arginine and LNAME were administered. "n"nResults: All treatment groups spent less immobility time than the control group (p< 0.05. Combined administration of Zn+ Mg+ Vit B1 caused the most reduction in immobility time. Administration of L-NAME in Zn+ Mg+ Vit B1 group caused reduction in immobility time while administration of L-arginine caused increase in immobility time in the same group. "nConclusion: Zinc, magnesium and thiamine can improve depressive symptoms by nitrergic pathway. These elements as supplement compounds could be alternatives for antidepressants in postpartum period.

  7. Effect of intracoronary administration of anisodamine on slow reflow phenomenon following primary percutaneous coronary intervention in patients with acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    FU Xiang-hua; XUE Ling; FAN Wei-ze; GU Xin-shun; WEI Yong-yun; JIANG Yun-fa; WU Wei-li; LI Shi-qiang; HAO Guo-zhen; WEI Qing-min

    2007-01-01

    Background Many basic and clinical studies have proved that anisodamine can produce significant effect on relieving microvascular spasm, improving and dredging the coronary microcirculation. It may be beneficial to the improvement of slow-reflow phenomenon (SRP) following percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI).So we investigated the effect of intracoronary administration of anisodamine on SRP of infarct related artery (IRA)following primary PCI in patients with ST segment elevated acute myocardial infarction (STEAMI).Methods Twenty-one patients with SRP from a total of 148 STEAMI patients accepted primary PCI were enrolled into this study from September 2004 to December 2005. When SRP happened, nitroglycerin (200 μg) was "bolus" injected firstly into IRA to exclude the spasm of epicardial artery and identify SRP as well as a baseline and self-control agent following PCI. Ten minutes later, 1000 μg of anisodamine was injected into IRA with SRP at 200 μg/s, while the coronary angiography (CAG) was taken before and at 1st, 3rd and 10th minute after administration of nitroglycerin or anisodamine,respectively. The corrected TIMI frame count (cTFC), TIMI myocardial perfusion grade (TMPG) and the diameter of IRA were calculated and analyzed by Gibson's TIMI frame count method using quantitative computer angiography (QCA)system to evaluate the influence of anisodamine on coronary flow and vessel lumen. In the meantime the invasive hemodynamic parameters of intracoronary and systemic artery (systolic, diastolic and mean pressure) and electrocardiogram (ECG) were measured and monitored. The changes of ventricular performance parameters and the adverse reaction were evaluated and followed-up at 1 month post-PCI.Results No significant changes in cTFCs and TMPGs were found at 1st, 3rd and 10th minute after intracoronary administration of nitroglycerin as compared with the baseline control (P>0.05). cTFCs were decreased by 58.3%, 56

  8. Protective effects of alginate–chitosan microspheres loaded with alkaloids from Coptis chinensis Franch. and Evodia rutaecarpa (Juss. Benth. (Zuojin Pill against ethanol-induced acute gastric mucosal injury in rats

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    Wang QS

    2015-11-01

    Full Text Available Qiang-Song Wang,1,2,* Xiao-Ning Zhu,1,* Heng-Li Jiang,1,* Gui-Fang Wang,3 Yuan-Lu Cui1 1Tianjin State Key Laboratory of Modern Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 2Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, 3Pharmacy Department, Baokang Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: Zuojin Pill (ZJP, a traditional Chinese medicine formula, consists of Coptis chinensis Franch. and Evodia rutaecarpa (Juss. Benth. in a ratio of 6:1 (w/w and was first recorded in “Danxi’s experiential therapy” for treating gastrointestinal disorders in the 15th century. However, the poor solubility of alkaloids from ZJP restricted the protective effect in treating gastritis and gastric ulcer. The aim of the study was to investigate the protective mechanism of mucoadhesive microspheres loaded with alkaloids from C. chinensis Franch. and E. rutaecarpa (Juss. Benth. on ethanol-induced acute gastric mucosal injury in rats. Surface morphology, particle size, drug loading, encapsulation efficiency, in vitro drug release, mucoadhesiveness, and fluorescent imaging of the microspheres in gastrointestinal tract were studied. The results showed that the mucoadhesive microspheres loaded with alkaloids could sustain the release of drugs beyond 12 hours and had gastric mucoadhesive property with 82.63% retention rate in vitro. The fluorescence tracer indicated high retention of mucoadhesive microspheres within 12 hours in vivo. The mucoadhesive microspheres loaded with alkaloids could reduce the gastric injury by decreasing the mucosal lesion index, increasing the percentage of inhibition and increasing the amount of mucus in the gastric mucosa in an ethanol-induced gastric mucosal injury rat model. Moreover, the

  9. Acute D-psicose administration decreases the glycemic responses to an oral maltodextrin tolerance test in normal adults.

    Science.gov (United States)

    Iida, Tetsuo; Kishimoto, Yuka; Yoshikawa, Yuko; Hayashi, Noriko; Okuma, Kazuhiro; Tohi, Mikiko; Yagi, Kanako; Matsuo, Tatsuhiro; Izumori, Ken

    2008-12-01

    An examination was conducted to verify D-psicose suppressed the elevation of blood glucose and insulin concentration in a dose-dependent manner under the concurrent administration of maltodextrin and D-psicose to healthy humans. Twenty subjects aged 20-39 y, 11 males and 9 females were recruited. A load test of oral maltodextrin was conducted as a randomized single blind study. The subjects took one of five test beverages (7.5 g D-psicose alone, 75 g maltodextrin alone, 75 g maltodextrin +2.5, 5 or 7.5 g D-psicose). Blood was collected before an intake and at 30, 60, 90 and 120 min after an intake. Intervals of administration were at least 1 wk. The load test with 75 g maltodextrin showed significant suppressions of the elevation of blood glucose and insulin concentration under the doses of 5 g or more D-psicose with dose dependency. An independent administration of 7.5 g D-psicose had no influence on blood glucose or insulin concentration. D-Psicose is considered efficacious in the suppression of the elevation of blood glucose concentration after eating in humans.

  10. Acute non-ST elevation myocardial infarction following paclitaxel administration for ovarian carcinoma: A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Kajal Shah

    2012-01-01

    Full Text Available We report a case of an acute non-ST elevation myocardial infarction (AMI induced by paclitaxel in a patient with ovarian cancer. A 45-year-old premenopausal lady without any co-morbidity was started on the first cycle of neoadjuvant chemotherapy with paclitaxel-based regimen for advanced stage ovarian cancer. The patient developed chest pain 3 h after paclitaxel infusion with characteristic electrocardiographic changes of antero-apical myocardial infarction. The patient recovered on conservative medical management with reversion of electrocardiogram (ECG changes. Cardiac ischemia and myocardial infarction, possibly due to coronary vasospasm, are rare adverse effects of paclitaxel with reported incidence of 0.26%. We have reported a case of paclitaxel-induced myocardial infarction with reversible cardiac dysfunction. The possibility of myocardial infarction should be considered in patients who develop chest pain or other symptoms after paclitaxel infusion.

  11. Effects of acute administration of omeprazole or ranitidine on basal and vagally stimulated gastric acid secretion and alkalinization of the duodenum in anaesthetized cats.

    Science.gov (United States)

    Fändriks, L; Jönson, C

    1990-02-01

    Experiments were performed on acutely vagotomized cats during chloralose anaesthesia. In order to avoid sympathoadrenergic influences, the adrenal glands were ligated and the splanchnic nerves were cut bilaterally in all animals. The gastric lumen was perfused with saline and the H+ secretion was calculated from pH measurements in the perfusate. HCO3- secretion by the duodenal mucosa was titrated in situ. Omeprazole (4 mg kg-1 i.v., dissolved in PEG400, 40% w/v) did not influence basal or vagally induced HCO3- secretions, but inhibited by about 80% the H+ secretory response induced by electric vagal stimulation. Acute administration of ranitidine (5 mg kg-1 i.v.) transiently lowered arterial pressure, an effect which was followed by a sustained compensatory tachycardia. Ranitidine raised basal duodenal HCO3- secretion by 50% and inhibited vagally induced gastric H+ secretion by about 70%, whereas vagally induced HCO3- secretion was not influenced. The results suggest that vagal nerve stimulation raises the duodenal bicarbonate secretion via a mechanism independent of the level of gastric H+ secretion.

  12. Prophylactic administration of non-organophosphate cholinesterase inhibitors before acute exposure to organophosphates: assessment using terbufos sulfone.

    Science.gov (United States)

    Lorke, Dietrich E; Nurulain, Syed M; Hasan, Mohamed Y; Kuča, Kamil; Petroianu, Georg A

    2014-10-01

    Poisoning with organophosphorus compounds (OPCs) poses a serious threat worldwide. OPC-induced mortality can be significantly reduced by prophylactic administration of reversible acetylcholinesterase (AChE) inhibitors. The only American Food and Drug Administration (FDA)-approved substance for such pre-treatment (to soman exposure) is presently pyridostigmine, although its efficacy is controversial. In search for more efficacious and broad-spectrum alternatives, we have assessed in vivo the mortality-reducing efficacy of a group of five compounds with known AChE inhibitory activity (pyridostigmine, physostigmine, ranitidine, tacrine and K-27), when given in equitoxic dosage (25% of LD01 ) 30 min before exposure to the OPC terbufos sulfone. Protection was quantified in rats by determining the relative risk of death (RR) using Cox analysis, with RR = 1 for animals given only terbufos sulfone, but no pre-treatment. All tested AChE inhibitors reduced terbufos sulfone-induced mortality significantly (p ≤ 0.05) as compared with the non-treatment group (RR = 1: terbufos sulfone only). Best in vivo protection from terbufos sulfone-induced mortality was achieved, when K-27 was given before terbufos sulfone exposure (RR = 0.06), which was significantly (P ≤ 0.05) superior to the pre-treatment with all other tested compounds, for example tacrine (RR = 0.21), pyridostigmine (RR = 0.28), physostigmine (RR = 0.29) and ranitidine (RR = 0.33). The differences in efficacy between tacrine, pyridostigmine, physostigmine and ranitidine were not statistically significant. Prophylactic administration of an oxime (such as K-27) in case of imminent OPC exposure may be a viable option.

  13. Acute effects of MDMA (3,4-methylenedioxymethamphetamine) on EEG oscillations: alone and in combination with ethanol or THC (delta-9-tetrahydrocannabinol)

    NARCIS (Netherlands)

    Lansbergen, M.M.; Dumont, G.J.H.; Gerven, J.M. van; Buitelaar, J.K.; Verkes, R.J.

    2011-01-01

    RATIONALE: Typical users of 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") are polydrug users, combining MDMA with alcohol or cannabis [most active compound: delta-9-tetrahydrocannabinol (THC)]. OBJECTIVES: The aim of the present study was to investigate whether co-administration of alcohol o

  14. Safety and efficacy of early administration of tirofiban in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Liu Yangchun; Su Qiang; Li Lang

    2014-01-01

    Background Tirofiban has been widely used as an adjunctive pharmacologic agent for revascularization in patients undergoing percutaneous coronary intervention,and the outcomes appear attractive.However,the potential benefits from early administration of tirofiban in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) remain unclear.Methods We conducted a search in MEDLINE,EMBASE,and the Cochrane Central Register of Controlled Trials up to September 2012 without language restriction.A total of eight randomized trials (n=1 577 patients) comparing early (emergency department or ambulance) versus late (catheterization laboratory) administration of tiroflban in STEMI patients undergoing PPCI were included in this meta-analysis.Risk ratio (RR) was computed from individual studies and pooled with random-or fixed-effect models.Results There were no differences in post-procedural Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 and Corrected TIMI Frame Count (RR=1.02,95% confidence interval (C/):0.99-1.05,P=0.18; weighted mean difference (WMD)=-0.93,95% CI:-5.37-3.52,P=0.68,respectively) between the two groups.Similarly,there were no significant differences in the incidence of 30-day mortality (RR=1.69,95% CI:0.69-4.13,P=0.25) and re-myocardial infarction (RR=0.71,95% CI:0.21-2.35,P=0.57) between early and late administration of tirofiban.As to the safety end points,no significant difference was observed in hospital minor bleeding (RR=1.08,95% CI:0.54-2.14,P=0.83) and hospital and 30-day major bleeding between the two groups (RR=0.98,95% CI:0.46-2.10,P=0.96; RR=1.32,95% CI:0.59-2.97,P=0.49,respectively).Conclusions Early administration of tiroflban in patients undergoing PPCI for STEMI was safe,but no beneficial effects on post-procedural angiographic or clinical outcomes could be identified as compared with late administration.Besides the negative finding,more high

  15. Differential effects of acute cortisol administration on deep and shallow episodic memory traces: a study on healthy males.

    Science.gov (United States)

    Cioncoloni, David; Galli, Giulia; Mazzocchio, Riccardo; Feurra, Matteo; Giovannelli, Fabio; Santarnecchi, Emiliano; Bonifazi, Marco; Rossi, Alessandro; Rossi, Simone

    2014-10-01

    We aimed at investigating rapid effects of plasma cortisol elevations on the episodic memory phase of encoding or retrieval, and on the strength of the memory trace. Participants were asked either to select a word containing the letter "e" (shallow encoding task) or to judge if a word referred to a living entity (deep encoding task). We intravenously administered a bolus of 20mg of cortisol either 5 min before encoding or 5 min before retrieval, in a between-subjects design. The study included only male participants tested in the late afternoon, and neutral words as stimuli. When cortisol administration occurred prior to retrieval, a main effect of group emerged. Recognition accuracy was higher for individuals who received cortisol compared to placebo. The higher discrimination accuracy for the cortisol group was significant for words encoded during deep but not shallow task. Cortisol administration before encoding did not affect subsequent retrieval performance (either for deep or shallow stimuli) despite a facilitatory trend. Because genomic mechanisms take some time to develop, such a mechanism cannot apply to our findings where the memory task was performed shortly after the enhancement of glucocorticoid levels. Therefore, glucocorticoids, through non-genomic fast effects, determine an enhancement in episodic memory if administered immediately prior to retrieval. This effect is more evident if the memory trace is laid down through deep encoding operations involving the recruitment of specific neural networks.

  16. Immunomodulating properties of gamma-hydroxybutyrate (GHB), flunitrazepam and ethanol in 'club drugs' users.

    Science.gov (United States)

    Pichini, Simona; Farré, Magi; Abanades, Sergio; Pacifici, Roberta; Zuccaro, Piergiorgio; Langohr, Klaus; de la Torre, Rafael

    2010-07-01

    Despite the increasing concern about gamma-hydroxybutyrate (GHB) toxicity in users, no studies have addressed GHB and other club drugs effects on the immune system under controlled administration. Lymphocyte subsets and functional responsiveness of lymphocytes to mitogenic stimulation were measured in 10 healthy male recreational users of GHB who participated in five experimental sessions within the framework of a clinical trial. The study was randomized, double blind, double dummy and cross-over. Drug conditions were: a single oral dose of GHB (40 mg/kg or 60 mg/kg), ethanol (0.7 g/kg), flunitrazepam (1.25 mg) and placebo. Acute GHB produced a time-dependent immune impairment in the first 4 hours after drug administration associated with an increase in cortisol secretion. Although total leukocyte count remained unchanged, there was a significant decrease in the CD4 T/CD8 T-cell ratio, as well as in the percentage of mature T lymphocytes, probably because of a decrease in both the percentage and absolute number of T helper cells. A significant decrease was also observed in natural killer cells and in functional responsiveness of lymphocytes to mitogenic stimulation. Flunitrazepam administration did not produce any change in the immune system, while ethanol intake produced a decrease in B lymphocytes and in lymphocyte proliferative response to mitogens. These results provide the first evidence that GHB intake under a controlled environmental setting impairs the immunological status and confirms the alterations in the immune function caused by ethanol.

  17. Neurophysiological effects of acute oxytocin administration: systematic review and meta-analysis of placebo-controlled imaging studies

    Science.gov (United States)

    Wigton, Rebekah; Radua, Jocham; Allen, Paul; Averbeck, Bruno; Meyer-Lindenberg, Andreas; McGuire, Philip; Shergill, Sukhi S.; Fusar-Poli, Paolo

    2015-01-01

    Background Oxytocin (OXT) plays a prominent role in social cognition and may have clinical applications for disorders such as autism, schizophrenia and social anxiety. The neural basis of its mechanism of action remains unclear. Methods We conducted a systematic literature review of placebo-controlled imaging studies using OXT as a pharmacological manipulator of brain activity. Results We identified a total of 21 studies for inclusion in our review, and after applying additional selection criteria, 11 of them were included in our fMRI voxel-based meta-analysis. The results demonstrate consistent alterations in activation of brain regions, including the temporal lobes and insula, during the processing of social stimuli, with some variation dependent on sex and task. The meta-analysis revealed significant left insular hyperactivation after OXT administration, suggesting a potential modulation of neural circuits underlying emotional processing. Limitations This quantitative review included only a limited number of studies, thus the conclusions of our analysis should be interpreted cautiously. This limited sample size precluded a more detailed exploration of potential confounding factors, such as sex or other demographic factors, that may have affected our meta-analysis. Conclusion Oxytocin has a wide range of effects over neural activity in response to social and emotional processing, which is further modulated by sex and task specificity. The magnitude of this neural activation is largest in the temporal lobes, and a meta-analysis across all tasks and both sexes showed that the left insula demonstrated the most robust activation to OXT administration. PMID:25520163

  18. Post-exposure administration of diazepam combined with soluble epoxide hydrolase inhibition stops seizures and modulates neuroinflammation in a murine model of acute TETS intoxication

    Energy Technology Data Exchange (ETDEWEB)

    Vito, Stephen T., E-mail: stvito@ucdavis.edu [Department of Entomology, College of Agricultural and Environmental Sciences, University of California-Davis, Davis, CA 95616 (United States); Austin, Adam T., E-mail: aaustin@ucdavis.edu [Department of Pediatrics, School of Medicine, University of California-Davis Medical Center, Sacramento, CA 95817 (United States); Banks, Christopher N., E-mail: Christopher.Banks@oehha.ca.gov [Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616 (United States); Inceoglu, Bora, E-mail: abinceoglu@ucdavis.edu [Department of Entomology, College of Agricultural and Environmental Sciences, University of California-Davis, Davis, CA 95616 (United States); Bruun, Donald A., E-mail: dabruun@ucdavis.edu [Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616 (United States); Zolkowska, Dorota, E-mail: dzolkowska@gmail.com [Department of Neurology, School of Medicine, University of California-Davis, Sacramento, CA 95817 (United States); Tancredi, Daniel J., E-mail: djtancredi@ucdavis.edu [Department of Pediatrics, School of Medicine, University of California-Davis Medical Center, Sacramento, CA 95817 (United States); Rogawski, Michael A., E-mail: rogawski@ucdavis.edu [Department of Neurology, School of Medicine, University of California-Davis, Sacramento, CA 95817 (United States); Hammock, Bruce D., E-mail: bdhammock@ucdavis.edu [Department of Entomology, College of Agricultural and Environmental Sciences, University of California-Davis, Davis, CA 95616 (United States); Lein, Pamela J., E-mail: pjlein@ucdavis.edu [Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616 (United States)

    2014-12-01

    Tetramethylenedisulfotetramine (TETS) is a potent convulsant poison for which there is currently no approved antidote. The convulsant action of TETS is thought to be mediated by inhibition of type A gamma-aminobutyric acid receptor (GABA{sub A}R) function. We, therefore, investigated the effects of post-exposure administration of diazepam, a GABA{sub A}R positive allosteric modulator, on seizure activity, death and neuroinflammation in adult male Swiss mice injected with a lethal dose of TETS (0.15 mg/kg, ip). Administration of a high dose of diazepam (5 mg/kg, ip) immediately following the second clonic seizure (approximately 20 min post-TETS injection) effectively prevented progression to tonic seizures and death. However, this treatment did not prevent persistent reactive astrogliosis and microglial activation, as determined by GFAP and Iba-1 immunoreactivity and microglial cell morphology. Inhibition of soluble epoxide hydrolase (sEH) has been shown to exert potent anti-inflammatory effects and to increase survival in mice intoxicated with other GABA{sub A}R antagonists. The sEH inhibitor TUPS (1 mg/kg, ip) administered immediately after the second clonic seizure did not protect TETS-intoxicated animals from tonic seizures or death. Combined administration of diazepam (5 mg/kg, ip) and TUPS (1 mg/kg, ip, starting 1 h after diazepam and repeated every 24 h) prevented TETS-induced lethality and influenced signs of neuroinflammation in some brain regions. Significantly decreased microglial activation and enhanced reactive astrogliosis were observed in the hippocampus, with no changes in the cortex. Combining an agent that targets specific anti-inflammatory mechanisms with a traditional antiseizure drug may enhance treatment outcome in TETS intoxication. - Highlights: • Acute TETS intoxication causes delayed and persistent neuroinflammation. • Diazepam given post-TETS prevents lethal tonic seizures but not neuroinflammation. • A soluble epoxide hydrolase

  19. Long-term effects of an acute and systemic administration of LPS on adult neurogenesis and spatial memory

    Directory of Open Access Journals (Sweden)

    Jorge eValero

    2014-04-01

    Full Text Available The cognitive reserve is the capacity of the brain to maintain normal performance while exposed to insults or ageing. Increasing evidences point to a role for the interaction between inflammatory conditions and cognitive reserve status during Alzheimer's disease (AD progression. The production of new neurons along adult life can be considered as one of the components of the cognitive reserve. Interestingly, adult neurogenesis is decreased in mouse models of AD and following inflammatory processes. The aim of this work is to reveal the long-term impact of a systemic inflammatory event on memory and adult neurogenesis in wild type (WT and triple transgenic mouse model of AD (3xTg-AD.4 month-old mice were intraperitoneally injected once with saline or lipopolysaccharide (LPS and their performance on spatial memory analyzed with the Morris water maze (MWM test 7 weeks later. Our data showed that a single intraperitoneal injection with LPS has a long-term impact in the production of hippocampal neurons. Consistently, LPS-treated WT mice showed less doublecortin-positive neurons, less synaptic contacts in newborn neurons, and decreased dendritic volume and complexity. These surprising observations were accompanied with memory deficits. 3xTg-AD mice showed a decrease in new neurons in the dentate gyrus compatible with, although exacerbated, the pattern observed in WT LPS-treated mice. In 3xTg-AD mice, LPS injection did not significantly affected the production of new neurons but reduced their number of synaptic puncta and impaired memory performance, when compared to the observations made in saline-treated 3xTg-AD mice. These data indicate that LPS treatment induces a long-term impairment on hippocampal neurogenesis and memory. Our results show that acute neuroinflammatory events influence the production of new hippocampal neurons, affecting the cognitive reserve and leading to the development of memory deficits associated to Alzheimer's disease

  20. The reinforcing properties of ethanol are quantitatively enhanced in adulthood by peri-adolescent ethanol, but not saccharin, consumption in female alcohol-preferring (P) rats.

    Science.gov (United States)

    Toalston, Jamie E; Deehan, Gerald A; Hauser, Sheketha R; Engleman, Eric A; Bell, Richard L; Murphy, James M; McBride, William J; Rodd, Zachary A

    2015-08-01

    Alcohol drinking during adolescence is associated in adulthood with heavier alcohol drinking and an increased rate of alcohol dependence. Past research in our laboratory has indicated that peri-adolescent ethanol consumption can enhance the acquisition and reduce the rate of extinction of ethanol self-administration in adulthood. Caveats of the past research include reinforcer specificity, increased oral consumption during peri-adolescence, and a lack of quantitative assessment of the reinforcing properties of ethanol. The current experiments were designed to determine the effects of peri-adolescent ethanol or saccharin drinking on acquisition and extinction of oral ethanol self-administration and ethanol seeking, and to quantitatively assess the reinforcing properties of ethanol (progressive ratio). Ethanol or saccharin access by alcohol-preferring (P) rats occurred during postnatal day (PND) 30-60. Animals began operant self-administration of ethanol or saccharin after PND 85. After 10 weeks of daily operant self-administration, rats were tested in a progressive ratio paradigm. Two weeks later, self-administration was extinguished in all rats. Peri-adolescent ethanol consumption specifically enhanced the acquisition of ethanol self-administration, reduced the rate of extinction for ethanol self-administration, and quantitatively increased the reinforcing properties of ethanol during adulthood. Peri-adolescent saccharin consumption was without effect. The data indicate that ethanol consumption during peri-adolescence results in neuroadaptations that may specifically enhance the reinforcing properties of ethanol during adulthood. This increase in the reinforcing properties of ethanol could be a part of biological sequelae that are the basis for the effects of adolescent alcohol consumption on the increase in the rate of alcoholism during adulthood.

  1. Acute administration of 3,4-methylenedioxymethamphetamine (MDMA) induces oxidative stress, lipoperoxidation and TNFα-mediated apoptosis in rat liver.

    Science.gov (United States)

    Cerretani, D; Bello, S; Cantatore, S; Fiaschi, A I; Montefrancesco, G; Neri, M; Pomara, C; Riezzo, I; Fiore, C; Bonsignore, A; Turillazzi, E; Fineschi, V

    2011-11-01

    Liver toxicity is one of the consequences of ecstasy (3,4-methylenedioxymethamphetamine MDMA) abuse and hepatocellular damage is reported after MDMA consumption. Various factors probably play a role in ecstasy-induced hepatotoxicity, namely its metabolism, the increased efflux of neurotransmitters, the oxidation of biogenic amines, and hyperthermia. MDMA undergoes extensive hepatic metabolism that involves the production of reactive metabolites which form adducts with intracellular nucleophilic sites. MDMA-induced-TNF-α can promote multiple mechanisms to initiate apoptosis in hepatocytes, activation of pro-apoptotic (BID, SMAC/DIABLO) and inhibition of anti-apoptotic (NF-κB, Bcl-2) proteins. The aim of the present study was to obtain evidence for the oxidative stress mechanism and apoptosis involved in ecstasy-induced hepatotoxicity in rat liver after a single 20 mg/kg, i.p. MDMA administration. Reduced and oxidized glutathione (GSH and GSSG), ascorbic acid (AA), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA), an indicator of lipid peroxidation, were determined in rat liver after 3 and 6h after MDMA treatment. The effect of a single MDMA treatment included decrease of GR and GPx activities (29% and 25%, respectively) and GSH/GSSG ratio (32%) with an increase of MDA (119%) after 3h from ecstasy administration compared to control rats. Liver cytosolic level of AA was increased (32%) after 6 h MDMA treatment. Our results demonstrate a strong positive reaction for TNFα (p<0.001) in hepatocytes and a diffuse apoptotic process in the liver specimens (p<0.001). There was correlation between immunohistochemical results and Western blotting which were quantitatively measured by densitometry, confirming the strong positivity for TNF-α (p<0.001) and NF-κB (p<0.001); weak and intense positivity reactions was confirmed for Bcl-2, SMAC/DIABLO (p<0.001) and BID reactions (p<0.001). The results obtained in the

  2. Behavioral and antiepileptic effects of acute administration of the extract of the plant Cestrum nocturnum Lin (lady of the night).

    Science.gov (United States)

    Pérez-Saad, Héctor; Buznego, María T

    2008-04-01

    Cestrum nocturnum is a garden shrub from the family Solanaceae and is used as a remedy for different health disorders. The aim of the present work was to investigate the potential neuropharmacological action profile of decoctions obtained from dry leaves of the plant. Decoctions were tested in different neuropharmacological models-Irwin test, exploratory behavior, tests for analgesia, isoniazid- and picrotoxin-induced convulsions, and maximal electroshock seizures-in mice, as well as in amphetamine-induced stereotypies and penicillin epileptic foci in rats. Decoctions of 1 and 5% (D1 and D5) induced restlessness, and the 30% decoction (D30) induced passivity. D5 and D30 reduced significantly exploratory behavior and amphetamine-induced stereotypies within a 3-hour observation period. The latter effect was apparent during the second 60 minutes. Decoctions reduced the amount of writhes induced by acetic acid in a dose-dependent manner, but were not effective in the hot plate model. The decoctions were not effective against pharmacologically induced convulsions. However, repeated administration of five doses of D5, at 1-hour intervals, reduced the amplitude of penicillin-induced epileptic spikes in both primary and secondary foci, in curarized rats. Taken together, the results suggest that C. nocturnum possesses active substances with analgesic activity provided through a peripheral action mechanism, in parallel with some psychoactive activity that does not fit well the neuropharmacological action profile of known reference neurotropic drugs.

  3. Treatment of ethanol-induced acute pulmonary hypertension and right ventricular dysfunction in pigs, by sildenafil analogue (UK343-664 or nitroglycerin

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    Sidi Avner

    2008-01-01

    Full Text Available In patients at risk for sudden ethanol (ETOH intravascular absorption, prompt treatment of pulmonary hypertension (PHTN will minimise the risk of cardiovascular decompensation. We investigated the haemodynamic effects of intravenous ETOH and the pulmonary vasodilatory effects of a sildenafil analogue (UK343-664 and nitroglycerin (NTG during ETOH-induced PHTN in pigs. We studied pulmonary and systemic haemodynamics, and right ventricular rate or time derivate of pressure rise during ventricular contraction ( =dP/dT, as an index of contractility, in 23 pigs. ETOH was infused at a rate of 50 mg/kg/min, titrated to achieve a twofold increase in mean pulmonary arterial pressure (MPAP, and then discontinued. The animals were randomised to receive an infusion of 2 ml/kg ( n = 7 normal saline, a 500-μg/kg bolus of UK343-664 ( n = 8, or NTG 1 μg/kg ( n = 8; each was given over 60 seconds. Following ETOH infusion, dP/dT decreased central venous pressure (CVP, and MPAP increased significantly, resulting in significantly increased pulmonary vascular resistance (PVR. Within 2 minutes after treatment with either drug, CVP, heart rate (HR, and the systemic vascular resistance-to-pulmonary vascular resistance (SVR/PVR ratio returned to baseline. However, at that time, only in the UK343-664 group, MPAP and dP/dT partially recovered and were different from the respective values at PHTN stage. NTG and UK343-664 decreased PVR within 2 minutes, from 1241±579 and 1224±494 dyne · cm/sec 5 , which were threefold-to-fourfold increased baseline values, to 672±308 and 538±203 dyne · cm/sec 5 respectively. However, only in the UK343-664 group, changes from baseline PVR values after treatment were significant compared to the maximal change during target PHTN. Neither drug caused a significant change in SVR. In this model of ETOH-induced PHTN, both UK343-664 and NTG were effective pulmonary vasodilators with a high degree of selectivity. However, the changes from

  4. Prenatal ethanol increases sucrose reinforcement, an effect strengthened by postnatal association of ethanol and sucrose.

    Science.gov (United States)

    Culleré, Marcela Elena; Spear, Norman E; Molina, Juan Carlos

    2014-02-01

    Late prenatal exposure to ethanol recruits sensory processing of the drug and of its motivational properties, an experience that leads to heightened ethanol affinity. Recent studies indicate common sensory and neurobiological substrates between this drug and sweet tastants. Using a recently developed operant conditioning technique for infant rats, we examined the effects of prenatal ethanol history upon sucrose self-administration (postnatal days, PDs 14-17). Prior to the last conditioning session, a low (0.5 g/kg) or a high (2.5 g/kg) ethanol dose were paired with sucrose. The intention was to determine if ethanol would inflate or devalue the reinforcing capability of the tastant and if these effects are dependent upon prenatal ethanol history. Male and female pups prenatally exposed to ethanol (2.0 g/kg) responded more when reinforced with sucrose than pups lacking this antenatal experience. Independently of prenatal status, a low ethanol dose (0.5 g/kg) enhanced the reinforcing capability of sucrose while the highest dose (2.5 g/kg) seemed to ameliorate the motivational properties of the tastant. During extinction (PD 18), two factors were critical in determining persistence of responding despite reinforcement omission. Pups prenatally exposed to ethanol that subsequently experienced the low ethanol dose paired with sucrose, showed higher resistance to extinction. The effects here reported were not associated with differential blood alcohol levels across prenatal treatments. These results indicate that fetal ethanol experience promotes affinity for a natural sweet reinforcer and that low doses of ethanol are also capable of enhancing the positive motivational consequences of sucrose when ethanol and sucrose are paired during infancy.

  5. Lithium-mediated protection against ethanol neurotoxicity

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    Jia Luo

    2010-06-01

    Full Text Available Lithium has long been used as a mood stabilizer in the treatment of manic-depressive (bipolar disorder. Recent studies suggest that lithium has neuroprotective properties and may be useful in the treatment of acute brain injuries such as ischemia and chronic neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis. One of the most important neuroprotective properties of lithium is its anti-apoptotic action. Ethanol is a neuroteratogen and fetal alcohol spectrum disorders (FASD are caused by maternal ethanol exposure during pregnancy. FASD is the leading cause of mental retardation. Ethanol exposure causes neuroapoptosis in the developing brain. Ethanol-induced loss of neurons in the central nervous system underlies many of the behavioral deficits observed in FASD. Excessive alcohol consumption is also associated with Wernicke–Korsakoff syndrome and neurodegeneration in the adult brain. Recent in vivo and in vitro studies indicate that lithium is able to ameliorate ethanol-induced neuroapoptosis. Lithium is an inhibitor of glycogen synthase kinase 3 (GSK3 which has recently been identified as a mediator of ethanol neurotoxicity. Lithium’s neuroprotection may be mediated by its inhibition of GSK3. In addition, lithium also affects many other signaling proteins and pathways that regulate neuronal survival and differentiation. This review discusses the recent evidence of lithium-mediated protection against ethanol neurotoxicity and potential underlying mechanisms.

  6. Zn(II)-curcumin protects against hemorheological alterations, oxidative stress and liver injury in a rat model of acute alcoholism.

    Science.gov (United States)

    Yu, Chuan; Mei, Xue-Ting; Zheng, Yan-Ping; Xu, Dong-Hui

    2014-03-01

    Curcumin can chelate metal ions, forming metallocomplexes. We compared the effects of Zn(II)-curcumin with curcumin against hemorheological alterations, oxidative stress and liver injury in a rat model of acute alcoholism. Oral administration of Zn(II)-curcumin dose-dependently prevented the ethanol-induced elevation of serum malondialdehyde (MDA) content and reductions in glutathione level and superoxide dismutase (SOD) activity. Zn(II)-curcumin also inhibited ethanol-induced liver injury. Additionally, Zn(II)-curcumin dose-dependently inhibited hemorheological abnormalities, including the ethanol-induced elevation of whole blood viscosity, plasma viscosity, blood viscosity at corrected hematocrit (45%), erythrocyte aggregation index, erythrocyte rigidity index and hematocrit. Compared to curcumin at the same dose, Zn(II)-curcumin more effectively elevated SOD activity, ameliorated liver injury and improved hemorheological variables. These results suggest that Zn(II)-curcumin protected the rats from ethanol-induced liver injury and hemorheological abnormalities via the synergistic effect of curcumin and zinc.

  7. Postmortem degradation of administered ethanol-d6 and production of endogenous ethanol: experimental studies using rats and rabbits.

    Science.gov (United States)

    Takayasu, T; Ohshima, T; Tanaka, N; Maeda, H; Kondo, T; Nishigami, J; Nagano, T

    1995-12-18

    Deuterium-labeled ethanol-d6 was employed to study the metabolism and postmortem change of ethanol in putrefied organ tissues. First, 4 ml/kg body weight of 25% (w/v) solution of ethanol-d6 was administered orally to each of 15 rats. The heart blood and organs were collected 15-90 min after the administration and the ethanol-d6 was analyzed by head space gas chromatography/mass spectrometry. The ethanol-d6 concentration in the organ tissues reached its maximum at 15 min after the administration and then gradually declined, showing the same pattern as human ethanol metabolism. Ethanol-d6 (3 ml of the same solution/kg body weight) was injected into the vein of a rabbit's ear (total of 12 rabbits). The rabbit was killed with carbon monoxide 30 min after the administration and the carcass was allowed to stand for 1-4 days at 30 degrees C in a moist chamber. The concentration of ethanol-d6 decreased moderately. Postmortem ethanol and 1-propanol concentrations, in contrast, showed marked increases 2.5 days and more after sacrifice in line with the degree of putrefaction of each organ tissue including skeletal muscle. This suggests the postmortem activation of micro-organism activity. These results indicate that ethanol concentrations in cadaver tissues must be carefully assessed with due consideration of postmortem degradation and production.

  8. 不同剂量乙醇对地西泮及氯胺酮用药小鼠学习记忆的影响%The effects of different doses of ethanol on learning and memory in mice with diazepam and ketamine administration

    Institute of Scientific and Technical Information of China (English)

    陈慧娟; 虞黎黎; 曹兆成; 戴平; 庞步军; 张妤; 张咏梅

    2012-01-01

    Objective To observe the effects of different doses of ethanol on learning and memory in mice with dia-zepam and ketamine administation. Methods In a stratified and random block design, 80 mice were divided into 10 groups (n=S each): saline + diazepam (group A) ; 10% ethanol + diazepam (group B); 20% ethanol + diazepam (group C); 40% ethanol + diazepam (group D); saline + ketamine (group E); 10% ethanol + ketamine (group F) ; 20% ethanol + ketamine (group G); 40% ethanol + ketamine (group H); saline + diazepam + ketamine (group I); 10% ethanol + diazepam + ketamine (group J). The step-through test was performed to observe latency and error times in each group at 1 , 24 and 48 h after drug administration. Results Compared with group A , the error times in group D decreased , but the mice of group D was in a state of lethargy , indicating that ethanol inhibited the cen-tral nervous system highly. Compared with group B , the latency in group C decreased and error times increased (P<0.05) , indicating that with the increase of the concentration of ethanol , the inhibition effect of ethanol on learning and memory in mice with diazepam administration enhanced . Compared with group E , the latency in group F and group G de-creased (P<0.05) , indicating that ethanol could enhance the inhibition effect of learning and memory in mice with ket-amine administration. Compared with group C, the error times in group G decreased and the latency increased (P<0.05) , indicating that the inhibition eliect of ethanol on learning and memory in mice with diazepam administration was stronger than ketamine. Conclusion The inhibition effect of 20% ethanol on learning and memory in mice with diaze-pam administration is stronger than ketamine.%目的 研究不同剂量乙醇对地西泮和氯胺酮用药小鼠学习记忆的影响.方法 按分层随机区组设计将80只小鼠分为10组(每组n=8):生理盐水+地西泮(A组);10%乙醇+地西泮(B组);20%乙醇+地西泮(C组);40%乙醇+

  9. Healthcare professionals’ views of the use and administration of two salvage therapy drugs for acute ulcerative colitis: a nested qualitative study within the CONSTRUCT trial

    Science.gov (United States)

    Clement, Clare; Rapport, Frances; Seagrove, Anne; Alrubaiy, Laith; Williams, John

    2017-01-01

    Objectives Insight into healthcare professionals’ views and experiences of the use of ciclosporin and infliximab as salvage therapies for acute ulcerative colitis (UC) and how this may affect participation in a comparison trial is lacking. The study aimed to capture views and opinions of healthcare professionals about the two drugs within the CONSTRUCT trial. Design An interview-based qualitative study using Framework Analysis embedded within an open-label, pragmatic randomised trial. Setting National Health Service Health Boards and Trusts, including large teaching and district hospitals in England, Scotland and Wales. Participants Principal Investigators (PIs) for trial sites (who were all consultant gastroenterologists) and nurses responsible for administering and monitoring the salvage therapy drugs across trial sites. 15 PIs and 8 nurses recruited from a range of sites stratified by site recruitment rates were interviewed. Results Interviews revealed that professionals made judgements regarding the salvage therapies largely based on experience of giving the two drugs and perceptions of effectiveness and adverse side effects. A clear preference for infliximab among nurses was revealed, largely based on experiences of administration and drug handling, with some doctors strongly favouring infliximab based on experience of prescribing the drug as well as patient views and the existing evidence base. Most doctors were more equivocal, and all were prepared to suspend preferences and wait for evidence of effectiveness and safety from the CONSTRUCT trial. PIs also questioned guidelines around drug use and restrictions placed on personal autonomy in delivering best patient care. Conclusions Findings highlight healthcare professionals’ preference for the salvage treatment, infliximab in treating steroid-resistant UC, largely based on resource intensive nursing requirements of intravenous administration of ciclosporin. Not all doctors expressed this preference, being

  10. Effect of acute administration of Pistacia lentiscus L. essential oil on rat cerebral cortex following transient bilateral common carotid artery occlusion

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    Quartu Marina

    2012-01-01

    Full Text Available Abstract Background Ischemia/reperfusion leads to inflammation and oxidative stress which damages membrane highly polyunsaturated fatty acids (HPUFAs and eventually induces neuronal death. This study evaluates the effect of the administration of Pistacia lentiscus L. essential oil (E.O., a mixture of terpenes and sesquiterpenes, on modifications of fatty acid profile and endocannabinoid (eCB congener concentrations induced by transient bilateral common carotid artery occlusion (BCCAO in the rat frontal cortex and plasma. Methods Adult Wistar rats underwent BCCAO for 20 min followed by 30 min reperfusion (BCCAO/R. 6 hours before surgery, rats, randomly assigned to four groups, were gavaged either with E.O. (200 mg/0.45 ml of sunflower oil as vehicle or with the vehicle alone. Results BCCAO/R triggered in frontal cortex a decrease of docosahexaenoic acid (DHA, the membrane highly polyunsaturated fatty acid most susceptible to oxidation. Pre-treatment with E.O. prevented this change and led further to decreased levels of the enzyme cyclooxygenase-2 (COX-2, as assessed by Western Blot. In plasma, only after BCCAO/R, E.O. administration increased both the ratio of DHA-to-its precursor, eicosapentaenoic acid (EPA, and levels of palmytoylethanolamide (PEA and oleoylethanolamide (OEA. Conclusions Acute treatment with E.O. before BCCAO/R elicits changes both in the frontal cortex, where the BCCAO/R-induced decrease of DHA is apparently prevented and COX-2 expression decreases, and in plasma, where PEA and OEA levels and DHA biosynthesis increase. It is suggested that the increase of PEA and OEA plasma levels may induce DHA biosynthesis via peroxisome proliferator-activated receptor (PPAR alpha activation, protecting brain tissue from ischemia/reperfusion injury.

  11. Effects of acute and long-term administration of escitalopram and citalopram on serotonin neurotransmission: an in vivo electrophysiological study in rat brain.

    Science.gov (United States)

    El Mansari, Mostafa; Sánchez, Connie; Chouvet, Guy; Renaud, Bernard; Haddjeri, Nasser

    2005-07-01

    The present study was undertaken to compare the acute and long-term effects of escitalopram and citalopram on rat brain 5-HT neurotransmission, using electrophysiological techniques. In hippocampus, after 2 weeks of treatment with escitalopram (10 mg/kg/day, s.c.) or citalopram (20 mg/kg/day, s.c.), the administration of the selective 5-HT(1A) receptor antagonist WAY-100,635 (20-100 microg/kg, i.v.) dose-dependently induced a similar increase in the firing activity of dorsal hippocampus CA(3) pyramidal neurons, thus revealing direct functional evidence of an enhanced tonic activation of postsynaptic 5-HT(1A) receptors. In dorsal raphe nucleus, escitalopram was four times more potent than citalopram in suppressing the firing activity of presumed 5-HT neurons (ED(50)=58 and 254 mug/kg, i.v., respectively). Interestingly, the suppressant effect of escitalopram (100 microg/kg, i.v.) was significantly prevented, but not reversed by R-citalopram (250 microg/kg, i.v.). Sustained administration of escitalopram and citalopram significantly decreased the spontaneous firing activity of presumed 5-HT neurons. This firing activity returned to control rate after 2 weeks in rats treated with escitalopram, but only after 3 weeks using citalopram, and was associated with a desensitization of somatodendritic 5-HT(1A) autoreceptors. These results suggest that the time course of the gradual return of presumed 5-HT neuronal firing activity, which was reported to account for the delayed effect of SSRI on 5-HT transmission, is congruent with the earlier onset of action of escitalopram vs citalopram in validated animal models of depression and anxiety.

  12. Hypolipidemic effects of acute and sub-chronic administration of an aqueous extract of Ajuga iva L. whole plant in normal and diabetic rats.

    Science.gov (United States)

    El-Hilaly, Jaouad; Tahraoui, Adil; Israili, Zafar H; Lyoussi, Badiâa

    2006-05-24

    Diabetes is often accompanied by lipid abnormalities, which contribute significantly to cardiovascular (CV) morbidity and mortality in diabetic patients. The plant Ajuga iva (L.) Schreiber (Labiatea) is used in the treatment of diabetes in Moroccan folk medicine. Previously, we have demonstrated potent hypoglycemic activity and relatively non-toxic nature of a lyophilized aqueous extract of the whole plant (AI-extract) in normal (normoglycemic) and streptozotocin (STZ)-diabetic rats. In this study, we examined the AI-extract for its possible lipid-lowering activity in normal and STZ-diabetic rats. Taurine (TR) and glibenclamide (GLB) were used as reference substances. As shown previously, the AI-extract (10 mg/kg; oral) reduced plasma glucose levels after acute (single) and sub-chronic (3 weeks) dosing both in normal and diabetic rats. In normal rats, single and repeated oral administration of the AI-extract, at a dose of 10 mg/kg produced a small but significant decrease in plasma CHL levels (PAjuga iva whole plant showed hypolipidemic activity, in addition to its hypoglycemic effect in normoglycemic and diabetic rats. In view of the hypoglycemic and hypolipidemic activity, and its relatively non-toxic nature (shown previously), Ajuga iva may be a candidate for development as an anti-diabetic agent in humans. Further studies are warranted to confirm our results and fractionate the AI-extract to isolate and identify the active principle(s), and to determine the exact mechanism(s) of action.

  13. Correlations between the Memory-Related Behavior and the Level of Oxidative Stress Biomarkers in the Mice Brain, Provoked by an Acute Administration of CB Receptor Ligands.

    Science.gov (United States)

    Kruk-Slomka, Marta; Boguszewska-Czubara, Anna; Slomka, Tomasz; Budzynska, Barbara; Biala, Grazyna

    2016-01-01

    The endocannabinoid system, through cannabinoid (CB) receptors, is involved in memory-related responses, as well as in processes that may affect cognition, like oxidative stress processes. The purpose of the experiments was to investigate the impact of CB1 and CB2 receptor ligands on the long-term memory stages in male Swiss mice, using the passive avoidance (PA) test, as well as the influence of these compounds on the level of oxidative stress biomarkers in the mice brain. A single injection of a selective CB1 receptor antagonist, AM 251, improved long-term memory acquisition and consolidation in the PA test in mice, while a mixed CB1/CB2 receptor agonist WIN 55,212-2 impaired both stages of cognition. Additionally, JWH 133, a selective CB2 receptor agonist, and AM 630, a competitive CB2 receptor antagonist, significantly improved memory. Additionally, an acute administration of the highest used doses of JWH 133, WIN 55,212-2, and AM 630, but not AM 251, increased total antioxidant capacity (TAC) in the brain. In turn, the processes of lipids peroxidation, expressed as the concentration of malondialdehyde (MDA), were more advanced in case of AM 251. Thus, some changes in the PA performance may be connected with the level of oxidative stress in the brain.

  14. Correlations between the Memory-Related Behavior and the Level of Oxidative Stress Biomarkers in the Mice Brain, Provoked by an Acute Administration of CB Receptor Ligands

    Directory of Open Access Journals (Sweden)

    Marta Kruk-Slomka

    2016-01-01

    Full Text Available The endocannabinoid system, through cannabinoid (CB receptors, is involved in memory-related responses, as well as in processes that may affect cognition, like oxidative stress processes. The purpose of the experiments was to investigate the impact of CB1 and CB2 receptor ligands on the long-term memory stages in male Swiss mice, using the passive avoidance (PA test, as well as the influence of these compounds on the level of oxidative stress biomarkers in the mice brain. A single injection of a selective CB1 receptor antagonist, AM 251, improved long-term memory acquisition and consolidation in the PA test in mice, while a mixed CB1/CB2 receptor agonist WIN 55,212-2 impaired both stages of cognition. Additionally, JWH 133, a selective CB2 receptor agonist, and AM 630, a competitive CB2 receptor antagonist, significantly improved memory. Additionally, an acute administration of the highest used doses of JWH 133, WIN 55,212-2, and AM 630, but not AM 251, increased total antioxidant capacity (TAC in the brain. In turn, the processes of lipids peroxidation, expressed as the concentration of malondialdehyde (MDA, were more advanced in case of AM 251. Thus, some changes in the PA performance may be connected with the level of oxidative stress in the brain.

  15. A case of marked diuresis by combined dopamine and atrial natriuretic peptide administration without renal injury in acute decompensated heart failure.

    Science.gov (United States)

    Kamiya, Masataka; Sato, Naoki; Akiya, Mai; Okazaki, Hirotake; Takahashi, Yasuhiro; Mizuno, Kyoichi

    2013-01-01

    Renal injury is an important factor for worsening outcome in acute decompensated heart failure (ADHF). An 81-year-old woman was admitted due to ADHF with dyspnea and mild peripheral edema. The patient was managed with intravenous administration of atrial natriuretic peptide (ANP) at a dose of 0.0125 μg/kg/minute, which did not control volume overload even at an increased dose of 0.025 μg/kg/minute. After a low dose of dopamine (DA) of 1.0 μg/kg/ minute was added, urine output increased markedly to 120 from 30 mL/hour. Furthermore, her heart rate decreased to 80-100 from 120 bpm and the congestion improved with a reduced brain natriuretic peptide level. Interestingly, the combination of ANP and DA therapy reduced serum creatinine as well as the levels of urinary liver-type fatty acid binding protein, a novel reno-tubular stress marker, by 98.9%, and an oxidative stress marker, urinary 8-hydroxydeoxyguanosine, by 88.2% from baseline levels. Thus, this ADHF patient, a nonresponder to ANP alone, improved without renal injury when administered combination therapy consisting of low doses of ANP and DA, suggesting that this combined therapy might be useful for better management of ADHF in patients without diuretic responses with ANP alone. Further prospective studies are warranted.

  16. Effects of acute nicotine administration on cognitive event-related potentials in tacrine-treated and non-treated patients with Alzheimer's disease.

    Science.gov (United States)

    Knott, V; Mohr, E; Mahoney, C; Engeland, C; Ilivitsky, V

    2002-01-01

    Earlier studies of cognitive event-related brain potentials (ERPs) reporting diminished amplitudes and delayed latencies of the P300 potential in dementia of the Alzheimer type (DAT), together with independent findings of the P300- and performance-enhancing properties of nicotine in normal adults, stimulated this study to explore the single-dose effects of nicotine on auditory and visual P300s in DAT. Thirteen patients, 6 currently receiving treatment with the cholinesterase inhibitor tacrine (tetrahydroaminoacridine; THA) and the remaining being medication free, were administered 2 mg of nicotine polacrilex under double-blind, randomized, placebo-controlled conditions. Prior to nicotine administration, THA-treated patients exhibited shorter auditory P300 latencies than non-treated patients. Acutely administered nicotine failed to alter auditory P300, but increased the amplitudes of visual P300s in both DAT patient groups. Neither THA treatment nor single-dose nicotine altered behavioural performance in the visual and auditory task paradigms. The results are discussed in relation to nicotinic cholinergic, attentional and cognitive processes in DAT.

  17. Ethanol Basics (Fact Sheet)

    Energy Technology Data Exchange (ETDEWEB)

    2015-01-01

    Ethanol is a widely-used, domestically-produced renewable fuel made from corn and other plant materials. More than 96% of gasoline sold in the United States contains ethanol. Learn more about this alternative fuel in the Ethanol Basics Fact Sheet, produced by the U.S. Department of Energy's Clean Cities program.

  18. KCNQ channels show conserved ethanol block and function in ethanol behaviour.

    Directory of Open Access Journals (Sweden)

    Sonia Cavaliere

    Full Text Available In humans, KCNQ2/3 channels form an M-current that regulates neuronal excitability, with mutations in these channels causing benign neonatal familial convulsions. The M-current is important in mechanisms of neural plasticity underlying associative memory and in the response to ethanol, with KCNQ controlling the release of dopamine after ethanol exposure. We show that dKCNQ is broadly expressed in the nervous system, with targeted reduction in neuronal KCNQ increasing neural excitability and KCNQ overexpression decreasing excitability and calcium signalling, consistent with KCNQ regulating the resting membrane potential and neural release as in mammalian neurons. We show that the single KCNQ channel in Drosophila (dKCNQ has similar electrophysiological properties to neuronal KCNQ2/3, including conserved acute sensitivity to ethanol block, with the fly channel (IC(50 = 19.8 mM being more sensitive than its mammalian ortholog (IC(50 = 42.1 mM. This suggests that the role of KCNQ in alcohol behaviour can be determined for the first time by using Drosophila. We present evidence that loss of KCNQ function in Drosophila increased sensitivity and tolerance to the sedative effects of ethanol. Acute activation of dopaminergic neurons by heat-activated TRP channel or KCNQ-RNAi expression produced ethanol hypersensitivity, suggesting that both act via a common mechanism involving membrane depolarisation and increased dopamine signalling leading to ethanol sedation.

  19. Autophagy and ethanol neurotoxicity.

    Science.gov (United States)

    Luo, Jia

    2014-01-01

    Excessive ethanol exposure is detrimental to the brain. The developing brain is particularly vulnerable to ethanol such that prenatal ethanol exposure causes fetal alcohol spectrum disorders (FASD). Neuronal loss in the brain is the most devastating consequence and is associated with mental retardation and other behavioral deficits observed in FASD. Since alcohol consumption during pregnancy has not declined, it is imperative to elucidate the underlying mechanisms and develop effective therapeutic strategies. One cellular mechanism that acts as a protective response for the central nervous system (CNS) is autophagy. Autophagy regulates lysosomal turnover of organelles and proteins within cells, and is involved in cell differentiation, survival, metabolism, and immunity. We have recently shown that ethanol activates autophagy in the developing brain. The autophagic preconditioning alleviates ethanol-induced neuron apoptosis, whereas inhibition of autophagy potentiates ethanol-stimulated reactive oxygen species (ROS) and exacerbates ethanol-induced neuroapoptosis. The expression of genes encoding proteins required for autophagy in the CNS is developmentally regulated; their levels are much lower during an ethanol-sensitive period than during an ethanol-resistant period. Ethanol may stimulate autophagy through multiple mechanisms; these include induction of oxidative stress and endoplasmic reticulum stress, modulation of MTOR and AMPK signaling, alterations in BCL2 family proteins, and disruption of intracellular calcium (Ca2+) homeostasis. This review discusses the most recent evidence regarding the involvement of autophagy in ethanol-mediated neurotoxicity as well as the potential therapeutic approach of targeting autophagic pathways.

  20. The effects of caffeine in the social interaction test and on exploration in rats: comparison with ethanol and clorazepate.

    Science.gov (United States)

    Nadal, R.A.; Pallares, M.A.; Ferré, N.S.

    1993-10-01

    The effects of caffeine (20mg/kg) in the holeboard and social interaction tests were compared with those of ethanol (0.4g and dipotassium clorazepate (3mg/kg), following acute administration in one group of rats or after five daily injections in another group. The rats were put in pairs into an unfamiliar arena with high levels of illumination (n = 80), or tested individually in the holeboard (n = 80). Acute caffeine produced no effect on the time spent in social interaction, although it enhanced the number of social contacts, and both genital and total sniffing. Following five injections, caffeine also increased the time spent in social interaction. Acute clorazepate enhanced this time but this effect showed partial tolerance after five injections. Clorazepate also enhanced the number and duration of social contacts, increasing social grooming and genital sniffing, regardless of the duration of the treatment. Ethanol increased the time spent in social interaction following five injections, and increased social grooming. In the holeboard, stimulant effects were observed for caffeine and clorazepate, showing partial tolerance and without any effect on head dipping. In the social interaction test, only a stimulant effect for caffeine was obtained. The results of this study suggest that, under some circumstances, caffeine may enhance social interaction, in a manner similar to standard anxiolytics. Such an effect is potentiated by repeated administration.

  1. Effects of ethanol feeding on hepatic lipid synthesis

    NARCIS (Netherlands)

    Tijburg, L.B.M.; MaQuedano, A.; Bijleveld, C.; Guzman, M.; Geelen, M.J.H.

    1988-01-01

    Rats were fed a high-fat, liquid diet containing either 36% of total calories as ethanol or an isocaloric amount of sucrose, for a period up to 35 days. At different time intervals we measured the effects of ethanol administration on the activities of a number of key enzymes involved in hepatic lipi

  2. Toxicological evaluation of ethanolic extract of Lychnophora trichocarpha, Brazilian arnica

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    Fernanda C. Ferrari

    2012-10-01

    Full Text Available The species of the genus Lychnophora, Asteraceae, are popularly known as "arnica" and are native from Brazilian savana (Cerrado. They are widely used in Brazilian folk medicine as anti-inflammatory, to treat bruise, pain, rheumatism and for insect bites. For evaluation of acute toxicity, the ethanolic extract was given to albino female and male mice. In open-field test, the extract of Lychnophora trichocarpha (Spreng. Spreng. (0.750 g/kg induced a significant inhibition of the spontaneous locomotor activity and exploratory behavior of the animals were observed 1 and 4 h after administration. In traction test, the same dose reduced the muscular force 1 h after administration. The exploratory behavior reduced significantly in the group that received 0.50 g/kg, 1 and 4 h after administration of the extract. The animals that received the doses of 0.25, 0.50 and 0.75 g/kg did not show any change of blood biochemical parameters comparing to control group and showed some histopathological changes such as congestion and inflammation of kidney and liver. The dose of 1.5 g/kg caused the most serious signs of toxicity. Histopathological changes observed was hemorrhage in 62.5% and pulmonary congestion in 100% of the animals. Brain and liver congestion was found in 62.5% of the animals.

  3. Pharmacokinetics of DA-125, a new anthracycline, after intravenous administration to uranyl nitrate-induced acute renal failure rats or protein-calorie malnutrition rats.

    Science.gov (United States)

    Kim, Y G; Yoon, E J; Yoon, W H; Shim, H J; Lee, S D; Kim, W B; Yang, J; Lee, M G

    1996-04-01

    The pharmacokinetics of DA-125 were compared after intravenous (i.v.) administration of the drug, 10 mg kg-1, to control male Sprague-Dawley rats (n = 9) and uranyl nitrate-induced acute renal failure (U-ARF, n = 12) rats, or male Sprague-Dawley rats fed on a 23% (control, n = 8) or a 5% (protein-calorie malnutrition, PCM, n = 9) protein diet. After i.v. administration of DA-125, almost 'constant' plasma concentrations of M1, M2, and M4 were maintained from 1-2 h to 8-10 h in all rat groups due to the continuous formation of M2 from M1 and M4 from M3. The plasma concentrations of M3 were the lowest among M1-M4 for all rat groups due to the rapid and almost complete conversion of M3 to M4 and other metabolite(s). The AUCt values of M1 (115 against 82.5 micrograms min mL-1), M2 (33.0 against 23.6 micrograms min mL-1), and M4 (26.3 against 15.1 micrograms min mL-1) were significantly higher in the U-ARF rats than in the control rats. The percentages of i.v. dose excreted in 24 h urine as M1 (under the detection limit against 0.316%), M2 (under the detection limit against 5.58%), and M4 (0.0174 against 0.719%)--expressed in terms of DA-125--were significantly lower in the U-ARF rats than in the control rats, and this could be due to the decreased kidney function in the U-ARF rats. However, the percentages of i.v. dose recovered from the GI tract at 24 h as M1 (0.0532% against under the detection limit), M3 (0.0286% against under the detection limit), and M4 (0.702% against 0.305%)--expressed in terms of DA-125--were significantly greater in the U-ARF rats than in the control rats. All U-ARF rats had ascites, but the concentrations of M1 (0.0320 micrograms mL-1), M2 (0.0265 micrograms mL-1), M3 (under the detection limit), and M4 (0.032 micrograms mL-1) in the ascites from one rat were almost negligible. The plasma concentrations and most of the pharmacokinetic parameters of M1, M2, and M4 were not significantly different between the PCM rats and their control rats.

  4. Acute Administration of MK-801 in an Animal Model of Psychosis in Rats Interferes with Cognitively Demanding Forms of Behavioral Flexibility on a Rotating Arena

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    Jan eSvoboda

    2015-04-01

    Full Text Available Patients with schizophrenia often manifest deficits in behavioral flexibility. Non-competitive NMDA receptor antagonists such as MK-801 induce schizophrenia-like symptoms in rodents, including cognitive functions. Despite work exploring flexibility has been done employing behavioral paradigms with simple stimuli, much less is known about what kinds of flexibility are affected in an MK-801 model of schizophrenia-like behavior in the spatial domain. We used a rotating arena-based apparatus (Carousel requiring rats to avoid an unmarked sector defined in either the reference frame of the rotating arena (arena frame task, AF or the stationary room (room frame task, RF. We investigated behavioral flexibility in four conditions involving different cognitive loads. Each condition encompassed an initial (five sessions and a test phase (five sessions in which some aspects of the task were changed to test flexibility in which rats were given saline, 0.05 mg/kg or 0.1 mg/kg MK-801 thirty minutes prior to a session. In the first condition, rats acquired avoidance in RF with clockwise rotation of the arena while in the test phase the arena rotated counterclockwise. In the second condition, rats initially acquired avoidance in RF with the sector on the north and then it was reversed to south (spatial reversal. In the third and fourth conditions, rats initially performed an AF (RF, respectively task, followed by an RF (AF, respectively task, testing the ability of cognitive set-shifting. We found no effect of MK-801 either on simple motor adjustment after reversal of arena rotation or on spatial reversal within the RF. In contrast, administration of MK-801 at a dose of 0.1 mg/kg interfered with set-shifting in both conditions. Furthermore, we observed MK-801 0.1 mg/kg elevated locomotion in all cases. These data suggest that blockade of NMDA receptors by acute system administration of MK-801 preferentially affects set-shifting in the cognitive domain rather

  5. Recovery of renal function after administration of adipose-tissue-derived stromal vascular fraction in rat model of acute kidney injury induced by ischemia/reperfusion injury.

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    Lee, Chunwoo; Jang, Myoung Jin; Kim, Bo Hyun; Park, Jin Young; You, Dalsan; Jeong, In Gab; Hong, Jun Hyuk; Kim, Choung-Soo

    2017-03-10

    Acute kidney injury (AKI) induced by ischemia/reperfusion (I/R) injury is a major challenge in critical care medicine. The purpose of this study is to determine the therapeutic effects of the adipose-tissue-derived stromal vascular fraction (SVF) and the optimal route for SVF delivery in a rat model of AKI induced by I/R injury. Fifty male Sprague-Dawley rats were randomly divided into five groups (10 animals per group): sham, nephrectomy control, I/R injury control, renal arterial SVF infusion and subcapsular SVF injection. To induce AKI by I/R injury, the left renal artery was clamped with a nontraumatic vascular clamp for 40 min, and the right kidney was removed. Rats receiving renal arterial infusion of SVF had a significantly reduced increase in serum creatinine compared with the I/R injury control group at 4 days after I/R injury. The glomerular filtration rate of the renal arterial SVF infusion group was maintained at a level similar to that of the sham and nephrectomy control groups at 14 days after I/R injury. Masson's trichrome staining showed significantly less fibrosis in the renal arterial SVF infusion group compared with that in the I/R injury control group in the outer stripe (P renal arterial SVF infusion and subcapsular SVF injection groups compared with the I/R injury control group in the outer stripe (P renal function is effectively rescued from AKI induced by I/R injury through the renal arterial administration of SVF in a rat model.

  6. Administration of alemtuzumab and G-CSF to adults with relapsed or refractory acute lymphoblastic leukemia: results of a phase II study.

    Science.gov (United States)

    Gorin, Norbert-Claude; Isnard, Françoise; Garderet, Laurent; Ikhlef, Souhila; Corm, Selim; Quesnel, Bruno; Legrand, Ollivier; Cachanado, Marine; Rousseau, Alexandra; Laporte, Jean-Philippe

    2013-10-01

    The outlook for adults with refractory and relapsed acute lymphocytic leukemia (ALL) is poor. CD52 is expressed in most patients with ALL. Alemtuzumab is an anti-CD52 humanized monoclonal antibody. This phase II study assessed the efficacy of alemtuzumab combined with granulocyte-colony stimulating factor (G-CSF) to boost antibody-dependent cell cytotoxicity mediated by neutrophils. Twelve patients with relapsed (n = 11) or refractory (n = 1) ALL, including four relapses postallogeneic stem cell transplantation, were treated and monitored between October 2006 and January 2011. Patients received 1 wk of alemtuzumab every other day at increasing doses of 3, 10, and 30 mg to test tolerance and 30 mg three times a week for 12-18 infusions. If in complete remission (CR), patients received maintenance therapy for 1 wk, every 2 months. G-CSF was administered at 5 μg/kg per day during alemtuzumab administration. The primary endpoint was disappearance of blast cells on a marrow aspirate. CD52 was expressed in all patients. Four patients reached CR. In one additional patient, clearance of blast cells was observed in peripheral blood but not in the marrow. The most frequent adverse events during course 1 of treatment were fever and chills (n = 3), skin rash (n = 3), and bronchospasm (n = 2). Tumor lysis syndrome was observed at treatment initiation in one patient who reached CR. All patients progressed within a few months and all but one died. The surviving patient is still alive after relapse and a second allogeneic stem cell transplantation. This study shows that in relapse/refractory ALL, alemtuzumab with G-CSF can produce good responses of short duration.

  7. Avaliação da toxicidade aguda e subaguda, em ratos, do extrato etanólico das folhas e do látex de Synadenium umbellatum Pax. Acute and subacute toxicity studies of the latex and of the ethanolic extract of the leaves of Synadenium umbellatum Pax in rats

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    Luiz C. Cunha

    2009-06-01

    Full Text Available O uso de plantas medicinais tem sido muito significativo nos últimos anos, sendo incentivado pela Organização Mundial de Saúde (OMS. Synadenium umbellatum Pax, Euphorbiacea (vulgo cola-nota, cancerola, milagrosa tem o látex usado empiricamente como antitumoral e antiinflamatório. Por existir espécies tóxicas nesta família e visando à segurança no uso de extratos vegetais, tal estudo avaliou a toxicidade pré-clínica do látex e do extrato etanólico das folhas (EEF de S. umbellatum, por via oral, em ratas Wistar. O estudo seguiu diretrizes do Guideline 423 (toxicidade aguda e Guideline 407 (toxicidade subaguda da OECD (Organisation for Economic Cooperation and Development. Na toxicidade aguda do látex e do EEF, não se observou letalidade nem alterações fisiológicas e comportamentais das ratas na dose de 2000 mg/kg, sendo praticamente atóxico. Porém, na análise histopatológica, o látex ocasionou congestão e infiltrado leucocitário nos rins, fígado e pulmões, efeitos não observados com o EEF. Na toxicidade subaguda, doses de 50, 100 e 200 mg/kg de EEF não produziram alterações dose-dependentes significativas nos parâmetros laboratoriais e fisiológicos, nem alterações macroscópicas e histopatológicas nos órgãos das ratas. Contudo, o uso crônico da planta S. umbellatum merece mais estudos.The use of medicinal plants has been being very significant in the last years, being the use encouraged by WHO. Synadenium umbellatum Pax, Euphorbiacea (popularly known as cola-note, cancerola, miraculous has the latex used empirically as anti-cancerous and anti-inflammatory. For there being toxic species in this family and aiming at the safety in the use of vegetable extracts, such study evaluated the pre-clinical toxicity of the latex and of the ethanolic extract of the leaves (EEL of S. umbellatum, administrated by oral route, in Wistar female rats. The study followed OECD's Guidelines for test of acute toxicity (Guideline

  8. Pharmacokinetic and pharmacodynamic drug interactions with ethanol (alcohol).

    Science.gov (United States)

    Chan, Lingtak-Neander; Anderson, Gail D

    2014-12-01

    Ethanol (alcohol) is one of the most widely used legal drugs in the world. Ethanol is metabolized by alcohol dehydrogenase (ADH) and the cytochrome P450 (CYP) 2E1 drug-metabolizing enzyme that is also responsible for the biotransformation of xenobiotics and fatty acids. Drugs that inhibit ADH or CYP2E1 are the most likely theoretical compounds that would lead to a clinically significant pharmacokinetic interaction with ethanol, which include only a limited number of drugs. Acute ethanol primarily alters the pharmacokinetics of other drugs by changing the rate and extent of absorption, with more limited effects on clearance. Both acute and chronic ethanol use can cause transient changes to many physiologic responses in different organ systems such as hypotension and impairment of motor and cognitive functions, resulting in both pharmacokinetic and pharmacodynamic interactions. Evaluating drug interactions with long-term use of ethanol is uniquely challenging. Specifically, it is difficult to distinguish between the effects of long-term ethanol use on liver pathology and chronic malnutrition. Ethanol-induced liver disease results in decreased activity of hepatic metabolic enzymes and changes in protein binding. Clinical studies that include patients with chronic alcohol use may be evaluating the effects of mild cirrhosis on liver metabolism, and not just ethanol itself. The definition of chronic alcohol use is very inconsistent, which greatly affects the quality of the data and clinical application of the results. Our study of the literature has shown that a significantly higher volume of clinical studies have focused on the pharmacokinetic interactions of ethanol and other drugs. The data on pharmacodynamic interactions are more limited and future research addressing pharmacodynamic interactions with ethanol, especially regarding the non-central nervous system effects, is much needed.

  9. Ethanol-induced hypothermia in rats is antagonized by dexamethasone

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    Carreño C.F.T.

    1997-01-01

    Full Text Available The effect of dexamethasone on ethanol-induced hypothermia was investigated in 3.5-month old male Wistar rats (N = 10 animals per group. The animals were pretreated with dexamethasone (2.0 mg/kg, ip; volume of injection = 1 ml/kg 15 min before ethanol administration (2.0, 3.0 and 4.0 g/kg, ip; 20% w/v and the colon temperature was monitored with a digital thermometer 30, 60 and 90 min after ethanol administration. Ethanol treatment produced dose-dependent hypothermia throughout the experiment (-1.84 ± 0.10, -2.79 ± 0.09 and -3.79 ± 0.15oC for 2.0, 3.0 and 4.0 g/kg ethanol, respectively, 30 min after ethanol but only the effects of 2.0 and 3.0 g/kg ethanol were significantly antagonized (-0.57 ± 0.09 and -1.25 ± 0.10, respectively, 30 min after ethanol by pretreatment with dexamethasone (ANOVA, P<0.05. These results are in agreement with data from the literature on the rapid antagonism by glucocorticoids of other effects of ethanol. The antagonism was obtained after a short period of time, suggesting that the effect of dexamethasone is different from the classical actions of corticosteroids

  10. Effect of capsaicin and chilli on ethanol induced gastric mucosal injury in the rat.

    Science.gov (United States)

    Kang, J Y; Teng, C H; Wee, A; Chen, F C

    1995-05-01

    Capsaicin, the pungent ingredient of chilli, is gastroprotective against experimental gastric injury when given intragastrically. Epidemiological and clinical data suggest that chilli ingestion may have a beneficial effect on human peptic ulcer disease. This study showed a gastroprotective effect of intragastric capsaicin, in doses of 2 and 5 mg, on ethanol induced gastric mucosal injury using macroscopic, histological, scanning electron microscopic, and biochemical indices. Subcutaneous administration of 2 mg of capsaicin had the same gastroprotective effect as intragastric administration. Acute intragastric administration and chronic ingestion of chilli powder in doses comparable with that consumed in humans (up to 200 mg in single doses or 200 mg daily for four weeks) likewise protected the gastric mucosa. Both the mucosa and gastric juice had higher mucus contents when capsaicin or chilli rather than saline or solvent was used before ethanol challenge. In control animals capsaicin also increased gastric juice mucus content although the mucosal content was unaffected. Increased gastric mucus production may therefore be one mechanism by which capsaicin and chilli exert their gastroprotective effect although an alternative explanation is that the reduction in mucosal mucus depletion is secondary to the protective effect of capsaicin and chilli.

  11. Fermentation method producing ethanol

    Science.gov (United States)

    Wang, Daniel I. C.; Dalal, Rajen

    1986-01-01

    Ethanol is the major end product of an anaerobic, thermophilic fermentation process using a mutant strain of bacterium Clostridium thermosaccharolyticum. This organism is capable of converting hexose and pentose carbohydrates to ethanol, acetic and lactic acids. Mutants of Clostridium thermosaccharolyticum are capable of converting these substrates to ethanol in exceptionally high yield and with increased productivity. Both the mutant organism and the technique for its isolation are provided.

  12. Chronobiology of ethanol: animal models.

    Science.gov (United States)

    Rosenwasser, Alan M

    2015-06-01

    Clinical and epidemiological observations have revealed that alcohol abuse and alcoholism are associated with widespread disruptions in sleep and other circadian biological rhythms. As with other psychiatric disorders, animal models have been very useful in efforts to better understand the cause and effect relationships underlying the largely correlative human data. This review summarizes the experimental findings indicating bidirectional interactions between alcohol (ethanol) consumption and the circadian timing system, emphasizing behavioral studies conducted in the author's laboratory. Together with convergent evidence from multiple laboratories, the work summarized here establishes that ethanol intake (or administration) alters fundamental properties of the underlying circadian pacemaker. In turn, circadian disruption induced by either environmental or genetic manipulations can alter voluntary ethanol intake. These reciprocal interactions may create a vicious cycle that contributes to the downward spiral of alcohol and drug addiction. In the future, such studies may lead to the development of chronobiologically based interventions to prevent relapse and effectively mitigate some of the societal burden associated with such disorders.

  13. Effectiveness of alcohol-based hand disinfectants in a public administration: Impact on health and work performance related to acute respiratory symptoms and diarrhoea

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    Hübner Nils-Olaf

    2010-08-01

    Full Text Available Abstract Background The economical impact of absenteeism and reduced productivity due to acute infectious respiratory and gastrointestinal disease is normally not in the focus of surveillance systems and may therefore be underestimated. However, large community studies in Europe and USA have shown that communicable diseases have a great impact on morbidity and lead to millions of lost days at work, school and university each year. Hand disinfection is acknowledged as key element for infection control, but its effect in open, work place settings is unclear. Methods Our study involved a prospective, controlled, intervention-control group design to assess the epidemiological and economical impact of alcohol-based hand disinfectants use at work place. Volunteers in public administrations in the municipality of the city of Greifswald were randomized in two groups. Participants in the intervention group were provided with alcoholic hand disinfection, the control group was unchanged. Respiratory and gastrointestinal symptoms and days of work were recorded based on a monthly questionnaire over one year. On the whole, 1230 person months were evaluated. Results Hand disinfection reduced the number of episodes of illness for the majority of the registered symptoms. This effect became statistically significant for common cold (OR = 0.35 [0.17 - 0.71], p = 0.003, fever (OR = 0.38 [0.14-0.99], p = 0.035 and coughing (OR = 0.45 [0.22 - 0.91], p = 0.02. Participants in the intervention group reported less days ill for most symptoms assessed, e.g. colds (2.07 vs. 2.78%, p = 0.008, fever (0.25 vs. 0.31%, p = 0.037 and cough (1.85 vs. 2.00%, p = 0.024. For diarrhoea, the odds ratio for being absent became statistically significant too (0.11 (CI 0.01 - 0.93. Conclusion Hand disinfection can easily be introduced and maintained outside clinical settings as part of the daily hand hygiene. Therefore it appears as an interesting, cost-efficient method within the scope

  14. Comparison between C-FOS Expression in Male and Female Mice During Morphine Withdrawal in the Presence and Absence of Acute Administration of Matricaria Recutita

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    Kesmati Mahnaz

    2009-06-01

    Full Text Available Background: There are some evidences that indicate there are sexual differences in drug abuse and response to synthetic and herbal drugs. It has been shown that the expression of C-FOS increases in many areas of brain during morphine withdrawal. Concerning the sedative effect of Matricaria recutita extract, the aim of this study was to compare expression of C-FOS transcription factor during morphine withdrawal with and without acute administration of Matricaria recutita on male and female adult mice.Materials and Methods: This study was done at Shahid Chamran University of Ahvaz in 2007 on NMRI mice. Male and female mice were assigned into 8 groups (morphine + saline; morphine + naloxone; morphine + Matricaria recutita + naloxone; and morphine + saline + naloxone. To develop morphine dependency, increasing doses of morphine (20, 40, 80 mg/kg injected subcutaneously for 4 days. Mice received a final morphine injection (40 mg/kg 3hours prior to naloxone (5 mg/kg on the day of testing (day 4. Matricaria recutita extract whit a dose of 30 mg/kg was administered intraperitoneally 5 minutes before naloxone injection. In cellular study, 90minute after naloxone injection, mice were decapitated and their brains were separated, then mRNA was extracted from brain tissue. Using DIG-labeled DNA probe of C-FOS, beta-actin and dot blot technique, expression of C-FOS was analyzed by Zero Dscan software. Statistical evaluation of data was performed using student t-test and ANOVA with one factor followed by Duncan test in SPSS software. P values less than 0.05 were considered significant. Results: The rate of expression of C-FOS increased in male mice but decreased significantly in female mice after naloxone-precipitated abstinence P<0.01(. Matricaria recutita attenuated the rate of expression of C-FOS in male mice but it showed synergistic effect on it in female mice P<0.05(.Conclusion: It seems that the cellular processes involving morphine dependency and

  15. Effects of aqueous and ethanol extract of dried leaves of Pseudocalymma alliaceum (Bignonaceae) on haematological and biochemical parameters of wistar rats

    Institute of Scientific and Technical Information of China (English)

    Carlos Granados-Echegoyen; Rafael Prez-Pacheco; Alfonso Alexander-Aguilera; Luicita Lagunez-Rivera; Nancy Alonso-Hernndez

    2015-01-01

    Objective: To perform the toxicological evaluation of aqueous and ethanol extract of dried leaves of Pseudocalymma alliaceum (P. alliaceum) in male Wistar rats by oral administration for 14 days, and to determine the biochemical and haematological status of blood. Methods: The animals were completely randomized into four groups of three rats each. Results: No deaths were reported after oral administration of the extracts, no physical signs of toxicity or adverse effects were observed. Hematological indices of red blood cell count, hemoglobin concentration and mean corpuscular hemoglobin showed no significant abnormality; however, white series levels decrease presenting a leukopenia. Glucose, creatinine and albumin increased, while urea decreased; aspartate aminotransferase values decreased with the aqueous extract at 50 and 100 mg/kg and increased with dose of 200 mg/kg, in contrast ethanol extract caused an increase in this parameter to the doses used. The alanine aminotransferase decreased with aqueous extract and increased with ethanol extract. Triglycerides decreased when used aqueous extract and reduced with ethanol extract at 100 and 200 mg/kg, in contrast to 50 mg/kg decreased to be compared with control group. Conclusion: The daily intake of P. alliaceum did not produce acute toxicity to 50 mg/kg which may be interpreted as toxic signs or biological damage, but liver and renal function changes at dosages of 100 and 200 mg/kg; however, the reduction ability of white blood cells count could be used as a basis for specific studies on the treatment of patients with leukemia.

  16. Acute ethanol intoxication aggravates traumatic brain injury in rats and its relation to oxygen free radicals%急性乙醇中毒对大鼠颅脑损伤后神经系统的影响及其氧自由基损伤机制的研究

    Institute of Scientific and Technical Information of China (English)

    汤崇辉; 许信龙; 傅小君; 魏晓捷; 潘红松; 方战舰

    2011-01-01

    目的 探讨急性乙醇中毒对大鼠颅脑创伤后神经系统的影响及其氧自由基损伤机制.方法 Feeney法制作大鼠重型颅脑损伤模型,乙醇灌胃法建立急性乙醇中毒模型.48只雄性SD大鼠随机分为单纯急性乙醇中毒组(A组)、单纯颅脑创伤组(B组)、急性乙醇中毒合并颅脑创伤组(C组)和假手术组(D组)各12只.在伤后1、6、24、72h进行行为学评分;在伤后72h,各组随机取其中6只在麻醉下经心脏灌注4%多聚甲醛固定脑组织,TUNEL法测凋亡细胞数;其余6只快速断头取水肿带脑组织,测定脑组织内SOD活性及MDA含量.结果 C组大鼠的行为学评分最低,恢复最慢;其脑组织内MDA含量最高,SOD含量最低;其神经细胞凋亡最多.结论 急性乙醇中毒可加重颅脑创伤后氧自由基的损害,增加神经细胞的凋亡,影响神经功能的恢复.%Objective To investigate the influence of acute ethanol intoxication (AEI) on traumatic brain injury (TBI) in rats and its relation to oxygen free radicals.Methods Severe traumatic brain injury model was established by Feeny method in rats, and acute ethanol intoxication was induced by gastric gavage.Forty- eight male SD rats were randomly divided into 4 groups: acute ethanol intoxication group (A), traumatic brain injury group (B), acute ethanol intoxication with traumatic brain injury group (C) and sham operation group (D).The behavioral scores were examined at 1h, 6h, 24h and 72h after injury.After 72h, 6 rats from each group were sacrificed and brain specimens were collected.The apoptotic cells were detected by TUNEL method; the superoxide dismutase (SOD) and malondialdehyde (MDA) were determined.Data were analyzed by one- way ANOVA Results The behavior score of group C was the lowest (P<0.05) and delayed to recover (P<0.05).In group C the content of MDA was the highestand SODwas the lowest(P<0.05); the percentage ofapoptosis cells was the highest among 4 groups (P<0.05).Conclusion

  17. Biotransformation of ethanol to ethyl glucuronide in a rat model after a single high oral dosage.

    Science.gov (United States)

    Wright, Trista H; Ferslew, Kenneth E

    2012-03-01

    Ethyl glucuronide (EtG) is a minor ethanol metabolite that confirms the absorption and metabolism of ethanol after oral or dermal exposure. Human data suggest that maximum blood EtG (BEtG) concentrations are reached between 3.5 and 5.5h after ethanol administration. This study was undertaken to determine if the Sprague-Dawley (SD) rat biotransforms ethanol to EtG after a single high oral dose of ethanol. SD rats (male, n=6) were gavaged with a single ethanol dose (4 g/kg), and urine was collected for 3 h in metabolic cages, followed by euthanization and collection of heart blood. Blood and urine were analyzed for ethanol and EtG by gas chromatography and enzyme immunoassay. Blood and urine ethanol concentrations were 195±23 and 218±19 mg/dL, whereas BEtG and urine EtG (UEtG) concentrations were 1,363±98 ng equivalents/mL and 210±0.29 mg equivalents/dL (X ± standard error of the mean [S.E.M.]). Sixty-six male SD rats were gavaged ethanol (4 g/kg) and placed in metabolic cages to determine the extent and duration of ethanol to EtG biotransformation and urinary excretion. Blood and urine were collected up to 24 h after administration for ethanol and EtG analysis. Maximum blood ethanol, urine ethanol, and UEtG were reached within 4 h, whereas maximum BEtG was reached 6 h after administration. Maximum concentrations were blood ethanol, 213±20 mg/dL; urine ethanol, 308±34 mg/dL; BEtG, 2,683±145 ng equivalents/mL; UEtG, 1.2±0.06 mg equivalents/mL (X±S.E.M.). Areas under the concentration-time curve were blood ethanol, 1,578 h*mg/dL; urine ethanol, 3,096 h*mg/dL; BEtG, 18,284 h*ng equivalents/mL; and UEtG, 850 h*mg equivalents/dL. Blood ethanol and BEtG levels were reduced to below limits of detection (LODs) within 12 and 18 h after ethanol administration. Urine ethanols were below LOD at 18 h, but UEtG was still detectable at 24h after administration. Our data prove that the SD rat biotransforms ethanol to EtG and excretes both in the urine and suggest that it

  18. Pulmonary hypertensive crisis following ethanol sclerotherapy for a complex vascular malformation.

    Science.gov (United States)

    Cordero-Schmidt, G; Wallenstein, M B; Ozen, M; Shah, N A; Jackson, E; Hovsepian, D M; Palma, J P

    2014-09-01

    Anhydrous ethanol is a commonly used sclerotic agent for treating vascular malformations. We describe the case of a full-term 15-day-old female with a complex venolymphatic malformation involving the face and orbit. During treatment of the lesion with ethanol sclerotherapy, she suffered acute pulmonary hypertensive crisis. We discuss the pathophysiology of pulmonary hypertension related to ethanol sclerotherapy, and propose that hemolysis plays a significant role. Recommendations for evaluation, monitoring and management of this complication are also discussed.

  19. Blockade of Ethanol Reward by the Kappa Opioid Receptor Agonist U50,488h

    OpenAIRE

    Logrip, Marian L.; Janak, Patricia H; Ron, Dorit

    2009-01-01

    Alcoholism is a pervasive social problem, and thus understanding factors which regulate alcohol (ethanol) reward is important for designing effective therapies. One putative regulatory system includes the kappa opioid receptor (KOR) and its endogenous ligand, dynorphin. Previously we demonstrated that acute ethanol increased preprodynorphin expression via brain-derived neurotrophic factor (BDNF) in striatal neurons, and that blockade of the KOR attenuated decreases in ethanol intake observed ...

  20. Phagocytosis and production of reactive oxygen species by peripheral blood phagocytes in patients with different stages of alcohol-induced liver disease: effect of acute exposure to low ethanol concentrations

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Schäfer, C.; Paulus, S. B.

    2003-01-01

    produced significantly more ROS than those of healthy controls. Basal values of ROS production from neutrophils correlated closely to markers of the severity of ALD. ROS formation was depressed dose-dependently by ethanol in the healthy controls but not in alcohol abusers. CONCLUSIONS: Changes in the ROS...

  1. IL-6-deficient Mice Are Susceptible to Ethanol-induced Hepatic Steatosis: IL-6 Protects against Ethanol-induced Oxidative Stress and Mitochondrial Permeability Transition in the Liver

    Institute of Scientific and Technical Information of China (English)

    Osama El-Assal; Feng Hong; Won-Ho Kim; Svetlana Radaeva; Bin Gao

    2004-01-01

    Interleukin-6 (IL-6)-deficient mice are prone to ethanol-induced apoptosis and steatosis in the liver; however, the underlying mechanism is not fully understood. Mitochondrial dysfunction caused by oxidative stress is an early event that plays an important role in the pathogenesis of alcoholic liver disease. Therefore, we hypothesize that the protective role of IL-6 in ethanol-induced liver injury is mediated via suppression of ethanol-induced oxidative stress and mitochondrial dysfunction. To test this hypothesis, we examined the effects of IL-6 on ethanol-induced oxidative stress, mitochondrial injury, and energy depletion in the livers of IL-6 (-/-) mice and hepatocytes from ethanol-fed rats. Ethanol consumption leads to stronger induction of malondialdehyde (MDA) in IL-6 (-/-) mice compared to wild-type control mice, which can be corrected by administration of IL-6. In vitro,IL-6 treatment prevents ethanol-mediated induction of reactive oxygen species (ROS), MDA, mitochondrial permeability transition (MPT), and ethanol-mediated depletion of adenosine triphosphate (ATP) in hepatocytes from ethanol-fed rats. Administration of IL-6 in vivo also reverses ethanol-induced MDA and ATP depletion in hepatocytes. Finally, IL-6 treatment induces metallothionein protein expression, but not superoxide dismutase and glutathione peroxidase in cultured hepatocytes. In conclusion, IL-6 protects against ethanol-induced oxidative stress and mitochondrial dysfunction in hepatocytes via induction of metallothionein protein expression, which may account for the protective role of IL-6 in alcoholic liver disease.

  2. IL-6-deficient Mice Are Susceptible to Ethanol-induced Hepatic Steatosis: IL-6 Protects against Ethanol-induced Oxidative Stress and Mitochondrial Permeability Transition in the Liver

    Institute of Scientific and Technical Information of China (English)

    OsamaEl-Assal; FengHong; Won-HoKim; SvetlanaRadaeva; BinGao

    2004-01-01

    Interleukin-6 (IL-6)-deficient mice are prone to ethanol-induced apoptosis and steatosis in the liver; however,the underlying mechanism is not fully understood. Mitochondrial dysfunction caused by oxidative stress is an early event that plays an important role in the pathogenesis of alcoholic liver disease. Therefore, we hypothesize that the protective role of IL-6 in ethanol-induced liver injury is mediated via suppression of ethanol-induced oxidative stress and mitochondrial dysfunction. To test this hypothesis, we examined the effects of IL-6 on ethanol-induced oxidative stress, mitochondrial injury, and energy depletion in the livers of IL-6 (-/-) mice and hepatocytes from ethanol-fed rats. Ethanol consumption leads to stronger induction of malondialdehyde (MDA) in IL-6 (-/-) mice compared to wild-type control mice, which can be corrected by administration of IL-6. In vitro,IL-6 treatment prevents ethanol-mediated induction of reactive oxygen species (ROS), MDA, mitochondrial permeability transition (MPT), and ethanol-mediated depletion of adenosine triphosphate (ATP) in hepatocytes from ethanol-fed rats. Administration of IL-6 in vivo also reverses ethanol-induced MDA and ATP depletion in hepatocytes. Finally, IL-6 treatment induces metallothionein protein expression, but not superoxide dismutase and glutathione peroxidase in cultured hepatocytes. In conclusion, IL-6 protects against ethanol-induced oxidative stress and mitochondrial dysfunction in hepatocytes v/a induction of metallothionein protein expression, which mav account for the nrotective role of IL-6 in alcoholic liver disease.

  3. Competitiveness of Brazilian Sugarcane Ethanol Compared to US Corn Ethanol

    OpenAIRE

    Crago, Christine Lasco; Khanna, Madhu; Barton, Jason; Giuliani, Eduardo; Amaral, Weber

    2010-01-01

    Corn ethanol produced in the US and sugarcane ethanol produced in Brazil are the world’s leading sources of biofuel. Current US biofuel policies create both incentives and constraints for the import of ethanol from Brazil, and together with the competitiveness and greenhouse gas intensity of sugarcane ethanol compared to corn ethanol will determine the extent of these imports. This study analyzes the supply-side determinants of this competitiveness and compares the greenhouse gas intensity of...

  4. Differential responses to acute administration of a new 5-HT7-R agonist as a function of adolescent pre-treatment: phMRI and immuno-histochemical study

    OpenAIRE

    Altabella, Luisa; Sbriccoli, Marco; Zoratto, Francesca; Poleggi, Anna; Vinci, Ramona; Lacivita, Enza; Leopoldo, Marcello; Laviola, Giovanni; Cardone, Franco; Canese, Rossella; Adriani, Walter

    2014-01-01

    LP-211 is a new, selective agonist of serotonin (5-hydroxytryptamine, 5-HT) receptor 7 (5-HT7-R), which is part of a neuro-transmission system with a proposed role in neural plasticity and in mood, cognitive and sleep regulation. Adolescent subchronic LP-211 treatment produces some persisting changes in rats' forebrain structural and functional parameters. Here, using pharmacological MRI (phMRI), we investigated the effect of acute administration with LP-211 (10 mg/kg i.p.), or vehicle, to ad...

  5. Protective effect of chelerythrine against ethanol-induced gastric ulcer in mice.

    Science.gov (United States)

    Li, Wei-Feng; Hao, Ding-Jun; Fan, Ting; Huang, Hui-Min; Yao, Huan; Niu, Xiao-Feng

    2014-02-01

    The quaternary benzo[c]phenanthridine alkaloid, chelerythrine (CHE), is of great practical and research interest because of its pronounced, widespread physiological effects, primarily antimicrobial and anti-inflammatory, arising from its ability to interact with proteins and DNA. Although CHE was originally shown to possess anti-inflammatory properties, its effects on acute gastric ulcer have not been previously explored. The aim of the present study is to evaluate the protective effect of CHE on ethanol induced gastric ulcer in mice. Administration of CHE at doses of 1, 5 and 10mg/kg bodyweight prior to ethanol ingestion dose-dependently inhibited gastric ulcer. The gastric mucosal lesion was assessed by ulcer area, gastric juice acidity, myeloperoxidase (MPO) activities, macroscopic and histopathological examinations. CHE significantly reduced the gastric ulcer index, myeloperoxidase activities, macroscopic and histological score in a dose-dependent manner. In addition, CHE also significantly inhibited nitric oxide (NO) concentration, pro-inflammatory interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) level in serum and gastric mucosal in the mice exposed to ethanol induced ulceration in a dose-dependent manner. In addition, immunohistochemical analysis revealed that CHE markedly attenuated the overexpression of nuclear factor-κB in gastric mucosa of mice. It was concluded that CHE represents a potential therapeutic option to reduce the risk of gastric ulceration. In addition, acute toxicity study revealed no abnormal sign to the mice treated with CHE (15mg/kg). These findings suggest that the gastroprotective activity of CHE might contribute in adjusting the inflammatory cytokine by regulating the NF-κB signalling pathway.

  6. Drugs targeting 5-hydroxytryptamine receptors in acute treatments of migraine attacks. A review of new drugs and new administration forms of established drugs

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer C; Pihl, Thomas Peter Boye; Hougaard, Anders

    2014-01-01

    of migraines. Areas covered: This evaluation reviews the recent advances in acute migraine therapy targeting the 5-HT receptor. Specifically, the authors review the pharmacokinetics, pharmacodynamics, clinical efficacy and safety of 5-HT1F receptor agonists and new formulations of sumatriptan...

  7. Examination of Acute Sensitivity to Morphine and Morphine Self-Administration Following Physical and Environmental Stressors in Fischer-344 and Lewis Female Rats

    Science.gov (United States)

    1997-01-16

    following prolonged exposure to the stressor (Menendez, Andres- Trelles , 11 Hidalgo) &, Baamonde, 1993; Prince &, Anisman, 1984). These studies...Menendez, L., Andres- Trelles , F., Hidalgo, A, & Baamonde, A (1993). Opioid footshock-induced analgesia in mice acutely falls by stress prolongation

  8. Short-term effect of prebiotics administration on stool characteristics and serum cytokines dynamics in very young children with acute diarrhea

    NARCIS (Netherlands)

    N. Vaisman (Nachum); J. Press (Josef); E. Leibovitz (Eugene); G. Boehm (Günther); V. Barak (Vivian)

    2010-01-01

    textabstractWe investigated the effect of a mixture of long-chain fructo-oligosaccharides, galacto-oligosaccharides and acidic oligosaccharides on the number and consistency of stools and on immune system biomarkers in 104 supplemented and non-supplemented subjects (aged 9-24 months) with acute diar

  9. Models of acute and chronic pancreatitis.

    Science.gov (United States)

    Lerch, Markus M; Gorelick, Fred S

    2013-06-01

    Animal models of acute and chronic pancreatitis have been created to examine mechanisms of pathogenesis, test therapeutic interventions, and study the influence of inflammation on the development of pancreatic cancer. In vitro models can be used to study early stage, short-term processes that involve acinar cell responses. Rodent models reproducibly develop mild or severe disease. One of the most commonly used pancreatitis models is created by administration of supraphysiologic concentrations of caerulein, an ortholog of cholecystokinin. Induction of chronic pancreatitis with factors thought to have a role in human disease, such as combinations of lipopolysaccharide and chronic ethanol feeding, might be relevant to human disease. Models of autoimmune chronic pancreatitis have also been developed. Most models, particularly of chronic pancreatitis, require further characterization to determine which features of human disease they include.

  10. Role of phosphodiesterase-4 on ethanol elicited locomotion and narcosis.

    Science.gov (United States)

    Baliño, Pablo; Ledesma, Juan Carlos; Aragon, Carlos M G

    2016-02-01

    The cAMP signaling pathway has emerged as an important modulator of the pharmacological effects of ethanol. In this respect, the cAMP-dependent protein kinase has been shown to play an important role in the modulation of several ethanol-induced behavioral actions. Cellular levels of cAMP are maintained by the activity of adenylyl cyclases and phosphodiesterases. In the present work we have focused on ascertaining the role of PDE4 in mediating the neurobehavioral effects of ethanol. For this purpose, we have used the selective PDE4 inhibitor Ro 20-1724. This compound has been proven to enhance cellular cAMP response by PDE4 blockade and can be administered systemically. Swiss mice were injected intraperitoneally (i.p.) with Ro 20-1724 (0-5 mg/kg; i.p.) at different time intervals before ethanol (0-4 g/kg; i.p.) administration. Immediately after the ethanol injection, locomotor activity, loss of righting reflex, PKA footprint and enzymatic activity were assessed. Pretreatment with Ro 20-1724 increased ethanol-induced locomotor stimulation in a dose-dependent manner. Doses that increased locomotor stimulation did not modify basal locomotion or the suppression of motor activity produced by high doses of this alcohol. Ro 20-1724 did not alter the locomotor activation produced by amphetamine or cocaine. The time of loss of righting reflex evoked by ethanol was increased after pretreatment with Ro 20-1724. This effect was selective for the narcotic effects of ethanol since Ro 20-1724 did not affect pentobarbital-induced narcotic effects. Moreover, Ro 20-1724 administration increased the PKA footprint and enzymatic activity response elicited by ethanol. These data provide further evidence of the key role of the cAMP signaling pathway in the central effects of ethanol.

  11. Short-term effect of prebiotics administration on stool characteristics and serum cytokines dynamics in very young children with acute diarrhea.

    Science.gov (United States)

    Vaisman, Nachum; Press, Josef; Leibovitz, Eugene; Boehm, Güenther; Barak, Vivian

    2010-07-01

    We investigated the effect of a mixture of long-chain fructo-oligosaccharides, galacto-oligosaccharides and acidic oligosaccharides on the number and consistency of stools and on immune system biomarkers in 104 supplemented and non-supplemented subjects (aged 9-24 months) with acute diarrhea. Interleukin-1 (IL-1), IL-1RA, IL-6, IL-8, IL-10, TNF-α and sIL-2R cytokine levels were determined. The significant decrease in number of stools and increase in stool consistency in the supplemented group was of little clinical relevance. The only significant change in pro- and anti-inflammatory cytokines was decreased TNF-α levels in the supplemented group. Prebiotic supplementation during acute diarrhea episodes did not influence the clinical course.

  12. Short-Term Effect of Prebiotics Administration on Stool Characteristics and Serum Cytokines Dynamics in Very Young Children with Acute Diarrhea

    Directory of Open Access Journals (Sweden)

    Nachum Vaisman

    2010-06-01

    Full Text Available We investigated the effect of a mixture of long-chain fructo-oligosaccharides, galacto-oligosaccharides and acidic oligosaccharides on the number and consistency of stools and on immune system biomarkers in 104 supplemented and non-supplemented subjects (aged 9–24 months with acute diarrhea. Interleukin-1 (IL-1, IL-1RA, IL-6, IL-8, IL-10, TNF-α and sIL-2R cytokine levels were determined. The significant decrease in number of stools and increase in stool consistency in the supplemented group was of little clinical relevance. The only significant change in pro- and anti-inflammatory cytokines was decreased TNF-α levels in the supplemented group. Prebiotic supplementation during acute diarrhea episodes did not influence the clinical course.

  13. Efficacy and safety of out-of-hospital intravenous metoprolol administration in anterior ST-segment elevation acute myocardial infarction: insights from the METOCARD-CNIC trial

    OpenAIRE

    Mateos, Alonso; García Lunar, Inés; García Ruiz, José María; Pizarro, Gonzalo; Fernández Jiménez, Rodrigo; Huertas, Pilar; García Álvarez, Ana; Fernández-Friera, Leticia; Bravo, Jesús; Flores Arias, José; Barreiro, María V.; Chayán Zas, Luisa; Corral, Ervigio; Fuster, Valentín; Sánchez Brunete, Vicente

    2015-01-01

    We seek to examine the efficacy and safety of prereperfusion emergency medical services (EMS)–administered intravenous metoprolol in anterior ST-segment elevation myocardial infarction patients undergoing eventual primary angioplasty. This is a prespecified subgroup analysis of the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction trial population, who all eventually received oral metoprolol within 12 to 24 hours. We studied patients receiving intravenous metoprol...

  14. Prolonged Increase in the Sensitivity of the Posterior Ventral Tegmental Area to the Reinforcing Effects of Ethanol following Repeated Exposure to Cycles of Ethanol Access and Deprivation

    OpenAIRE

    Rodd, Zachary A.; Bell, Richard L.; McQueen, Victoria K.; Davids, Michelle R.; Hsu, Cathleen C.; Murphy, James M.; Li, Ting-Kai; Lumeng, Lawrence; McBride, William J.

    2005-01-01

    The posterior ventral tegmental area (VTA) is a neuroanatomical substrate mediating the reinforcing effects of ethanol in rats. Repeated alcohol deprivations produce robust ethanol intakes of alcohol-preferring (P) rats during relapse and increase the reinforcing effects of oral alcohol self-administration. The objective of this study was to test the hypothesis that alcohol drinking and repeated alcohol deprivations will increase the reinforcing effects of ethanol within the posterior VTA of ...

  15. Acute administration of nicotine into the higher order auditory Te2 cortex specifically decreases the fear-related charge of remote emotional memories.

    Science.gov (United States)

    Cambiaghi, Marco; Grosso, Anna; Renna, Annamaria; Concina, Giulia; Sacchetti, Benedetto

    2015-12-01

    Nicotine elicits several behavioural effects on mood as well as on stress and anxiety processes. Recently, it was found that the higher order components of the sensory cortex, such as the secondary auditory cortex Te2, are essential for the long-term storage of remote fear memories. Therefore, in the present study, we examined the effects of acute nicotine injection into the higher order auditory cortex Te2, on the remote emotional memories of either threat or incentive experiences in rats. We found that intra-Te2 nicotine injection decreased the fear-evoked responses to a tone previously paired with footshock. This effect was cue- and dose-specific and was not due to any interference with auditory stimuli processing, innate anxiety and fear processes, or with motor responses. Nicotine acts acutely in the presence of threat stimuli but it did not determine the permanent degradation of the fear-memory trace, since memories tested one week after nicotine injection were unaffected. Remarkably, nicotine did not affect the memory of a similar tone that was paired to incentive stimuli. We conclude from our results that nicotine, when acting acutely in the auditory cortex, relieves the fear charge embedded by learned stimuli.

  16. Inhibitors of biofilm formation by fuel ethanol contaminants

    Science.gov (United States)

    Industrial fuel ethanol production suffers from chronic and acute infections that reduce yields and cause “stuck fermentations” that result in costly shutdowns. Lactic acid bacteria, particularly Lactobacillus sp., are recognized as major contaminants. In previous studies, we observed that certain...

  17. Gastroprotective Effect of Ethanolic Extract of Curcuma xanthorrhiza Leaf against Ethanol-Induced Gastric Mucosal Lesions in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Nurhidayah Ab. Rahim

    2014-01-01

    Full Text Available Herbal medicines appeared promising in prevention of many diseases. This study was conducted to investigate the gastroprotective effect of Curcuma xanthorrhiza leaf in the rats induced gastric ulcer by ethanol. Normal and ulcer control received carboxymethycellulose (5 mL/kg orally, positive control was administered with 20 mg/kg omeprazole (reference drug and 2 groups were received 250 mg/kg and 500 mg/kg of the leaf extract, respectively. To induce of gastric ulcers formation, ethanol (5 mL/kg was given orally to all groups except normal control. Gross ulcer areas, histology, and amount of prostaglandin E2, superoxide dismutase and malondialdehyde were assessed to determine the potentiality of extract in prevention against gastric ulcers. Oral administration of extract showed significant gastric protection effect as the ulcer areas was remarkably decreased. Histology observation showed less edema and leucocytes infiltration as compared with the ulcer control which exhibited severe gastric mucosa injury. Furthermore, the leaf extract elevated the mucus weight, level of prostaglandin E2 and superoxide dismutase. The extract also reduced malondialdehyde amount significantly. Results showed leaf extract of Curcuma xanthorrhiza can enhanced the gastric protection and sustained the integrity of gastric mucosa structure. Acute toxicity test did not showed any sign of toxicity (2 g/kg and 5 g/kg.

  18. Drug interaction between ethanol and 3,4-methylenedioxymethamphetamine ("ecstasy").

    Science.gov (United States)

    Upreti, Vijay V; Eddington, Natalie D; Moon, Kwan-Hoon; Song, Byoung-Joon; Lee, Insong J

    2009-07-24

    Alcohol (ethanol) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are frequently co-abused, but recent findings indicate a harmful drug interaction between these two agents. In our previous study, we showed that MDMA exposure inhibits the activity of the acetaldehyde (ACH) metabolizing enzyme, aldehyde dehydrogenase2 (ALDH2). Based on this finding, we hypothesized that the co-administration of MDMA and ethanol would reduce the metabolism of ACH and result in increased accumulation of ACH. Rats were treated with MDMA or vehicle and then administered a single dose of ethanol. Liver ALDH2 activity decreased by 35% in the MDMA-treated rats compared to control rats. The peak concentration and the area under the concentration versus time curve of plasma ACH were 31% and 59% higher, respectively, in the MDMA-ethanol group compared to the ethanol-only group. In addition, the MDMA-ethanol group had 80% higher plasma transaminase levels than the ethanol-only group, indicating greater hepatocellular damage. Our results not only support a drug interaction between MDMA and ethanol but a novel underlying mechanism for the interaction.

  19. Roles for the endocannabinoid system in ethanol-motivated behavior.

    Science.gov (United States)

    Henderson-Redmond, Angela N; Guindon, Josée; Morgan, Daniel J

    2016-02-04

    Alcohol use disorder represents a significant human health problem that leads to substantial loss of human life and financial cost to society. Currently available treatment options do not adequately address this human health problem, and thus, additional therapies are desperately needed. The endocannabinoid system has been shown, using animal models, to modulate ethanol-motivated behavior, and it has also been demonstrated that chronic ethanol exposure can have potentially long-lasting effects on the endocannabinoid system. For example, chronic exposure to ethanol, in either cell culture or preclinical rodent models, causes an increase in endocannabinoid levels that results in down-regulation of the cannabinoid receptor 1 (CB1) and uncoupling of this receptor from downstream G protein signaling pathways. Using positron emission tomography (PET), similar down-regulation of CB1 has been noted in multiple regions of the brain in human alcoholic patients. In rodents, treatment with the CB1 inverse agonist SR141716A (Rimonabant), or genetic deletion of CB1 leads to a reduction in voluntary ethanol drinking, ethanol-stimulated dopamine release in the nucleus accumbens, operant self-administration of ethanol, sensitization to the locomotor effects of ethanol, and reinstatement/relapse of ethanol-motivated behavior. Although the clinical utility of Rimonabant or other antagonists/inverse agonists for CB1 is limited due to negative neuropsychiatric side effects, negative allosteric modulators of CB1 and inhibitors of endocannabinoid catabolism represent therapeutic targets worthy of additional examination.

  20. Is there a role for leukotrienes as mediators of ethanol-induced gastric mucosal damage

    Energy Technology Data Exchange (ETDEWEB)

    Wallace, J.L.; Beck, P.L.; Morris, G.P. (Queen' s Univ., Kingston, Ontario (Canada))

    1988-01-01

    The role of leukotriene (LT) C{sub 4} as a mediator of ethanol-induced gastric mucosal damage was investigated. Rats were pretreated with a number of compounds, including inhibitors of leukotriene biosynthesis and agents that have previously been shown to reduce ethanol-induced damage prior to oral administration of absolute ethanol. Ethanol administration resulted in a fourfold increase in LTC{sub 4} synthesis. LTC{sub 4} synthesis could be reduced significantly by pretreatment with L651,392 or dexamethosone without altering the susceptibility of the gastric mucosa to ethanol-induced damage. Furthermore, changes in LBT{sub 4} synthesis paralleled the changes in LTC{sub 4} synthesis observed after ethanol administration. The effects of ethanol on gastric eicosanoid synthesis were further examined using an ex vivo gastric chamber preparation that allowed for application of ethanol to only one side of the stomach. These studies confirm that ethanol can stimulate gastric leukotriene synthesis independent of the production of hemorrhagic damage. Inhibition of LTC{sub 4} synthesis does not confer protection to the mucosa, suggesting that LTC{sub 4} does not play an important role in the etiology of ethanol-induced gastric damage.

  1. Studies on psychomotoric effects and pharmacokinetic interactions of the new calcium sensitizing drug levosimendan and ethanol.

    Science.gov (United States)

    Antila, S; Järvinen, A; Akkila, J; Honkanen, T; Karlsson, M; Lehtonen, L

    1997-07-01

    Levosimendan (CAS 141505-33-1) is a calcium sensitizing drug intended for the treatment of congestive heart failure. In animal experiments levosimendan has potentiated the sedative effects of ethanol. Due to poor water solubility of the compound, ethanol is used as a diluent in the intravenous formulation. In this study the possible interactions between levosimendan and ethanol in human have been studied. Twelve healthy male volunteers were included in this double-blind, randomized, cross-over study. The study consisted of three treatment periods: levosimendan 1 mg intravenously, levosimendan combined with ethanol orally and ethanol 0.8 g/kg alone. Blood samples for determination of levosimendan and ethanol concentrations were collected for 8 h after the dosing. To observe possible pharmacodynamic interactions psychomotoric tests were made before drug administration and 1h, 2h, 3h and 6h thereafter. These tests included Digit symbol substitution test, Maddox wing, Critical Flicker fusion and VAS-test for subjective assessment of performance status. Plasma levosimendan concentrations were not changed by the concomitant ethanol administration. Ethanol did not alter the pharmacokinetics of levosimendan except the volume of distribution of central compartment which was decreased. Levosimendan did neither affect elimination of ethanol. Levosimendan did not potentiate the psychomotoric effects of ethanol neither did it have any psychomotoric effects itself. In conclusion, levosimendan is not likely to have any psychomotoric adverse effects or any clinically significant interactions with ethanol.

  2. Bioavailability of ethanol is reduced in several commonly used liquid diets.

    Science.gov (United States)

    de Fiebre, N C; de Fiebre, C M; Booker, T K; Nelson, S; Collins, A C

    1994-01-01

    Liquid diets are often used as a vehicle for chronically treating laboratory animals with ethanol. However, a recent report suggested that one or more components of these diets may bind ethanol which could result in a decrease in the bioavailability of ethanol. Consequently, we compared the blood ethanol concentration vs. time curves obtained following the intragastric (i.g.) administration of ethanol dissolved in water or in one of three liquid diets (Bioserv AIN-76, Sustacal, or Carnation Slender) using the long-sleep (LS) and short-sleep (SS) mouse lines. The initial rates of absorption were generally the same for the water-ethanol and diet-ethanol groups, but the diets generally produced lower peak levels and the areas under the ethanol concentration-time curves were less for all of the liquid diets than for the control, ethanol-water solution. In vitro dialysis experiments indicated that the Bioserv diet binds ethanol in a saturable manner. Therefore, it may be that the slower release of ethanol, which should occur as a result of binding, serves to increase the role of first pass metabolism in regulating ethanol concentrations following oral administration. Because the effects of the diets were seen even after pyrazole treatment, it may be that the lower blood ethanol levels arise because metabolism by gastric ADH, rather than hepatic ADH, is responsible for a major portion of ethanol metabolism as ethanol is slowly released by the diets. If so, the observation that the diet/water differences were uniformly greater in the LS mice may indicate that LS-SS differences in gastric ADH exist.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Cytisine modulates chronic voluntary ethanol consumption and ethanol-induced striatal up-regulation of ΔFosB in mice.

    Science.gov (United States)

    Sajja, Ravi Kiran; Rahman, Shafiqur

    2013-06-01

    Chronic administration of ethanol induces persistent accumulation of ΔFosB, an important transcription factor, in the midbrain dopamine system. This process underlies the progression to addiction. Previously, we have shown that cytisine, a neuronal nicotinic acetylcholine receptor (nAChR) partial agonist, reduces various ethanol-drinking behaviors and ethanol-induced striatal dopamine function. However, the effects of cytisine on chronic ethanol drinking and ethanol-induced up-regulation of striatal ΔFosB are not known. Therefore, we examined the effects of cytisine on chronic voluntary ethanol consumption and associated striatal ΔFosB up-regulation in C57BL/6J mice using behavioral and biochemical methods. Following the chronic voluntary consumption of 15% (v/v) ethanol under a 24-h two-bottle choice intermittent access (IA; 3 sessions/week) or continuous access (CA; 24 h/d and 7 d/week) paradigm, mice received repeated intraperitoneal injections of saline or cytisine (0.5 or 3.0 mg/kg). Ethanol and water intake were monitored for 24 h post-treatment. Pretreatment with cytisine (0.5 or 1.5 mg/kg) significantly reduced ethanol consumption and preference in both paradigms at 2 h and 24 h post-treatment. The ΔFosB levels in the ventral and dorsal striatum were determined by Western blotting 18-24 h after the last point of ethanol access. In addition, cytisine (0.5 mg/kg) significantly attenuated up-regulation of ΔFosB in the ventral and dorsal striatum following chronic ethanol consumption in IA and CA paradigms. The results indicate that cytisine modulates chronic voluntary ethanol consumption and reduces ethanol-induced up-regulation of striatal ΔFosB. Further, the data suggest a critical role of nAChRs in chronic ethanol-induced neurochemical adaptations associated with ethanol addiction.

  4. Enhancement of germ cell apoptosis induced by ethanol in transgenic mice overexpressing Fas Ligand

    Institute of Scientific and Technical Information of China (English)

    HENG CHUAN XIA; FENG LI; ZHEN LI; ZU CHUAN ZHANG

    2003-01-01

    It was suggested that chronic ethanol exposure could result in testicular germ cell apoptosis, but the mechanism is still unclear. In the present study, we use a model of transgenic mice ubiquitously overexpressing human FasL to investigate whether Fas ligand plays a role in ethanol-induced testicular germ cell apoptosis. Both wild-type (WT)mice and transgenic (TG) mice were treated with acute ethanol (20% v/v) by introperitoneal injection for five times.After ethanol injection, WT mice displayed up-regulation of Fas ligand in the testes, which was shown by FITCconjugated flow cytometry and western blotting. Moreover, TG mice exhibited significantly more apoptotic germ cells than WT mice did after ethanol injection, which was demonstrated by DNA fragmentation, PI staining flow cytometry and TUNEL staining. In addition, histopathological examination revealed that degenerative changes of epithelial component of the tubules occurred in FasL overexpressing transgenic mice while testicular morphology was normal in wild-type mice after acute ethanol exposure, suggesting FasL expression determines the sensitivity of testes to ethanol in mice. In summary, we provide the direct evidences that Fas ligand mediates the apoptosis of testicular germ cells induced by acute ethanol using FasL transgenic mice.

  5. Ethanol-nicotine interactions in long-sleep and short-sleep mice

    Energy Technology Data Exchange (ETDEWEB)

    de Fiebre, C.M.; Marks, M.J.; Collins, A.C. (Univ. of Colorado, Boulder (USA))

    1990-05-01

    The possibility that common genetic factors regulate initial sensitivities to ethanol and nicotine as well as the development of cross-tolerance between these agents was explored using the long-sleep (LS) and short-sleep (SS) mice. The LS mice proved to be more sensitive to an acute challenge with nicotine than were the SS mice. Segregation analysis (F1, F2, backcross) indicated that ethanol sensitivity and nicotine sensitivity segregate together. Acute pretreatment with nicotine did not significantly affect sensitivity to ethanol, but ethanol pretreatment altered nicotine responsiveness. The LS mice develop more tolerance to nicotine and ethanol than do the SS and they also develop more cross-tolerance. These genetically determined differences in initial sensitivities, and tolerance and cross-tolerance development are not readily explained by differences in brain nicotinic receptor numbers.

  6. Ex vivo binding of t-( sup 35 S) butylbicyclophosphorothionate: A biochemical tool to study the pharmacology of ethanol at the gamma-aminobutyric acid-coupled chloride channel

    Energy Technology Data Exchange (ETDEWEB)

    Sanna, E.; Concas, A.; Serra, M.; Santoro, G.; Biggio, G. (Univ. of Cagliari (Italy))

    1991-03-01

    The effects of acute administration of ethanol on t-(35S)Butylbiclophosphorothionate (35S-TBPS) binding measured ex vivo in unwashed membrane preparations of rat cerebral cortex were investigated. Ethanol, given i.g., decreased in a dose-related (0.5-4 g/kg) and time-dependent manner the binding of 35S-TBPS. This effect was similar to that induced by the administration of diazepam (0.5-4 mg/kg i.p.). Scatchard plot analysis of this radioligand binding revealed that ethanol, differently from diazepam, decreased the apparent affinity of 35S-TBPS recognition sites whereas it failed to change the density of these binding sites. The effect of ethanol on 35S-TBPS binding could not be reversed by the previous administration to rats of the benzodiazepine receptor antagonist, Ro 15-1788 (ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H- imidazo (1,5a) (1,4) benzodiazepine-3-carboxylate). Vice versa, the benzodiazepine receptor partial inverse agonist, Ro 15-4513 (ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H- imidazo (1,5a) (4,4) benzodiazepine-3-carboxylate) (8 mg/kg i.p.), prevented completely ethanol-induced decrease of 35S-TBPS binding. The ability of Ro 15-4513 to prevent the action of ethanol was shared by the anxiogenic and proconvulsant beta-carboline derivatives, FG 7142 (N-methyl-beta-carboline-3-carboxamide) (12.5 mg/kg i.p.) and ethyl-beta-carboline-3-carboxylate (0.6 mg/kg i.v.), which, per se, enhanced this parameter. Moreover, ethanol (0.5-4 g/kg) was able to reverse the increase of 35S-TBPS binding elicited by the s.c. injection of isoniazid (350 mg/kg) and to clearly attenuate the severity of tonic-clonic seizures produced by this inhibitor of the GABAergic transmission.

  7. Ethanol tolerance in yeasts.

    Science.gov (United States)

    Casey, G P; Ingledew, W M

    1986-01-01

    It is now certain that the inherent ethanol tolerance of the Saccharomyces strain used is not the prime factor regulating the level of ethanol that can be produced in a high sugar brewing, wine, sake, or distillery fermentation. In fact, in terms of the maximum concentration that these yeasts can produce under batch (16 to 17% [v/v]) or fed-batch conditions, there is clearly no difference in ethanol tolerance. This is not to say, however, that under defined conditions there is no difference in ethanol tolerance among different Saccharomyces yeasts. This property, although a genetic determinant, is clearly influenced by many factors (carbohydrate level, wort nutrition, temperature, osmotic pressure/water activity, and substrate concentration), and each yeast strain reacts to each factor differently. This will indeed lead to differences in measured tolerance. Thus, it is extremely important that each of these be taken into consideration when determining "tolerance" for a particular set of fermentation conditions. The manner in which each alcohol-related industry has evolved is now known to have played a major role in determining traditional thinking on ethanol tolerance in Saccharomyces yeasts. It is interesting to speculate on how different our thinking on ethanol tolerance would be today if sake fermentations had not evolved with successive mashing and simultaneous saccharification and fermentation of rice carbohydrate, if distillers' worts were clarified prior to fermentation but brewers' wort were not, and if grape skins with their associated unsaturated lipids had not been an integral part of red wine musts. The time is now ripe for ethanol-related industries to take advantage of these findings to improve the economies of production. In the authors' opinion, breweries could produce higher alcohol beers if oxygenation (leading to unsaturated lipids) and "usable" nitrogen source levels were increased in high gravity worts. White wine fermentations could also, if

  8. Chronic and acute effects of 3,4-methylenedioxy-N-methylamphetamine ('Ecstasy') administration on the dynorphinergic system in the rat brain.

    Science.gov (United States)

    Di Benedetto, M; D'addario, C; Candeletti, S; Romualdi, P

    2006-01-01

    The prodynorphin system is implicated in the neurochemical mechanism of psychostimulants. Exposure to different drugs of abuse can induce neuroadaptations in the brain and affect opioid gene expression. The present study aims to examine the possibility of a common neurobiological substrate in drug addiction processes. We studied the effects of single and repeated 3,4-methylenedioxy-N-methylamphetamine ('Ecstasy') on the gene expression of the opioid precursor prodynorphin, and on the levels of peptide dynorphin A in the rat brain. Acute (8 mg/kg, intraperitoneally) 3,4-methylenedioxy-N-methylamphetamine markedly raised, two hours later, prodynorphin mRNA levels in the prefrontal cortex, and in the caudate putamen, whereas it decreased gene expression in the ventral tegmental area. Chronic (8 mg/kg, intraperitoneally, twice a day for 7 days) 3,4-methylenedioxy-N-methylamphetamine increased prodynorphin mRNA in the nucleus accumbens, hypothalamus and caudate putamen and decreased it in the ventral tegmental area. Dynorphin A levels increased after chronic treatment in the ventral tegmental area and decreased after acute treatment in the nucleus accumbens, prefrontal cortex and hypothalamus. These findings confirm the role of the dynorphinergic system in mediating the effects of drugs of abuse, such as 3,4-methylenedioxy-N-methylamphetamine, in various regions of the rat brain, which may be important sites for the opioidergic mechanisms activated by addictive drugs.

  9. Reduced Plasma Nonesterified Fatty Acid Levels and the Advent of an Acute Lung Injury in Mice after Intravenous or Enteral Oleic Acid Administration

    Directory of Open Access Journals (Sweden)

    Cassiano Felippe Gonçalves de Albuquerque

    2012-01-01

    Full Text Available Although exerting valuable functions in living organisms, nonesterified fatty acids (NEFAs can be toxic to cells. Increased blood concentration of oleic acid (OLA and other fatty acids is detected in many pathological conditions. In sepsis and leptospirosis, high plasma levels of NEFA and low albumin concentrations are correlated to the disease severity. Surprisingly, 24 h after intravenous or intragastric administration of OLA, main NEFA levels (OLA inclusive were dose dependently decreased. However, lung injury was detected in intravenously treated mice, and highest dose killed all mice. When administered by the enteral route, OLA was not toxic in any tested conditions. Results indicate that OLA has important regulatory properties on fatty acid metabolism, possibly lowering circulating fatty acid through activation of peroxisome proliferator-activated receptors. The significant reduction in blood NEFA levels detected after OLA enteral administration can contribute to the already known health benefits brought about by unsaturated-fatty-acid-enriched diets.

  10. Testosterone-estradiol-binding globulin in patients with Turner's syndrome: effects of estrogens and acute growth hormone administration

    Energy Technology Data Exchange (ETDEWEB)

    Bergink, E.W.; Wolf, D.L.; Wittliff, J.L.; Bruining, G.J.; Bryson, M.F.; Forbes, G.B.

    1976-06-01

    The TeBG activity of plasma from patients with Turner's syndrome was measured quantitatively using polyacrylamide gel electrophoresis. Human growth hormone administration did not significantly change the plasma TeBG levels. However, oral replacement therapy with estrogens elevated plasma TeBG within 3 days; after 9 days these levels reached a maximum of three- to four-fold greater than that observed at a time prior to therapy.

  11. Sorghum to Ethanol Research

    Energy Technology Data Exchange (ETDEWEB)

    Dahlberg, Jeffrey A. [Univ. of California, Parlier, CA (United States). Kearney Research and Extension Center; Wolfrum, Edward J. [National Renewable Energy Lab. (NREL), Golden, CO (United States). Process and Analytical Engineering Group

    2010-09-28

    The development of a robust source of renewable transportation fuel will require a large amount of biomass feedstocks. It is generally accepted that in addition to agricultural and forestry residues, we will need crops grown specifically for subsequent conversion into fuels. There has been a lot of research on several of these so-called "dedicated bioenergy crops" including switchgrass, miscanthus, sugarcane, and poplar. It is likely that all of these crops will end up playing a role as feedstocks, depending on local environmental and market conditions. Many different types of sorghum have been grown to produce syrup, grain, and animal feed for many years. It has several features that may make it as compelling as other crops mentioned above as a renewable, sustainable biomass feedstock; however, very little work has been done to investigate sorghum as a dedicated bioenergy crop. The goal of this project was to investigate the feasibility of using sorghum biomass to produce ethanol. The work performed included a detailed examination of the agronomics and composition of a large number of sorghum varieties, laboratory experiments to convert sorghum to ethanol, and economic and life-cycle analyses of the sorghum-to-ethanol process. This work showed that sorghum has a very wide range of composition, which depended on the specific sorghum cultivar as well as the growing conditions. The results of laboratory- and pilot-scale experiments indicated that a typical high-biomass sorghum variety performed very similarly to corn stover during the multi-step process required to convert biomass feedstocks to ethanol; yields of ethanol for sorghum were very similar to the corn stover used as a control in these experiments. Based on multi-year agronomic data and theoretical ethanol production, sorghum can achieve more than 1,300 gallons of ethanol per acre given the correct genetics and environment. In summary, sorghum may be a compelling dedicated bioenergy crop that could help

  12. Sorghum to Ethanol Research

    Energy Technology Data Exchange (ETDEWEB)

    Dahlberg, Jeff; Wolfrum, Ed

    2010-06-30

    The development of a robust source of renewable transportation fuel will require a large amount of biomass feedstocks. It is generally accepted that in addition to agricultural and forestry residues, we will need crops grown specifically for subsequent conversion into fuels. There has been a lot of research on several of these so-called dedicated bioenergy crops including switchgrass, miscanthus, sugarcane, and poplar. It is likely that all of these crops will end up playing a role as feedstocks, depending on local environmental and market conditions. Many different types of sorghum have been grown to produce syrup, grain, and animal feed for many years. It has several features that may make it as compelling as other crops mentioned above as a renewable, sustainable biomass feedstock; however, very little work has been done to investigate sorghum as a dedicated bioenergy crop. The goal of this project was to investigate the feasibility of using sorghum biomass to produce ethanol. The work performed included a detailed examination of the agronomics and composition of a large number of sorghum varieties, laboratory experiments to convert sorghum to ethanol, and economic and life-cycle analyses of the sorghum-to-ethanol process. This work showed that sorghum has a very wide range of composition, which depended on the specific sorghum cultivar as well as the growing conditions. The results of laboratory- and pilot-scale experiments indicated that a typical high-biomass sorghum variety performed very similarly to corn stover during the multi-step process required to convert biomass feedstocks to ethanol; yields of ethanol for sorghum were very similar to the corn stover used as a control in these experiments. Based on multi-year agronomic data and theoretical ethanol production, sorghum can achieve more than 1,300 gallons of ethanol per acre given the correct genetics and environment. In summary, sorghum may be a compelling dedicated bioenergy crop that could help

  13. Sorghum to Ethanol Research

    Energy Technology Data Exchange (ETDEWEB)

    Jeff Dahlberg, Ph D; Ed Wolfrum, Ph D

    2010-06-30

    The development of a robust source of renewable transportation fuel will require a large amount of biomass feedstocks. It is generally accepted that in addition to agricultural and forestry residues, we will need crops grown specifically for subsequent conversion into fuels. There has been a lot of research on several of these so-called "dedicated bioenergy crops" including switchgrass, miscanthus, sugarcane, and poplar. It is likely that all of these crops will end up playing a role as feedstocks, depending on local environmental and market conditions. Many different types of sorghum have been grown to produce syrup, grain, and animal feed for many years. It has several features that may make it as compelling as other crops mentioned above as a renewable, sustainable biomass feedstock; however, very little work has been done to investigate sorghum as a dedicated bioenergy crop. The goal of this project was to investigate the feasibility of using sorghum biomass to produce ethanol. The work performed included a detailed examination of the agronomics and composition of a large number of sorghum varieties, laboratory experiments to convert sorghum to ethanol, and economic and life-cycle analyses of the sorghum-to-ethanol process. This work showed that sorghum has a very wide range of composition, which depended on the specific sorghum cultivar as well as the growing conditions. The results of laboratory- and pilot-scale experiments indicated that a typical high-biomass sorghum variety performed very similarly to corn stover during the multi-step process required to convert biomass feedstocks to ethanol; yields of ethanol for sorghum were very similar to the corn stover used as a control in these experiments. Based on multi-year agronomic data and theoretical ethanol production, sorghum can achieve more than 1,300 gallons of ethanol per acre given the correct genetics and environment. In summary, sorghum may be a compelling dedicated bioenergy crop that could help

  14. Antifertility potential of the ethanolic extract of Caesalpinia pulcherrima Linn. leaves

    Institute of Scientific and Technical Information of China (English)

    Sunil Kumar; Jitender Singh; Anupama Baghotia; Vineet Mehta; Vikas Thakur; Manjusha Choudhary; Surender Verma; Dinesh Kumar

    2013-01-01

    Objective: To assess the antifertility activity of ethanolic extract of Caesalpinia pulcherrima Linn (C. pulcherrima) leaves in albino female mice. Methods: Acute toxicity study of the extract was carried out in adult albino mice. The antifertility activity of the extract at dose levels (200 and 400 mg/kg, orally) was evaluated in two experimental animal models i.e. antiimplantation and esterogenic/antiestrogenic activity in female mice by observing no. of implants, estrus cycle, vaginal cornification, uertus weight and cholesterol content. Results: The extract was found to be safe up to a dose of 4 000 mg/kg body weight when administered orally. A good antiimplantation (66.66 %) activity in female mice was observed at the tested dose levels (200 and 400 mg/kg, orally). The extract further showed more significant (P<0.05) increase in uterine weight and cholesterol content in immature mice. Simultaneous administration of extract alongwith ethinyl estradiol showed significant estrogenic activity. Conclusion: The results suggest that ethanolic extract of C. pulcherrima leaves possess significant antifertility activity, therefore, justifying the traditional use of this plant in fertility regulation.

  15. Comparative study of equimolar doses of gamma-hydroxybutyrate (GHB), 1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL) on catalepsy after acute and chronic administration.

    Science.gov (United States)

    Towiwat, Pasarapa; Phattanarudee, Siripan; Maher, Timothy J

    2013-01-01

    Gamma-hydroxybutyrate (GHB), and its precursors 1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL) are known drugs of abuse. The ability of acute and chronic administration of equimolar doses of GHB (200mg/kg), 1,4-BD (174mg/kg) and GBL (166mg/kg) to produce catalepsy in male Swiss Webster mice was examined. GHB, 1,4-BD, GBL produced catalepsy when injected acutely. Drug treatment was then continued for 14days. Tolerance development was determined on days 6, 14, and challenged with a higher dose on day 15 in those chronically pretreated mice, and compared with naïve mice. Chronic GHB produced tolerance to catalepsy, as evidenced from area under the curve (AUC) of catalepsy versus time (min-sec) on days 6 (678±254), 14 (272±247), which were less than those on day 1 (1923±269). However, less tolerance was seen from GBL or 1,4-BD, as AUCs on days 6 and 14 were not significantly lower than that of day 1. In conclusion, although equimolar doses were used, expecting similar levels of GHB in the body, 1,4-BD and GBL shared only some of the in vivo effects of GHB. The rate of metabolic conversion of 1,4-BD and GBL into GHB might be responsible for the differences in the tolerance development to these drugs.

  16. Continuous administration of insulin-like growth factor-I and basic fibroblast growth factor does not affect left ventricular geometry after acute myocardial infarction in rats.

    Science.gov (United States)

    Scheinowitz, M; Abramov, D; Kotlyar, A; Savion, N; Eldar, M

    1998-02-28

    We examined the long-term effect of exogenous administration of bFGF and IGF-I on myocardial geometry in 72 Sprague-Dawley male rats subjected to AMI. A preloaded miniature osmotic pump subsequently implanted in the peritoneum for continuous infusion (1 week) of IGF-I, bFGF, IGF-I+bFGF or rat albumin. Six weeks following AMI the rats were killed and cross-section slices were analyzed for left ventricular geometry. No differences were observed between IGF-I-treated, bFGF-treated, IGF-I+bFGF-treated and control groups in all parameters of the left ventricle.

  17. Experimental Models in Syrian Golden Hamster Replicate Human Acute Pancreatitis.

    Science.gov (United States)

    Wang, Yunan; Kayoumu, Abudurexiti; Lu, Guotao; Xu, Pengfei; Qiu, Xu; Chen, Liye; Qi, Rong; Huang, Shouxiong; Li, Weiqin; Wang, Yuhui; Liu, George

    2016-06-15

    The hamster has been shown to share a variety of metabolic similarities with humans. To replicate human acute pancreatitis with hamsters, we comparatively studied the efficacy of common methods, such as the peritoneal injections of caerulein, L-arginine, the retrograde infusion of sodium taurocholate, and another novel model with concomitant administration of ethanol and fatty acid. The severity of pancreatitis was evaluated by serum amylase activity, pathological scores, myeloperoxidase activity, and the expression of inflammation factors in pancreas. The results support that the severity of pathological injury is consistent with the pancreatitis induced in mice and rat using the same methods. Specifically, caerulein induced mild edematous pancreatitis accompanied by minimal lung injury, while L-arginine induced extremely severe pancreatic injury including necrosis and neutrophil infiltration. Infusion of Na-taurocholate into the pancreatic duct induced necrotizing pancreatitis in the head of pancreas and lighter inflammation in the distal region. The severity of acute pancreatitis induced by combination of ethanol and fatty acids was between the extent of caerulein and L-arginine induction, with obvious inflammatory cells infiltration. In view of the advantages in lipid metabolism features, hamster models are ideally suited for the studies of pancreatitis associated with altered metabolism in humans.

  18. Ethanol sclerotherapy of peripheral venous malformations

    Energy Technology Data Exchange (ETDEWEB)

    Rimon, U. E-mail: rimonu@sheba.health.gov.il; Garniek, A.; Galili, Y.; Golan, G.; Bensaid, P.; Morag, B

    2004-12-01

    Background: venous malformations are congenital lesions that can cause pain, decreased range of movement, compression on adjacent structures, bleeding, consumptive coagulopathy and cosmetic deformity. Sclerotherapy alone or combined with surgical excision is the accepted treatment in symptomatic malformations after failed treatment attempts with tailored compression garments. Objectives: to report our experience with percutaneous sclerotherapy of peripheral venous malformations with ethanol 96%. Patients and methods: 41 sclerotherapy sessions were performed on 21 patients, aged 4-46 years, 15 females and 6 males. Fourteen patients were treated for painful extremity lesions, while five others with face and neck lesions and two with giant chest malformations had treatment for esthetic reasons. All patients had a pre-procedure magnetic resonance imaging (MRI) study. In all patients, 96% ethanol was used as the sclerosant by direct injection using general anesthesia. A minimum of 1-year clinical follow-up was performed. Follow-up imaging studies were performed if clinically indicated. Results: 17 patients showed complete or partial symptomatic improvement after one to nine therapeutic sessions. Four patients with lower extremity lesions continue to suffer from pain and they are considered as a treatment failure. Complications were encountered in five patients, including acute pulmonary hypertension with cardiovascular collapse, pulmonary embolus, skin ulcers (two) and skin blisters. All patients fully recovered. Conclusion: sclerotherapy with 96% ethanol for venous malformations was found to be effective for symptomatic improvement, but serious complications can occur.

  19. The Effects of Administration of Mangosteen Pericap's Ethanolic Extract and Xanthone on Angiogenesis of Gastric Ulcer Healing in Wistar Rats Observed Through the Increase in the level of NO and VEGF and CD-31 Expressions

    Directory of Open Access Journals (Sweden)

    Ika Kustiyah Oktaviyanti

    2011-12-01

    Full Text Available BACKGROUND: NSAIDs can cause gastric ulcer or may delay the healing of it. Upon exposure to indomethacin, gastric ulcer can occur due to oxidants. Mangosteen rind contains xanthone, which is a natural antioxidant. Administration of this antioxidant may increase angiogenesis that can accelerate healing of gastric ulcer. METHODS: This study used an experimental method with randomized post test control only design using Wistar rats. The rats were put on fasting for 24 hours, then a single dose of 30mg/kg body weight (BW Indomethacine was given. The rats were divided into control group and treatment group. The treatment group was further divided into two subgroups: one group was given a daily 200 mg/kg BW mangosteen pericap extract, and the other group was given 35 mg/kg BW Xanthone. Both the control group and treatment group were decapitated on the 3rd day, 6th day and 12th day, respectively. After decapitation, the stomach of each rat was taken and divided into two portions, one portion was used for NO examination by ELISA, and the other portion for hispathological examination and immunohistochemical analysis for assessing CD 31 and VEGF expressions. RESULTS: Administration of mangoosteen pericap and xanthone could accelerate healing of gastric ulcers as compared with the control, as shown by the decrease in the severity level of the ulcers. Mangoosteen pericap and xanthone could also increase NO, VEGF expression, and CD-31 as compared with the control, especially on the 3rd day of treatment. Explanation of this finding might be that the antioxidants contained in the mangoosteen pericap or in xanthone could bind with radical superoxide and accelerate release of free NO. The increase of NO caused increase of VEGF and CD-31 that could accelerate angiogenesis, which eventually could accelerate healing of the gastric ulcers. CONCLUSIONS: The effect of mangosteen pericap's extract and xanthone can improve healing of gastric ulcers by increasing nitric

  20. A fast-track anaemia clinic in the Emergency Department: feasibility and efficacy of intravenous iron administration for treating sub-acute iron deficiency anaemia

    Science.gov (United States)

    Quintana-Díaz, Manuel; Fabra-Cadenas, Sara; Gómez-Ramírez, Susana; Martínez-Virto, Ana; García-Erce, José A.; Muñoz, Manuel

    2016-01-01

    Background Clinically significant anaemia, requiring red blood cell transfusions, is frequently observed in Emergency Departments (ED). To optimise blood product use, we developed a clinical protocol for the management of iron-deficiency anaemia in a fast-track anaemia clinic within the ED. Materials and methods From November 2010 to January 2014, patients presenting with sub-acute, moderate-to-severe anaemia (haemoglobin [Hb] <11 g/dL) and confirmed or suspected iron deficiency were referred to the fast-track anaemia clinic. Those with absolute or functional iron deficiency were given intravenous (IV) ferric carboxymaltose 500–1,000 mg/week and were reassessed 4 weeks after receiving the total iron dose. The primary study outcome was the haematological response (Hb≥12 g/dL and/or Hb increment ≥2 g/dL). Changes in blood and iron parameters, transfusion rates and IV iron-related adverse drug effects were secondary outcomes. Results Two hundred and two anaemic patients with iron deficiency (150 women/52 men; mean age, 64 years) were managed in the fast-track anaemia clinic, and received a median IV iron dose of 1,500 mg (1,000–2,000 mg). Gastro-intestinal (44%) or gynaecological (26%) bleeding was the most frequent cause of the anaemia. At follow-up (183 patients), the mean Hb increment was 3.9±2.2 g/dL; 84% of patients were classified as responders and blood and iron parameters normalised in 90%. During follow-up, 35 (17%) patients needed transfusions (2 [range: 1–3] units per patient) because they had low Hb levels, symptoms of anaemia and/or were at risk. Eight mild and one moderate, self-limited adverse drug effects were witnessed. Discussion Our data support the feasibility of a clinical protocol for management of sub-acute anaemia with IV iron in the ED. IV iron was efficacious, safe and well tolerated. Early management of anaemia will improve the use of blood products in the ED. PMID:26674819

  1. Phosphorylation Regulates Removal of Synaptic N-Methyl-d-Aspartate Receptors after Withdrawal from Chronic Ethanol Exposure

    OpenAIRE

    Clapp, Peter; Gibson, Emily S.; Dell'Acqua, Mark L.; Hoffman, Paula L.

    2010-01-01

    Alterations in N-methyl-d-aspartate receptor (NMDAR) protein levels or subcellular localization in brain after chronic ethanol exposure may contribute to withdrawal-associated seizures and neurotoxicity. We have investigated synaptic localization of NMDARs in cultured hippocampal pyramidal neurons after prolonged (7 days) exposure to, and acute withdrawal from, 80 mM ethanol using fluorescence immunocytochemistry techniques. After chronic ethanol exposure, there was a significant increase in ...

  2. [Does intravenous gadolinium-DTPA administration have advantages in magnetic resonance imaging of acute injuries or chronic damage to the knee joint?].

    Science.gov (United States)

    Jerosch, J; Castro, W H; Müller, U; Assheuer, J

    1994-12-01

    79 patients with acute or chronic lesions of the knee were evaluated by MRI prior to and after application of Gd-DTPA. The MRI examination was performed by a 1.0 tesla imager with SE as well as FEDIF sequences. These MR studies were compared prior to and after intravenous Gd-DTPA application, focusing on the visibility and the definition of a possible lesion, and scored with a 3-point score. Statistic analysis and case analysis revealed that in patients with meniscus degeneration without a tear, Gd application yields no additional diagnostic information. However, in patients with meniscus tears Gd-DTPA significantly facilitates the definition of the lesion. Furthermore, Gd-DTPA makes differentiation possible between the synovial fluid and the synovial membrane. Whereas in cases with capsule or collateral ligament tears Gd-DTPA facilitates the documentation of the lesion, we found no advantage in using Gd-DPTA in patients with ACL tears. In patients with chondropathia patellae Gd-DTPA application supports the visualization of the secondary synovial reaction.

  3. Protective effect of N-Acetylcysteine against ethanol-induced gastric ulcer: a pharmacological assessment in mice

    Directory of Open Access Journals (Sweden)

    Ausama Ayoob Jaccob

    2015-06-01

    Aim: Since there is an increasing need for gastric ulcer therapies with optimum benefit-risk profile. This study was conducted to investigate gastro-protective effects of N-Acetylcysteine (NAC against ethanol-induced gastric ulcer models in mice. Materials and Methods: Forty-two mice were allocated into six groups consisting of 7 mice each. Groups 1 (normal control and 2 (ulcer control received distilled water at a dose of 10 ml/kg, groups 3, 4 and 5 were given NAC at doses 100, 300 and 500 mg/kg, respectively, and the 6th group received ranitidine (50 mg/kg. All drugs administered orally once daily for 7 days, on the 8th day absolute ethanol (7 ml/kg was administrated orally to all mice to induce the acute ulcer except normal control group. Then 3 h after, all animals were sacrificed then consequently the stomachs were excised for examination. Results: NAC administration at the tested doses showed a dose-related potent gastro-protective effect with significant increase in curative ratio, PH of gastric juice and mucus content viscosity seen with the highest dose of NAC and it is comparable with that observed in ranitidine group. Conclusion: The present findings demonstrate that, oral NAC shows significant gastro-protective effects comparable to ranitidine confirmed by antisecretory, cytoprotective, histological and biochemical data but the molecular mechanisms behind such protection are complex. [J Intercult Ethnopharmacol 2015; 4(2.000: 90-95

  4. Effects of ethanol feeding on the activity and regulation of hepatic carnitine palmitoyltransferase I

    NARCIS (Netherlands)

    Guzman, M.; Geelen, M.J.H.

    1988-01-01

    The effects of ethanol administration on activity and regulation of carnitine palmitoyltransferase I (CPT-I) were studied in hepatocytes isolated from rats fed a liquid, high-fat diet containing 36% of total calories as ethanol or an isocaloric amount of sucrose. Cells were isolated at several time

  5. Ethanol Sensitization during Adolescence or Adulthood Induces Different Patterns of Ethanol Consumption without Affecting Ethanol Metabolism

    Science.gov (United States)

    Carrara-Nascimento, Priscila F.; Hoffmann, Lucas B.; Contó, Marcos B.; Marcourakis, Tania; Camarini, Rosana

    2017-01-01

    In previous study, we demonstrated that ethanol preexposure may increase ethanol consumption in both adolescent and adult mice, in a two-bottle choice model. We now questioned if ethanol exposure during adolescence results in changes of consumption pattern using a three-bottle choice procedure, considering drinking-in-the-dark and alcohol deprivation effect as strategies for ethanol consumption escalation. We also analyzed aldehyde dehydrogenase (ALDH) activity as a measurement of ethanol metabolism. Adolescent and adult Swiss mice were treated with saline (SAL) or 2.0 g/kg ethanol (EtOH) during 15 days (groups: Adolescent-SAL, Adolescent-EtOH, Adult-SAL and Adult-EtOH). Five days after the last injection, mice were exposed to the three-bottle choice protocol using sucrose fading procedure (4% + sucrose vs. 8%–15% ethanol + sucrose vs. water + sucrose) for 2 h during the dark phase. Sucrose was faded out from 8% to 0%. The protocol was composed of a 6-week acquisition period, followed by four withdrawals and reexposures. Both adolescent and adult mice exhibited ethanol behavioral sensitization, although the magnitude of sensitization in adolescents was lower than in adults. Adolescent-EtOH displayed an escalation of 4% ethanol consumption during acquisition that was not observed in Adult-EtOH. Moreover, Adult-EtOH consumed less 4% ethanol throughout all the experiment and less 15% ethanol in the last reexposure period than Adolescent-EtOH. ALDH activity varied with age, in which older mice showed higher ALDH than younger ones. Ethanol pretreatment or the pattern of consumption did not have influence on ALDH activity. Our data suggest that ethanol pretreatment during adolescence but not adulthood may influence the pattern of ethanol consumption toward an escalation in ethanol consumption at low dose, without exerting an impact on ALDH activity.

  6. Tetrahydroxystilbene glucoside protects against ethanol-induced liver injury in mice by inhibition of expression of inflammatuion-related factors

    Institute of Scientific and Technical Information of China (English)

    熊章鄂

    2013-01-01

    Objective To investigate the protective effects of tetrahydroxystilbene glucoside(TSG)against acute ethanol-induced liver injury in mice and to explore the possible mechanisms involved.Methods Kunming mice were

  7. Acute Toxicities of the Saxitoxin Congeners Gonyautoxin 5, Gonyautoxin 6, Decarbamoyl Gonyautoxin 2&3, Decarbamoyl Neosaxitoxin, C-1&2 and C-3&4 to Mice by Various Routes of Administration

    Directory of Open Access Journals (Sweden)

    Andrew I. Selwood

    2017-02-01

    Full Text Available Paralytic shellfish poisoning results from consumption of seafood naturally contaminated by saxitoxin and its congeners, the paralytic shellfish toxins (PSTs. The levels of such toxins are regulated internationally, and maximum permitted concentrations in seafood have been established in many countries. A mouse bioassay is an approved method for estimating the levels of PSTs in seafood, but this is now being superseded in many countries by instrumental methods of analysis. Such analyses provide data on the levels of many PSTs in seafood, but for risk assessment, knowledge of the relative toxicities of the congeners is required. These are expressed as “Toxicity Equivalence Factors” (TEFs. At present, TEFs are largely based on relative specific activities following intraperitoneal injection in a mouse bioassay rather than on acute toxicity determinations. A more relevant parameter for comparison would be median lethal doses via oral administration, since this is the route through which humans are exposed to PSTs. In the present study, the median lethal doses of gonyautoxin 5, gonyautoxin 6, decarbamoyl neosaxitoxin and of equilibrium mixtures of decarbamoyl gonyautoxins 2&3, C1&2 and C3&4 by oral administration to mice have been determined and compared with toxicities via intraperitoneal injection. The results indicate that the TEFs of several of these substances require revision in order to more accurately reflect the risk these toxins present to human health.

  8. Acute Toxicities of the Saxitoxin Congeners Gonyautoxin 5, Gonyautoxin 6, Decarbamoyl Gonyautoxin 2&3, Decarbamoyl Neosaxitoxin, C-1&2 and C-3&4 to Mice by Various Routes of Administration.

    Science.gov (United States)

    Selwood, Andrew I; Waugh, Craig; Harwood, David T; Rhodes, Lesley L; Reeve, John; Sim, Jim; Munday, Rex

    2017-02-21

    Paralytic shellfish poisoning results from consumption of seafood naturally contaminated by saxitoxin and its congeners, the paralytic shellfish toxins (PSTs). The levels of such toxins are regulated internationally, and maximum permitted concentrations in seafood have been established in many countries. A mouse bioassay is an approved method for estimating the levels of PSTs in seafood, but this is now being superseded in many countries by instrumental methods of analysis. Such analyses provide data on the levels of many PSTs in seafood, but for risk assessment, knowledge of the relative toxicities of the congeners is required. These are expressed as "Toxicity Equivalence Factors" (TEFs). At present, TEFs are largely based on relative specific activities following intraperitoneal injection in a mouse bioassay rather than on acute toxicity determinations. A more relevant parameter for comparison would be median lethal doses via oral administration, since this is the route through which humans are exposed to PSTs. In the present study, the median lethal doses of gonyautoxin 5, gonyautoxin 6, decarbamoyl neosaxitoxin and of equilibrium mixtures of decarbamoyl gonyautoxins 2&3, C1&2 and C3&4 by oral administration to mice have been determined and compared with toxicities via intraperitoneal injection. The results indicate that the TEFs of several of these substances require revision in order to more accurately reflect the risk these toxins present to human health.

  9. The acute toxicity of Najanajaatra venom (NNAV) by oral and intravenous administration%中华眼镜蛇毒口服和静脉注射单次给药对小鼠毒性作用的比较

    Institute of Scientific and Technical Information of China (English)

    张甜; 薛洁; 王响英; 朱路佳; 孙志红; 秦正红

    2016-01-01

    目的:比较中华眼镜蛇毒(NNAV)经口灌服、静脉注射两种染毒途径的半数致死量(LD50),观察两种染毒途径小鼠的急性中毒症状,寻找可能发生毒性作用的靶器官。方法:小鼠经口灌服、静脉注射NNAV后,测定半数致死量(LD50)。观察14 d内小鼠的活动、体征及死亡情况,并对死亡小鼠和存活14 d小鼠的主要脏器进行病理组织学检查。结果:小鼠经口灌服、静脉注射NNAV的LD50分别为102.3、0.624 mg/kg ,95% CI 84.9~123、0.572~0.680 mg/kg。NNAV经口灌服小鼠中毒症状出现快,喘息、强直性抽搐、呼吸抑制、心衰很快死亡;急性中毒受损器官主要为肺毛细血管充血,局部肺泡间隔增宽伴少量炎性细胞浸润;肝血管充血。NNAV静脉注射小鼠中毒症状为瘫卧、呼吸功能麻痹,心肺功能衰竭而死亡。急性中毒受损器官主要为肺泡腔内及细支气管内有红细胞,血管壁周围有水肿;肝细胞弥漫性肿大,致肝小叶结构不清,肝细胞肿胀,基质稀疏,有的呈气球样变,肝血窦受压变狭或消失。结论:NNAV口服染毒的毒性剂量明显低于静脉注射,二种染毒途径动物急性中毒器官的受损程度也有所不同;NNAV两种染毒途径存活14 d的小鼠其组织病理改变均可恢复。%Objective:To compare the lethal dose 50 (LD50 ) of Najanajaatra venom (NNAV) with two routes of drug administration and to explore the target organs of acute toxicity of NNAV ,and to observe the acute poisoning symptoms of the mice and organ lesions with oral and intravenous administration of NNAV . Methods: Two different modes of drug administration (oral administration and intravenous injection) were used to determine the LD50 .Within 14 of survival time period ,the activities ,signs and death of the mice were observed .Then ,pathology analysis was applied to the main organs of the dead and survival

  10. Thrombus aspiration plus intra-infarct-related artery administration of tirofiban improves myocardial perfusion during primary angioplasty for acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    YAN Hong-bing; ZHANG Xiao-jiang; LI Wen-zheng; LI Shi-ying; SONG Li; WANG Jian; WU Zheng; CHI Yun-peng; ZHENG Bin; ZHAO Han-jun; LI Qing-xiang

    2010-01-01

    Background We developed a new combined strategy of thrombus aspiration plus intra-infarct-related artery (IRA) bolus administration of tirofiban via the aspiration catheter in patients with ST-segment elevation myocardial infarction (STEMI). This strategy can reduce the distal embolism and achieve highly localized concentrations of tirofiban, which can improve myocardial reperfusion without increasing the risk of bleeding. The aim of this study was to investigate whether this combined strategy is superior to thrombus aspiration alone in improving myocardial perfusion in patients with STEMI undergoing primary angioplasty.Results Baseline characteristics of the two groups were well-balanced. The TIMI 3 flow showed a better tendency in the intra-IRA group than in the aspiration alone group (97.22% vs. 87.04%, X~2=7.863, P=0.049). The peak of CK-MB (83.9 (68.9-310.5) U/L vs. 126.1 (74.7-356.7) U/L, P=0.034) and Tnl (42.7 (14.7-113.9) ng/ml vs. 72.5 (59.8-135.3) ng/ml, FMD.029) were lower in the intra-IRA group than in the aspiration alone group. LVEF in the hospital favored the intra-IRA group, (45.7±8.3)% to (42.9±12.1)%, t=1.98, P=0.049. There was a tendency towards a lower MACE at 9-month follow-up in the intra-IRA group although it did not reach statistical difference (Log-rank X~2=2.865, P=0.09). There was no statistical difference in any bleeding events between the two groups.Conclusions Thrombus aspiration plus intra-IRA bolus administration of tirofiban combined with angioplasty may be related with improved myocardium perfusion, saved more myocardium, and resulted in a better clinical prognosis.

  11. 联用乳酸杆菌和丁酸梭菌对小鼠急性溃疡性结肠炎的影响%Influence of combined administration of lactobacilli and clostridium butyricum on acute mice ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    左和宁; 杨伟峰

    2009-01-01

    Objective To investigate the therapeutic effect of combined administration of lactobacilli and clostridium butyricum on acute mice ulcerative colitis, and explore its therapeutic mechanism.Methods Dextran sulfate sodium (DSS)-induced mice model of acute ulcerative colitis was established. After administration of lactobacilli and clostridium butyricum, the pathological change of tunica mucosa coli was observed and the expression levels of tumor necorisis factor (TNF-α) and tissue factor (TF) were measured.Results Lactobacilli and clostridium butyricum significantly alleviated the damage of tunica mucosa coli and suppressed the expression of TNF-αand TF. By comparison, there were the lightest histological damage and the lowest expression of TNF-αand TF when lactobacilli and clostridium butyricum were administrated combined.Conclusion Both lactobacilli and clostridium butyricum show therapeutic effect on DSS-induced mice ulcerative colitis. The coordinate repression on expression of TNF-αand TF may be the molecular mechanism of the co-effect on mice UC.%目的 观察联用乳酸杆菌和丁酸梭菌对小鼠急性溃疡性结肠炎的疗效并探讨其治疗机制.方法 建立DSS诱导的小鼠急性溃疡性结肠炎(UC)模型,观察给予乳酸杆菌和丁酸梭菌治疗后,小鼠结肠黏膜的病理改变和TNF-α和组织因子(TF)表达的变化.结果 乳酸杆菌和丁酸梭菌可明显减轻小鼠结肠黏膜的损伤;可明显抑制TNF-α和TF的表达,尤以两菌合用组抑制作用最强.结论 乳酸杆菌和丁酸梭菌对DSS诱导的UC有治疗作用,对TNF-α和TF表达的协同抑制作用可能是其发挥协调治疗作用的分子机制.

  12. Acute caffeine administration impact on working memory-related brain activation and functional connectivity in the elderly: a BOLD and perfusion MRI study.

    Science.gov (United States)

    Haller, S; Rodriguez, C; Moser, D; Toma, S; Hofmeister, J; Sinanaj, I; Van De Ville, D; Giannakopoulos, P; Lovblad, K-O

    2013-10-10

    In young individuals, caffeine-mediated blockade of adenosine receptors and vasoconstriction has direct repercussions on task-related activations, changes in functional connectivity, as well as global vascular effects. To date, no study has explored the effect of caffeine on brain activation patterns during highly demanding cognitive tasks in the elderly. This prospective, placebo-controlled crossover design comprises 24 healthy elderly individuals (mean age 68.8 ± 4.0 years, 17 females) performing a 2-back working memory (WM) task in functional magnetic resonance imaging (fMRI). Analyses include complimentary assessment of task-related activations (general linear model, GLM), functional connectivity (tensorial independent component analysis, TICA), and baseline perfusion (arterial spin labeling). Despite a reduction in whole-brain global perfusion (-22.7%), caffeine-enhanced task-related GLM activation in a local and distributed network is most pronounced in the bilateral striatum and to a lesser degree in the right middle and inferior frontal gyrus, bilateral insula, left superior and inferior parietal lobule as well as in the cerebellum bilaterally. TICA was significantly enhanced (+8.2%) in caffeine versus placebo in a distributed and task-relevant network including the pre-frontal cortex, the supplementary motor area, the ventral premotor cortex and the parietal cortex as well as the occipital cortex (visual stimuli) and basal ganglia. The inverse comparison of placebo versus caffeine had no significant difference. Activation strength of the task-relevant-network component correlated with response accuracy for caffeine yet not for placebo, indicating a selective cognitive effect of caffeine. The present findings suggest that acute caffeine intake enhances WM-related brain activation as well as functional connectivity of blood oxygen level-dependent fMRI in elderly individuals.

  13. Acute administration of ivacaftor to people with cystic fibrosis and a G551D-CFTR mutation reveals smooth muscle abnormalities

    Science.gov (United States)

    Adam, Ryan J.; Hisert, Katherine B.; Dodd, Jonathan D.; Grogan, Brenda; Launspach, Janice L.; Barnes, Janel K.; Gallagher, Charles G.; Sieren, Jered P.; Gross, Thomas J.; Fischer, Anthony J.; Cavanaugh, Joseph E.; Hoffman, Eric A.; Singh, Pradeep K.; Welsh, Michael J.; McKone, Edward F.; Stoltz, David A.

    2016-01-01

    BACKGROUND. Airflow obstruction is common in cystic fibrosis (CF), yet the underlying pathogenesis remains incompletely understood. People with CF often exhibit airway hyperresponsiveness, CF transmembrane conductance regulator (CFTR) is present in airway smooth muscle (ASM), and ASM from newborn CF pigs has increased contractile tone, suggesting that loss of CFTR causes a primary defect in ASM function. We hypothesized that restoring CFTR activity would decrease smooth muscle tone in people with CF. METHODS. To increase or potentiate CFTR function, we administered ivacaftor to 12 adults with CF with the G551D-CFTR mutation; ivacaftor stimulates G551D-CFTR function. We studied people before and immediately after initiation of ivacaftor (48 hours) to minimize secondary consequences of CFTR restoration. We tested smooth muscle function by investigating spirometry, airway distensibility, and vascular tone. RESULTS. Ivacaftor rapidly restored CFTR function, indicated by reduced sweat chloride concentration. Airflow obstruction and air trapping also improved. Airway distensibility increased in airways less than 4.5 mm but not in larger-sized airways. To assess smooth muscle function in a tissue outside the lung, we measured vascular pulse wave velocity (PWV) and augmentation index, which both decreased following CFTR potentiation. Finally, change in distensibility of <4.5-mm airways correlated with changes in PWV. CONCLUSIONS. Acute CFTR potentiation provided a unique opportunity to investigate CFTR-dependent mechanisms of CF pathogenesis. The rapid effects of ivacaftor on airway distensibility and vascular tone suggest that CFTR dysfunction may directly cause increased smooth muscle tone in people with CF and that ivacaftor may relax smooth muscle. FUNDING. This work was funded in part from an unrestricted grant from the Vertex Investigator-Initiated Studies Program. PMID:27158673

  14. Xylose fermentation to ethanol

    Energy Technology Data Exchange (ETDEWEB)

    McMillan, J.D.

    1993-01-01

    The past several years have seen tremendous progress in the understanding of xylose metabolism and in the identification, characterization, and development of strains with improved xylose fermentation characteristics. A survey of the numerous microorganisms capable of directly fermenting xylose to ethanol indicates that wild-type yeast and recombinant bacteria offer the best overall performance in terms of high yield, final ethanol concentration, and volumetric productivity. The best performing bacteria, yeast, and fungi can achieve yields greater than 0.4 g/g and final ethanol concentrations approaching 5%. Productivities remain low for most yeast and particularly for fungi, but volumetric productivities exceeding 1.0 g/L-h have been reported for xylose-fermenting bacteria. In terms of wild-type microorganisms, strains of the yeast Pichia stipitis show the most promise in the short term for direct high-yield fermentation of xylose without byproduct formation. Of the recombinant xylose-fermenting microorganisms developed, recombinant E. coli ATTC 11303 (pLOI297) exhibits the most favorable performance characteristics reported to date.

  15. Effect of methionine load on homocysteine levels, lipid peroxidation and DNA damage in rats receiving ethanol

    Directory of Open Access Journals (Sweden)

    Alceu Afonso Jordao Júnior

    2009-12-01

    Full Text Available Changes in the metabolism of methionine can cause hyperhomocysteinemia, inducing a triad of atherosclerosis, hypertension, and increased oxidative stress. The generation of free radicals and oxidative damage to DNA is important in the liver damage caused by ethanol. In this study, the effect of methionine overload associated or otherwise with acute administration of ethanol on homocysteine values, damage to DNA, lipoperoxidation and vitamin E was evaluated. Thirty rats were divided into 3 groups: Group Ethanol 24 hours (EG24, Group Methionine 24 hours (MG24, and Group Methionine and Ethanol 24 hours (MEG24. TBARS, vitamin E, GS and, homocysteine values were determined and the Comet assay was carried out. Increased GSH, vitamin E and homocysteine levels were observed for MEG24, and increased TBARS were observed in EG24. The Comet assay showed an increase in DNA damage in EG24 and DNA protection in MEG24. The administration of ethanol decreased antioxidant levels and increased TBARS, indicating the occurrence of oxidative stress with possible DNA damage. The combination of methionine and ethanol had a protective effect against the ethanol-induced damage, but increased the levels of homocysteine.Alterações no metabolismo da metionina podem ocasionar hiper-homocisteinemia, quadro indutivo de aterosclerose, hipertensão e aumento do estresse oxidativo. A geração de radicais livres e dano oxidativo ao DNA são importantes na injúria hepática provocada pelo etanol. Neste estudo avaliaram-se os efeitos da sobrecarga de metionina associada ou não à administração aguda de etanol sobre valores de homocisteína, dano ao DNA, lipoperoxidação e vitamina E. Foram utilizados 30 ratos Wistar distribuídos em 3 Grupos: Grupo Etanol 24 horas (GE24, Grupo Metionina 24 horas (GM24 e Grupo Metionina e Etanol 24 horas (GME24. Realizaram-se determinações hepáticas de SRATB, vitamina E, GSH, homocisteína e Teste do Cometa e determinações plasm

  16. Investigation of the possible protective role of gallic acid on paraoxanase and arylesterase activities in livers of rats with acute alcohol intoxication.

    Science.gov (United States)

    Kartkaya, Kazim; Oğlakçi, Ayşegül; Şentürk, Hakan; Bayramoğlu, Gökhan; Canbek, Mediha; Kanbak, Güngör

    2013-04-01

    Gallic acid, a polyphenyl class natural product from gallnut and green tea, is known to be antioxidant, anti-inflammatory and radical scavenger. In this study, we aimed to investigate the possible protective effects of gallic acid on paraoxonase and arylesterase activities in liver exposed to acute alcohol intoxication. Paraoxonase and arylesterase activities in liver tissue and serum aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase levels were measured. Histological investigations were also made. In our study, we observed a significant increase of serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities, which are indicators of liver damage after acute ethanol consumption. Gallic acid therapy has significantly reduced the increase in these biomarkers, indicating a possible hepatoprotective effect of gallic acid. Ethanol consumption caused a significant decrease in liver paraoxonase activity (P Gallic acid treatment partly restored this decreased paraoxonase activity, which resulted from ethanol administration. A gallic acid dose of 100 mg/kg was observed as highest restoring effect for paraoxonase activity (P gallic acid treatment restored the loss of this activity due to ethanol exposure (P gallic acid ameliorates the liver damage caused by excessive alcohol consumption in a dose-dependent way. Our results in this study showed that gallic acid might have a protective effect against alcoholic liver disease.

  17. EFFECTS OF ETHANOL AND HYDROGEN PEROXIDE ON MOUSE LIMB BUD MESENCHYME DIFFERENTIATION AND CELL DEATH

    Science.gov (United States)

    Many of the morphological defects associated with embryonic alcohol exposure are a result of cell death. During limb development, ethanol administration produces cell death in the limb and digital defects, including postaxial ectrodactyly. Because an accumulation of reactive oxyg...

  18. Effects of valproic acid and dexamethasone administration on early bio-markers and gene expression profile in acute kidney ischemia-reperfusion injury in the rat.

    Directory of Open Access Journals (Sweden)

    Ryan W Speir

    Full Text Available Renal ischemia-reperfusion (IR causes acute kidney injury (AKI with high mortality and morbidity. The objective of this investigation was to ameliorate kidney IR injury and identify novel biomarkers for kidney injury and repair. Under general anesthesia, left renal ischemia was induced in Wister rats by occluding renal artery for 45 minutes, followed by reperfusion and right nephrectomy. Thirty minutes prior to ischemia, rats (n = 8/group received Valproic Acid (150 mg/kg; VPA, Dexamethasone (3 mg/kg; Dex or Vehicle (saline intraperitoneally. Animals were sacrificed at 3, 24 or 120 h post-IR. Plasma creatinine (mg/dL at 24 h was reduced (P<0.05 in VPA (2.7±1.8 and Dex (2.3±1.2 compared to Vehicle (3.8±0.5 group. At 3 h, urine albumin (mg/mL was higher in Vehicle (1.47±0.10, VPA (0.84±0.62 and Dex (1.04±0.73 compared to naïve (uninjured/untreated control (0.14±0.26 group. At 24 h post-IR urine lipocalin-2 (μg/mL was higher (P<0.05 in VPA, Dex and Vehicle groups (9.61-11.36 compared to naïve group (0.67±0.29; also, kidney injury molecule-1 (KIM-1; ng/mL was higher (P<0.05 in VPA, Dex and Vehicle groups (13.7-18.7 compared to naïve group (1.7±1.9. Histopathology demonstrated reduced (P<0.05 ischemic injury in the renal cortex in VPA (Grade 1.6±1.5 compared to Vehicle (Grade 2.9±1.1. Inflammatory cytokines IL1β and IL6 were downregulated and anti-apoptotic molecule BCL2 was upregulated in VPA group. Furthermore, kidney DNA microarray demonstrated reduced injury, stress, and apoptosis related gene expression in the VPA administered rats. VPA appears to ameliorate kidney IR injury via reduced inflammatory cytokine, apoptosis/stress related gene expression, and improved regeneration. KIM-1, lipocalin-2 and albumin appear to be promising early urine biomarkers for the diagnosis of AKI.

  19. Effects of Valproic Acid and Dexamethasone Administration on Early Bio-Markers and Gene Expression Profile in Acute Kidney Ischemia-Reperfusion Injury in the Rat

    Science.gov (United States)

    Speir, Ryan W.; Stallings, Jonathan D.; Andrews, Jared M.; Gelnett, Mary S.; Brand, Timothy C.; Salgar, Shashikumar K.

    2015-01-01

    Renal ischemia-reperfusion (IR) causes acute kidney injury (AKI) with high mortality and morbidity. The objective of this investigation was to ameliorate kidney IR injury and identify novel biomarkers for kidney injury and repair. Under general anesthesia, left renal ischemia was induced in Wister rats by occluding renal artery for 45 minutes, followed by reperfusion and right nephrectomy. Thirty minutes prior to ischemia, rats (n = 8/group) received Valproic Acid (150 mg/kg; VPA), Dexamethasone (3 mg/kg; Dex) or Vehicle (saline) intraperitoneally. Animals were sacrificed at 3, 24 or 120 h post-IR. Plasma creatinine (mg/dL) at 24 h was reduced (P<0.05) in VPA (2.7±1.8) and Dex (2.3±1.2) compared to Vehicle (3.8±0.5) group. At 3 h, urine albumin (mg/mL) was higher in Vehicle (1.47±0.10), VPA (0.84±0.62) and Dex (1.04±0.73) compared to naïve (uninjured/untreated control) (0.14±0.26) group. At 24 h post-IR urine lipocalin-2 (μg/mL) was higher (P<0.05) in VPA, Dex and Vehicle groups (9.61–11.36) compared to naïve group (0.67±0.29); also, kidney injury molecule-1 (KIM-1; ng/mL) was higher (P<0.05) in VPA, Dex and Vehicle groups (13.7–18.7) compared to naïve group (1.7±1.9). Histopathology demonstrated reduced (P<0.05) ischemic injury in the renal cortex in VPA (Grade 1.6±1.5) compared to Vehicle (Grade 2.9±1.1). Inflammatory cytokines IL1β and IL6 were downregulated and anti-apoptotic molecule BCL2 was upregulated in VPA group. Furthermore, kidney DNA microarray demonstrated reduced injury, stress, and apoptosis related gene expression in the VPA administered rats. VPA appears to ameliorate kidney IR injury via reduced inflammatory cytokine, apoptosis/stress related gene expression, and improved regeneration. KIM-1, lipocalin-2 and albumin appear to be promising early urine biomarkers for the diagnosis of AKI. PMID:25970334

  20. Pharmacological characterization of the nociceptin/orphanin FQ receptor on ethanol-mediated motivational effects in infant and adolescent rats.

    Science.gov (United States)

    Miranda-Morales, Roberto Sebastián; Pautassi, Ricardo M

    2016-02-01

    Activation of nociceptin/orphanin FQ (NOP) receptors attenuates ethanol drinking and prevents relapse in adult rodents. In younger rodents (i.e., infant rats), activation of NOP receptors blocks ethanol-induced locomotor activation but does not attenuate ethanol intake. The aim of the present study was to extend the analysis of NOP modulation of ethanol's effects during early ontogeny. Aversive and anxiolytic effects of ethanol were measured in infant and adolescent rats via conditioned taste aversion and the light-dark box test; whereas ethanol-induced locomotor activity and ethanol intake was measured in adolescents only. Before these tests, infant rats were treated with the natural ligand of NOP receptors, nociceptin (0.0, 0.5 or 1.0 μg) and adolescent rats were treated with the specific agonist Ro 64-6198 (0.0, 0.1 or 0.3 mg/kg). The activation of NOP receptors attenuated ethanol-induced anxiolysis in adolescents only, and had no effect on ethanol's aversive effects. Administration of Ro 64-6198 blocked ethanol-induced locomotor activation but did not modify ethanol intake patterns. The attenuation of ethanol stimulating and anxiolytic effect by activation of NOP receptors indicates a modulatory role of this receptor on ethanol effects, which is expressed early in ontogeny.

  1. Environmental Enrichment Blunts Ethanol Consumption after Restraint Stress in C57BL/6 Mice

    Science.gov (United States)

    Marianno, Priscila; Abrahao, Karina Possa

    2017-01-01

    Elevated alcohol intake after abstinence is a key feature of the addiction process. Some studies have shown that environmental enrichment (EE) affects ethanol intake and other reinforcing effects. However, different EE protocols may vary in their ability to influence alcohol consumption and stress-induced intake. The present study evaluated whether short (3 h) or continuous (24 h) EE protocols affect ethanol consumption after periods of withdrawal. Mice were challenged with stressful stimuli (24 h isolation and restraint stress) to evaluate the effects of stress on drinking. Male C57BL/6 mice were subjected to a two-bottle choice drinking-in-the-dark paradigm for 15 days (20% ethanol and water, 2 h/day, acquisition phase). Control mice were housed under standard conditions (SC). In the first experiment, one group of mice was housed under EE conditions 24 h/day (EE24h). In the second experiment, the exposure to EE was reduced to 3 h/day (EE3h). After the acquisition phase, the animals were deprived of ethanol for 6 days, followed by 2 h ethanol access once a week. Animals were tested in the elevated plus maze (EPM) during ethanol withdrawal. During the last 2 weeks, the mice were exposed to 24 h ethanol access. A 1-h restraint stress test was performed immediately before the last ethanol exposure. EE24h but not EE3h increased anxiety-like behavior during withdrawal compared to controls. Neither EE24h nor EE3h affected ethanol consumption during the 2 h weekly exposure periods. However, EE24h and EE3h mice that were exposed to acute restraint stress consumed less ethanol than controls during a 24 h ethanol access. These results showed that EE reduces alcohol intake after an acute restraint stress. PMID:28107511

  2. A Sustainable Ethanol Distillation System

    Directory of Open Access Journals (Sweden)

    Yuelei Yang

    2012-01-01

    Full Text Available The discarded fruit and vegetable waste from the consumer and retailer sectors provide a reliable source for ethanol production. In this paper, an ethanol distillation system has been developed to remove the water contents from the original wash that contains only around 15% of the ethanol. The system has an ethanol production capacity of over 100,000 liters per day. It includes an ethanol condenser, a wash pre-heater, a main exhaust heat exchanger as well as a fractionating column. One unique characteristic of this system is that it utilizes the waste heat rejected from a power plant to vaporize the ethanol, thus it saves a significant amount of energy and at the same time reduces the pollution to the environment.

  3. Effects of Preconceptional Ethanol Consumption on ADHD-Like Symptoms in Sprague-Dawley Rat Offsprings

    Science.gov (United States)

    Choi, Inah; Kim, Pitna; Joo, So Hyun; Kim, Min Kyeong; Park, Jin Hee; Kim, Hee Jin; Ryu, Jong Hoon; Cheong, Jae Hoon; Shin, Chan Young

    2012-01-01

    Ethanol exposure during gestational period is related to growth retardation, morphological abnormality, and even in neurological abnormalities including attention deficit/hyperactivity disorder (ADHD)-like behaviors on offspring. However, relatively little is known about the effects of maternal ethanol consumption prior to conception on their offspring. In this study, we investi-gated whether maternal ethanol administration during preconceptional phase produces ADHD-like behaviors in the rat offspring. Sprague-Dawley (SD) female rats were administrated ethanol via intragastric intubation with dosing regimen of 6 g/kg daily for 10 consecutive days and treated female rats then mated with non-treated male SD rats after 8 weeks. Another group subjected to the same procedure as those conducted on ethanol treated group except the saline administration instead of ethanol. Offspring was tested for their ADHD-like behaviors using open field test, Y maze test and impulsivity test that is performed in the aversive electronic foot shock paradigm. Offspring of preconceptional ethanol treated (EtOH) group showed hyperlocomotive activity, attention deficit and impulsivity. And reduction of striatal dopamine transporter (DAT) level was observed by Western blot in the EtOH group, compared to control (Con) group, while the immunohistochemical analysis exhibited increased expression of norepinephrine transporter (NET) in the frontal cortex. These results suggest that maternal ethanol consumption in the preconceptional phase induces ADHD-like behaviors in offspring that might be related to the abnormal expression of DAT and NET in rat. PMID:24116300

  4. Acute Toxicity Test of Oral Administration of Artequick in KM mice%青蒿素哌喹片对昆明种小鼠灌胃给药的急性毒性试验

    Institute of Scientific and Technical Information of China (English)

    徐勤; 李晓波; 刘婵; 袁征; 宋健平; 关业枝; 王琪

    2014-01-01

    Objective To study the acute toxicity of artequick after oral administration in mice. Methods By using the Bliss method,the LD50 and its 95 % confidence of artequick in mice were determined after single oral administration for evaluation of the toxicity within 14 days. The gross anatomy and histopathological examination for the dead mice were also carried out. Results After single oral administration,the mice showed various degrees of toxic reaction, showing as less spontaneous activities,closing eyes,face lying,incoordination,tremor,terror,forced paroxysmal spasm,and opisthotonus. The LD50 of artequick in mice was 2802.38 mg·kg-1 and its 95 % confidence was 2343.51~3520.11 mg·kg-1. No abnormal alteration was shown in the organs of all the postmortem mice after the gross anatomy. Conclusion Single oral administration of Artequick has some toxic effects in mice,and the target of toxic organs may be involved the central nervous system.%目的:研究青蒿素哌喹片(ATQ)对昆明种小鼠灌胃给药的急性毒性。方法按 Bliss 法设计试验,对小鼠单次灌胃 ATQ,测定 ATQ 对小鼠半数致死量(LD50)和 LD50的95%可信限,观察14 d 内小鼠的毒性反应和死亡情况,对小鼠进行大体解剖,肉眼观察并进行组织病理学检查。结果 ATQ 单次灌胃给药可使小鼠出现不同程度的毒性反应,包括自发活动减少、闭眼、俯卧、运动失调、震颤、惊跳、强制性-阵挛性抽搐、角弓反张。小鼠 LD50为2802.38 mg·kg-1,LD50的95%可信限为2343.51~3520.11 mg·kg-1,死亡小鼠肉眼观察未发现各脏器异常。结论 ATQ 对小鼠单次灌胃给药具有一定的毒性,涉及的毒性靶器官可能是中枢神经系统。

  5. Systemic corticosteroids and early administration of antiviral agents for pneumonia with acute wheezing due to influenza A(H1N1pdm09 in Japan.

    Directory of Open Access Journals (Sweden)

    Koichiro Kudo

    Full Text Available BACKGROUND: Pneumonia patients with wheezing due to influenza A(H1N1pdm09 were frequently treated with systemic corticosteroids in Japan although systemic corticosteroid for critically ill patients with pneumonia caused by influenza A(H1N1pdm09 has been controversial. Applicability of systemic corticosteroid treatment needs to be evaluated. METHODS/PRINCIPAL FINDINGS: We retrospectively reviewed 89 subjects who were diagnosed with influenza A(H1N1pdm09 and admitted to a national hospital, Tokyo during the pandemic period. The median age of subjects (45 males was 8 years (range, 0-71. All subjects were treated with antiviral agents and the median time from symptom onset to initiation of antiviral agents was 2 days (range, 0-7. Subjects were classified into four groups: upper respiratory tract infection, wheezing illness, pneumonia with wheezing, and pneumonia without wheezing. The characteristics of each group was evaluated. A history of asthma was found more frequently in the wheezing illness (55.6% and pneumonia with wheezing (43.3% groups than in the other two groups (p = 0.017. Corticosteroid treatment was assessed among subjects with pneumonia. Oxygen saturation was lower in subjects receiving corticosteroids (steroid group than in subjects not receiving corticosteroids (no-steroid group (p<0.001. The steroid group required greater oxygen supply than the no-steroid group (p<0.001. No significant difference was found by the Kaplan-Meier method between the steroid and the no-steroid groups in hours to fever alleviation from the initiation of antiviral agents and hospitalization days. In logistic regression analysis, wheezing, pneumonia and oxygen saturation were independent factors associated with using systemic corticosteroids. CONCLUSION: Patients with wheezing and a history of asthma were frequently found in the study subjects. Systemic corticosteroids together with early administration of antiviral agents to pneumonia with wheezing and

  6. Administrating Solr

    CERN Document Server

    Mohan, Surendra

    2013-01-01

    A fast-paced, example-based guide to learning how to administrate, monitor, and optimize Apache Solr.""Administrating Solr"" is for developers and Solr administrators who have a basic knowledge of Solr and who are looking for ways to keep their Solr server healthy and well maintained. A basic working knowledge of Apache Lucene is recommended, but this is not mandatory.

  7. Assessment of acute and subchronic oral toxicity of ethanolic extract of Pothomorphe umbellata L. Miq (Pariparoba Avaliação da toxidade oral aguda e subcrônica de extrato etanólico de Pothomorphe umbellata L. Miq. (Parapiroba

    Directory of Open Access Journals (Sweden)

    Sonia Barros

    2005-03-01

    Full Text Available There is a high degree of concern regarding the secure use of plant extracts and, for this very reason, preclinical and clinic toxicological evaluation of these extracts are needed. With the aim to assure the quality and the safety of the extract and due to the scarcity of literature information about Pariparoba extract toxicity, our purpose was to investigate the acute and subchronic toxicity of the standardized ethanolic dried root extract of Pothomorphe umbellata L. Miq. This extract was administered orally to adult swiss mice and wistar rats and the mutagenic potencial of the extract was also evaluated. The extract showed to be non toxic.Existe uma grande preocupação quanto ao uso seguro de extratos vegetais e, por esta razão, a necessidade de estudos toxicológicos pré-clínicos e clínicos destes extratos. O objetivo deste trabalho foi o de avaliar a toxicidade aguda e subcrônica do extrato hidroalcoólico liofilizado de Pothomorphe umbellata L. Miq., administrado por via oral para animais de laboratório. O potencial mutagênico do extrato foi também avaliado pelo teste do micronúcleo. Os resultados dos estudos a curto e médio prazo demonstraram que o extrato não apresenta propriedades tóxicas.

  8. NEUROPEPTIDE Y (NPY) SUPPRESSES ETHANOL DRINKING IN ETHANOL-ABSTINENT, BUT NOT NON-ETHANOL-ABSTINENT, WISTAR RATS

    OpenAIRE

    Gilpin, N.W.; Stewart, R B; Badia-Elder, N.E.

    2008-01-01

    In outbred rats, increases in brain neuropeptide Y (NPY) activity suppress ethanol consumption in a variety of access conditions, but only following a history of ethanol dependence. NPY reliably suppresses ethanol drinking in alcohol-preferring (P) rats and this effect is augmented following a period of ethanol abstinence. The purpose of this experiment was to examine the effects of NPY on 2-bottle choice ethanol drinking and feeding in Wistar rats that had undergone chronic ethanol vapor exp...

  9. Administrative Circulars

    CERN Multimedia

    Département des Ressources humaines

    2004-01-01

    Administrative Circular N° 2 (Rev. 2) - May 2004 Guidelines and procedures concerning recruitment and probation period of staff members This circular has been revised. It cancels and replaces Administrative Circular N° 2 (Rev. 1) - March 2000. Administrative Circular N° 9 (Rev. 3) - May 2004 Staff members contracts This circular has been revised. It cancels and replaces Administrative Circular N° 9 (Rev. 2) - March 2000. Administrative Circular N° 26 (Rev. 4) - May 2004 Procedure governing the career evolution of staff members This circular has also been revised. It Administrative Circulars Administrative Circular N° 26 (Rev. 3) - December 2001 and brings up to date the French version (Rev. 4) published on the HR Department Web site in January 2004. Operational Circular N° 7 - May 2004 Work from home This circular has been drawn up. Operational Circular N° 8 - May 2004 Dealing with alcohol-related problems...

  10. Differential responses to acute administration of a new 5-HT7-R agonist as a function of adolescent pre-treatment: phMRI and immuno-histochemical study

    Directory of Open Access Journals (Sweden)

    Luisa eAltabella

    2014-12-01

    Full Text Available LP-211 is a new, selective agonist of serotonin (5-hydroxytryptamine, 5-HT receptor 7 (5-HT7-R, which is part of a neuro-transmission system with a proposed role in neural plasticity and in mood, cognitive or sleep regulation. Adolescent subchronic LP-211 treatment produces some persisting changes in rats’ forebrain structural and functional parameters. Here, using pharmacological MRI (phMRI, we investigated the effect of acute administration with LP-211 (10 mg/kg i.p., or vehicle, to adult rats previously exposed to the same drug (0.25 mg/kg/day for 5 days, or vehicle, during adolescence (44 to 48 post-natal days; histology and immuno-histochemistry were performed ex vivo to evaluate neuro-anatomical and physiological long-term adaptation to pharmacological pre-treatment. The phMRI signal reveals forebrain areas (i.e. hippocampus, orbital prefrontal cortex, activated in response to LP-211 challenge independently of adolescent pre-treatment. In septum and nucleus accumbens, sensitized activation was found in adolescent pre-treated rats but not in vehicle-exposed controls. Immuno-histochemical analyses showed marked differences in septum as long-term consequence of the adolescent pre-treatment: increased level of 5-HT7-R, increased number of 5-HT7-R positive cells, and enhanced astrocyte activation. For nucleus accumbens, immuno-histochemical analyses did not reveal any difference between adolescent pre-treated rats and vehicle-exposed controls. In conclusion, subchronic LP-211 administration during adolescence is able to induce persistent physiological changes in the septal 5-HT7-R expression and astrocyte response that can still be observed in adulthood. Data shed new insights into roles of 5-HT7-R for normal and pathologic behavioral regulations.

  11. Differential responses to acute administration of a new 5-HT7-R agonist as a function of adolescent pre-treatment: phMRI and immuno-histochemical study.

    Science.gov (United States)

    Altabella, Luisa; Sbriccoli, Marco; Zoratto, Francesca; Poleggi, Anna; Vinci, Ramona; Lacivita, Enza; Leopoldo, Marcello; Laviola, Giovanni; Cardone, Franco; Canese, Rossella; Adriani, Walter

    2014-01-01

    LP-211 is a new, selective agonist of serotonin (5-hydroxytryptamine, 5-HT) receptor 7 (5-HT7-R), which is part of a neuro-transmission system with a proposed role in neural plasticity and in mood, cognitive and sleep regulation. Adolescent subchronic LP-211 treatment produces some persisting changes in rats' forebrain structural and functional parameters. Here, using pharmacological MRI (phMRI), we investigated the effect of acute administration with LP-211 (10 mg/kg i.p.), or vehicle, to adult rats previously exposed to the same drug (0.25 mg/kg/day for 5 days), or vehicle, during adolescence (44-48 post-natal days); histology and immuno-histochemistry were performed ex vivo to evaluate neuro-anatomical and physiological long-term adaptation to pharmacological pre-treatment. The phMRI signal reveals forebrain areas (i.e., hippocampus, orbital prefrontal cortex), activated in response to LP-211 challenge independently of adolescent pre-treatment. In septum and nucleus accumbens, sensitized activation was found in adolescent pre-treated rats but not in vehicle-exposed controls. Immuno-histochemical analyses showed marked differences in septum as long-term consequence of the adolescent pre-treatment: increased level of 5-HT7-R, increased number of 5-HT7-R positive cells, and enhanced astrocyte activation. For nucleus accumbens, immuno-histochemical analyses did not reveal any difference between adolescent pre-treated rats and vehicle-exposed controls. In conclusion, subchronic LP-211 administration during adolescence is able to induce persistent physiological changes in the septal 5-HT7-R expression and astrocyte response that can still be observed in adulthood. Data shed new insights into roles of 5-HT7-R for normal and pathologic behavioral regulations.

  12. Effects of ethanolic extract of pine needles (Pinus eldarica Medw. on reserpine-induced depression-like behavior in male Wistar rats

    Directory of Open Access Journals (Sweden)

    Samira Bolandghamat

    2011-01-01

    Full Text Available Background: In this study, the antidepressant activity of ethanolic extract of Pinus eldarica Medw needles was assessed using forced swimming test (FST in rats. Materials and Methods: Male Wistar rats were randomly divided into six Groups and treated as follows: first group was received only reserpine (6 mg/kg, i.p., second group was received reserpine (6 mg/kg, i.p. and imipramine (10 mg/kg, i.p., three experimental groups received reserpine (6 mg/kg, i.p. and three doses of pine needle extract (100, 300, and 500 mg/kg, p.o. respectively and the final group (control group received only vehicle (5% DMSO, i.p.. Results: Acute oral administration of ethanolic extract of P. eldarica Medw needles at a dosage of 300 mg/kg reduced reserpine-induced increase in immobility time in the FST, demonstrating an antidepressant effect in the FST. Additionally, extract treatment did not modify the ambulation and rearing evaluated in open field test, indicating that antidepressant effect found in the forced swimming test was not based on the stimulation of locomotor activity. Conclusion: These results indicate that ethanolic extract of Pinus eldarica needles possesses an antidepressant activity.

  13. Steam reforming of ethanol

    DEFF Research Database (Denmark)

    Trane-Restrup, Rasmus; Dahl, Søren; Jensen, Anker Degn

    2013-01-01

    Steam reforming (SR) of oxygenated species like bio-oil or ethanol can be used to produce hydrogen or synthesis gas from renewable resources. However, deactivation due to carbon deposition is a major challenge for these processes. In this study, different strategies to minimize carbon deposition...... on Ni-based catalysts during SR of ethanol were investigated in a flow reactor. Four different supports for Ni were tested and Ce0.6Zr0.4O2 showed the highest activity, but also suffered from severe carbon deposition at 600 °C or below. Operation at 600 °C or above were needed for full conversion...... 400 ppm of the carbon in the feed at approx. 600 °C. The different promoters did not influence the product distribution to any significant extent. Selective poisoning with small amounts of K2SO4 on Ni–CeO2/MgAl2O4 at 600 °C decreased carbon deposition from 900 to 200 ppm of the carbon in the feed...

  14. Toxic acute hepatitis associated to the administration of prostaglandin in a dog Hepatite tóxica aguda associada à administração de prostaglandina em cão

    Directory of Open Access Journals (Sweden)

    Mariana Isa Poci Palumbo

    2011-09-01

    Full Text Available Prostaglandin F2? can be used in dogs to increase ejaculate volume in cases of artificial insemination, semen cryopreservation or reproductive biotechnologies. Side effects after administration of PGF2? in dogs as tachycardia, tachypnea, salivation, vomiting, diarrhea and seizures are usually dose- dependent. This paper reports the occurrence of acute toxic hepatitis after the application of PGF2? in a dog, and discusses the importance of using this drug with caution in dogs.A prostaglandina F2? pode ser usada em caes para aumentar o volume do ejaculado em casos de inseminação artificial, criopreservação seminal ou biotecnologias de reprodução. Os efeitos colaterais após a administração da PGF2a, como taquicardia, salivação, emese, diarréia e convulsões geralmente são relacionadas com a dose utilizada. Esse trabalho objetiva relatar a ocorrência de hepatite tóxica aguda após a administração de PGF2a em um cão, e discutir a importância de se utilizar essa droga com cautela nessa espécie.

  15. Ethanol impairs mucosal immunity against Streptococcus pneumoniae infection by disrupting interleukin 17 gene expression.

    Science.gov (United States)

    Trevejo-Nunez, Giraldina; Chen, Kong; Dufour, Jason P; Bagby, Gregory J; Horne, William T; Nelson, Steve; Kolls, Jay K

    2015-05-01

    Acute ethanol intoxication suppresses the host immune responses against Streptococcus pneumoniae. As interleukin 17 (IL-17) is a critical cytokine in host defense against extracellular pathogens, including S. pneumoniae, we hypothesized that ethanol impairs mucosal immunity against this pathogen by disrupting IL-17 production or IL-17 receptor (IL-17R) signaling. A chronic ethanol feeding model in simian immunodeficiency virus (SIV)-infected rhesus macaques and acute ethanol intoxication in a murine model were used. Transcriptome analysis of bronchial brushes in the nonhuman primate model showed downregulation of the expression of IL-17-regulated chemokines in ethanol-fed animals, a finding also replicated in the murine model. Surprisingly, recombinant CXCL1 and CXCL5 but not IL-17 or IL-23 plus IL-1β rescued bacterial burden in the ethanol group to control levels. Taken together, the results of this study suggest that ethanol impairs IL-17-mediated chemokine production in the lung. Thus, exogenous luminal restoration of IL-17-related chemokines, CXCL1 and CXCL5, improves host defenses against S. pneumoniae.

  16. Study of individual erythrocyte deformability susceptibility to INFeD and ethanol using a microfluidic chip

    Science.gov (United States)

    Liu, Lihong; Huang, Sha; Xu, Xiaoying; Han, Jongyoon

    2016-01-01

    Human red blood cells (RBCs) deformability in vitro was assessed during iron dextran (INFeD) loading and/or ethanol co-administration using microfluidic deformability screening. The results showed donor-specific variations in dose dependent deformability shift were revealed below 500 μg/mL iron dextran. Two out of nine blood samples exhibited significant cell stiffening at 500 μg/mL iron dextran loading concentration (p < 0.05, Tukey test). More interestingly, co-administration of moderate amount of ethanol was identified to have significant protective effects on RBC deformability. We also noted that ethanol can reverse the deformability of impaired RBCs. Meanwhile obvious donor dependent response to ethanol administration on RBC deformability was noted using our biomimetic microfluidic chip. PMID:26964754

  17. Administrative Reform

    DEFF Research Database (Denmark)

    Plum, Maja

    Through the example of a Danish reform of educational plans in early childhood education, the paper critically addresses administrative educational reforms promoting accountability, visibility and documentation. Drawing on Foucaultian perspectives, the relation between knowledge and governing...... of administrative technology, tracing how the humanistic values of education embed and are embedded within ‘the professional nursery teacher' as an object and subject of administrative practice. Rather than undermining the humanistic potential of education, it is argued that the technology of accounting...

  18. 替罗非班治疗急性心肌梗死的疗效和安全性观察%Efficiency and safety for intravenously administration of urokinase and tirofiban in treating acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    干志红; 苟华良; 孙向阳

    2012-01-01

    目的 观察替罗非班治疗急性心肌梗死(AMI)与尿激酶静脉溶栓合用的安全性及疗效.方法 对122例AMI患者随机分为治疗组60例,对照组62例.两组患者均给予静脉溶栓、硝酸甘油、培哚普利/或氯沙坦、美托洛尔、拜阿司匹林、氯吡格雷、阿托伐他汀钙、依诺肝素等作为基础治疗.治疗组在溶栓后静脉泵入替罗非班,先0.4μg/(kg·min)× 30min,后0.15μg/(kg·min).观察梗死血管再通、出血并发症、主要心脏不良事件(MACE).结果 梗死血管再通率治疗组比对照组显著提高,P<0.05,差异有统计学意义.出血并发症两组无统计学意义,P>0.05.MACE治疗组比对照组显著降低,差异有统计学意义(P<0.05).结论 替罗非班在治疗AMI与尿激酶静脉溶栓合用是安全有效的.%To assess the efficiency and safety for intravenously administration of urokinase and tirofiban for the treatment of acute myocardial infarction. Methods 122 patients with acute myocardial infarction were randomly divided into two groups. 60 were in tirofiban group and 62 in basic therapy group. Patients in both groups took intravenous thrombolysis together with nitroglycerine, perindopril or losartan, metoprolol, aspirin, clopidogrel, atorvastatin calcium, enoxaparin etc. as basic medication. For patients in tirofiban group, tirofiban was additionally administrated by intravenous micro-pump with 0.4μg/(kg·min) for 30 minutes and 0.15μg/(kg·min) for maintenance after thrombolysis. Development of infarction related artery refu-sion, hemorrhage and major adverse cardiac events were observed and recorded. Results The infarction related artery refusion rate in tirofiban group was significantly higher than basic therapy group (P>0.05). There was no major difference in the incidence of hemorrhage between two groups (P<0.05). The development of major adverse cardiac events was significantly lower in tirofiban group than basic therapy group (P <0

  19. Brain Acetaldehyde Exposure Impacts upon Neonatal Respiratory Plasticity and Ethanol-Related Learning in Rodents

    Science.gov (United States)

    Acevedo, María B.; D'Aloisio, Génesis; Haymal, Olga B.; Molina, Juan C.

    2017-01-01

    Prior studies indicate that neonates are very sensitive to ethanol's positive reinforcing effects and to its depressant effects upon breathing. Acetaldehyde (ACD) appears to play a major role in terms of modulating early reinforcing effects of the drug. Yet, there is no pre-existing literature relative to the incidence of this metabolite upon respiratory plasticity. The present study analyzed physiological and behavioral effects of early central administrations of ethanol, acetaldehyde or vehicle. Respiration rates (breaths/min) were registered at post-natal days (PDs) 2 and 4 (post-administration time: 5, 60, or 120 min). At PD5, all pups were placed in a context (plethysmograph) where they had previously experienced the effects of central administrations and breathing patterns were recorded. Following this test, pups were evaluated using and operant conditioning procedure where ethanol or saccharin served as positive reinforcers. Body temperatures were also registered prior to drug administrations as well as at the beginning and the end of each specific evaluation. Across days, breathing responses were high at the beginning of the evaluation session and progressively declined as a function of the passage of time. At PDs 2 and 4, shortly after central administration (5 min), ACD exerted a significant depression upon respiration frequencies. At PD5, non-intoxicated pups with a prior history of ACD central administrations, exhibited a marked increase in respiratory frequencies; a result that probably indicates a conditioned compensatory response. When operant testing procedures were conducted, prior ethanol or ACD central administrations were found to reduce the reinforcing effects of ethanol. This was not the case when saccharin was employed as a reinforcer. As a whole, the results indicate a significant role of central ACD upon respiratory plasticity of the neonate and upon ethanol's reinforcing effects; phenomena that affect the physiological integrity of the

  20. Moderate alcohol consumption and increased bone mineral density: potential ethanol and non-ethanol mechanisms.

    Science.gov (United States)

    Jugdaohsingh, R; O'Connell, M A; Sripanyakorn, S; Powell, J J

    2006-08-01

    Mounting epidemiological evidence indicates an association between the moderate ingestion of alcoholic beverages and higher bone mineral density (v. abstainers). More limited findings provide some evidence for translation of this association into reduced fracture risk, but further studies are required. Here, these data are reviewed and caveats in their assimilation, comparison and interpretation as well as in the use and application of bone health indices are discussed. Whilst it is concluded that evidence is now strong for the moderate alcohol-bone health association, at least in relation to bone mineral density, mechanisms are less clear. Both ethanol and non-ethanol components have been implicated as factors that positively affect bone health in the light of moderate consumption of alcoholic beverages, and four particular areas are discussed. First, recent findings suggest that moderate ethanol consumption acutely inhibits bone resorption, in a non-parathyroid hormone- and non-calcitonin-dependent fashion, which can only partly be attributed to an energy effect. Second, critical review of the literature does not support a role for moderate ethanol consumption affecting oestrogen status and leading to a knock-on effect on bone. Third, Si is present at high levels in certain alcoholic beverages, especially beer, and may have a measurable role in promoting bone formation. Fourth, a large body of work indicates that phytochemicals (e.g. polyphenols) from alcoholic beverages could influence bone health, but human data are lacking. With further work it is hoped to be able to model epidemiological observations and provide a clear pathway between the magnitude of association and the relative contribution of these mechanisms for the major classes of alcoholic beverage.

  1. Bio-ethanol

    DEFF Research Database (Denmark)

    Wenzel, Henrik

    2007-01-01

    , however, shown that by following this path, we will lose more than we gain on both CO2 emission and fossil fuel dependency. Being renewable, CO2 neutral and storable, biomass is a priority resource for fossil fuel substitution in general. Investigations of the magnitude of biomass that is or can be made...... available for energy purposes - be it from waste, agricultural residues or energy crops - show, however, that biomass is very limited compared to the potential use of it. Even in the most optimistic near term scenarios (30 years ahead), the total physically available biomass can at maximum substitute around......, but they do not improve the energy balance enough for bio-ethanol to compete with alternative uses of the biomass. When using biomass to substitute fossil fuels in heat & power production, a close to 100% substitution efficiency is achieved. The best alternative for CO2 reduction and oil saving is, therefore...

  2. Protective effect of quercetin in the regression of ethanol-induced hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Vidhya A

    2009-01-01

    Full Text Available This study examined the protective effects of quercetin on chronic ethanol-induced liver injury. Rats were treated with ethanol at a dose of 4 g/100 g/day for 90 days. After ethanol intoxication, levels of serum amino transferases were significantly elevated. Decreased activity of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase was also observed on ethanol administration. Increased amounts of lipid peroxidation products viz. hydroperoxides, conjugated dienes and malodialdehyde were observed on ethanol intoxication. Ethanol administration resulted in significant decrease in liver glutathione content. After 90 days, the control animals were divided into two groups, the control group and the control+quercetin group. Ethanol-treated group was divided into two groups, abstention group and quercetin-supplemented group. After 30 days, the animals were sacrificed and various biochemical parameters were analyzed. The changes in enzyme activities as well as levels of lipid peroxidation products were reversed to a certain extent by quercetin. Quercetin supplementation resulted in increase of glutathione content to a significant level compared to normal abstention group. Quercetin supplemented group showed a faster recovery than abstention group. This shows the protective effect of quercetin against chronic ethanol induced hepatotoxicity. Histopathological study is also in line with these results.

  3. Administrative Ecology

    Science.gov (United States)

    McGarity, Augustus C., III; Maulding, Wanda

    2007-01-01

    This article discusses how all four facets of administrative ecology help dispel the claims about the "impossibility" of the superintendency. These are personal ecology, professional ecology, organizational ecology, and community ecology. Using today's superintendency as an administrative platform, current literature describes a preponderance of…

  4. Dietary betaine promotes generation of hepatic S-adenosylmethionine and protects the liver from ethanol-induced fatty infiltration.

    Science.gov (United States)

    Barak, A J; Beckenhauer, H C; Junnila, M; Tuma, D J

    1993-06-01

    Previous studies have shown that ethanol feeding to rats alters methionine metabolism by decreasing the activity of methionine synthetase. This is the enzyme that converts homocysteine in the presence of vitamin B12 and N5-methyltetrahydrofolate to methionine. The action of the ethanol results in an increase in the hepatic level of the substrate N5-methyltetrahydrofolate but as an adaptive mechanism, betaine homocysteine methyltransferase, is induced in order to maintain hepatic S-adenosylmethionine at normal levels. Continued ethanol feeding, beyond 2 months, however, produces depressed levels of hepatic S-adenosylmethionine. Because betaine homocysteine methyltransferase is induced in the livers of ethanol-fed rats, this study was conducted to determine what effect the feeding of betaine, a substrate of betaine homocysteine methyltransferase, has on methionine metabolism in control and ethanol-fed animals. Control and ethanol-fed rats were given both betaine-lacking and betaine-containing liquid diets for 4 weeks, and parameters of methionine metabolism were measured. These measurements demonstrated that betaine administration doubled the hepatic levels of S-adenosylmethionine in control animals and increased by 4-fold the levels of hepatic S-adenosylmethionine in the ethanol-fed rats. The ethanol-induced infiltration of triglycerides in the liver was also reduced by the feeding of betaine to the ethanol-fed animals. These results indicate that betaine administration has the capacity to elevate hepatic S-adenosylmethionine and to prevent the ethanol-induced fatty liver.

  5. Acute pancreatitis

    Science.gov (United States)

    ... its blood vessels. This problem is called acute pancreatitis. Acute pancreatitis affects men more often than women. Certain ... pancreatitis; Pancreas - inflammation Images Digestive system Endocrine glands Pancreatitis, acute - CT scan Pancreatitis - series References Forsmark CE. Pancreatitis. ...

  6. Cystitis - acute

    Science.gov (United States)

    Uncomplicated urinary tract infection; UTI - acute cystitis; Acute bladder infection; Acute bacterial cystitis ... cause. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  7. Differential rearing conditions and alcohol-preferring rats: consumption of and operant responding for ethanol.

    Science.gov (United States)

    Deehan, Gerald A; Palmatier, Matthew I; Cain, Mary E; Kiefer, Stephen W

    2011-04-01

    Exposing rats to differential rearing conditions during early postweaning development has been shown to produce changes in a number of behaviors displayed during adulthood. The purpose of the present studies was to investigate whether rearing alcohol-preferring (P) and nonpreferring (NP) rats in an environmental enrichment condition (EC), a social condition (SC), or an impoverished condition (IC) would differentially affect self-administration of 10% ethanol. In Experiment 1, rats were tested for consumption of 10% ethanol in limited- and free-access tests. For Experiment 2, rats were trained to respond in an operant chamber for ethanol and then provided concurrent access to 10% ethanol and water. Each solution was presented in a separate liquid dipper after meeting the schedule of reinforcement on distinct levers. After concurrent access tests, the water lever/dipper was inactivated and a progressive ratio (PR) schedule was initiated. Three successive solutions (10% ethanol, 15% ethanol, and 10% sucrose) were tested under the PR. For P rats, rearing in an EC reduced ethanol consumption, preference, and motivation to obtain ethanol, relative to P rats reared in an IC. Thus, exposure to a novel environment immediately after weaning acted to decrease the reinforcing properties of ethanol in an animal model for alcoholism.

  8. Comparative abuse liability of GHB and ethanol in humans.

    Science.gov (United States)

    Johnson, Matthew W; Griffiths, Roland R

    2013-04-01

    Gamma-hydroxybutyric acid (GHB; sodium oxybate) is approved for narcolepsy symptom treatment, and it is also abused. This study compared the participant-rated, observer-rated effects, motor/cognitive, physiological, and reinforcing effects of GHB and ethanol in participants with histories of sedative (including alcohol) abuse. Fourteen participants lived on a residential unit for ∼1 month. Sessions were conducted Monday through Friday. Measures were taken before and repeatedly up to 24 hours after drug administration. Participants were administered GHB (1, 2, 4, 6, 8, and 10 g/70 kg), ethanol (12, 24, 48, 72, 96, and 120 g/70 kg), or placebo in a double-blind, within-subjects design. For safety, GHB and ethanol were administered in an ascending dose sequence, with placebos and both drugs intermixed across sessions. The sequence for each drug was stopped if significant impairment or intolerable effects occurred. Only 9 and 10 participants received the full dose range for GHB and ethanol, respectively. The highest doses of GHB and ethanol showed onset within 30 minutes, with peak effects at 60 minutes. GHB effects dissipated between 4 and 6 hours, whereas ethanol effects dissipated between 6 and 8 hours. Dose-related effects were observed for both drugs on a variety of measures assessing sedative drug effects, abuse liability, performance impairment, and physiological effects. Within-session measures of abuse liability were similar between the two drugs. However, postsession measures of abuse liability, including a direct preference test between the highest tolerated doses of each drug, suggested somewhat greater abuse liability for GHB, most likely as a result of the delayed aversive ethanol effects (e.g., headache).

  9. Hidratación oral continua o a dosis fraccionadas en niños deshidratados por diarrea aguda Oral rehydration in continuous administration or in fractionated doses in dehydrated children with acute diarrhea

    Directory of Open Access Journals (Sweden)

    Felipe Mota-Hernández

    2002-01-01

    means, standard deviations and medians, according the distribution of simple and relative frequencies. Results. The mean stool output in the AL group was 11.0±7.5 g/kg/h; as compared to 7.1±7.4 in the FD group (p=0.03. ORS intake, rehydration time, and mean diuresis values were similar in both groups (p>0.05. Six patients in the AL group and five in the FD group had high stool output (>10 g/kg/h, that improved after administration of rice starch solution. One patient in the AL group and two in the FD group had persistent vomiting that improved with gastroclisis. No patient required intravenous rehydration. Conclusions. These results suggest that ORS administration ad libitum under supervision, is a technique as safe and effective as the fractionated doses technique, for the treatment of dehydrated children due to acute diarrhea.

  10. 附子不同炮制品灌胃Beagle犬的急性毒性研究%Acute Toxicity Study on Intragastric Administration of Different ProcessedRadix Aconiti Lateralis PraeparataProducts to Beagle Dogs

    Institute of Scientific and Technical Information of China (English)

    宋玉琴; 张雪; 董艳红; 代良萍; 彭成; 谢晓芳

    2015-01-01

    This article was aimed to study the acute toxicities on intragastric administration of differentRadix Aconiti Lateralis Praeparataprocessed products to Beagle dogs. A total of 16 healthy and qualified Beagle dogs were randomly divided into the blank group,Pao-Fu-Pian(PFP) group,Pao-Tian-Xiong(PTX) group andHei-Shun-Pian(HSP) group according to the body weight. The intragastric administration of 4 g crude herb per kg was given. Before medication, 1 h, 24 h, and 3, 7, 14 days after medication, the body weight, food consumption, rectal temperature, electrocardiogram, blood routine and blood biochemistry were measured. The results showed that after medication, all dogs in three experimental groups were depressed. And there were significant differences in the electrolytes of blood. Among them, the HSP group was the most obvious one. The red blood cells, blood sugar and triglycerides of dogs in the PFP group had significant difference. The lymphocytes and blood sugar had significant difference of dogs in the PTX group. However, after the medication of HSP, the lymphocytes of the dogs were decreased significantly. It was concluded that the toxicity of three processed products followed the order of HSP > PFP > PTX.%目的:探讨附子不同炮制品灌胃Beagle犬的急性毒性。方法:取健康、合格Beagle犬16只,按体质量随机分为空白组、刨附片组、炮天雄组和黑顺片组。以4 g生药/kg灌胃给药,实验前及给药后1 h、24 h和第3、7、14天测定体质量、耗食量、肛温、心电图及血常规、血生化。结果:3个实验组Beagle犬在给药后均精神萎靡,血液电解质有显著性差异,其中黑顺片组最明显;刨附片组犬的红细胞、血糖和甘油三酯有显著性差异;炮天雄组犬的淋巴细胞和血糖有显著性差异,而黑顺片给药后犬的淋巴细胞显著降低。结论:3个炮制品毒性大小依次为黑顺片>刨附片>炮天雄。

  11. Chronic ethanol exposure decreases CB1 receptor function at GABAergic synapses in the rat central amygdala.

    Science.gov (United States)

    Varodayan, Florence P; Soni, Neeraj; Bajo, Michal; Luu, George; Madamba, Samuel G; Schweitzer, Paul; Parsons, Loren H; Roberto, Marisa

    2016-07-01

    The endogenous cannabinoids (eCBs) influence the acute response to ethanol and the development of tolerance, dependence and relapse. Chronic alcohol exposure alters eCB levels and Type 1 cannabinoid receptor (CB1 ) expression and function in brain regions associated with addiction. CB1 inhibits GABA release, and GABAergic dysregulation in the central nucleus of the amygdala (CeA) is critical in the transition to alcohol dependence. We investigated possible disruptions in CB1 signaling of rat CeA GABAergic transmission following intermittent ethanol exposure. In the CeA of alcohol-naive rats, CB1 agonist WIN 55,212-2 (WIN) decreased the frequency of spontaneous and miniature GABAA receptor-mediated inhibitory postsynaptic currents (s/mIPSCs). This effect was prevented by CB1 antagonism, but not Type 2 cannabinoid receptor (CB2 ) antagonism. After 2-3 weeks of intermittent ethanol exposure, these WIN inhibitory effects were attenuated, suggesting ethanol-induced impairments in CB1 function. The CB1 antagonist AM251 revealed a tonic eCB/CB1 control of GABAergic transmission in the alcohol-naive CeA that was occluded by calcium chelation in the postsynaptic cell. Chronic ethanol exposure abolished this tonic CB1 influence on mIPSC, but not sIPSC, frequency. Finally, acute ethanol increased CeA GABA release in both naive and ethanol-exposed rats. Although CB1 activation prevented this effect, the AM251- and ethanol-induced GABA release were additive, ruling out a direct participation of CB1 signaling in the ethanol effect. Collectively, these observations demonstrate an important CB1 influence on CeA GABAergic transmission and indicate that the CeA is particularly sensitive to alcohol-induced disruptions of CB1 signaling.

  12. Environmental Releases in the Fuel Ethanol Industry

    Science.gov (United States)

    Corn ethanol is the largest produced alternate biofuel in the United States. More than 13 billion gallons of ethanol were produced in 2010. The projected corn ethanol production is 15 billion gallons by 2015. With increased production of ethanol, the environmental releases from e...

  13. Increased acetylcholine esterase activity produced by the administration of an aqueous extract of the seed kernel of Thevetia peruviana and its role on acute and subchronic intoxication in mice

    Directory of Open Access Journals (Sweden)

    Rubén Marroquín-Segura

    2014-01-01

    Full Text Available Background: The real mechanism for Thevetia peruviana poisoning remains unclear. Cholinergic activity is important for cardiac function regulation, however, the effect of T. peruviana on cholinergic activity is not well-known. Objective: To study the effect of the acute administration of an aqueous extract of the seed kernel of T. peruviana on the acetylcholine esterase (AChE activity in CD1 mice as well its implications in the sub-chronic toxicity of the extract. Materials and Methods: A dose of 100 mg/kg of the extract was administered to CD1 mice and after 7 days, serum was obtained for ceruloplasmin (CP quantitation and liver function tests. Another group of mice received a 50 mg/kg dose of the extract 3 times within 1 h time interval and AChE activity was determined for those animals. Heart tissue histological preparation was obtained from a group of mice that received a daily 50 mg/kg dose of the extract by a 30-days period. Results: CP levels for the treated group were higher than those for the control group (Student′s t-test, P ≤ 0.001. AChE activity in the treated group was significantly higher than the control group (Tukey test, control vs. T. peruviana, P ≤ 0.001. Heart tissue histological preparations showed leukocyte infiltrates and necrotic areas, consistent with infarcts. Conclusion: The increased levels of AChE and the hearth tissue infiltrative lesions induced by the aqueous seed kernel extract of T. peruviana explains in part the poisoning caused by this plant, which can be related to an inflammatory process.

  14. Identification by selective ion monitoring of 1-methyl-1,2,3,4-tetrahydro-beta-carboline in human platelets and plasma after ethanol intake.

    Sc