Anti-inflammatory and antioxidant effects of umbelliferone in chronic alcohol-fed rats

Science.gov (United States)

Sim, Mi-Ok; Lee, Hae-In; Ham, Ju Ri; Seo, Kwon-Il; Kim, Myung-Joo

2015-01-01

BACKGROUND/OBJECTIVES Inflammation is associated with various types of acute and chronic alcohol liver diseases. In this study, we examined whether umbelliferone (7-hydroxycoumarin, UF) ameliorates chronic alcohol-induced liver damage by modulating inflammatory response and the antioxidant system. METHODS Rats were fed a Liber-Decarli liquid diet containing 5% alcohol with or without UF (0.05 g/L) for 8 weeks, while normal rats received an isocaloric carbohydrate liquid diet. RESULTS Chronic alcohol intake significantly increased serum tumor necrosis factor-α (TNF-α) and interleukin 6 levels and decreased interleukin 10 level; however, UF supplementation reversed the cytokines related to liver damage. UF significantly suppressed hepatic lipopolysaccharide binding protein, toll-like receptor 4 (TLR4), nuclear factor kappa B, and TNF-α gene expression increases in response to chronic alcohol intake. Masson's trichrome staining revealed that UF improved mild hepatic fibrosis caused by alcohol, and UF also significantly increased the mRNA expressions and activities of superoxide dismutase and catalase in liver, and thus, decreased lipid peroxide and mitochondrial hydrogen peroxide levels. CONCLUSIONS The findings of this study indicate that UF protects against alcohol-induced liver damage by inhibiting the TLR4 signaling pathway and activating the antioxidant system. PMID:26244074

Organic honey supplementation reverses pesticide-induced genotoxicity by modulating DNA damage response.

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Alleva, Renata; Manzella, Nicola; Gaetani, Simona; Ciarapica, Veronica; Bracci, Massimo; Caboni, Maria Fiorenza; Pasini, Federica; Monaco, Federica; Amati, Monica; Borghi, Battista; Tomasetti, Marco

2016-10-01

Glyphosate (GLY) and organophosphorus insecticides such as chlorpyrifos (CPF) may cause DNA damage and cancer in exposed individuals through mitochondrial dysfunction. Polyphenols ubiquitously present in fruits and vegetables, have been viewed as antioxidant molecules, but also influence mitochondrial homeostasis. Here, honey containing polyphenol compounds was evaluated for its potential protective effect on pesticide-induced genotoxicity. Honey extracts from four floral organic sources were evaluated for their polyphenol content, antioxidant activity, and potential protective effects on pesticide-related mitochondrial destabilization, reactive oxygen and nitrogen species formation, and DNA damage response in human bronchial epithelial and neuronal cells. The protective effect of honey was, then evaluated in a residential population chronically exposed to pesticides. The four honey types showed a different polyphenol profile associated with a different antioxidant power. The pesticide-induced mitochondrial dysfunction parallels ROS formation from mitochondria (mtROS) and consequent DNA damage. Honey extracts efficiently inhibited pesticide-induced mtROS formation, and reduced DNA damage by upregulation of DNA repair through NFR2. Honey supplementation enhanced DNA repair activity in a residential population chronically exposed to pesticides, which resulted in a marked reduction of pesticide-induced DNA lesions. These results provide new insight regarding the effect of honey containing polyphenols on pesticide-induced DNA damage response. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Protective Effects of Korean Red Ginseng against Alcohol-Induced Fatty Liver in Rats

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Hyo Jin Lee

2015-06-01

Full Text Available The present study tested the hypothesis that Korean red ginseng (KRG provides a protective effect against alcoholic fatty liver. Male Sprague-Dawley rats were divided into four groups and fed a modified Lieber-DeCarli diet containing 5% (w/v alcohol or an isocaloric amount of dextrin-maltose for the controls for 6 weeks: normal control (CON, alcohol control (ET, and ET treated with 125 or 250 mg/kg body weight/day of KRG (RGL or RGH, respectively. Compared with the CON group, the ET group exhibited a significant increase in triglycerides, total cholesterol and the presence of lipid droplets in the liver, and a decrease in fat mass, which were all attenuated by KRG supplementation in adose-dependent manner. The mitigation was accompanied by AMP-activated protein kinase (AMPK signaling pathways in the liver and adipose tissue. In addition, suppression in the alcohol-induced changes of adipose adipokine mRNA expression was also observed in KRG supplementation group. These findings suggest that KRG may have the potential to ameliorate alcoholic fatty liver by suppressing inappropriate lysis of adipose tissue and preventing unnecessary de novo lipogenesis in the liver, which are mediated by AMPK signaling pathways. A mechanism for an interplay between the two organs is still needed to be examined with further assays.

Supplemental and highly-elevated tocopherol doses differentially regulate allergic inflammation: reversibility of α-tocopherol and γ-tocopherol's effects

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McCary, Christine A.; Abdala-Valencia, Hiam; Berdnikovs, Sergejs; Cook-Mills, Joan M.

2011-01-01

We have reported that supplemental doses of the α- and γ-tocopherol isoforms of vitamin E decrease and increase, respectively, allergic lung inflammation. We have now assessed whether these effects of tocopherols are reversible. For these studies, mice were treated with antigen and supplemental tocopherols in a first phase of treatment followed by a 4 week clearance phase and then the mice received a second phase of antigen and tocopherol treatments. The pro-inflammatory effects of supplemental levels of γ-tocopherol in phase 1 were only partially reversed by supplemental α-tocopherol in phase 2 but were completely reversed by raising α-tocopherol levels 10-fold in phase 2. When γ-tocopherol levels were increased 10-fold (highly-elevated tocopherol) so that the lung tissue γ-tocopherol levels were equal to the lung tissue levels of supplemental α-tocopherol, γ-tocopherol reduced leukocyte numbers in the lung lavage fluid. In contrast to the lung lavage fluid, highly-elevated levels of γ-tocopherol increased inflammation in the lung tissue. These regulatory effects of highly-elevated tocopherols on tissue inflammation and lung lavage fluid were reversible in a second phase of antigen challenge without tocopherols. In summary, the pro-inflammatory effects of supplemental γ-tocopherol on lung inflammation were partially reversed by supplemental levels of α-tocopherol but were completely reversed by highly-elevated-levels of α-tocopherol. Also, highly-elevated levels of γ-tocopherol were inhibitory and reversible in lung lavage but, importantly, were pro-inflammatory in lung tissue sections. These results have implications for future studies with tocopherols and provide a new context in which to review vitamin E studies in the literature. PMID:21317387

Two weeks taurine supplementation reverses endothelial dysfunction in young male type 1 diabetics.

LENUS (Irish Health Repository)

Moloney, Michael A

2010-10-01

Type 1 diabetics have a well-recognised risk of accelerated cardiovascular disease. Even in the absence of clinical signs there are detectable abnormalities of conduit vessel function. Our group has previously reported reversal of endothelial dysfunction in diabetics with pravastatin. In young asymptomatic smokers, taurine supplementation has a beneficial impact on macrovascular function, assessed by FMD, and shows an up-regulation of nitric oxide from monocyte-endothelial cell interactions. We hypothesise that taurine supplementation reverses early endothelial abnormalities in young male type 1 diabetics, as assessed by applanation tonometry, brachial artery ultrasound and laser Doppler fluximetry. Asymptomatic, male diabetics (n=9) were scanned prior to treatment and then randomised in a double-blind cross-over fashion to receive either 2 weeks placebo or taurine. Control patients (n=10) underwent a baseline scan. Assessed diabetics had detectable, statistically significant abnormalities when compared with controls, in both arterial stiffness (augmentation index) and brachial artery reactivity (FMD). Both of these parameters were returned to control levels with 2 weeks taurine supplementation. In conclusion, 2 weeks taurine supplementation reverses early, detectable conduit vessel abnormalities in young male diabetics. This may have important implications in the long-term treatment of diabetic patients and their subsequent progression towards atherosclerotic disease.

Posterior reversible encephalopathy syndrome in chronic alcoholism with acute psychiatric symptoms.

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Kimura, Ryo; Yanagida, Makoto; Kugo, Aki; Taguchi, Satoki; Matsunaga, Hidenori

2010-01-01

To highlight the association between posterior reversible encephalopathy syndrome (PRES) and chronic alcoholism. We present a case report, a review of the literature and a discussion. We report on the case of a 51-year-old man with chronic alcoholism, who suddenly developed visual disturbance and confusion. Magnetic resonance imaging (MRI) on admission demonstrated abnormal findings. However, clinical symptoms and imaging promptly improved, indicating the diagnosis of PRES. PRES should be considered when making a diagnosis for disturbed consciousness in alcoholic patients. Copyright 2010 Elsevier Inc. All rights reserved.

Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in Mice.

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Hao, Lijun; Xie, Yuxi; Wu, Guikai; Cheng, Aibin; Liu, Xiaogang; Zheng, Rongjuan; Huo, Hong; Zhang, Junwei

2015-01-01

We investigated the effects of Hericium erinaceus (HEM) on liver injury induced by acute alcohol administration in mice. Mice received ethanol (5 g/kg BW) by gavage every 12 hrs for a total of 3 doses. HEM (200 mg/kg BW) was gavage before ethanol administration. Subsequent serum alanine aminotransferase (ALT) level, aspartate aminotransaminase (AST) level, Maleic dialdehyde (MDA) level, hepatic total antioxidant status (TAOS), and activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were determined by ELISA and immunohistochemistry, respectively. HEM administration markedly (P < 0.05) decreased serum ALT, AST, and MDA levels. The hepatic histopathological observations showed that HEM had a relatively significant role in mice model, which had alcoholic liver damage. In conclusion, we observed that HEM (200 mg/kg BW) supplementation could restrain the hepatic damage caused by acute alcohol exposure.

Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in Mice

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Lijun Hao

2015-01-01

Full Text Available We investigated the effects of Hericium erinaceus (HEM on liver injury induced by acute alcohol administration in mice. Mice received ethanol (5 g/kg BW by gavage every 12 hrs for a total of 3 doses. HEM (200 mg/kg BW was gavage before ethanol administration. Subsequent serum alanine aminotransferase (ALT level, aspartate aminotransaminase (AST level, Maleic dialdehyde (MDA level, hepatic total antioxidant status (TAOS, and activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB were determined by ELISA and immunohistochemistry, respectively. HEM administration markedly (P<0.05 decreased serum ALT, AST, and MDA levels. The hepatic histopathological observations showed that HEM had a relatively significant role in mice model, which had alcoholic liver damage. In conclusion, we observed that HEM (200 mg/kg BW supplementation could restrain the hepatic damage caused by acute alcohol exposure.

Reversibility of increased formation of catecholamines in patients with alcoholic liver disease

DEFF Research Database (Denmark)

Parlesak, Alexandr; Reisenauer, C.; Biermann, J.

2004-01-01

BACKGROUND: While chronic alcohol abuse has been shown to be associated with increased production of catecholamines, little is known about the reversibility of this increased sympathetic activity and the influence of severity of alcoholic liver disease (ALD). The aim of the present study...... was to investigate whether the increase in urinary excretion rates and plasma levels of catecholamines in alcohol-abusing patients are reversible during prolonged abstinence, especially with respect to the severity of ALD. METHODS: Urinary excretion rates and plasma levels of noradrenaline (NA), adrenaline (A...... concentrations of NA and A were increased in ALD1 and ALD2 about 2-fold, while those of DA were elevated only moderately compared to HC. During exercise under a load of 100 watts, the increases in plasma levels of NA and A with reference to the resting values were nearly identical in all three groups. Already...

Studies on reversibility of cerebral atrophy in alcoholics by computed tomography

International Nuclear Information System (INIS)

Nakamura, Kiyoshi; Kikuchi, Yoshito; Sanga, Kenji; Nakamura, Kazuyoshi; Kawamura, Toshiaki; Domon, Yuji; Mitamura, Akira; Hayashi, Yu; Ogata, Motoyo.

1987-01-01

Only sparse data exist concerning objectively quantified reversibility of cerebral atrophy (CA) in alcoholics by computed tomography (CT). This study explored reversible CA changes from measurements of the area seen on repeated CT scans, which were acquired over a period of 6 - 191 weeks in 44 alcoholics. In the group of abstinent alcoholics, significant recovery of CA was observed in all 6 regions of interest (ROI) at the second CT scan, as compared with that at the first CT scan. Measurements obtained from CT revealed aggravation of CA in the bilateral anterior horns, right cella media, and frontal subarachnoid space in the group with drinking alcoholics. The rate of recovery was significantly higher with the interval between the first and second CT scans and the duration of abstinence being longer. For the frontal area, it tended to be better when the degree of CA was severer at the first CT scan. There was no significant correlation between the rate of recovery and age or the duration of drinking habit in any of the ROIs. The beginning of CA recovery after abstinence is likely to depend on the brain sites; The cella media seemed to be the first to recover from CA. (Namekawa, K.)

Lactobacillus salivarius reverse diabetes-induced intestinal defense impairment in mice through non-defensin protein.

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Chung, Pei-Hsuan; Wu, Ying-Ying; Chen, Pei-Hsuan; Fung, Chang-Phone; Hsu, Ching-Mei; Chen, Lee-Wei

2016-09-01

Altered intestinal microbiota and subsequent endotoxemia play pathogenic roles in diabetes. We aimed to study the mechanisms of intestinal defense impairment in type 1 diabetes and the effects of Lactobacillus salivarius as well as fructooligosaccharides (FOS) supplementation on diabetes-induced bacterial translocation. Alterations in the enteric microbiome, expression of mucosal antibacterial proteins and bacteria-killing activity of the intestinal mucosa in streptozotocin (STZ)-induced diabetic mice and Ins2(Akita) mice were investigated. The effects of dead L. salivarius (2×10(8)CFU/ml) and FOS (250 mg per day) supplementation for 1 week on endotoxin levels and Klebsiella pneumoniae translocation were also examined. Finally, germ-free mice were cohoused with wild-type or Ins2(Akita) mice for 2 weeks to examine the contribution of microbiota on the antibacterial protein expression. STZ-induced diabetic mice developed intestinal defense impairment as demonstrated by decreased mucosal bacteria-killing activity; reduction of non-defensin family proteins, such as Reg3β, Reg3γ, CRP-ductin and RELMβ, but not the defensin family proteins; and increased bacterial translocation. Intestinal bacteria overgrowth, enteric dysbiosis and increased intestinal bacterial translocation, particularly pathogenic K. pneumoniae in STZ-induced diabetic mice and Ins2(Akita) mice, were noted. Treating diabetic mice with dead L. salivarius or FOS reversed enteric dysbiosis, restored mucosal antibacterial protein and lessened endotoxin levels as well as K. pneumoniae translocation. Moreover, germ-free mice cohoused with wild-type mice demonstrated more intestinal Reg3β and RELMβ expression than those cohoused with Ins2(Akita) mice. These results indicate that hyperglycemia induces enteric dysbiosis, reduction of non-defensin proteins as well as bacteria-killing activity of the intestinal mucosa and intestinal defense impairment. Reversal of enteric dysbiosis with dead L. salivarius or

Combined effect of selenium and ascorbic acid on alcohol induced hyperlipidemia in male guinea pigs.

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Asha, G S; Indira, M

2004-02-01

Alcoholics usually suffer from malnutrition and are especially deficient in micronutrients like vitamin C, selenium and Zn. In the present study, combined effects of selenium and ascorbic acid on alcohol-induced hyperlipidemia were studied in guinea pigs. Four groups of male guinea pigs were maintained for 45 days as follows: control (1 mg ascorbate (AA)/100 g body mass/day), ethanol (900 mg ethanol/100 g body mass + 1 mg AA/100 g body mass/day), selenium+ascorbic acid [(25 mg AA + 0.05 mg Se)/100 g body mass/day], ethanol+selenium+ascorbic acid [(25 mg AA + 0.05 mg Se + 900 mg ethanol)/100 g body mass/day]. Co-administration of selenium and ascorbic acid along with alcohol reduced the concentration of all lipids, as also evidenced from the decreased activities of hydroxymethylglutaryl-CoA reductase and enhanced activities of plasma lecithin cholesterol acyl transferase and lipoprotein lipase. Concentrations of bile acids were increased. We conclude that the supplementation of Se and ascorbic acid reduced alcohol induced hyperlipidemia, by decreased synthesis and increased catabolism.

A critical role of lateral hypothalamus in context-induced relapse to alcohol seeking after punishment-imposed abstinence.

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Marchant, Nathan J; Rabei, Rana; Kaganovsky, Konstantin; Caprioli, Daniele; Bossert, Jennifer M; Bonci, Antonello; Shaham, Yavin

2014-05-28

In human alcoholics, abstinence is often self-imposed, despite alcohol availability, because of the negative consequences of excessive use. During abstinence, relapse is often triggered by exposure to contexts associated with alcohol use. We recently developed a rat model that captures some features of this human condition: exposure to the alcohol self-administration environment (context A), after punishment-imposed suppression of alcohol self-administration in a different environment (context B), provoked renewal of alcohol seeking in alcohol-preferring P rats. The mechanisms underlying context-induced renewal of alcohol seeking after punishment-imposed abstinence are unknown. Here, we studied the role of the lateral hypothalamus (LH) and its forebrain projections in this effect. We first determined the effect of context-induced renewal of alcohol seeking on Fos (a neuronal activity marker) expression in LH. We next determined the effect of LH reversible inactivation by GABAA + GABAB receptor agonists (muscimol + baclofen) on this effect. Finally, we determined neuronal activation in brain areas projecting to LH during context-induced renewal tests by measuring double labeling of the retrograde tracer cholera toxin subunit B (CTb; injected in LH) with Fos. Context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with increased Fos expression in LH. Additionally, renewal was blocked by muscimol + baclofen injections into LH. Finally, double-labeling analysis of CTb + Fos showed that context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with selective activation of accumbens shell neurons projecting to LH. The results demonstrate an important role of LH in renewal of alcohol seeking after punishment-imposed abstinence and suggest a role of accumbens shell projections to LH in this form of relapse. Copyright © 2014 the authors 0270-6474/14/347447-11$15.00/0.

Curcumin confers neuroprotection against alcohol-induced hippocampal neurodegeneration via CREB-BDNF pathway in rats.

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Motaghinejad, Majid; Motevalian, Manijeh; Fatima, Sulail; Hashemi, Hajar; Gholami, Mina

2017-03-01

Alcohol abuse causes severe damage to the brain neurons. Studies have reported the neuroprotective effects of curcumin against alcohol-induced neurodegeneration. However, the precise mechanism of action remains unclear. Seventy rats were equally divided into 7 groups (10 rats per group). Group 1 received normal saline (0.7ml/rat) and group 2 received alcohol (2g/kg/day) for 21days. Groups 3, 4, 5 and 6 concurrently received alcohol (2g/kg/day) and curcumin (10, 20, 40 and 60mg/kg, respectively) for 21days. Animals in group 7 self- administered alcohol for 21days. Group 8 treated with curcumin (60mg/kg, i.p.) alone for 21days. Open Field Test (OFT) was used to investigate motor activity in rats. Hippocampal oxidative, antioxidative and inflammatory factors were evaluated. Furthermore, brain cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and brain derived neurotrophic factor (BDNF) levels were studied at gene level by reverse transcriptase polymerase chain reaction (RT-PCR). In addition, protein expression for BDNF, CREB, phosphorylated CREB (CREB-P), Bax and Bcl-2 was determined by western blotting. Voluntary and involuntary administration of alcohol altered motor activity in OFT, and curcumin treatment inhibited this alcohol-induced motor disturbance. Also, alcohol administration augmented lipid peroxidation, mitochondrial oxidized glutathione (GSSG), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and Bax levels in isolated hippocampal tissues. Furthermore, alcohol-induced significant reduction were observed in reduced form of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities and CREB, BDNF and Bcl-2 levels. Also curcumin alone did not change the behavior and biochemical and molecular parameters. Curcumin can act as a neuroprotective agent against neurodegenerative effects of alcohol abuse, probably via activation of CREB-BDNF signaling pathway

Free radical scavenging reverses fructose-induced salt-sensitive hypertension

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Zenner ZP

2017-12-01

Full Text Available Zachary P Zenner, Kevin L Gordish, William H Beierwaltes Department of Internal Medicine, Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, MI, USA Abstract: We have previously reported that a moderate dietary supplementation of 20% fructose but not glucose leads to a salt-sensitive hypertension related to increased proximal sodium–hydrogen exchanger activity and increased renal sodium retention. We also found that while high salt increased renal nitric oxide formation, this was retarded in the presence of fructose intake. We hypothesized that at least part of the pathway leading to fructose-induced salt-sensitive hypertension could be due to fructose-induced formation of reactive oxygen species and inappropriate stimulation of renin secretion, all of which would contribute to an increase in blood pressure. We found that both 20% fructose intake and a high-salt diet stimulated 8-isoprostane excretion. The superoxide dismutase (SOD mimetic tempol significantly reduced this elevated excretion. Next, we placed rats on a high-salt diet (4% for 1 week in combination with normal rat chow or 20% fructose with or without chronic tempol administration. A fructose plus high-salt diet induced a rapid increase (15 mmHg in systolic blood pressure and reversed high salt suppression of plasma renin activity. Tempol treatment reversed the pressor response and restored high salt suppression of renin. We conclude that fructose-induced salt-sensitive hypertension is driven by increased renal reactive oxygen species formation associated with salt retention and an enhanced renin–angiotensin system. Keywords: reactive oxygen species, tempol, sodium, renin, oxidative stress

Reverse osmosis influence over the content of metals and organic acids in low alcoholic beverages

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Andrieş Mitică Tiberiu

2017-01-01

Full Text Available Wine is defined as an alcoholic beverage resulted from fermentation of grape must, having ethanol content higher than 8.5% (v/v. Wine consumption has health benefits related to the high concentration of polyphenolic compounds with antioxidant activity and cardiovascular protection effects. However, the alcohol content restricts wine consumption, but wines with low-alcohol content can be obtained with the help of the dealcoholisation process, after it was produced through alcoholic fermentation. The purpose of this work is to evaluate the organic acid concentration, metal content and other physical-chemical parameters of low alcoholic beverages obtained from grape must by a process which involves reverse osmosis, mixing in a variable ratio the permeate and concentrate and then fermentation. For the experiments, a Muscat Ottonel grape must from Iaşi vineyard was used. There were ten variants of beverages (wines with low alcoholic concentration, by mixing known quantities of the two phases resulting from the reverse osmosis process. These beverages (wines had an alcoholic concentration starting from 2.5% (v/v in the first variant, up to 7% (v/v in the tenth variant. Alcoholic concentration varies for each variant by 0.5% (v/v. After fermentation in 50 L stainless steel tanks, the samples were filtered with 0.45μm sterile membrane and bottled in 0.75 L glass bottles. After 2 months of storage at constant temperature, the beverage samples were analyzed to determine the metal content (AAS method, organic acids concentration (HPLC method, and other physical-chemical characteristics (OIV standard methods. The results obtained indicate that the very complex physical-chemical composition of the low alcoholic beverages analyzed is influenced by the specific chemical composition of a given grape must, as well as by the use of products obtained from reverse osmosis.

Dietary l-threonine supplementation attenuates lipopolysaccharide-induced inflammatory responses and intestinal barrier damage of broiler chickens at an early age.

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Chen, Yueping; Zhang, Hao; Cheng, Yefei; Li, Yue; Wen, Chao; Zhou, Yanmin

2018-06-01

This study was conducted to investigate the protective effects of l-threonine (l-Thr) supplementation on growth performance, inflammatory responses and intestinal barrier function of young broilers challenged with lipopolysaccharide (LPS). A total of 144 1-d-old male chicks were allocated to one of three treatments: non-challenged broilers fed a basal diet (control group), LPS-challenged broilers fed a basal diet without l-Thr supplementation and LPS-challenged broilers fed a basal diet supplemented with 3·0 g/kg l-Thr. LPS challenge was performed intraperitoneally at 17, 19 and 21 d of age, whereas the control group received physiological saline injection. Compared with the control group, LPS challenge impaired growth performance of broilers, and l-Thr administration reversed LPS-induced increase in feed/gain ratio. LPS challenge elevated blood cell counts related to inflammation, and pro-inflammatory cytokine concentrations in serum (IL-1β and TNF-α), spleen (IL-1β and TNF-α) and intestinal mucosa (jejunal interferon-γ (IFN-γ) and ileal IL-1β). The concentrations of intestinal cytokines in LPS-challenged broilers were reduced by l-Thr supplementation. LPS administration increased circulating d-lactic acid concentration, whereas it reduced villus height, the ratio between villus height and crypt depth and goblet density in both jejunum and ileum. LPS-induced decreases in jejunal villus height, intestinal villus height:crypt depth ratio and ileal goblet cell density were reversed with l-Thr supplementation. Similarly, LPS-induced alterations in the intestinal mRNA abundances of genes related to intestinal inflammation and barrier function (jejunal toll-like receptor 4, IFN- γ and claudin-3, and ileal IL-1 β and zonula occludens-1) were normalised with l-Thr administration. It can be concluded that l-Thr supplementation could attenuate LPS-induced inflammatory responses and intestinal barrier damage of young broilers.

Alcohol-induced histone acetylation reveals a gene network involved in alcohol tolerance.

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Alfredo Ghezzi

Full Text Available Sustained or repeated exposure to sedating drugs, such as alcohol, triggers homeostatic adaptations in the brain that lead to the development of drug tolerance and dependence. These adaptations involve long-term changes in the transcription of drug-responsive genes as well as an epigenetic restructuring of chromosomal regions that is thought to signal and maintain the altered transcriptional state. Alcohol-induced epigenetic changes have been shown to be important in the long-term adaptation that leads to alcohol tolerance and dependence endophenotypes. A major constraint impeding progress is that alcohol produces a surfeit of changes in gene expression, most of which may not make any meaningful contribution to the ethanol response under study. Here we used a novel genomic epigenetic approach to find genes relevant for functional alcohol tolerance by exploiting the commonalities of two chemically distinct alcohols. In Drosophila melanogaster, ethanol and benzyl alcohol induce mutual cross-tolerance, indicating that they share a common mechanism for producing tolerance. We surveyed the genome-wide changes in histone acetylation that occur in response to these drugs. Each drug induces modifications in a large number of genes. The genes that respond similarly to either treatment, however, represent a subgroup enriched for genes important for the common tolerance response. Genes were functionally tested for behavioral tolerance to the sedative effects of ethanol and benzyl alcohol using mutant and inducible RNAi stocks. We identified a network of genes that are essential for the development of tolerance to sedation by alcohol.

Therapeutic role of ursolic acid on ameliorating hepatic steatosis and improving metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease rats.

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Li, Songtao; Liao, Xilu; Meng, Fanyu; Wang, Yemei; Sun, Zongxiang; Guo, Fuchuan; Li, Xiaoxia; Meng, Man; Li, Ying; Sun, Changhao

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases around the world, and is closely associated with obesity, diabetes, and insulin resistance. Ursolic acid (UA), an ubiquitous triterpenoid with multifold biological roles, is distributed in various plants. This study was conducted to investigate the therapeutic effect and potential mechanisms of UA against hepatic steatosis in a high-fat diet (HFD)-induced obese non-alcoholic fatty liver disease (NAFLD) rat model. Obese NAFLD model was established in Sprague-Dawley rats by 8-week HFD feeding. Therapeutic role of UA was evaluated using 0.125%, 0.25%, 0.5% UA-supplemented diet for another 6 weeks. The results from both morphologic and histological detections indicated that UA significantly reversed HFD-induced hepatic steatosis and liver injury. Besides, hepatic peroxisome proliferator-activated receptor (PPAR)-α was markedly up-regulated at both mRNA and protein levels by UA. Knocking down PPAR-α significantly inhibited the anti-steatosis role of UA in vitro. HFD-induced adverse changes in the key genes, which participated in hepatic lipid metabolism, were also alleviated by UA treatment. Furthermore, UA significantly ameliorated HFD-induced metabolic disorders, including insulin resistance, inflammation and oxidative stress. These results demonstrated that UA effectively ameliorated HFD-induced hepatic steatosis through a PPAR-α involved pathway, via improving key enzymes in the controlling of lipids metabolism. The metabolic disorders were accordingly improved with the decrease of hepatic steatosis. Thereby, UA could be a promising candidate for the treatment of NAFLD.

Therapeutic role of ursolic acid on ameliorating hepatic steatosis and improving metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease rats.

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Songtao Li

Full Text Available BACKGROUND: Non-alcoholic fatty liver disease (NAFLD is one of the most prevalent liver diseases around the world, and is closely associated with obesity, diabetes, and insulin resistance. Ursolic acid (UA, an ubiquitous triterpenoid with multifold biological roles, is distributed in various plants. This study was conducted to investigate the therapeutic effect and potential mechanisms of UA against hepatic steatosis in a high-fat diet (HFD-induced obese non-alcoholic fatty liver disease (NAFLD rat model. METHODOLOGY/PRINCIPAL FINDINGS: Obese NAFLD model was established in Sprague-Dawley rats by 8-week HFD feeding. Therapeutic role of UA was evaluated using 0.125%, 0.25%, 0.5% UA-supplemented diet for another 6 weeks. The results from both morphologic and histological detections indicated that UA significantly reversed HFD-induced hepatic steatosis and liver injury. Besides, hepatic peroxisome proliferator-activated receptor (PPAR-α was markedly up-regulated at both mRNA and protein levels by UA. Knocking down PPAR-α significantly inhibited the anti-steatosis role of UA in vitro. HFD-induced adverse changes in the key genes, which participated in hepatic lipid metabolism, were also alleviated by UA treatment. Furthermore, UA significantly ameliorated HFD-induced metabolic disorders, including insulin resistance, inflammation and oxidative stress. CONCLUSIONS/SIGNIFICANCE: These results demonstrated that UA effectively ameliorated HFD-induced hepatic steatosis through a PPAR-α involved pathway, via improving key enzymes in the controlling of lipids metabolism. The metabolic disorders were accordingly improved with the decrease of hepatic steatosis. Thereby, UA could be a promising candidate for the treatment of NAFLD.

Protective influences of N-acetylcysteine against alcohol abstinence-induced depression by regulating biochemical and GRIN2A, GRIN2B gene expression of NMDA receptor signaling pathway in rats.

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Yawalkar, Rutuja; Changotra, Harish; Gupta, Girdhari Lal

2018-04-25

Evidences have indicated a high degree of comorbidity of alcoholism and depression. N-acetylcysteine (NAC) has shown its clinical efficiency in the treatment of several psychiatric disorders and is identified as a multi-target acting drug. The ability of NAC to prevent alcohol abstinence-induced depression-like effects and underlying mechanism(s) have not been adequately addressed. This study was aimed to investigate the beneficial effects of NAC in the alcohol abstinence-induced depression developed following long-term voluntary alcohol intake. For evaluation of the effects of NAC, Sprague-Dawley rats were enabled to voluntary drinking of 4.5%, 7.5% and 9% v/v alcohol for fifteen days. NAC (25, 50, and 100 mg/kg) and fluoxetine (5 mg/kg) were injected intraperitoneally for three consecutive days during the alcohol abstinence period on the days 16, 17, 18. The behavioral studies were conducted employing forced swim test (FST), and tail suspension test (TST) on day 18 to determine the effects of N-acetylcysteine and fluoxetine in the ethanol withdrawal induced-depression. Blood alcohol concentration, alcohol biomarkers like SGPT, SGOT, ALP, GGT, and MCV were estimated by using commercially available kits. Serotonin concentrations were measured in the plasma, hippocampus and pre-frontal cortex using the rat ELISA kit. The expression of GRIN1, GRIN2A, GRIN2B genes for the N-methyl d-aspartate receptors (NMDAR) subunits in the hippocampus and the prefrontal cortex were also examined by reverse-transcription quantitative polymerase chain reaction. The results revealed that alcohol abstinence group depicted increased immobility time in FST and TST. Further, NAC exerted significant protective effect at the doses 50 mg/kg and 100 mg/kg, but 25 mg/kg showed insignificant protection against alcohol abstinence-induced depression. The increased level of biochemical parameters following ethanol abstinence were also reversed by NAC at the dose of 100 mg/kg. The

No association between alcohol supplementation and autoantibodies to DNA damage in postmenopausal women in a controlled feeding study.

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Mahabir, S; Baer, D J; Johnson, L L; Frenkel, K; Dorgan, J F; Cambell, W; Hartman, T J; Clevidence, B; Albanes, D; Judd, J T; Taylor, P R

2005-08-01

Alcohol consumption is linked to increased breast cancer risk. Since oestrogens increase breast cancer risk, possibly through oxidative damage, and we have shown that alcohol consumption increases serum oestrogens, we tested whether moderate alcohol supplementation increased oxidative DNA damage among healthy postmenopausal women not on hormone replacement therapy in a randomized controlled crossover study. We used serum 5-hydroxymethyl-2-deoxyuridine (5-HMdU) autoantibodies (aAbs) as a marker of oxidative DNA damage. The results showed no evidence for increased or decreased levels of oxidative DNA damage among women who consumed 15 g or 30 g alcohol per day for 8 weeks compared with women in the 0 g alcohol group. We conclude that among healthy women, it is possible that an 8-week trial of moderate alcohol supplementation might be too short to make enough 5-HMdU aAbs to compare differences by alcohol dose. In future studies, a panel of biomarkers for DNA damage should be used.

Resveratrol reverses morphine-induced neuroinflammation in morphine-tolerant rats by reversal HDAC1 expression

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Ru-Yin Tsai

2016-06-01

Conclusion: Resveratrol restores the antinociceptive effect of morphine by reversing morphine infusion-induced spinal cord neuroinflammation and increase in TNFR1 expression. The reversal of the morphine-induced increase in TNFR1 expression by resveratrol is partially due to reversal of the morphine infusion-induced increase in HDAC1 expression. Resveratrol pretreatment can be used as an adjuvant in clinical pain management for patients who need long-term morphine treatment or with neuropathic pain.

Effects of L-glutamine supplementation on maternal and fetal hemodynamics in gestating ewes exposed to alcohol

OpenAIRE

Sawant, Onkar B.; Ramadoss, Jayanth; Hankins, Gary D.; Wu, Guoyao; Washburn, Shannon E.

2014-01-01

Not much is known about effects of gestational alcohol exposure on maternal and fetal cardiovascular adaptations. This study determined whether maternal binge alcohol exposure and L-glutamine supplementation could affect maternal-fetal hemodynamics and fetal regional brain blood flow during the brain growth spurt period. Pregnant sheep were randomly assigned to one of four groups: saline control, alcohol (1.75–2.5 g/kg body weight), glutamine (100 mg/kg body weight) or alcohol + glutamine. A ...

Failure of carnitine in improving hepatic nitrogen content in alcoholic and non-alcoholic malnourished rats

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Luciana P. Rodrigues

2010-01-01

Full Text Available AIMS: To investigate the effect of carnitine supplementation on alcoholic malnourished rats' hepatic nitrogen content. METHODS: Malnourished rats, on 50% protein-calorie restriction with free access to water (malnutrition group and malnourished rats under the same conditions with free access to a 20% alcohol/water solution (alcohol group were studied. After the undernourishment period (4 weeks with or without alcohol, both groups were randomly divided into two subgroups, one of them nutritionally recovered for 28 days with free access to a normal diet and water (recovery groups and the other re-fed with free access to diet and water plus carnitine (0.1 g/g body weight/day by gavage (carnitine groups. No alcohol intake was allowed during the recovery period. RESULTS: The results showed: i no difference between the alcohol/no alcohol groups, with or without carnitine, regarding body weight gain, diet consumption, urinary nitrogen excretion, plasma free fatty acids, lysine, methionine, and glycine. ii Liver nitrogen content was highest in the carnitine recovery non-alcoholic group (from 1.7 to 3.3 g/100 g, P.05 was highest in the alcoholic animals. CONCLUSION: Carnitine supplementation did not induce better nutritional recovery.

Gut microbiota modulates alcohol withdrawal-induced anxiety in mice.

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Xiao, Hui-Wen; Ge, Chang; Feng, Guo-Xing; Li, Yuan; Luo, Dan; Dong, Jia-Li; Li, Hang; Wang, Haichao; Cui, Ming; Fan, Sai-Jun

2018-05-01

Excessive alcohol consumption remains a major public health problem that affects millions of people worldwide. Accumulative experimental evidence has suggested an important involvement of gut microbiota in the modulation of host's immunological and neurological functions. However, it is previously unknown whether enteric microbiota is implicated in the formation of alcohol withdrawal-induced anxiety. Using a murine model of chronic alcoholism and withdrawal, we examined the impact of alcohol consumption on the possible alterations of gut microbiota as well as alcohol withdrawal-induced anxiety and behavior changes. The 16S rRNA sequencing revealed that alcohol consumption did not alter the abundance of bacteria, but markedly changed the composition of gut microbiota. Moreover, the transplantation of enteric microbes from alcohol-fed mice to normal healthy controls remarkably shaped the composition of gut bacteria, and elicited behavioral signs of alcohol withdrawal-induced anxiety. Using quantitative real-time polymerase chain reaction, we further confirmed that the expression of genes implicated in alcohol addiction, BDNF, CRHR1 and OPRM1, was also altered by transplantation of gut microbes from alcohol-exposed donors. Collectively, our findings suggested a possibility that the alterations of gut microbiota composition might contribute to the development of alcohol withdrawal-induced anxiety, and reveal potentially new etiologies for treating alcohol addiction. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

Effect of specific amino acids on hepatic lipid metabolism in fructose-induced non-alcoholic fatty liver disease.

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Jegatheesan, Prasanthi; Beutheu, Stéphanie; Ventura, Gabrielle; Sarfati, Gilles; Nubret, Esther; Kapel, Nathalie; Waligora-Dupriet, Anne-Judith; Bergheim, Ina; Cynober, Luc; De-Bandt, Jean-Pascal

2016-02-01

Fructose diets have been shown to induce insulin resistance and to alter liver metabolism and gut barrier function, ultimately leading to non-alcoholic fatty liver disease. Citrulline, Glutamine and Arginine may improve insulin sensitivity and have beneficial effects on gut trophicity. Our aim was to evaluate their effects on liver and gut functions in a rat model of fructose-induced non-alcoholic fatty liver disease. Male Sprague-Dawley rats (n = 58) received a 4-week fructose (60%) diet or standard chow with or without Citrulline (0.15 g/d) or an isomolar amount of Arginine or Glutamine. All diets were made isonitrogenous by addition of non-essential amino acids. At week 4, nutritional and metabolic status (plasma glucose, insulin, cholesterol, triglycerides and amino acids, net intestinal absorption) was determined; steatosis (hepatic triglycerides content, histological examination) and hepatic function (plasma aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin) were assessed; and gut barrier integrity (myeloperoxidase activity, portal endotoxemia, tight junction protein expression and localization) and intestinal and hepatic inflammation were evaluated. We also assessed diets effects on caecal microbiota. In these experimental isonitrogenous fructose diet conditions, fructose led to steatosis with dyslipidemia but without altering glucose homeostasis, liver function or gut permeability. Fructose significantly decreased Bifidobacterium and Lactobacillus and tended to increase endotoxemia. Arginine and Glutamine supplements were ineffective but Citrulline supplementation prevented hypertriglyceridemia and attenuated liver fat accumulation. While nitrogen supply alone can attenuate fructose-induced non-alcoholic fatty liver disease, Citrulline appears to act directly on hepatic lipid metabolism by partially preventing hypertriglyceridemia and steatosis. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition

Role of microRNAs in Alcohol-Induced Multi-Organ Injury

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Sathish Kumar Natarajan

2015-11-01

Full Text Available Alcohol consumption and its abuse is a major health problem resulting in significant healthcare cost in the United States. Chronic alcoholism results in damage to most of the vital organs in the human body. Among the alcohol-induced injuries, alcoholic liver disease is one of the most prevalent in the United States. Remarkably, ethanol alters expression of a wide variety of microRNAs that can regulate alcohol-induced complications or dysfunctions. In this review, we will discuss the role of microRNAs in alcoholic pancreatitis, alcohol-induced liver damage, intestinal epithelial barrier dysfunction, and brain damage including altered hippocampus structure and function, and neuronal loss, alcoholic cardiomyopathy, and muscle damage. Further, we have reviewed the role of altered microRNAs in the circulation, teratogenic effects of alcohol, and during maternal or paternal alcohol consumption.

Effects of alcohol-induced working memory decline on alcohol consumption and adverse consequences of use.

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Lechner, William V; Day, Anne M; Metrik, Jane; Leventhal, Adam M; Kahler, Christopher W

2016-01-01

Alcohol use appears to decrease executive function acutely in a dose-dependent manner, and lower baseline executive function appears to contribute to problematic alcohol use. However, no studies, to our knowledge, have examined the relationship between individual differences in working memory (a subcomponent of executive function) after alcohol consumption and drinking behaviors and consequences. The current study assessed the relationship between drinking behavior, alcohol-related consequences, and alcohol-induced changes in working memory (as assessed by Trail Making Test-B). Participants recruited from the community (n = 41), 57.3 % male, mean age 39.2, took part in a three-session, within-subjects, repeated-measures design. Participants were administered a placebo, 0.4 g/kg, or 0.8 g/kg dose of alcohol. Working memory, past 30-day alcohol consumption, and consequences of alcohol use were measured at baseline; working memory was measured again after each beverage administration. Poorer working memory after alcohol administration (controlling for baseline working memory) was significantly associated with a greater number of drinks consumed per drinking day. Additionally, we observed a significant indirect relationship between the degree of alcohol-induced working memory decline and adverse consequences of alcohol use, which was mediated through greater average drinks per drinking day. It is possible that greater individual susceptibility to alcohol-induced working memory decline may limit one's ability to moderate alcohol consumption as evidenced by greater drinks per drinking day and that this results in more adverse consequences of alcohol use.

Acute alcohol-induced liver injury

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Gavin Edward Arteel

2012-06-01

Full Text Available Alcohol consumption is customary in most cultures and alcohol abuse is common worldwide. For example, more than 50% of Americans consume alcohol, with an estimated 23.1% of Americans participating in heavy and/or binge drinking at least once a month. A safe and effective therapy for alcoholic liver disease (ALD in humans is still elusive, despite significant advances in our understanding of how the disease is initiated and progresses. It is now clear that acute alcohol binges not only can be acutely toxic to the liver, but also can contribute to the chronicity of ALD. Potential mechanisms by which acute alcohol causes damage include steatosis, dysregulated immunity and inflammation and altered gut permeability. Recent interest in modeling acute alcohol exposure has yielded new insights into potential mechanisms of acute injury, that also may well be relevant for chronic ALD. Recent work by this group on the role of PAI-1 and fibrin metabolism in mediating acute alcohol-induced liver damage serve as an example of possible new targets that may be useful for alcohol abuse, be it acute or chronic.

Maternal PUFA omega-3 supplementation prevents hyperoxia-induced pulmonary hypertension in the offspring.

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Zhong, Ying; Catheline, Daniel; Houeijeh, Ali; Sharma, Dyuti; Du, Li-Zhong; Besengez, Capucine; Deruelle, Philippe; Legrand, Philippe; Storme, Laurent

2018-03-29

Pulmonary hypertension (PH) and right ventricular hypertrophy (RVH) affect 16-25% of premature infants with bronchopulmonary dysplasia (BPD), contributing significantly to perinatal morbidity and mortality. Polyunsaturated fatty acids ω-3 (PUFA ω-3) can improve vascular remodeling, angiogenesis, and inflammation under pathophysiological conditions. However, the effects of PUFA ω-3 supplementation in BPD-associated PH are unknown. The present study aimed to evaluate the effects of PUFA ω-3 on pulmonary vascular remodeling, angiogenesis, and inflammatory response in a hyperoxia-induced rat model of PH. From embryonic day 15, pregnant Spague-Dawley rats were supplemented daily with PUFA ω-3, PUFA ω-6, or normal saline (0.2 ml/day). After birth, pups were pooled, assigned as 12 per litter, and randomly to either in air or continuous oxygen exposure (FiO2 = 85%) for 20 days, then sacrificed for pulmonary hemodynamic and morphometric analysis. We found that PUFA ω-3 supplementation improved survival, decreased right ventricular systolic pressure and RVH caused by hyperoxia, and significantly improved alveolarization, vascular remodeling, and vascular density. PUFA ω-3 supplementation produced a higher level of total ω-3 in lung tissue and breast milk, and was found reversing the reduced levels of VEGFA, VEGFR-2, ANGPT-1, TIE-2, eNOS, and NO concentrations in lung tissue, and the increased ANGPT-2 levels in hyperoxia-exposed rats. The beneficial effects of PUFA ω-3 in improving lung injuries were also associated with an inhibition of leukocyte infiltration, and reduced expression of proinflammatory cytokines IL-1β, IL-6 and TNF-α. These data indicated that maternal PUFA ω-3 supplementation strategies could effectively protect against infant PH induced by hyperoxia.

Persistent fibrosis in the liver of choline-deficient and iron-supplemented L-amino acid-defined diet-induced nonalcoholic steatohepatitis rat due to continuing oxidative stress after choline supplementation

International Nuclear Information System (INIS)

Takeuchi-Yorimoto, Ayano; Noto, Takahisa; Yamada, Atsushi; Miyamae, Yoichi; Oishi, Yuji; Matsumoto, Masahiro

2013-01-01

Nonalcoholic steatohepatitis (NASH) is characterized by combined pathology of steatosis, lobular inflammation, fibrosis, and hepatocellular degeneration, with systemic symptoms of diabetes or hyperlipidemia, all in the absence of alcohol abuse. Given the therapeutic importance and conflicting findings regarding the potential for healing the histopathologic features of NASH in humans, particularly fibrosis, we investigated the reversibility of NASH-related findings in Wistar rats fed a choline-deficient and iron-supplemented L-amino acid-defined (CDAA) diet for 12 weeks, with a recovery period of 7 weeks, during which the diets were switched to a choline-sufficient and iron-supplemented L-amino acid-defined (CSAA) one. Analysis showed that steatosis and inflammation were significantly resolved by the end of the recovery period, along with decreases in AST and ALT activities within 4 weeks. In contrast, fibrosis remained even after the recovery period, to an extent similar to that in continuously CDAA-fed animals. Real-time reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemical investigations revealed that expression of some factors indicating oxidative stress (CYP2E1, 4-HNE, and iNOS) were elevated, whereas catalase and SOD1 were decreased, and a hypoxic state and CD34-positive neovascularization were evident even after the recovery period, although the fibrogenesis pathway by activated α-SMA-positive hepatic stellate cells via TGF-β and TIMPs decreased to the CSAA group level. In conclusion, persistent fibrosis was noted after the recovery period of 7 weeks, possibly due to sustained hypoxia and oxidative stress supposedly caused by capillarization. Otherwise, histopathological features of steatosis and inflammation, as well as serum AST and ALT activities, were recovered. - Highlights: ► NASH-like liver lesions are induced in rats by feeding a CDAA diet. ► Steatosis and lobular inflammation are resolved after switching to a

Persistent fibrosis in the liver of choline-deficient and iron-supplemented L-amino acid-defined diet-induced nonalcoholic steatohepatitis rat due to continuing oxidative stress after choline supplementation

Energy Technology Data Exchange (ETDEWEB)

Takeuchi-Yorimoto, Ayano, E-mail: ayano.takeuchi@astellas.com [Drug Safety Research Labs, Astellas Pharma Inc., Osaka 532-8514 (Japan); Noto, Takahisa [Drug Safety Research Labs, Astellas Pharma Inc., Osaka 532-8514 (Japan); Yamada, Atsushi [Drug Safety Research Division, Astellas Research Technologies Co., Ltd., Osaka 532-8514 (Japan); Miyamae, Yoichi; Oishi, Yuji; Matsumoto, Masahiro [Drug Safety Research Labs, Astellas Pharma Inc., Osaka 532-8514 (Japan)

2013-05-01

Nonalcoholic steatohepatitis (NASH) is characterized by combined pathology of steatosis, lobular inflammation, fibrosis, and hepatocellular degeneration, with systemic symptoms of diabetes or hyperlipidemia, all in the absence of alcohol abuse. Given the therapeutic importance and conflicting findings regarding the potential for healing the histopathologic features of NASH in humans, particularly fibrosis, we investigated the reversibility of NASH-related findings in Wistar rats fed a choline-deficient and iron-supplemented L-amino acid-defined (CDAA) diet for 12 weeks, with a recovery period of 7 weeks, during which the diets were switched to a choline-sufficient and iron-supplemented L-amino acid-defined (CSAA) one. Analysis showed that steatosis and inflammation were significantly resolved by the end of the recovery period, along with decreases in AST and ALT activities within 4 weeks. In contrast, fibrosis remained even after the recovery period, to an extent similar to that in continuously CDAA-fed animals. Real-time reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemical investigations revealed that expression of some factors indicating oxidative stress (CYP2E1, 4-HNE, and iNOS) were elevated, whereas catalase and SOD1 were decreased, and a hypoxic state and CD34-positive neovascularization were evident even after the recovery period, although the fibrogenesis pathway by activated α-SMA-positive hepatic stellate cells via TGF-β and TIMPs decreased to the CSAA group level. In conclusion, persistent fibrosis was noted after the recovery period of 7 weeks, possibly due to sustained hypoxia and oxidative stress supposedly caused by capillarization. Otherwise, histopathological features of steatosis and inflammation, as well as serum AST and ALT activities, were recovered. - Highlights: ► NASH-like liver lesions are induced in rats by feeding a CDAA diet. ► Steatosis and lobular inflammation are resolved after switching to a

Acute liver injury induced by weight-loss herbal supplements.

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Chen, Gary C; Ramanathan, Vivek S; Law, David; Funchain, Pauline; Chen, George C; French, Samuel; Shlopov, Boris; Eysselein, Viktor; Chung, David; Reicher, Sonya; Pham, Binh V

2010-11-27

We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients demonstrated findings consistent with drug-induced acute liver injury. To our knowledge, we are the first institute to report acute liver injury from both of these two types of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a cautious approach when consuming herbal supplements for the purpose of weight loss.

The safe operation zone of the spark ignition engine working with dual renewable supplemented fuels (hydrogen+ethyl alcohol)

Energy Technology Data Exchange (ETDEWEB)

Al-Baghdadi, Maher Abdul-Resul Sadiq [Babylon Univ., Dept. of Mechanical Engineering, Babylon (Iraq)

2001-04-01

The effect of the amount of hydrogen/ethyl alcohol addition on the performance and pollutant emission of a four-stroke spark ignition engine has been studied. The results of the study show that all engine performance parameters have been improved when operating the gasoline spark ignition engine with dual addition of hydrogen and ethyl alcohol. The important improvements of alcohol addition are to reduce the NOx emission while increasing the higher useful compression ratio and output power of hydrogen-supplemented engine. An equation has been derived from experimental data to specify the least quantity of ethyl alcohol blended with gasoline and satisfying constant NOx emission when hydrogen is added. A chart limiting the safe operation zone of the engine fueled with dual renewable supplemented fuel, (hydrogen and ethyl alcohol) has been produced. The safe zone provides lower NOx and CO emission, lower s.f.c. and higher brake power compared to an equivalent gasoline engine. When ethyl alcohol is increased over 30%, it causes unstable engine operation which can be related to the fact that the fuel is not vaporized, and this causes a reduction in both brake power and efficiency. (Author)

Chronic ethanol intake induces partial microglial activation that is not reversed by long-term ethanol withdrawal in the rat hippocampal formation.

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Cruz, Catarina; Meireles, Manuela; Silva, Susana M

2017-05-01

Neuroinflammation has been implicated in the pathogenesis of several disorders. Activation of microglia leads to the release of pro-inflammatory mediators and microglial-mediated neuroinflammation has been proposed as one of the alcohol-induced neuropathological mechanisms. The present study aimed to examine the effect of chronic ethanol exposure and long-term withdrawal on microglial activation and neuroinflammation in the hippocampal formation. Male rats were submitted to 6 months of ethanol treatment followed by a 2-month withdrawal period. Stereological methods were applied to estimate the total number of microglia and activated microglia detected by CD11b immunohistochemistry in the hippocampal formation. The expression levels of the pro-inflammatory cytokines TNF-α, COX-2 and IL-15 were measured by qRT-PCR. Alcohol consumption was associated with an increase in the total number of activated microglia but morphological assessment indicated that microglia did not exhibit a full activation phenotype. These data were supported by functional evidence since chronic alcohol consumption produced no changes in the expression of TNF-α or COX-2. The levels of IL-15 a cytokine whose expression is increased upon activation of both astrocytes and microglia, was induced by chronic alcohol treatment. Importantly, the partial activation of microglia induced by ethanol was not reversed by long-term withdrawal. This study suggests that chronic alcohol exposure induces a microglial phenotype consistent with partial activation without significant increase in classical cytokine markers of neuroinflammation in the hippocampal formation. Furthermore, long-term cessation of alcohol intake is not sufficient to alter the microglial partial activation phenotype induced by ethanol. Copyright © 2017 Elsevier B.V. All rights reserved.

Detection of new human metabolic urinary markers in chronic alcoholism and their reversal by aqueous extract of Tinospora cordifolia stem.

Science.gov (United States)

Mittal, Ashwani; Dabur, Rajesh

2015-05-01

We have studied urine metabolic signature of chronic alcoholism (CA) before and after treatment with an Ayurvedic drug Tinospora cordifolia aqueous extract (TCE). Urinary metabolites of chronic alcoholics and apparently healthy subjects were profiled using HPLC-Q-TOF-MS. Discrimination models from the initial data sets were able to correctly assign the unknown samples to the CA, treated or healthy groups in validation sets with r(2) > 0.98. Metabolic signature in CA patients include changed tryptophan, fatty acids and pyrimidines metabolism. Several novel biomarkers of alcoholism were observed in urine for the first time which includes, 5-hydroxyindole, phenylacetic acid, picolinic acid, quinaldic acid, histidine, cystathionine, riboflavin, tetrahydrobiopterin and chenodeoxyglycocholic acid, in addition to previously reported biomarkers. Treatment of CA with TCE reverted the levels of most of the biomarkers except tetrahydrobiopterin levels. These results suggested that the measurement of these urine metabolites could be used as a non-invasive diagnostic method for the detection of CA. As TCE treatment significantly reversed the affected pathways without any side effect. Overall, the present data depicts that TCE may be used either alone or adjunct in reducing alcohol-induced disorders. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Postnatal nutritional treatment of neurocognitive deficits in fetal alcohol spectrum disorder.

Science.gov (United States)

Bastons-Compta, A; Astals, M; Andreu-Fernandez, V; Navarro-Tapia, E; Garcia-Algar, O

2018-04-01

Ethanol is the most important teratogen agent in humans. Prenatal alcohol exposure can lead to a wide range of adverse effects, which are broadly termed as fetal alcohol spectrum disorder (FASD). The most severe consequence of maternal alcohol abuse is the development of fetal alcohol syndrome, defined by growth retardation, facial malformations, and central nervous system impairment expressed as microcephaly and neurodevelopment abnormalities. These alterations generate a broad range of cognitive abnormalities such as learning disabilities and hyperactivity and behavioural problems. Socioeconomic status, ethnicity, differences in genetic susceptibility related to ethanol metabolism, alcohol consumption patterns, obstetric problems, and environmental influences like maternal nutrition, stress, and other co-administered drugs are all factors that may influence FASD manifestations. Recently, much attention has been paid to the role of nutrition as a protective factor against alcohol teratogenicity. There are a great number of papers related to nutritional treatment of nutritional deficits due to several factors associated with maternal consumption of alcohol and with eating and social disorders in FASD children. Although research showed the clinical benefits of nutritional interventions, most of work was in animal models, in a preclinical phase, or in the prenatal period. However, a minimum number of studies refer to postnatal nutrition treatment of neurodevelopmental deficits. Nutritional supplementation in children with FASD has a dual objective: to overcome nutritional deficiencies and to reverse or improve the cognitive deleterious effects of prenatal alcohol exposure. Further research is necessary to confirm positive results, to determine optimal amounts of nutrients needed in supplementation, and to investigate the collective effects of simultaneous multiple-nutrient supplementation.

Metagenomic analyses of alcohol induced pathogenic alterations in the intestinal microbiome and the effect of Lactobacillus rhamnosus GG treatment.

Directory of Open Access Journals (Sweden)

Lara Bull-Otterson

Full Text Available Enteric dysbiosis plays an essential role in the pathogenesis of alcoholic liver disease (ALD. Detailed characterization of the alterations in the gut microbiome is needed for understanding their pathogenic role in ALD and developing effective therapeutic approaches using probiotic supplementation. Mice were fed liquid Lieber-DeCarli diet without or with alcohol (5% v/v for 6 weeks. A subset of mice were administered the probiotic Lactobacillus rhamnosus GG (LGG from 6 to 8 weeks. Indicators of intestinal permeability, hepatic steatosis, inflammation and injury were evaluated. Metagenomic analysis of the gut microbiome was performed by analyzing the fecal DNA by amplification of the V3-V5 regions of the 16S rRNA gene and large-scale parallel pyrosequencing on the 454 FLX Titanium platform. Chronic ethanol feeding caused a decline in the abundance of both Bacteriodetes and Firmicutes phyla, with a proportional increase in the gram negative Proteobacteria and gram positive Actinobacteria phyla; the bacterial genera that showed the biggest expansion were the gram negative alkaline tolerant Alcaligenes and gram positive Corynebacterium. Commensurate with the qualitative and quantitative alterations in the microbiome, ethanol caused an increase in plasma endotoxin, fecal pH, hepatic inflammation and injury. Notably, the ethanol-induced pathogenic changes in the microbiome and the liver were prevented by LGG supplementation. Overall, significant alterations in the gut microbiome over time occur in response to chronic alcohol exposure and correspond to increases in intestinal barrier dysfunction and development of ALD. Moreover, the altered bacterial communities of the gut may serve as significant therapeutic target for the prevention/treatment of chronic alcohol intake induced intestinal barrier dysfunction and liver disease.

Naringin Reverses Hepatocyte Apoptosis and Oxidative Stress Associated with HIV-1 Nucleotide Reverse Transcriptase Inhibitors-Induced Metabolic Complications

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Oluwafeyisetan O. Adebiyi

2015-12-01

Full Text Available Nucleoside Reverse Transcriptase Inhibitors (NRTIs have not only improved therapeutic outcomes in the treatment of HIV infection but have also led to an increase in associated metabolic complications of NRTIs. Naringin’s effects in mitigating NRTI-induced complications were investigated in this study. Wistar rats, randomly allotted into seven groups (n = 7 were orally treated daily for 56 days with 100 mg/kg zidovudine (AZT (groups I, II III, 50 mg/kg stavudine (d4T (groups IV, V, VI and 3 mL/kg of distilled water (group VII. Additionally, rats in groups II and V were similarly treated with 50 mg/kg naringin, while groups III and VI were treated with 45 mg/kg vitamin E. AZT or d4T treatment significantly reduced body weight and plasma high density lipoprotein concentrations but increased liver weights, plasma triglycerides and total cholesterol compared to controls, respectively. Furthermore, AZT or d4T treatment significantly increased oxidative stress, adiposity index and expression of Bax protein, but reduced Bcl-2 protein expression compared to controls, respectively. However, either naringin or vitamin E significantly mitigated AZT- or d4T-induced weight loss, dyslipidemia, oxidative stress and hepatocyte apoptosis compared to AZT- or d4T-only treated rats. Our results suggest that naringin reverses metabolic complications associated with NRTIs by ameliorating oxidative stress and apoptosis. This implies that naringin supplements could mitigate lipodystrophy and dyslipidemia associated with NRTI therapy.

Intestinal CYP2E1: A mediator of alcohol-induced gut leakiness

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Christopher B. Forsyth

2014-01-01

Full Text Available Chronic alcohol use can result in many pathological effects including alcoholic liver disease (ALD. While alcohol is necessary for the development of ALD, only 20–30% of alcoholics develop alcoholic steatohepatitis (ASH with progressive liver disease leading to cirrhosis and liver failure (ALD. This suggests that while chronic alcohol consumption is necessary it is not sufficient to induce clinically relevant liver damage in the absence of a secondary risk factor. Studies in rodent models and alcoholic patients show that increased intestinal permeability to microbial products like endotoxin play a critical role in promoting liver inflammation in ALD pathogenesis. Therefore identifying mechanisms of alcohol-induced intestinal permeability is important in identifying mechanisms of ALD and for designing new avenues for therapy. Cyp2e1 is a cytochrome P450 enzyme that metabolizes alcohol has been shown to be upregulated by chronic alcohol use and to be a major source of oxidative stress and liver injury in alcoholics and in animal and in vitro models of chronic alcohol use. Because Cyp2e1 is also expressed in the intestine and is upregulated by chronic alcohol use, we hypothesized it could play a role in alcohol-induced intestinal hyperpermeability. Our in vitro studies with intestinal Caco-2 cells and in mice fed alcohol showed that circadian clock proteins CLOCK and PER2 are required for alcohol-induced permeability. We also showed that alcohol increases Cyp2e1 protein and activity but not mRNA in Caco-2 cells and that an inhibitor of oxidative stress or siRNA knockdown of Cyp2e1 prevents the increase in CLOCK or PER2 proteins and prevents alcohol-induced hyperpermeability. With our collaborators we have also shown that Cyp2e1 knockout mice are resistant to alcohol-induced gut leakiness and liver inflammation. Taken together our data support a novel Cyp2e1-circadian clock protein mechanism for alcohol-induced gut leakiness that could provide new

Anterior Cingulate Cortex Contributes to Alcohol Withdrawal- Induced and Socially Transferred Hyperalgesia.

Science.gov (United States)

Smith, Monique L; Walcott, Andre T; Heinricher, Mary M; Ryabinin, Andrey E

2017-01-01

Pain is often described as a "biopsychosocial" process, yet social influences on pain and underlying neural mechanisms are only now receiving significant experimental attention. Expression of pain by one individual can be communicated to nearby individuals by auditory, visual, and olfactory cues. Conversely, the perception of another's pain can lead to physiological and behavioral changes in the observer, which can include induction of hyperalgesia in "bystanders" exposed to "primary" conspecifics in which hyperalgesia has been induced directly. The current studies were designed to investigate the neural mechanisms responsible for the social transfer of hyperalgesia in bystander mice housed and tested with primary mice in which hyperalgesia was induced using withdrawal (WD) from voluntary alcohol consumption. Male C57BL/6J mice undergoing WD from a two-bottle choice voluntary alcohol-drinking procedure served as the primary mice. Mice housed in the same room served as bystanders. Naïve, water-drinking controls were housed in a separate room. Immunohistochemical mapping identified significantly enhanced Fos immunoreactivity (Fos-ir) in the anterior cingulate cortex (ACC) and insula (INS) of bystander mice compared to naïve controls, and in the dorsal medial hypothalamus (DMH) of primary mice. Chemogenetic inactivation of the ACC but not primary somatosensory cortex reversed the expression of hyperalgesia in both primary and bystander mice. These studies point to an overlapping neural substrate for expression of socially transferred hyperalgesia and that expressed during alcohol WD.

Cellular and molecular mechanisms of alcohol-induced osteopenia.

Science.gov (United States)

Luo, Zhenhua; Liu, Yao; Liu, Yitong; Chen, Hui; Shi, Songtao; Liu, Yi

2017-12-01

Alcoholic beverages are widely consumed, resulting in a staggering economic cost in different social and cultural settings. Types of alcohol consumption vary from light occasional to heavy, binge drinking, and chronic alcohol abuse at all ages. In general, heavy alcohol consumption is widely recognized as a major epidemiological risk factor for chronic diseases and is detrimental to many organs and tissues, including bones. Indeed, recent findings demonstrate that alcohol has a dose-dependent toxic effect in promoting imbalanced bone remodeling. This imbalance eventually results in osteopenia, an established risk factor for osteoporosis. Decreased bone mass and strength are major hallmarks of osteopenia, which is predominantly attributed not only to inhibition of bone synthesis but also to increased bone resorption through direct and indirect pathways. In this review, we present knowledge to elucidate the epidemiology, potential pathogenesis, and major molecular mechanisms and cellular effects that underlie alcoholism-induced bone loss in osteopenia. Novel therapeutic targets for correcting alcohol-induced osteopenia are also reviewed, such as modulation of proinflammatory cytokines and Wnt and mTOR signaling and the application of new drugs.

Turmeric Extract Rescues Ethanol-Induced Developmental Defect in the Zebrafish Model for Fetal Alcohol Spectrum Disorder (FASD).

Science.gov (United States)

Muralidharan, Pooja; Connors, Craig T; Mohammed, Arooj S; Sarmah, Swapnalee; Marrs, Kathleen; Marrs, James A; Chism, Grady W

2017-09-01

Prenatal ethanol exposure causes the most frequent preventable birth disorder, fetal alcohol spectrum disorder (FASD). The effect of turmeric extracts in rescuing an ethanol-induced developmental defect using zebrafish as a model was determined. Ethanol-induced oxidative stress is one of the major mechanisms underlying FASD. We hypothesize that antioxidant inducing properties of turmeric may alleviate ethanol-induced defects. Curcuminoid content of the turmeric powder extract (5 mg/mL turmeric in ethanol) was determined by UPLC and found to contain Curcumin (124.1 ± 0.2 μg/mL), Desmethoxycurcumin (43.4 ± 0.1 μg/mL), and Bisdemethoxycurcumin (36.6 ± 0.1 μg/mL). Zebrafish embryos were treated with 100 mM (0.6% v/v) ethanol during gastrulation through organogenesis (2 to 48 h postfertilization (hpf)) and supplemented with turmeric extract to obtain total curcuminoid concentrations of 0, 1.16, 1.72, or 2.32 μM. Turmeric supplementation showed significant rescue of the body length at 72 hpf compared to ethanol-treated embryos. The mechanism underlying the rescue remains to be determined. © 2017 Institute of Food Technologists®.

Alcohol-Induced Impairment of Balance is Antagonized by Energy Drinks.

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Marczinski, Cecile A; Fillmore, Mark T; Stamates, Amy L; Maloney, Sarah F

2018-01-01

The acute administration of alcohol reliably impairs balance and motor coordination. While it is common for consumers to ingest alcohol with other stimulant drugs (e.g., caffeine, nicotine), little is known whether prototypical alcohol-induced balance impairments are altered by stimulant drugs. The purpose of this study was to examine whether the coadministration of a high-caffeine energy drink with alcohol can antagonize expected alcohol-induced increases in body sway. Sixteen social drinkers (of equal gender) participated in 4 separate double-blind dose administration sessions that involved consumption of alcohol and energy drinks, alone and in combination. Following dose administration, participants completed automated assessments of balance stability (both eyes open and eyes closed) measured using the Biosway Portable Balance System. Participants completed several subjective measures including self-reported ratings of sedation, stimulation, fatigue, and impairment. Blood pressure and pulse rate were recorded repeatedly. The acute administration of alcohol increased body sway, and the coadministration of energy drinks antagonized this impairment. When participants closed their eyes, alcohol-induced body sway was similar whether or not energy drinks were ingested. While alcohol administration increased ratings of sedation and fatigue, energy drink administration increased ratings of stimulation and reduced ratings of fatigue. Modest increases in systolic and diastolic blood pressure following energy drink administration were also observed. Visual assessment of balance impairment is frequently used to indicate that an individual has consumed too much alcohol (e.g., as part of police-standardized field sobriety testing or by a bartender assessing when someone should no longer be served more alcohol). The current findings suggest that energy drinks can antagonize alcohol-induced increases in body sway, indicating that future work is needed to determine whether this

Effects of Chronic Alcohol Exposure on the Modulation of Ischemia-Induced Glutamate Release via Cannabinoid Receptors in the Dorsal Hippocampus.

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Zheng, Lei; Wu, Xiaoda; Dong, Xiao; Ding, Xinli; Song, Cunfeng

2015-10-01

Chronic alcohol consumption is a critical contributing factor to ischemic stroke, as it enhances ischemia-induced glutamate release, leading to more severe excitotoxicity and brain damage. But the neural mechanisms underlying this phenomenon are poorly understood. We evaluated the effects of chronic alcohol exposure on the modulation of ischemia-induced glutamate release via CB1 and CB2 cannabinoid receptors during middle cerebral artery occlusion, using in vivo microdialysis coupled with high-performance liquid chromatography, in alcohol-naïve rats or rats after 1 or 30 days of withdrawal from chronic ethanol intake (6% v/v for 14 days). Intra-dorsal hippocampus (DH) infusions of ACEA or JWH133, selective CB1 or CB2 receptor agonists, respectively, decreased glutamate release in the DH in alcohol-naïve rats in a dose-dependent manner. Such an effect was reversed by co-infusions of SR141716A or AM630, selective CB1 or CB2 receptor antagonists, respectively. After 30 days, but not 1 day of withdrawal, ischemia induced an enhancement in glutamate release in the DH, as compared with non-alcohol-treated control group. Intra-DH infusions of JWH133, but not ACEA, inhibited ischemia-induced glutamate release in the DH after 30 days of withdrawal. Finally, 1 day of withdrawal did not alter the protein level of CB1 or CB2 receptors in the DH, as compared to non-alcohol-treated control rats. Whereas 30 days of withdrawal robustly decreased the protein level of CB1 receptors, but failed to alter the protein level of CB2 receptors, in the DH, as compared to non-alcohol-treated control rats. Together, these findings suggest that loss of expression/function of CB1 receptors, but not CB2 receptors in the DH, is correlated with the enhancement of ischemia-induced glutamate release after prolonged alcohol withdrawal. Copyright © 2015 by the Research Society on Alcoholism.

Alcohol-induced sexual behavior on campus.

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Meilman, P W

1993-07-01

This study investigated the prevalence of alcohol-related sexual activity on campus. Since coming to college, 35% of the students had engaged in some form of sexual activity that was influenced by drinking. Because they had been drinking, 18% had engaged in sexual intercourse, and 15% had abandoned safe-sex techniques. For the categories any form of sexual activity and abandonment of safe-sex techniques, a significantly greater percentage of women were affected by alcohol use, but this was not true for sexual intercourse. The survey showed no significant differences between undergraduate and graduate students. All three variables showed a relationship with heavier alcohol use and with binge drinking. Academic excellence was negatively correlated with alcohol-induced sexual intercourse.

Supplemental and highly-elevated tocopherol doses differentially regulate allergic inflammation: reversibility of α-tocopherol and γ-tocopherol's effects

OpenAIRE

McCary, Christine A.; Abdala-Valencia, Hiam; Berdnikovs, Sergejs; Cook-Mills, Joan M.

2011-01-01

We have reported that supplemental doses of the α- and γ-tocopherol isoforms of vitamin E decrease and increase, respectively, allergic lung inflammation. We have now assessed whether these effects of tocopherols are reversible. For these studies, mice were treated with antigen and supplemental tocopherols in a first phase of treatment followed by a 4 week clearance phase and then the mice received a second phase of antigen and tocopherol treatments. The pro-inflammatory effects of supplement...

Role of IRAK-M in alcohol induced liver injury.

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Yipeng Wang

Full Text Available Increasing evidence suggests that innate immunity plays an important role in alcohol-induced liver injury and most studies have focused on positive regulation of innate immunity. The main objective of this study was to investigate the negative regulator of innate immunity, IL-1/Toll-like receptor (TLR signaling pathways and interleukin receptor-associated kinase-M (IRAK-M in alcoholic liver injury. We established an alcohol-induced liver injury model using wild type and IRAK-M deficient B6 mice and investigated the possible mechanisms. We found that in the absence of IRAK-M, liver damage by alcohol was worse with higher alanine transaminase (ALT, more immune cell infiltration and increased numbers of IFNγ producing cells. We also found enhanced phagocytic activity in CD68(+ cells. Moreover, our results revealed altered gut bacteria after alcohol consumption and this was more striking in the absence of IRAK-M. Our study provides evidence that IRAK-M plays an important role in alcohol-induced liver injury and IRAK-M negatively regulates the innate and possibly the adaptive immune response in the liver reacting to acute insult by alcohol. In the absence of IRAK-M, the hosts developed worse liver injury, enhanced gut permeability and altered gut microbiota.

Chronic alcohol feeding potentiates hormone-induced calcium signalling in hepatocytes.

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Bartlett, Paula J; Antony, Anil Noronha; Agarwal, Amit; Hilly, Mauricette; Prince, Victoria L; Combettes, Laurent; Hoek, Jan B; Gaspers, Lawrence D

2017-05-15

Chronic alcohol consumption causes a spectrum of liver diseases, but the pathogenic mechanisms driving the onset and progression of disease are not clearly defined. We show that chronic alcohol feeding sensitizes rat hepatocytes to Ca 2+ -mobilizing hormones resulting in a leftward shift in the concentration-response relationship and the transition from oscillatory to more sustained and prolonged Ca 2+ increases. Our data demonstrate that alcohol-dependent adaptation in the Ca 2+ signalling pathway occurs at the level of hormone-induced inositol 1,4,5 trisphosphate (IP 3 ) production and does not involve changes in the sensitivity of the IP 3 receptor or size of internal Ca 2+ stores. We suggest that prolonged and aberrant hormone-evoked Ca 2+ increases may stimulate the production of mitochondrial reactive oxygen species and contribute to alcohol-induced hepatocyte injury. ABSTRACT: 'Adaptive' responses of the liver to chronic alcohol consumption may underlie the development of cell and tissue injury. Alcohol administration can perturb multiple signalling pathways including phosphoinositide-dependent cytosolic calcium ([Ca 2+ ] i ) increases, which can adversely affect mitochondrial Ca 2+ levels, reactive oxygen species production and energy metabolism. Our data indicate that chronic alcohol feeding induces a leftward shift in the dose-response for Ca 2+ -mobilizing hormones resulting in more sustained and prolonged [Ca 2+ ] i increases in both cultured hepatocytes and hepatocytes within the intact perfused liver. Ca 2+ increases were initiated at lower hormone concentrations, and intercellular calcium wave propagation rates were faster in alcoholics compared to controls. Acute alcohol treatment (25 mm) completely inhibited hormone-induced calcium increases in control livers, but not after chronic alcohol-feeding, suggesting desensitization to the inhibitory actions of ethanol. Hormone-induced inositol 1,4,5 trisphosphate (IP 3 ) accumulation and phospholipase C

An experimental study on effect of antioxidant vitamin E in stress and alcohol induced changes in male fertility in albino rats.

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Sanghishetti Vijay Prasad, Nayak BB, Ghongane BB, Raul AR, Vijay Kumar AN, Mutalik MM, Kapure NL.

2012-09-01

Full Text Available Introduction: Physical and Psychological stresses are believed to reduce sexual functions, resulting fromneurotransmission changes in various erectile response pathways and reduced blood flow in genital organs.Intake of alcohol depends on numerous genetic and environmental factors. Stress has long been thought to influence the alcohol drinking in humans. Forced swimming in laboratory animals has been widely used as a model of stress to study the physiological changes and the capacity of the organism in response to stress. Aim: 1. To assess the effect of forced swimming stress on seminal fluid profile, Serum testosterone level, Testicular lipid peroxidation levels. 2. To assess the effect of Vitamin E on stress induced changes. Method: Adult male albino rats weighing 200 – 220 g, aged 12-15 weeks were used in this study. The animals were randomly divided into four groups of 6 animals each. Group1 (control received distilled water, Group 2 (Forced Swimming Stress received distilled water Group 3: subjected to Forced Swimming stress with 20% alcohol intake p.o. Group 4: Swimming stress with 20% alcohol treated with Vitamin E(200mg/kg/day orally. The following parameters were studied in all groups 1. Body weight. 2. Sperm count Motility and Life /death Ratio (SLDR. 3. Serum Testosterone 4. Testicular Malondialdehyde level (MDA. Results: Forced swimming stress caused loss in body wt, reduction in sperm count, motility and SLDR in sperm analysis, reduction in serum testosterone and increase testicular MDA levels compared to control. All the changes were statistically significant. When alcohol was added along with forced swimming it caused further loss in body wt, sperm count, motility and SLDR, serum testosterone level and slightly further increase in MDA levels. These observations were also statistically significant. In case of group IV in which Vitamin E was administered long with stress with alcohol it showed a trend of reversal phenomenon of

Risperidone-induced reversible neutropenia.

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Kattalai Kailasam, Vasanth; Chima, Victoria; Nnamdi, Uchechukwu; Sharma, Kavita; Shah, Kairav

2017-01-01

This case report presents a 44-year-old man with a history of schizophrenia who developed neutropenia on risperidone therapy. The patient's laboratory reports showed a gradual decline of leukocytes and neutrophils after resolution and rechallenging. This was reversed with the discontinuation of risperidone and by switching to olanzapine. In this case report, we also discuss the updated evidence base for management of risperidone-induced neutropenia.

Aminocaproic Acid and Tranexamic Acid Fail to Reverse Dabigatran-Induced Coagulopathy.

Science.gov (United States)

Levine, Michael; Huang, Margaret; Henderson, Sean O; Carmelli, Guy; Thomas, Stephen H

In recent years, dabigatran has emerged as a popular alternative to warfarin for treatment of atrial fibrillation. If rapid reversal is required, however, no reversal agent has clearly been established. The primary purpose of this manuscript was to evaluate the efficacy of tranexamic acid and aminocaproic acid as agents to reverse dabigatran-induced coagulopathy. Rats were randomly assigned to 6 groups. Each rat received either dabigatran or oral placebo, followed by saline, tranexamic acid, or aminocaproic acid. An activated clotting test was used to measure the coagulopathy. Neither tranexamic acid nor aminocaproic acid successfully reversed dabigatran-induced coagulopathy. In this rodent model of dabigatran-induced coagulopathy, neither tranexamic acid nor aminocaproic acid were able to reverse the coagulopathy.

Gender and Impulsivity: Effects on Cue-Induced Alcohol Craving.

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Yarmush, Devorah E; Manchery, Linda; Luehring-Jones, Peter; Erblich, Joel

2016-05-01

Numerous studies have demonstrated that trait impulsivity is linked to increased risk of developing alcohol-use disorders and other substance abuse. Impulsivity has also been shown in some studies to potentiate cue-induced drug cravings. Despite considerable evidence of gender differences in impulsivity and drug craving among individuals suffering from alcohol dependence and other drug use, little research has focused on these processes in healthy young men and women who may be at risk for developing alcohol-use disorders. The objective of this study was to investigate the relationship between impulsivity and cue-induced craving, as well as possible gender differences in these effects among healthy young adults. To that end, female (n = 22) and male (n = 14) social drinkers aged 18 to 25, recruited from an urban university campus, completed the Barratt Impulsiveness Scale and reported their alcohol cravings immediately before and after laboratory exposure to alcohol cues. Findings indicated that exposure to cues elicited increased alcohol cravings, but these effects did not differ by gender. Interestingly, a significant interaction of impulsivity and gender revealed that impulsivity predicted significantly higher cue-induced cravings in women, but not men. Findings underscore the importance of better understanding the interaction of situational factors (e.g., exposure to alcohol cues) and dispositional factors (e.g., impulsivity) as potential contributors to drinking motivation. Future prospective research is needed to identify gender-specific risk factors for the development of problem drinking. Copyright © 2016 by the Research Society on Alcoholism.

Protective Role of Dietary Curcumin in the Prevention of the Oxidative Stress Induced by Chronic Alcohol with respect to Hepatic Injury and Antiatherogenic Markers

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Ravi Varatharajalu

2016-01-01

Full Text Available Curcumin, an antioxidant compound found in Asian spices, was evaluated for its protective effects against ethanol-induced hepatosteatosis, liver injury, antiatherogenic markers, and antioxidant status in rats fed with Lieber-deCarli low menhaden (2.7% of total calories from ω-3 polyunsaturated fatty acids (PUFA and Lieber-deCarli high menhaden (13.8% of total calories from ω-3 PUFA alcohol-liquid (5% diets supplemented with or without curcumin (150 mg/kg/day for 8 weeks. Treatment with curcumin protected against high ω-3 PUFA and ethanol-induced hepatosteatosis and increase in liver injury markers, alanine aminotransferase, and aspartate aminotransferase. Curcumin upregulated paraoxonase 1 (PON1 mRNA and caused significant increase in serum PON1 and homocysteine thiolactonase activities as compared to high ω-3 PUFA and ethanol group. Moreover, treatment with curcumin protected against ethanol-induced oxidative stress by increasing the antioxidant glutathione and decreasing the lipid peroxidation adduct 4-hydroxynonenal. These results strongly suggest that chronic ethanol in combination with high ω-3 PUFA exacerbated hepatosteatosis and liver injury and adversely decreases antiatherogenic markers due to increased oxidative stress and depletion of glutathione. Curcumin supplementation significantly prevented these deleterious actions of chronic ethanol and high ω-3 PUFA. Therefore, we conclude that curcumin may have therapeutic potential to protect against chronic alcohol-induced liver injury and atherosclerosis.

Consumption estimation of non alcoholic beverages, sodium, food supplements and oil.

Science.gov (United States)

López Díaz-Ufano, María Luisa

2015-02-26

The interest in the type and quantity of non alcoholic beverage, sodium, food supplements and oil consumption is not new, and numerous approaches have been used to assess beverage intake, but the validity of these approaches has not been well established. The need to intake liquids varies depending on the diet, the physical activity carried out, the environmental temperature, the humidity, etc. The variety of beverages in the diet can contribute to increasing the micro nutrient intake: vitamins, antioxidants, minerals. Risks associated to high sodium consumption are: an increase in high blood pressure, vascular endothelial deterioration, bone demineralisation, kidney disease, stomach cancer. Progress in health, investigation, education, etc. are leading to an increase in food supplement consumption. Olive oil represents one of the basic pillars of the Mediterranean diet and its normal presence in nutrition guarantees an adequate content of some important nutrients; not only oleic acid and linoleic acid but also tocopherols, phytoesterols and phenolic compounds. Biomarkers of intake are able to objectively assess dietary intake/status without the bias of self-reported dietary intake errors and also overcome the problem of intra-individual diet variability. Furthermore, some methods of of measuring dietary intake used biomarkers to validate the data it collects. Biological markers may offer advantages and be able to improve the estimates of dietary intake assessment, which impact into the statistical power of the study. There is a surprising paucity of studies that systematically examine the correlation of beverages intake and hydration biomarker in different populations. There is no standardized questionnaire developed as a research tool for the evaluation of non alcoholic beverages, sodium, food supplements and oil intake in the general population. Sometimes, the information comes from different sources or from different methodological characteristics which raises

Docosahexaenoic acid prevents trans-10, cis-12 conjugated linoleic acid-induced non-alcoholic fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation

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Background: Concomitant supplementation with docosahexaenoic acid (22:6 n-3; DHA) prevented t10, c12- conjugated linoleic acid (CLA)-induced non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Effective dose of DHA and mechanisms involved are poorly understood. Methods: We examined abi...

Epigenetic Targets for Reversing Immune Defects Caused by Alcohol Exposure

Science.gov (United States)

Curtis, Brenda J.; Zahs, Anita; Kovacs, Elizabeth J.

2013-01-01

Alcohol consumption alters factors that modify gene expression without changing the DNA code (i.e., epigenetic modulators) in many organ systems, including the immune system. Alcohol enhances the risk for developing several serious medical conditions related to immune system dysfunction, including acute respiratory distress syndrome (ARDS), liver cancer, and alcoholic liver disease (ALD). Binge and chronic drinking also render patients more susceptible to many infectious pathogens and advance the progression of HIV infection by weakening both innate and adaptive immunity. Epigenetic mechanisms play a pivotal role in these processes. For example, alcohol-induced epigenetic variations alter the developmental pathways of several types of immune cells (e.g., granulocytes, macrophages, and T-lymphocytes) and through these and other mechanisms promote exaggerated inflammatory responses. In addition, epigenetic mechanisms may underlie alcohol’s ability to interfere with the barrier functions of the gut and respiratory systems, which also contribute to the heightened risk of infections. Better understanding of alcohol’s effects on these epigenetic processes may help researchers identify new targets for the development of novel medications to prevent or ameliorate alcohol’s detrimental effects on the immune system. PMID:24313169

Inhibitory Effects of Pretreatment with Radon on Acute Alcohol-Induced Hepatopathy in Mice

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Teruaki Toyota

2012-01-01

Full Text Available We previously reported that radon inhalation activates antioxidative functions in the liver and inhibits carbon tetrachloride-induced hepatopathy in mice. In addition, it has been reported that reactive oxygen species contribute to alcohol-induced hepatopathy. In this study, we examined the inhibitory effects of radon inhalation on acute alcohol-induced hepatopathy in mice. C57BL/6J mice were subjected to intraperitoneal injection of 50% alcohol (5 g/kg bodyweight after inhaling approximately 4000 Bq/m3 radon for 24 h. Alcohol administration significantly increased the activities of glutamic oxaloacetic transaminase (GOT, glutamic pyruvic transaminase (GPT in serum, and the levels of triglyceride and lipid peroxide in the liver, suggesting acute alcohol-induced hepatopathy. Radon inhalation activated antioxidative functions in the liver. Furthermore, pretreatment with radon inhibited the depression of hepatic functions and antioxidative functions. These findings suggested that radon inhalation activated antioxidative functions in the liver and inhibited acute alcohol-induced hepatopathy in mice.

Protective function of complement against alcohol-induced rat liver damage.

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Bykov, Igor L; Väkevä, Antti; Järveläinen, Harri A; Meri, Seppo; Lindros, Kai O

2004-11-01

The complement system can promote tissue damage or play a homeostatic role in the clearance and disposal of damaged tissue. We assessed the role of the terminal complement pathway in alcohol-induced liver damage in complement C6 (C6-/-) genetically deficient rats. C6-/- and corresponding C6+/+ rats were continuously exposed to ethanol by feeding ethanol-supplemented liquid diet for six weeks. Liver samples were analyzed for histopathology and complement component deposition by immunofluorescence microscopy. Prostaglandin E receptors and cytokine mRNA levels were analyzed by RT-PCR and plasma cytokines by ELISA. Deposition of complement components C1, C3, C8 and C9 was observed in C6+/+ rats, but not in C6-/- animals. The histopathological changes, the liver weight increase and the elevation of the plasma pro-/anti-inflammatory TNF-alpha/IL-10 ratio were, on the other hand, more marked in C6-/- rats. Furthermore, ethanol enhanced the hepatic mRNA expression of the prostaglandin E receptors EP2R and EP4R exclusively in the C6-/- rats. Our results indicate that a deficient terminal complement pathway predisposes to tissue injury and promotes a pro-inflammatory cytokine response. This suggests that an intact complement system has a protective function in the development of alcoholic liver damage.

A novel reverse osmosis membrane modified by polyvinyl alcohol with maleic anhydride crosslinking

Science.gov (United States)

Samnani, Mohit; Rathod, Harshad; Raval, Hiren

2018-03-01

In the era of increasing energy crisis, it is inevitable to decrease process energy consumption to increase process viability and curtail green-house gas emission. The Reverse Osmosis plant requires significant energy to transfer water overcoming the osmotic pressure. This paper focuses on increasing the water flux for Thin Film Composite Reverse Osmosis (TFC RO) membrane without compromising salt rejection performance leading to the environmentally friendly and economically attractive process. The virgin TFC RO membrane was exposed to solution of sodium hypochlorite of concentration 2000 mg l-1 for 1 h to activate the surface of the membrane, followed by the treatment with the mixture of polyvinyl alcohol and maleic anhydride with varying concentrations for 1 h and curing in the oven at 80 °C temperature for 10 min. Out of all the treated membranes, the membrane treated with 2000 mg l-1 polyvinyl alcohol and 1000 mg l-1 maleic anhydride demonstrated the highest salt rejection of 96.83 % with 2% increase as compared to the virgin TFC RO membrane. The water flux of the membrane was around 44% higher than the virgin TFC RO membrane. The membrane samples were characterized by atomic force micrographs, ATR-FTIR, Nuclear magnetic resonance and Dynamic mechanical analysis.

Binge Alcohol Exposure Transiently Changes the Endocannabinoid System: A Potential Target to Prevent Alcohol-Induced Neurodegeneration

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Daniel J. Liput

2017-11-01

Full Text Available Excessive alcohol consumption leads to neurodegeneration, which contributes to cognitive decline that is associated with alcohol use disorders (AUDs. The endocannabinoid system has been implicated in the development of AUDs, but little is known about how the neurotoxic effects of alcohol impact the endocannabinoid system. Therefore, the current study investigated the effects of neurotoxic, binge-like alcohol exposure on components of the endocannabinoid system and related N-acylethanolamines (NAEs, and then evaluated the efficacy of fatty acid amide hydrolase (FAAH inhibition on attenuating alcohol-induced neurodegeneration. Male rats were administered alcohol according to a binge model, which resulted in a transient decrease in [3H]-CP-55,940 binding in the entorhinal cortex and hippocampus following two days, but not four days, of treatment. Furthermore, binge alcohol treatment did not change the tissue content of the three NAEs quantified, including the endocannabinoid and anandamide. In a separate study, the FAAH inhibitor, URB597 was administered to rats during alcohol treatment and neuroprotection was assessed by FluoroJade B (FJB staining. The administration of URB597 during binge treatment did not significantly reduce FJB+ cells in the entorhinal cortex or hippocampus, however, a follow up “target engagement” study found that NAE augmentation by URB597 was impaired in alcohol intoxicated rats. Thus, potential alcohol induced alterations in URB597 pharmacodynamics may have contributed to the lack of neuroprotection by FAAH inhibition.

Cue-induced alcohol-seeking behaviour is reduced by disrupting the reconsolidation of alcohol-related memories.

Science.gov (United States)

von der Goltz, Christoph; Vengeliene, Valentina; Bilbao, Ainhoa; Perreau-Lenz, Stephanie; Pawlak, Cornelius R; Kiefer, Falk; Spanagel, Rainer

2009-08-01

In humans, the retrieval of memories associated with an alcohol-related experience frequently evokes alcohol-seeking behaviour. The reconsolidation hypothesis states that a consolidated memory could again become labile and susceptible to disruption after memory retrieval. The aim of our study was to examine whether retrieval of alcohol-related memories undergoes a reconsolidation process. For this purpose, male Wistar rats were trained to self-administer ethanol in the presence of specific conditioned stimuli. Thereafter, animals were left undisturbed in their home cages for the following 21 days. Memory retrieval was performed in a single 5-min exposure to all alcohol-associated stimuli. The protein synthesis inhibitor anisomycin, the non-competitive N-methyl-D: -aspartate (NMDA) receptor antagonist MK-801 and acamprosate, a clinically used drug known to reduce a hyper-glutamatergic state, were given immediately after retrieval of alcohol-related memories. The impact of drug treatment on cue-induced alcohol-seeking behaviour was measured on the following day and 7 days later. Administration of both anisomycin and MK-801 reduced cue-induced alcohol-seeking behaviour, showing that memory reconsolidation was disrupted by these compounds. However, acamprosate had no effect on the reconsolidation process, suggesting that this process is not dependent on a hyper-glutamatergic state but is more related to protein synthesis and NMDA receptor activity. Pharmacological disruption of reconsolidation of alcohol-associated memories can be achieved by the use of NMDA antagonists and protein synthesis inhibitors and may thus provide a potential new therapeutic strategy for the prevention of relapse in alcohol addiction.

Protective Effects of Lemon Juice on Alcohol-Induced Liver Injury in Mice

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Tong Zhou

2017-01-01

Full Text Available Chronic excessive alcohol consumption (more than 40–80 g/day for males and more than 20–40 g/day for females could induce serious liver injury. In this study, effects of lemon juice on chronic alcohol-induced liver injury in mice were evaluated. The serum biochemical profiles and hepatic lipid peroxidation levels, triacylglycerol (TG contents, antioxidant enzyme activities, and histopathological changes were examined for evaluating the hepatoprotective effects of lemon juice in mice. In addition, the in vitro antioxidant capacities of lemon juice were determined. The results showed that lemon juice significantly inhibited alcohol-induced increase of alanine transaminase (ALT, aspartate transaminase (AST, hepatic TG, and lipid peroxidation levels in a dose-dependent manner. Histopathological changes induced by alcohol were also remarkably improved by lemon juice treatment. These findings suggest that lemon juice has protective effects on alcohol-induced liver injury in mice. The protective effects might be related to the antioxidant capacity of lemon juice because lemon juice showed in vitro antioxidant capacity.

Zinc supplementation alleviates the progression of diabetic nephropathy by inhibiting the overexpression of oxidative-stress-mediated molecular markers in streptozotocin-induced experimental rats.

Science.gov (United States)

Barman, Susmita; Pradeep, Seetur R; Srinivasan, Krishnapura

2018-04-01

Zinc deficiency during diabetes projects a role for zinc nutrition in the management of diabetic nephropathy. The current study explored whether zinc supplementation protects against diabetic nephropathy through modulation of kidney oxidative stress and stress-induced expression related to the inflammatory process in streptozotocin-induced diabetic rats. Groups of hyperglycemic rats were exposed to dietary interventions for 6 weeks with zinc supplementation (5 times and 10 times the normal level). Supplemental-zinc-fed diabetic groups showed a significant reversal of increased kidney weight and creatinine clearance. There was a significant reduction in hyperlipidemic condition along with improved PUFA:SFA ratio in the renal tissue. Expression of the lipid oxidative marker and expression of inflammatory markers, cytokines, fibrosis factors and apoptotic regulatory proteins observed in diabetic kidney were beneficially modulated by zinc supplementation, the ameliorative effect being concomitant with elevated antiapoptosis. There was a significant reduction in advanced glycation, expression of the receptor of the glycated products and oxidative stress markers. Zinc supplementation countered the higher activity and expression of polyol pathway enzymes in the kidney. Overexpression of the glucose transporters, as an adaptation to the increased need for glucose transport in diabetic condition, was minimized by zinc treatment. The pathological abnormalities in the renal architecture of diabetic animals were corrected by zinc intervention. Thus, dietary zinc supplementation has a significant beneficial effect in the control of diabetic nephropathy. This was exerted through a protective influence on oxidative-stress-induced cytokines, inflammatory proliferation and consequent renal injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Conditions that Stabilize Membrane Domains Also Antagonize n-Alcohol Anesthesia

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Machta, Benjamin B.; Gray, Ellyn; Nouri, Mariam; McCarthy, Nicola L. C.; Gray, Erin M.; Miller, Ann L.; Brooks, Nicholas J.; Veatch, Sarah L.

2016-08-01

Diverse molecules induce general anesthesia with potency strongly correlated both with their hydrophobicity and their effects on certain ion channels. We recently observed that several n-alcohol anesthetics inhibit heterogeneity in plasma membrane derived vesicles by lowering the critical temperature ($T_c$) for phase separation. Here we exploit conditions that stabilize membrane heterogeneity to further test the correlation between the anesthetic potency of n-alcohols and effects on $T_c$. First we show that hexadecanol acts oppositely to n-alcohol anesthetics on membrane mixing and antagonizes ethanol induced anesthesia in a tadpole behavioral assay. Second, we show that two previously described `intoxication reversers' raise $T_c$ and counter ethanol's effects in vesicles, mimicking the findings of previous electrophysiological and behavioral measurements. Third, we find that hydrostatic pressure, long known to reverse anesthesia, also raises $T_c$ in vesicles with a magnitude that counters the effect of butanol at relevant concentrations and pressures. Taken together, these results demonstrate that $\\Delta T_c$ predicts anesthetic potency for n-alcohols better than hydrophobicity in a range of contexts, supporting a mechanistic role for membrane heterogeneity in general anesthesia.

Alcoholic beverages induce superconductivity in FeTe1-xSx

International Nuclear Information System (INIS)

Deguchi, K; Kawasaki, Y; Ozaki, T; Tsuda, S; Yamaguchi, T; Takano, Y; Mizuguchi, Y

2011-01-01

We found that hot alcoholic beverages were effective in inducing superconductivity in FeTe 0.8 S 0.2 . Heating the FeTe 0.8 S 0.2 compound in various alcoholic beverages enhances the superconducting properties compared to a pure water-ethanol mixture as a control. Heating with red wine for 24 h leads to the largest shielding volume fraction of 62.4% and the highest zero resistivity temperature of 7.8 K. Some components present in alcoholic beverages, other than water and ethanol, have the ability to induce superconductivity in the FeTe 0.8 S 0.2 compound.

Death from seizures induced by chronic alcohol abuse--does it exist?

DEFF Research Database (Denmark)

Christoffersen, S

2007-01-01

aetiologies, but in police reports a person known to have seizures is most likely to be reported as suffering from epilepsy. It is a well-known fact that alcoholics have seizures either due to "alcohol-induced epilepsy" or due to withdrawal from drinking. It also seems to be generally accepted that alcoholics...... may die from these seizures. A literature study was performed of deaths due to alcohol-induced seizures, either during withdrawal or as late-onset seizures where the aetiology was established as long time alcohol abuse and a necropsy had shown no other possible cause of death than a seizure. RESULTS......: It was not possible to find any well-documented cases. It is, however, difficult to compare cases in the literature, as there is no generally accepted classification or nomenclature of seizures related to alcohol abuse....

Physical exercise as a supplement to outpatient treatment of alcohol use disorders – design and preliminary results of a randomized controlled trial

DEFF Research Database (Denmark)

Sari, Sengül; Bilberg, Randi Marie; Roessler, Kirsten Kaya

Background and aim Alcohol use disorder is a widespread problem in Denmark and has severe impacts on health and quality of life of each individual. The clinical treatment of alcohol use disorder involves evidence-based knowledge on medical treatment, physical training, and psychological management...... the study and inform about the first preliminary results. Perspectives If this study detects a positive relationship between exercise as a supplement to alcohol treatment and patients’ alcohol intake, quality of life, fitness, well-being, anxiety, depression and interpersonal problems...

Light-induced reversible expansion of individual gold nanoplates

Directory of Open Access Journals (Sweden)

Jinsheng Lu

2017-10-01

Full Text Available Light-induced mechanical response of materials has been extensively investigated and widely utilized to convert light energy into mechanical energy directly. The metallic nanomaterials have excellent photothermal properties and show enormous potential in micromechanical actuators, etc. However, the photo-thermo-mechanical properties of individual metallic nanostructures have yet to be well investigated. Here, we experimentally demonstrate a way to realize light-induced reversible expansion of individual gold nanoplates on optical microfibers. The light-induced thermal expansion coefficient is obtained as 21.4 ± 4.6 ∼ 31.5 ± 4.2 μ·K-1 when the light-induced heating temperature of the gold nanoplates is 240 ∼ 490 °C. The photo-thermo-mechanical response time of the gold nanoplates is about 0.3 ± 0.1 s. This insight into the photo-thermo-mechanical properties of the gold nanoplates could deepen the understanding of the light-induced reversible expansion behavior in nanoscale and pave the way for applications based on this piezoelectric-like response, such as light-driven metallic micromotors.

The Molecular Circadian Clock and Alcohol-Induced Liver Injury

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Uduak S. Udoh

2015-10-01

Full Text Available Emerging evidence from both experimental animal studies and clinical human investigations demonstrates strong connections among circadian processes, alcohol use, and alcohol-induced tissue injury. Components of the circadian clock have been shown to influence the pathophysiological effects of alcohol. Conversely, alcohol may alter the expression of circadian clock genes and the rhythmic behavioral and metabolic processes they regulate. Therefore, we propose that alcohol-mediated disruption in circadian rhythms likely underpins many adverse health effects of alcohol that cut across multiple organ systems. In this review, we provide an overview of the circadian clock mechanism and showcase results from new studies in the alcohol field implicating the circadian clock as a key target of alcohol action and toxicity in the liver. We discuss various molecular events through which alcohol may work to negatively impact circadian clock-mediated processes in the liver, and contribute to tissue pathology. Illuminating the mechanistic connections between the circadian clock and alcohol will be critical to the development of new preventative and pharmacological treatments for alcohol use disorders and alcohol-mediated organ diseases.

Effect of naltrexone and ondansetron on alcohol cue-induced activation of the ventral striatum in alcohol-dependent people.

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Myrick, Hugh; Anton, Raymond F; Li, Xingbao; Henderson, Scott; Randall, Patrick K; Voronin, Konstantin

2008-04-01

Medication for the treatment of alcoholism is currently not particularly robust. Neuroimaging techniques might predict which medications could be useful in the treatment of alcohol dependence. To explore the effect of naltrexone, ondansetron hydrochloride, or the combination of these medications on cue-induced craving and ventral striatum activation. Functional brain imaging was conducted during alcohol cue presentation. Participants were recruited from the general community following media advertisement. Experimental procedures were performed in the magnetic resonance imaging suite of a major training hospital and medical research institute. Ninety non-treatment-seeking alcohol-dependent (by DSM-IV criteria) and 17 social drinking (analysis but intermediate in a region-specific analysis. Consistent with animal data that suggest that both naltrexone and ondansetron reduce alcohol-stimulated dopamine output in the ventral striatum, the current study found evidence that these medications, alone or in combination, could decrease alcohol cue-induced activation of the ventral striatum, consistent with their putative treatment efficacy.

A review of dietary supplement-induced renal dysfunction.

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Gabardi, Steven; Munz, Kristin; Ulbricht, Catherine

2007-07-01

Complementary and alternative medicine (CAM) is a multibillion-dollar industry. Almost half of the American population uses some form of CAM, with many using them in addition to prescription medications. Most patients fail to inform their health care providers of their CAM use, and physicians rarely inquire. Annually, thousands of dietary supplement-induced adverse events are reported to Poison Control Centers nationwide. CAM manufacturers are not responsible for proving safety and efficacy, because the Food and Drug Administration does not regulate them. However, concern exists surrounding the safety of CAM. A literature search using MEDLINE and EMBASE was undertaken to explore the impact of CAM on renal function. English-language studies and case reports were selected for inclusion but were limited to those that consisted of human subjects, both adult and pediatric. This review provides details on dietary supplements that have been associated with renal dysfunction and focuses on 17 dietary supplements that have been associated with direct renal injury, CAM-induced immune-mediated nephrotoxicity, nephrolithiasis, rhabdomyolysis with acute renal injury, and hepatorenal syndrome. It is concluded that it is imperative that use of dietary supplements be monitored closely in all patients. Health care practitioners must take an active role in identifying patients who are using CAM and provide appropriate patient education.

Calcium supplementation decreases BCP-induced inflammatory processes in blood cells through the NLRP3 inflammasome down-regulation.

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Lagadec, Patricia; Balaguer, Thierry; Boukhechba, Florian; Michel, Grégory; Bouvet-Gerbettaz, Sébastien; Bouler, Jean-Michel; Scimeca, Jean-Claude; Rochet, Nathalie

2017-07-15

Interaction of host blood with biomaterials is the first event occurring after implantation in a bone defect. This study aimed at investigating the cellular and molecular consequences arising at the interface between whole blood and biphasic calcium phosphate (BCP) particles. We observed that, due to calcium capture, BCP inhibited blood coagulation, and that this inhibition was reversed by calcium supplementation. Therefore, we studied the impact of calcium supplementation on BCP effects on blood cells. Comparative analysis of BCP and calcium supplemented-BCP (BCP/Ca) effects on blood cells showed that BCP as well as BCP/Ca induced monocyte proliferation, as well as a weak but significant hemolysis. Our data showed for the first time that calcium supplementation of BCP microparticles had anti-inflammatory properties compared to BCP alone that induced an inflammatory response in blood cells. Our results strongly suggest that the anti-inflammatory property of calcium supplemented-BCP results from its down-modulating effect on P2X7R gene expression and its capacity to inhibit ATP/P2X7R interactions, decreasing the NLRP3 inflammasome activation. Considering that monocytes have a vast regenerative potential, and since the excessive inflammation often observed after bone substitutes implantation limits their performance, our results might have great implications in terms of understanding the mechanisms leading to an efficient bone reconstruction. Although scaffolds and biomaterials unavoidably come into direct contact with blood during bone defect filling, whole blood-biomaterials interactions have been poorly explored. By studying in 3D the interactions between biphasic calcium phosphate (BCP) in microparticulate form and blood, we showed for the first time that calcium supplementation of BCP microparticles (BCP/Ca) has anti-inflammatory properties compared to BCP-induced inflammation in whole blood cells and provided information related to the molecular mechanisms

Isoflavonoid compounds extracted from Pueraria lobata suppress alcohol preference in a pharmacogenetic rat model of alcoholism.

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Lin, R C; Guthrie, S; Xie, C Y; Mai, K; Lee, D Y; Lumeng, L; Li, T K

1996-06-01

The extract from an edible vine, Pueraria lobata, has long been used in China to lessen alcohol intoxication. We have previously shown that daidzin, one of the major components from this plant extract, is efficacious in lowering blood alcohol levels and shortens sleep time induced by alcohol ingestion. This study was conducted to test the antidipsotropic effect of daidzin and two other major isoflavonoids, daidzein and puerarin, from Pueraria lobata administered by the oral route. An alcohol-preferring rat model, the selectively-bred P line of rats, was used for the study. All three isoflavonoid compounds were effective in suppressing voluntary alcohol consumption by the P rats. When given orally to P rats at a dose of 100 mg/kg/day, daidzein, daidzin, and puerarin decreased ethanol intake by 75%, 50%, and 40%, respectively. The decrease in alcohol consumption was accompanied by an increase in water intake, so that the total fluid volume consumed daily remained unchanged. The effects of these isoflavonoid compounds on alcohol and water intake were reversible. Suppression of alcohol consumption was evident after 1 day of administration and became maximal after 2 days. Similarly, alcohol preference returned to baseline levels 2 days after discontinuation of the isoflavonoids. Rats receiving the herbal extracts ate the same amounts of food as control animals, and they gained weight normally during the experiments. When administered orally, none of these compounds affected the activities of liver alcohol dehydrogenase and aldehyde dehydrogenase. Therefore, the reversal of alcohol preference produced by these compounds may be mediated via the CNS. Data demonstrate that isoflavonoid compounds extracted from Pueraria lobata is effective in suppressing the appetite for alcohol when taken orally, raising the possibility that other constituents of edible plants may exert similar and more potent actions.

Caffeine antagonism of alcohol-induced driving impairment.

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Liguori, A; Robinson, J H

2001-07-01

The extent to which caffeine antagonizes alcohol-induced impairment of simulated automobile driving at the current lowest legal American limit (0.08% BrAC) was the focus of this study. Fifteen adults swallowed a capsule (0, 200, or 400 mg caffeine) then drank a beverage (0.0 or 0.6 g/kg ethanol) in a within-subject, double-blind, randomized procedure. Forty-five minutes later, participants completed a test battery of subjective effects scales, dynamic posturography, critical flicker fusion (CFF), choice reaction time (CRT), divided attention (Stroop test), and simulated driving. Alcohol alone increased ratings of 'dizzy', 'drug effect', and 'high', slowed CRT and brake latency, and increased body sway. Caffeine alone increased ratings of 'alert' and 'jittery', but did not significantly affect body sway or psychomotor performance. Both caffeine doses comparably counteracted alcohol impairment of brake latency but not CRT or body sway. Brake latency with either alcohol-caffeine combination remained significantly longer than that with placebo. Stroop and CFF performance were unaffected by any drug condition. The results suggest that caffeine may increase alertness and improve reaction time after alcohol use but will not completely counteract alcohol impairment in a driver.

Genetic susceptibility factors for alcohol-induced chronic pancreatitis.

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Aghdassi, Ali A; Weiss, F Ulrich; Mayerle, Julia; Lerch, Markus M; Simon, Peter

2015-07-01

Chronic pancreatitis is a progressive inflammatory disease of the pancreas and frequently associated with immoderate alcohol consumption. Since only a small proportion of alcoholics eventually develop chronic pancreatitis genetic susceptibility factors have long been suspected to contribute to the pathogenesis of the disease. Smaller studies in ethnically defined populations have found that not only polymorphism in proteins involved in the metabolism of ethanol, such as Alcohol Dehydrogenase and Aldehyde Dehydrogenase, can confer a risk for developing chronic pancreatitis but also mutations that had previously been reported in association with idiopathic pancreatitis, such as SPINK1 mutations. In a much broader approach employing genome wide search strategies the NAPS study found that polymorphisms in the Trypsin locus (PRSS1 rs10273639), and the Claudin 2 locus (CLDN2-RIPPLY1-MORC4 locus rs7057398 and rs12688220) confer an increased risk of developing alcohol-induced pancreatitis. These results from North America have now been confirmed by a European consortium. In another genome wide approach polymorphisms in the genes encoding Fucosyltransferase 2 (FUT2) non-secretor status and blood group B were not only found in association with higher serum lipase levels in healthy volunteers but also to more than double the risk for developing alcohol-associated chronic pancreatitis. These novel genetic associations will allow to investigate the pathophysiological and biochemical basis of alcohol-induced chronic pancreatitis on a cellular level and in much more detail than previously possible. Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Gender differences in alcohol-induced neurotoxicity and brain damage.

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Alfonso-Loeches, Silvia; Pascual, María; Guerri, Consuelo

2013-09-06

Considerable evidence has demonstrated that women are more vulnerable than men to the toxic effects of alcohol, although the results as to whether gender differences exist in ethanol-induced brain damage are contradictory. We have reported that ethanol, by activating the neuroimmune system and Toll-like receptors 4 (TLR4), can cause neuroinflammation and brain injury. However, whether there are gender differences in alcohol-induced neuroinflammation and brain injury are currently controversial. Using the brains of TLR4(+/+) and TLR4(-/-) (TLR4-KO) mice, we report that chronic ethanol treatment induces inflammatory mediators (iNOS and COX-2), cytokines (IL-1β, TNF-α), gliosis processes, caspase-3 activation and neuronal loss in the cerebral cortex of both female and male mice. Conversely, the levels of these parameters tend to be higher in female than in male mice. Using an in vivo imaging technique, our results further evidence that ethanol treatment triggers higher GFAP levels and lower MAP-2 levels in female than in male mice, suggesting a greater effect of ethanol-induced astrogliosis and less MAP-2(+) neurons in female than in male mice. Our results further confirm the pivotal role of TLR4 in alcohol-induced neuroinflammation and brain damage since the elimination of TLR4 protects the brain of males and females against the deleterious effects of ethanol. In short, the present findings demonstrate that, during the same period of ethanol treatment, females are more vulnerable than males to the neurotoxic/neuroinflammatory effects of ethanol, thus supporting the view that women are more susceptible than men to the medical consequences of alcohol abuse. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Reversible Posterior Leukoencephalopathy Syndrome Induced by Pazopanib

International Nuclear Information System (INIS)

Chelis, Leonidas; Kakolyris, Stylianos; Souftas, Vasilios; Amarantidis, Kiriakos; Xenidis, Nikolaos; Chamalidou, Eleni; Dimopoulos, Prokopios; Michailidis, Prodromos; Christakidis, Evagelos; Prassopoulos, Panagiotis

2012-01-01

The reversible posterior leukoencephalopathy syndrome is a clinical/radiological syndrome characterized by headache, seizures, impaired vision, acute hypertension, and typical magnetic resonance imaging findings. There are several reports in the literature that depict its occurrence in cancer patients. The list of common anticancer and supportive care drugs that predispose to reversible posterior leukoencephalopathy syndrome is expanding and includes not only a large number of chemotherapeutic agents but also an increased number of new targeted drugs, particularly angiogenesis inhibitors such as bevacizumab,sorefenib and sunitinib. Pazopanib is an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit which after a positive phase III randomized clinical trial in patients with advanced renal cell cancer received FDA approval for the treatment of advanced renal cell carcinoma. Until now no cases of reversible posterior leukoencephalopathy syndrome induced by pazopanib have been reported. We present the case of a 40 years old female patient with heavily pre-treated metastatic renal cell carcinoma who received pazopanib as salvage treatment. After 21 days of pazopanib therapy the patient referred to the emergency department with epileptic seizure, impaired vision at both eyes and headache. MRI of the brain revealed subcortical oedema at the occipital and parietal lobes bilaterally. She was treated with anticonvulsants, i.v. administration of mannitol and antihypertensives and she recovered completely from her symptoms and was discharged on the tenth hospital day. A brain MRI performed 3 weeks after showed that the subcortical oedema had been subsided. In conclusion this is the first case of pazopanib induced reversible posterior leukoencephalopathy syndrome. Although usually reversible, this syndrome is a serious and potentially life threatening adverse effect, if untreated, that should

Reversible Posterior Leukoencephalopathy Syndrome Induced by Pazopanib

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Chelis Leonidas

2012-10-01

Full Text Available Abstract Background The reversible posterior leukoencephalopathy syndrome is a clinical/radiological syndrome characterized by headache, seizures, impaired vision, acute hypertension, and typical magnetic resonance imaging findings. There are several reports in the literature that depict its occurrence in cancer patients. The list of common anticancer and supportive care drugs that predispose to reversible posterior leukoencephalopathy syndrome is expanding and includes not only a large number of chemotherapeutic agents but also an increased number of new targeted drugs, particularly angiogenesis inhibitors such as bevacizumab,sorefenib and sunitinib. Pazopanib is an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit which after a positive phase III randomized clinical trial in patients with advanced renal cell cancer received FDA approval for the treatment of advanced renal cell carcinoma. Until now no cases of reversible posterior leukoencephalopathy syndrome induced by pazopanib have been reported. Case report We present the case of a 40 years old female patient with heavily pre-treated metastatic renal cell carcinoma who received pazopanib as salvage treatment. After 21 days of pazopanib therapy the patient referred to the emergency department with epileptic seizure, impaired vision at both eyes and headache. MRI of the brain revealed subcortical oedema at the occipital and parietal lobes bilaterally. She was treated with anticonvulsants, i.v. administration of mannitol and antihypertensives and she recovered completely from her symptoms and was discharged on the tenth hospital day. A brain MRI performed 3 weeks after showed that the subcortical oedema had been subsided. Conclusion In conclusion this is the first case of pazopanib induced reversible posterior leukoencephalopathy syndrome. Although usually reversible, this syndrome is a serious and

Shanxi Aged Vinegar Protects against Alcohol-Induced Liver Injury via Activating Nrf2-Mediated Antioxidant and Inhibiting TLR4-Induced Inflammatory Response

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Ting Xia

2018-06-01

Full Text Available Shanxi aged vinegar (SAV is a typical fermented and antioxidant food, which has various health-promoting effects. This work aimed to explore the effects of SAV on alcohol-induced liver injury. A mice model of alcoholic liver injury was established to illuminate its potential mechanisms. All mice pretreated with SAV and then received an ethanol solution (50% w/v, 4.8 g/kg b.w.. The results showed that SAV ameliorated alcohol-induced histological changes and elevation of liver enzymes. SAV attenuated alcohol-induced oxidative stress by declining levels of hepatic oxidants, and restoring depletion of antioxidant enzyme activities in mice livers. Moreover, SAV alleviated alcohol-induced oxidative damage by activating nuclear factor erythroid-2-related factor 2 (Nrf2-mediated signal pathway. In addition, SAV prevented alcohol-induced inflammation by suppressing lipopolysaccharide (LPS level and activities of pro-inflammatory enzymes, and regulating inflammatory cytokines. SAV inhibited alcohol-induced inflammation through down-regulating the expression of Toll-like receptor 4 (TLR4-mediated inflammatory response. The findings provide crucial evidence for elucidating the hepatoprotective mechanisms of SAV and encourage the future application of SAV as a functional food for liver protection.

Alcohol-induced changes in the brain as assessed by MRI and CT

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Geibprasert, Sasikhan [University of Toronto, Hospital for Sick Children, Division of Neuroradiology, Department of Diagnostic Imaging, Toronto, ON (Canada); Gallucci, Massimo [University Hospital ' ' S. Salvatore' ' , Division of Neuroradiology, Department of Diagnostic Imaging, L' Aquila (Italy); Krings, Timo [University of Toronto, Toronto Western Hospital, Division of Neuroradiology, Department of Medical Imaging, Toronto, ON (Canada)

2010-06-15

This review provides an overview of structural magnetic resonance imaging and computed tomography findings of direct and indirect alcohol-related toxic effects on the brain. In addition to ethanol-related changes to the brain, this article will also describe imaging findings in the acute setting of methanol and ethylene glycol poisoning. Alcohol will lead to brain atrophy, osmotic myelinolysis, Marchiafava-Bignami disease and, especially when related to malnutrition, may also cause Wernicke encephalopathy. Brain atrophy can be reversible if alcohol abuse is stopped. If not treated, Wernicke encephalopathy can lead to coma and death and an early diagnosis is important for immediate initiation of thiamine substitution. As clinical symptoms are often unspecific, the radiologist plays an important role in the detection of alcohol abuse and its related clinical conditions. (orig.)

Alcohol-induced changes in the brain as assessed by MRI and CT

International Nuclear Information System (INIS)

Geibprasert, Sasikhan; Gallucci, Massimo; Krings, Timo

2010-01-01

This review provides an overview of structural magnetic resonance imaging and computed tomography findings of direct and indirect alcohol-related toxic effects on the brain. In addition to ethanol-related changes to the brain, this article will also describe imaging findings in the acute setting of methanol and ethylene glycol poisoning. Alcohol will lead to brain atrophy, osmotic myelinolysis, Marchiafava-Bignami disease and, especially when related to malnutrition, may also cause Wernicke encephalopathy. Brain atrophy can be reversible if alcohol abuse is stopped. If not treated, Wernicke encephalopathy can lead to coma and death and an early diagnosis is important for immediate initiation of thiamine substitution. As clinical symptoms are often unspecific, the radiologist plays an important role in the detection of alcohol abuse and its related clinical conditions. (orig.)

Light/Dark Shifting Promotes Alcohol-Induced Colon Carcinogenesis: Possible Role of Intestinal Inflammatory Milieu and Microbiota

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Faraz Bishehsari

2016-12-01

Full Text Available Background: Colorectal cancer (CRC is associated with the modern lifestyle. Chronic alcohol consumption—a frequent habit of majority of modern societies—increases the risk of CRC. Our group showed that chronic alcohol consumption increases polyposis in a mouse mode of CRC. Here we assess the effect of circadian disruption—another modern life style habit—in promoting alcohol-associated CRC. Method: TS4Cre × adenomatous polyposis coli (APClox468 mice underwent (a an alcohol-containing diet while maintained on a normal 12 h light:12 h dark cycle; or (b an alcohol-containing diet in conjunction with circadian disruption by once-weekly 12 h phase reversals of the light:dark (LD cycle. Mice were sacrificed after eight weeks of full alcohol and/or LD shift to collect intestine samples. Tumor number, size, and histologic grades were compared between animal groups. Mast cell protease 2 (MCP2 and 6 (MCP6 histology score were analyzed and compared. Stool collected at baseline and after four weeks of experimental manipulations was used for microbiota analysis. Results: The combination of alcohol and LD shifting accelerated intestinal polyposis, with a significant increase in polyp size, and caused advanced neoplasia. Consistent with a pathogenic role of stromal tryptase-positive mast cells in colon carcinogenesis, the ratio of mMCP6 (stromal/mMCP2 (intraepithelial mast cells increased upon LD shifting. Baseline microbiota was similar between groups, and experimental manipulations resulted in a significant difference in the microbiota composition between groups. Conclusions: Circadian disruption by Light:dark shifting exacerbates alcohol-induced polyposis and CRC. Effect of circadian disruption could, at least partly, be mediated by promoting a pro-tumorigenic inflammatory milieu via changes in microbiota.

Prevention of congenital defects induced by prenatal alcohol exposure (Conference Presentation)

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Sheehan, Megan M.; Karunamuni, Ganga; Pedersen, Cameron J.; Gu, Shi; Doughman, Yong Qiu; Jenkins, Michael W.; Watanabe, Michiko; Rollins, Andrew M.

2017-02-01

Nearly 2 million women in the United States alone are at risk for an alcohol-exposed pregnancy, including more than 600,000 who binge drink. Even low levels of prenatal alcohol exposure (PAE) can lead to a variety of birth defects, including craniofacial and neurodevelopmental defects, as well as increased risk of miscarriages and stillbirths. Studies have also shown an interaction between drinking while pregnant and an increase in congenital heart defects (CHD), including atrioventricular septal defects and other malformations. We have previously established a quail model of PAE, modeling a single binge drinking episode in the third week of a woman's pregnancy. Using optical coherence tomography (OCT), we quantified intraventricular septum thickness, great vessel diameters, and atrioventricular valve volumes. Early-stage ethanol-exposed embryos had smaller cardiac cushions (valve precursors) and increased retrograde flow, while late-stage embryos presented with gross head/body defects, and exhibited smaller atrio-ventricular (AV) valves, interventricular septum, and aortic vessels. We previously showed that supplementation with the methyl donor betaine reduced gross defects, improved survival rates, and prevented cardiac defects. Here we show that these preventative effects are also observed with folate (another methyl donor) supplementation. Folate also appears to normalize retrograde flow levels which are elevated by ethanol exposure. Finally, preliminary findings have shown that glutathione, a crucial antioxidant, is noticeably effective at improving survival rates and minimizing gross defects in ethanol-exposed embryos. Current investigations will examine the impact of glutathione supplementation on PAE-related CHDs.

Vinclozolin exposure in utero induces postpubertal prostatitis and reduces sperm production via a reversible hormone-regulated mechanism.

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Cowin, Prue A; Gold, Elspeth; Aleksova, Jasna; O'Bryan, Moira K; Foster, Paul M D; Scott, Hamish S; Risbridger, Gail P

2010-02-01

Vinclozolin is an endocrine-disrupting chemical (EDC) that binds with high affinity to the androgen receptor (AR) and blocks the action of gonadal hormones on male reproductive organs. An alternative mechanism of action of Vinclozolin involves transgenerational effects on the male reproductive tract. We previously reported in utero Vinclozolin exposure-induced prostatitis (prostate inflammation) in postpubertal rats concurrent with down-regulation of AR and increased nuclear factor-kappaB activation. We postulated the male reproductive abnormalities induced by in utero Vinclozolin exposure could be reversed by testosterone supplementation, in contrast to the permanent modifications involving DNA methyltransferases (Dnmts) described by others. To test this hypothesis, we administered high-dose testosterone at puberty to Vinclozolin-treated rats and determined the effect on anogenital distance (AGD); testicular germ cell apoptosis, concentration of elongated spermatids, and the onset of prostatitis. Concurrently we examined Dnmt1, -3A, -3B, and -3L mRNA expression. Consistent with previous reports, in utero exposure to Vinclozolin significantly reduced AGD, increased testicular germ cell apoptosis 3-fold, reduced elongated spermatid number by 40%, and induced postpubertal prostatitis in 100% of exposed males. Administration of high-dose testosterone (25 mg/kg) at puberty normalized AGD, reduced germ cell apoptosis, and restored elongated spermatid number. Testosterone restored AR and nuclear factor-kappaB expression in the prostate and abolished Vinclozolin-induced prostatitis. Altered Dnmt expression was evident with in utero Vinclozolin exposure and was not normalized after testosterone treatment. These data demonstrate in utero Vinclozolin-induced male reproductive tract abnormalities are AR mediated and reversible and involve a mechanism independent of Dnmt expression.

The Effects of Syzygium samarangense, Passiflora edulis and Solanum muricatum on Alcohol-Induced Liver Injury

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Yu-Jie Zhang

2016-09-01

Full Text Available Previous studies have shown that fruits have different effects on alcohol metabolism and alcohol-induced liver injury. The present work selected three fruits and aimed at studying the effects of Syzygium samarangense, Passiflora edulis and Solanum muricatum on alcohol-induced liver injury in mice. The animals were treated daily with alcohol and fruit juices for fifteen days. Chronic treatment with alcohol increased the levels of aspartate transaminase (AST, alanine transaminase (ALT, total bilirubin (TBIL, triglyceride (TG, malondialdehyde (MDA, and decreased total protein (TP. Histopathological evaluation also showed that ethanol induced extensive fat droplets in hepatocyte cytoplasm. Syzygium samarangense and Passiflora edulis normalized various biochemical parameters. Solanum muricatum increased the level of ALT and induced infiltration of inflammatory cells in the liver. These results strongly suggest that treatment with Syzygium samarangense and Passiflora edulis could protect liver from the injury of alcohol, while Solanum muricatum could aggravate the damage.

Effects of Beverages on Alcohol Metabolism: Potential Health Benefits and Harmful Impacts

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Fang Wang

2016-03-01

Full Text Available Nonalcoholic beverages are usually consumed accompanying alcoholic drinks, and their effects on alcohol metabolism are unclear in vivo. In this study, the effects of 20 nonalcoholic beverages on alcohol metabolism and liver injury caused by alcohol were evaluated in mice. Kunming mice were orally fed with alcohol (52%, v/v and beverages. The concentrations of ethanol and acetaldehyde in blood as well as the activities of alcohol dehydrogenase (ADH and aldehyde dehydrogenase (ALDH in liver were assessed to indicate alcohol metabolism. The levels of aspartate aminotransferase (AST and alanine transaminase (ALT in serum as well as the levels of malonaldehyde (MDA and superoxide dismutase (SOD in liver were measured to reflect the alcohol-induced liver injury. The results showed that the treatment of soda water, green tea and honey chrysanthemum tea could accelerate ethanol metabolism and prevent liver injuries caused by alcohol when companied with excessive alcohol drinking. They might be potential dietary supplements for the alleviation of harmful effects from excessive alcohol consumption. On the contrary, some beverages such as fresh orange juice and red bull are not advised to drink when companied with alcohol consumption due to their adverse effects on ethanol induced liver injury.

Inactivation of Ca2+-induced ciliary reversal by high-salt extraction in the cilia of Paramecium.

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Kutomi, Osamu; Seki, Makoto; Nakamura, Shogo; Kamachi, Hiroyuki; Noguchi, Munenori

2013-10-01

Intracellular Ca(2+) induces ciliary reversal and backward swimming in Paramecium. However, it is not known how the Ca(2+) signal controls the motor machinery to induce ciliary reversal. We found that demembranated cilia on the ciliated cortical sheets from Paramecium caudatum lost the ability to undergo ciliary reversal after brief extraction with a solution containing 0.5 M KCl. KNO(3), which is similar to KCl with respect to chaotropic effect; it had the same effect as that of KCl on ciliary response. Cyclic AMP antagonizes Ca(2+)-induced ciliary reversal. Limited trypsin digestion prevents endogenous A-kinase and cAMP-dependent phosphorylation of an outer arm dynein light chain and induces ciliary reversal. However, the trypsin digestion prior to the high-salt extraction did not affect the inhibition of Ca(2+)-induced ciliary reversal caused by the high-salt extraction. Furthermore, during the course of the high-salt extraction, some axonemal proteins were extracted from ciliary axonemes, suggesting that they may be responsible for Ca(2+)-induced ciliary reversal.

Reversal of rocuronium-induced profound neuromuscular block by sugammadex in Duchenne muscular dystrophy.

NARCIS (Netherlands)

Boer, H.D. de; Egmond, J. van; Booij, L.H.D.J.; Driessen, J.J.

2009-01-01

A case is reported in which a child with Duchenne muscular dystrophy received a dose of sugammadex to reverse a rocuronium-induced profound neuromuscular block. Sugammadex is the first selective relaxant binding agent and reverses rocuronium- and vecuronium-induced neuromuscular block. A fast and

Mechanisms of Alcohol-Induced Endoplasmic Reticulum Stress and Organ Injuries

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Cheng Ji

2012-01-01

Full Text Available Alcohol is readily distributed throughout the body in the blood stream and crosses biological membranes, which affect virtually all biological processes inside the cell. Excessive alcohol consumption induces numerous pathological stress responses, part of which is endoplasmic reticulum (ER stress response. ER stress, a condition under which unfolded/misfolded protein accumulates in the ER, contributes to alcoholic disorders of major organs such as liver, pancreas, heart, and brain. Potential mechanisms that trigger the alcoholic ER stress response are directly or indirectly related to alcohol metabolism, which includes toxic acetaldehyde and homocysteine, oxidative stress, perturbations of calcium or iron homeostasis, alterations of S-adenosylmethionine to S-adenosylhomocysteine ratio, and abnormal epigenetic modifications. Interruption of the ER stress triggers is anticipated to have therapeutic benefits for alcoholic disorders.

Role of hypoxia inducing factor-1β in alcohol-induced autophagy, steatosis and liver injury in mice.

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Hong-Min Ni

Full Text Available Chronic alcohol causes liver hypoxia and steatosis, which eventually develops into alcoholic liver disease (ALD. While it has been known that alcohol consumption activates hepatic hypoxia inducing factor-1α (HIF-1α, conflicting results regarding the role of HIF-1α in alcohol-induced liver injury and steatosis in mice have been reported. In the present study, we aimed to use hepatocyte-specific HIF-1β knockout mice to eliminate the possible compensatory effects of the single knockout of the 1α subunit of HIF to study the role of HIFs in ALD. C57BL/6 wild type mice were treated with acute ethanol to mimic human binge drinking. Matched wild-type and hepatocyte specific HIF-1β knockout mice were also subjected to a recently established Gao-binge alcohol model to mimic chronic plus binge conditions, which is quite common in human alcoholics. We found that acute alcohol treatment increased BNIP3 and BNIP3L/NIX expression in primary cultured hepatocytes and in mouse livers, suggesting that HIF may be activated in these models. We further found that hepatocyte-specific HIF-1β knockout mice developed less steatosis and liver injury following the Gao-binge model or acute ethanol treatment compared with their matched wild type mice. Mechanistically, protection against Gao-binge treatment-induced steatosis and liver injury was likely associated with increased FoxO3a activation and subsequent induction of autophagy in hepatocyte-specific HIF-1β knockout mice.

Idarucizumab for Reversing Dabigatran-Induced Anticoagulation: A Systematic Review.

Science.gov (United States)

Thibault, Nathan; Morrill, Amanda M; Willett, Kristine C

The approval of the oral direct thrombin inhibitor, dabigatran etexilate, gave patients an alternative to oral anticoagulation with warfarin. Like all anticoagulants, the primary adverse event (AE) associated with dabigatran is bleeding. Until the FDA approval of idarucizumab, there had been no reversal agent for dabigatran-induced anticoagulation in patients with life-threatening or uncontrollable bleeding, or those requiring emergent procedures. The primary purpose of this review is to summarize the safety and efficacy of idarucizumab, a monoclonal antibody fragment, and its use as a reversal agent for dabigatran. A literature search was conducted through MEDLINE (1946 to November week 1 2015) and Embase (1980-2015 week 46) using the search term idarucizumab. Clinicaltrials.gov was consulted for a comprehensive list of ongoing and completed studies. Additional studies were identified through bibliographical citations. Clinical trials in animals and humans published in English evaluating the safety and efficacy of idarucizumab for reversal of anticoagulant treatment with dabigatran were included for review. Idarucizumab has been shown to significantly reverse the anticoagulant effects of dabigatran in both healthy volunteers and patients requiring a reversal agent because of either overt bleeding or an emergency surgery or invasive procedure. The most common AEs were headache, nasopharyngitis, back pain, skin irritation, hypokalemia, delirium, constipation, pyrexia, and pneumonia. Deaths reported in idarucizumab studies were attributed to either the index event or a preexisting comorbidity. Most adverse effects were minor, but 21 serious AEs have been reported in the published data including thrombotic events. Given the increased use of direct oral anticoagulants, such as dabigatran, a need for specific reversal agents exists. Idarucizumab has been shown to be safe and effective in the reversal of dabigatran-induced anticoagulation in patients requiring emergent

Dietary supplement enriched in antioxidants and omega-3 protects from progressive light-induced retinal degeneration.

Science.gov (United States)

Ramchani-Ben Othman, Khaoula; Cercy, Christine; Amri, Mohamed; Doly, Michel; Ranchon-Cole, Isabelle

2015-01-01

In the present study, we have evaluated one of the dietary supplements enriched with antioxidants and fish oil used in clinical care for patient with age-related macular degeneration. Rats were orally fed by a gastric canula daily with 0.2 ml of water or dietary supplement until they were sacrificed. After one week of treatment, animals were either sacrificed for lipid analysis in plasma and retina, or used for evaluation of rod-response recovery by electroretinography (ERG) followed by their sacrifice to measure rhodopsin content, or used for progressive light-induced retinal degeneration (PLIRD). For PLIRD, animals were transferred to bright cyclic light for one week. Retinal damage was quantified by ERG, histology and detection of apoptotic nuclei. Animals kept in dim-cyclic-light were processed in parallel. PLIRD induced a thinning of the outer nuclear layer and a reduction of the b-wave amplitude of the ERG in the water group. Retinal structure and function were preserved in supplemented animals. Supplement induced a significant increase in omega-3 fatty acids in plasma by 168% for eicosapentaenoic acid (EPA), 142% for docosapentaenoic acid (DPA) and 19% for docosahexaenoic acid (DHA) and a decrease in the omega-6 fatty acids, DPA by 28%. In the retina, supplement induced significant reduction of linolenic acid by 67% and an increase in EPA and DPA by 80% and 72%, respectively, associated with significant decrease in omega-6 DPA by 42%. Supplement did not affect rhodopsin content or rod-response recovery. The present data indicate that supplement rapidly modified the fatty acid content and induced an accumulation of EPA in the retina without affecting rhodopsin content or recovery. In addition, it protected the retina from oxidative stress induced by light. Therefore, this supplement might be beneficial to slow down progression of certain retinal degeneration.

Dietary supplement enriched in antioxidants and omega-3 protects from progressive light-induced retinal degeneration.

Directory of Open Access Journals (Sweden)

Khaoula Ramchani-Ben Othman

Full Text Available In the present study, we have evaluated one of the dietary supplements enriched with antioxidants and fish oil used in clinical care for patient with age-related macular degeneration. Rats were orally fed by a gastric canula daily with 0.2 ml of water or dietary supplement until they were sacrificed. After one week of treatment, animals were either sacrificed for lipid analysis in plasma and retina, or used for evaluation of rod-response recovery by electroretinography (ERG followed by their sacrifice to measure rhodopsin content, or used for progressive light-induced retinal degeneration (PLIRD. For PLIRD, animals were transferred to bright cyclic light for one week. Retinal damage was quantified by ERG, histology and detection of apoptotic nuclei. Animals kept in dim-cyclic-light were processed in parallel. PLIRD induced a thinning of the outer nuclear layer and a reduction of the b-wave amplitude of the ERG in the water group. Retinal structure and function were preserved in supplemented animals. Supplement induced a significant increase in omega-3 fatty acids in plasma by 168% for eicosapentaenoic acid (EPA, 142% for docosapentaenoic acid (DPA and 19% for docosahexaenoic acid (DHA and a decrease in the omega-6 fatty acids, DPA by 28%. In the retina, supplement induced significant reduction of linolenic acid by 67% and an increase in EPA and DPA by 80% and 72%, respectively, associated with significant decrease in omega-6 DPA by 42%. Supplement did not affect rhodopsin content or rod-response recovery. The present data indicate that supplement rapidly modified the fatty acid content and induced an accumulation of EPA in the retina without affecting rhodopsin content or recovery. In addition, it protected the retina from oxidative stress induced by light. Therefore, this supplement might be beneficial to slow down progression of certain retinal degeneration.

Acute versus chronic alcohol consumption in acetaminophen-induced hepatotoxicity

DEFF Research Database (Denmark)

Schmidt, L.E.; Dalhoff, K.P.; Poulsen, Henrik E.

2002-01-01

. With a time to NAC less than 12 hours, the mortality rate was 0.42% (95% CI, 0.05-2.7). When time to NAC exceeded 12, 24, and 48 hours, the mortality rate increased to 6.1%, 13%, and 19%, respectively. Chronic alcohol abuse was an independent risk factor of mortality (odds ratio [OR], 3.52; 95% CI, 1...... was confirmed as the major risk factor in acetaminophen-induced hepatotoxicity and mortality. Chronic alcohol abuse was an independent risk factor that could be counteracted by concomitant acute alcohol ingestion. We suggest that patients with chronic alcoholism and suspected acetaminophen poisoning due......The aim of this study was to determine by multivariate analysis how alcohol and other factors affect the clinical course and outcome in patients with acetaminophen (paracetamol) poisoning. A total of 645 consecutive patients admitted from 1994 to 2000 with single-dose acetaminophen poisoning were...

Social transfer of alcohol withdrawal-induced hyperalgesia in female prairie voles.

Science.gov (United States)

Walcott, Andre T; Smith, Monique L; Loftis, Jennifer M; Ryabinin, Andrey E

2018-03-27

The expression of pain serves as a way for animals to communicate potential dangers to nearby conspecifics. Recent research demonstrated that mice undergoing alcohol or morphine withdrawal, or inflammation, could socially communicate their hyperalgesia to nearby mice. However, it is unknown whether such social transfer of hyperalgesia can be observed in other species of rodents. Therefore, the present study investigated if the social transfer of hyperalgesia occurs in the highly social prairie vole (Microtus ochrogaster). We observe that adult female prairie voles undergoing withdrawal from voluntary two-bottle choice alcohol drinking display an increase in nociception. This alcohol withdrawal-induced hypersensitiity is socially transferred to female siblings within the same cage and female strangers housed in separate cages within the same room. These experiments reveal that the social transfer of pain phenomenon is not specific to inbred mouse strains and that prairie voles display alcohol withdrawal and social transfer-induced hyperalgesia.

Antioxidative Diet Supplementation Reverses High-Fat Diet-Induced Increases of Cardiovascular Risk Factors in Mice

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Hilda Vargas-Robles

2015-01-01

Full Text Available Obesity is a worldwide epidemic that is characterized not only by excessive fat deposition but also by systemic microinflammation, high oxidative stress, and increased cardiovascular risk factors. While diets enriched in natural antioxidants showed beneficial effects on oxidative stress, blood pressure, and serum lipid composition, diet supplementation with synthetic antioxidants showed contradictive results. Thus, we tested in C57Bl/6 mice whether a daily dosage of an antioxidative mixture consisting of vitamin C, vitamin E, L-arginine, eicosapentaenoic acid, and docosahexaenoic acid (corabion would affect cardiovascular risk factors associated with obesity. Obese mice showed increased serum triglyceride and glucose levels and hypertension after eight weeks of being fed a high-fat diet (HFD. Importantly, corabion ameliorated all of these symptoms significantly. Oxidative stress and early signs of systemic microinflammation already developed after two weeks of high-fat diet and were significantly reduced by daily doses of corabion. Of note, the beneficial effects of corabion could not be observed when applying its single antioxidative components suggesting that a combination of various nutrients is required to counteract HFD-induced cardiovascular risk factors. Thus, daily consumption of corabion may be beneficial for the management of obesity-related cardiovascular complications.

DNA Methylation program in normal and alcohol-induced thinning cortex.

Science.gov (United States)

Öztürk, Nail Can; Resendiz, Marisol; Öztürk, Hakan; Zhou, Feng C

2017-05-01

While cerebral underdevelopment is a hallmark of fetal alcohol spectrum disorders (FASD), the mechanism(s) guiding the broad cortical neurodevelopmental deficits are not clear. DNA methylation is known to regulate early development and tissue specification through gene regulation. Here, we examined DNA methylation in the onset of alcohol-induced cortical thinning in a mouse model of FASD. C57BL/6 (B6) mice were administered a 4% alcohol (v/v) liquid diet from embryonic (E) days 7-16, and their embryos were harvested at E17, along with isocaloric liquid diet and lab chow controls. Cortical neuroanatomy, neural phenotypes, and epigenetic markers of methylation were assessed using immunohistochemistry, Western blot, and methyl-DNA assays. We report that cortical thickness, neuroepithelial proliferation, and neuronal migration and maturity were found to be deterred by alcohol at E17. Simultaneously, DNA methylation, including 5-methylcytosine (5mC) and 5-hydroxcylmethylcytosine (5hmC), which progresses as an intrinsic program guiding normal embryonic cortical development, was severely affected by in utero alcohol exposure. The intricate relationship between cortical thinning and this DNA methylation program disruption is detailed and illustrated. DNA methylation, dynamic across the multiple cortical layers during the late embryonic stage, is highly disrupted by fetal alcohol exposure; this disruption occurs in tandem with characteristic developmental abnormalities, ranging from structural to molecular. Finally, our findings point to a significant question for future exploration: whether epigenetics guides neurodevelopment or whether developmental conditions dictate epigenetic dynamics in the context of alcohol-induced cortical teratogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Maltol, a Food Flavoring Agent, Attenuates Acute Alcohol-Induced Oxidative Damage in Mice

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Ye Han

2015-01-01

Full Text Available The purpose of this study was to evaluate the hepatoprotective effect of maltol, a food-flavoring agent, on alcohol-induced acute oxidative damage in mice. Maltol used in this study was isolated from red ginseng (Panax ginseng C.A Meyer and analyzed by high performance liquid chromatography (HPLC and mass spectrometry. For hepatoprotective activity in vivo, pretreatment with maltol (12.5, 25 and 50 mg/kg; 15 days drastically prevented the elevated activities of aspartate transaminase (AST, alanine transaminase (ALT, alkaline phosphatase (ALP and triglyceride (TG in serum and the levels of malondialdehyde (MDA, tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β in liver tissue (p < 0.05. Meanwhile, the levels of hepatic antioxidant, such as catalase (CAT, superoxide dismutase (SOD, glutathione peroxidase (GSH-Px were elevated by maltol pretreatment, compared to the alcohol group (p < 0.05. Histopathological examination revealed that maltol pretreatment significantly inhibited alcohol-induced hepatocyte apoptosis and fatty degeneration. Interestingly, pretreatment of maltol effectively relieved alcohol-induced oxidative damage in a dose-dependent manner. Maltol appeared to possess promising anti-oxidative and anti-inflammatory capacities. It was suggested that the hepatoprotective effect exhibited by maltol on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties.

Lower risk for alcohol-induced cirrhosis in wine drinkers

DEFF Research Database (Denmark)

Becker, Ulrik; Grønbaek, Morten; Johansen, Ditte

2002-01-01

Although there is a well-known relationship between total alcohol intake and future risk for cirrhosis, other factors such as the type of alcohol consumed are sparsely studied. The aim of this study was to assess the effects of wine compared with other types of alcoholic beverages on risk...... for alcohol-induced cirrhosis. In 3 prospective studies, 30,630 participants from the Copenhagen area were followed-up for a total observation time of 417,325 person-years. Information on weekly intake of beer, wine, and spirits, and sex, age, body mass index, smoking habits, and education was obtained from...... with increasing alcohol intake. Individuals who drank more than 5 drinks per day had a relative risk of 14 to 20 for developing cirrhosis compared with non- or light drinkers. However, compared with individuals who drank no wine (relative risk set at 1.0), individuals drinking 16% to 30% wine of their total...

Strain-dependent sex differences in the effects of alcohol on cocaine-induced taste aversions.

Science.gov (United States)

Jones, Jermaine D; Busse, Gregory D; Riley, Anthony L

2006-04-01

Research using the conditioned taste aversion procedure has reported that a cocaine/alcohol combination induces a significantly stronger taste aversion than either cocaine or alcohol alone. These findings suggest that the co-administration of alcohol intensifies the aversive effects of cocaine. Although the behavioral interaction of cocaine and alcohol is well established, little is known about how the effects of this drug combination might be modulated by a variety of subject variables. The current investigation addressed this by assessing if the ability of alcohol to potentiate cocaine-induced taste aversions is dependent upon the strain and/or sex of the subject. In this series of studies, male and female rats of Long-Evans (Experiment 1) and Sprague-Dawley (Experiment 2) descent were given limited access to a novel saccharin solution to drink and were then injected with either vehicle, cocaine (20 mg/kg), alcohol (0.56 g/kg) or the alcohol/cocaine combination. This procedure was repeated every fourth day for a total of four conditioning trials. All subjects were then compared on an Aversion Test that followed the fourth conditioning cycle. In three of the groups tested (male Long-Evans; male and female Sprague-Dawley), cocaine induced a significant taste aversion that was unaffected by the co-administration of alcohol. However, in female Long-Evans subjects, the addition of alcohol significantly strengthened the avoidance of the saccharin solution. Although the effects of alcohol on cocaine-induced taste aversions are dependent upon an interaction of sex and strain, the basis for this SexxStrain interaction is not known. That such an interaction is evident suggests that attention to such factors in assessing the effects of drug combinations is important to understanding the likelihood of the use and abuse of such drugs.

Protective Effects of Rooibos (Aspalathus linearis and/or Red Palm Oil (Elaeis guineensis Supplementation on tert-Butyl Hydroperoxide-Induced Oxidative Hepatotoxicity in Wistar Rats

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Olawale R. Ajuwon

2013-01-01

Full Text Available The possible protective effects of an aqueous rooibos extract (Aspalathus linearis, red palm oil (RPO (Elaeis guineensis, or their combination on tert-butyl-hydroperoxide-(t-BHP-induced oxidative hepatotoxicity in Wistar rats were investigated. tert-butyl hydroperoxide caused a significant (P<0.05 elevation in conjugated dienes (CD and malondialdehyde (MDA levels, significantly (P<0.05 decreased reduced glutathione (GSH and GSH : GSSG ratio, and induced varying changes in activities of catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase in the blood and liver. This apparent oxidative injury was associated with histopathological changes in liver architecture and elevated levels of serum alanine aminotransferase (ALT, aspartate aminotransferase (AST, and lactate dehydrogenase (LDH. Supplementation with rooibos, RPO, or their combination significantly (P<0.05 decreased CD and MDA levels in the liver and reduced serum level of ALT, AST, and LDH. Likewise, changes observed in the activities of antioxidant enzymes and impairment in redox status in the erythrocytes and liver were reversed. The observed protective effects when rooibos and RPO were supplemented concomitantly were neither additive nor synergistic. Our results suggested that rooibos and RPO, either supplemented alone or combined, are capable of alleviating t-BHP-induced oxidative hepatotoxicity, and the mechanism of this protection may involve inhibition of lipid peroxidation and modulation of antioxidants enzymes and glutathione status.

Ethyl Alcohol Extract of Hizikia fusiforme Induces Caspase ...

African Journals Online (AJOL)

Ethyl Alcohol Extract of Hizikia fusiforme Induces Caspase-dependent Apoptosis in Human Leukemia U937 Cells by Generation of Reactive Oxygen Species. C-H Kang, S-H Kang, S-H Boo, S-Y Park, D-O Moon, G-Y Kim ...

Maternal supplementation with conjugated linoleic acid in the setting of diet-induced obesity normalises the inflammatory phenotype in mothers and reverses metabolic dysfunction and impaired insulin sensitivity in offspring.

Science.gov (United States)

Segovia, Stephanie A; Vickers, Mark H; Zhang, Xiaoyuan D; Gray, Clint; Reynolds, Clare M

2015-12-01

Maternal consumption of a high-fat diet significantly impacts the fetal environment and predisposes offspring to obesity and metabolic dysfunction during adulthood. We examined the effects of a high-fat diet during pregnancy and lactation on metabolic and inflammatory profiles and whether maternal supplementation with the anti-inflammatory lipid conjugated linoleic acid (CLA) could have beneficial effects on mothers and offspring. Sprague-Dawley rats were fed a control (CD; 10% kcal from fat), CLA (CLA; 10% kcal from fat, 1% total fat as CLA), high-fat (HF; 45% kcal from fat) or high fat with CLA (HFCLA; 45% kcal from fat, 1% total fat as CLA) diet ad libitum 10days prior to and throughout gestation and lactation. Dams and offspring were culled at either late gestation (fetal day 20, F20) or early postweaning (postnatal day 24, P24). CLA, HF and HFCLA dams were heavier than CD throughout gestation. Plasma concentrations of proinflammatory cytokines interleukin-1β and tumour necrosis factor-α were elevated in HF dams, with restoration in HFCLA dams. Male and female fetuses from HF dams were smaller at F20 but displayed catch-up growth and impaired insulin sensitivity at P24, which was reversed in HFCLA offspring. HFCLA dams at P24 were protected from impaired insulin sensitivity as compared to HF dams. Maternal CLA supplementation normalised inflammation associated with consumption of a high-fat diet and reversed associated programming of metabolic dysfunction in offspring. This demonstrates that there are critical windows of developmental plasticity in which the effects of an adverse early-life environment can be reversed by maternal dietary interventions. Copyright © 2015 Elsevier Inc. All rights reserved.

Acute Alcohol Intoxication Exacerbates Rhabdomyolysis-Induced Acute Renal Failure in Rats.

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Tsai, Jen-Pi; Lee, Chung-Jen; Subeq, Yi-Maun; Lee, Ru-Ping; Hsu, Bang-Gee

2017-01-01

Traumatic and nontraumatic rhabdomyolysis can lead to acute renal failure (ARF), and acute alcohol intoxication can lead to multiple abnormalities of the renal tubules. We examined the effect of acute alcohol intoxication in a rat model of rhabdomyolysis and ARF. Intravenous injections of 5 g/kg ethanol were given to rats over 3 h, followed by glycerol-induced rhabdomyolysis. Biochemical parameters, including blood urea nitrogen (BUN), creatinine (Cre), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and creatine phosphokinase (CPK), were measured before and after induction of rhabdomyolysis. Renal tissue injury score, renal tubular cell expression of E-cadherin, nuclear factor-κB (NF-κB), and inducible nitric oxide synthase (iNOS) were determined. Relative to rats in the vehicle group, rats in the glycerol-induced rhabdomyolysis group had significantly increased serum levels of BUN, Cre, GOT, GPT, and CPK, elevated renal tissue injury scores, increased expression of NF-κB and iNOS, and decreased expression of E-cadherin. Ethanol exacerbated all of these pathological responses. Our results suggest that acute alcohol intoxication exacerbates rhabdomyolysis-induced ARF through its pro-oxidant and inflammatory effects.

Supplementation of fenugreek leaves lower lipid profile in streptozotocin-induced diabetic rats.

Science.gov (United States)

Annida, B; Stanely Mainzen Prince, P

2004-01-01

The present study was undertaken to evaluate the lipid-lowering effect of fenugreek leaves in diabetes mellitus. Albino Wistar rats were randomly divided into six groups: normal untreated rats; streptozotocin (STZ)-induced diabetic rats; STZ-induced rats + fenugreek leaves (0.5 g/kg of body weight); STZ-induced rats + fenugreek leaves (1 g/kg of body weight); STZ-induced rats + glibenclamide (600 microg/kg of body weight); and STZ-induced rats + insulin (6 units/kg of body weight). Rats were made diabetic by STZ (40 mg/kg) injected intraperitoneally. Fenugreek leaves were supplemented in the diet daily to diabetic rats for 45 days, and food intake was recorded daily. Blood glucose, total cholesterol, triglycerides, and free fatty acids were determined in serum, liver, heart, and kidney. Our results show that blood glucose and serum and tissue lipids were elevated in STZ-induced diabetic rats. Supplementation of fenugreek leaves lowered the lipid profile in STZ-induced diabetic rats.

A Sustained Depressive State Promotes a Guanfacine Reversible Susceptibility to Alcohol Seeking in Rats

NARCIS (Netherlands)

Riga, D.; Schmitz, L.J.M.; van der Harst, J.E.; van Mourik, Y.; Hoogendijk, W.J.G.; Smit, A.B.; de Vries, T.J.; Spijker, S.

2014-01-01

High rates of comorbidity between alcohol use disorder (AUD) and major depressive disorder (MDD) are reported. Preclinical models examining effects of primary depression on secondary AUD are currently absent, preventing adequate testing of drug treatment. Here, we combined social defeat-induced

Effect of a heme oxygenase-1 inducer on NADPH oxidase ...

African Journals Online (AJOL)

Acute alcohol consumption leads to fatty liver. Although fatty liver is a reversible injury, its progression can develop into more severe liver problems including steatohepatitis and cirrhosis [1]. Previous studies showed that oxidative stress is an important factor contributing to the development of alcohol-induced liver injury [2].

N-Acetylcysteine Reverses Cocaine Induced Metaplasticity

Science.gov (United States)

Moussawi, Khaled; Pacchioni, Alejandra; Moran, Megan; Olive, M. Foster; Gass, Justin T.; Lavin, Antonieta; Kalivas, Peter W

2009-01-01

Cocaine addiction is characterized by an impaired ability to develop adaptive behaviors that can compete with cocaine seeking, implying a deficit in the ability to induce plasticity in cortico-accumbens circuitry critical for regulating motivated behavior. RWe found that rats withdrawn from cocaine self-administration had a marked in vivo deficit in the ability to develop long-term potentation (LTP) and depression (LTD) in the nucleus accumbens core subregion following stimulation of prefrontal cortex. N-acetylcysteine treatment prevents relapse in animal models and craving in humans by activating cystine-glutamate exchange and thereby stimulating extrasynaptic metabotropic glutamate receptors (mGluR). N-acetylcysteine treatment restored the ability to induce LTP and LTD by indirectly stimulating mGluR2/3 and mGluR5, respectively. Cocaine self-administration induces metaplasticity that inhibits the further induction of synaptic plasticity, and this impairment can be reversed by N-acetylcysteine, a drug that also prevents relapse. PMID:19136971

N-Acetylcysteine reverses cocaine-induced metaplasticity.

Science.gov (United States)

Moussawi, Khaled; Pacchioni, Alejandra; Moran, Megan; Olive, M Foster; Gass, Justin T; Lavin, Antonieta; Kalivas, Peter W

2009-02-01

Cocaine addiction is characterized by an impaired ability to develop adaptive behaviors that can compete with cocaine seeking, implying a deficit in the ability to induce plasticity in cortico-accumbens circuitry crucial for regulating motivated behavior. We found that rats withdrawn from cocaine self-administration had a marked in vivo deficit in the ability to develop long-term potentiation (LTP) and long-term depression (LTD) in the nucleus accumbens core subregion after stimulation of the prefrontal cortex. N-acetylcysteine (NAC) treatment prevents relapse in animal models and craving in humans by activating cystine-glutamate exchange and thereby stimulating extrasynaptic metabotropic glutamate receptors (mGluR). NAC treatment of rats restored the ability to induce LTP and LTD by indirectly stimulating mGluR2/3 and mGluR5, respectively. Our findings show that cocaine self-administration induces metaplasticity that inhibits further induction of synaptic plasticity, and this impairment can be reversed by NAC, a drug that also prevents relapse.

Increases in anxiety-like behavior induced by acute stress are reversed by ethanol in adolescent but not adult rats.

Science.gov (United States)

Varlinskaya, Elena I; Spear, Linda P

2012-01-01

Repeated exposure to stressors has been found to increase anxiety-like behavior in laboratory rodents, with the social anxiety induced by repeated restraint being extremely sensitive to anxiolytic effects of ethanol in both adolescent and adult rats. No studies, however, have compared social anxiogenic effects of acute stress or the capacity of ethanol to reverse this anxiety in adolescent and adult animals. Therefore, the present study was designed to investigate whether adolescent [postnatal day (P35)] Sprague-Dawley rats differ from their adult counterparts (P70) in the impact of acute restraint stress on social anxiety and in their sensitivity to the social anxiolytic effects of ethanol. Animals were restrained for 90 min, followed by examination of stress- and ethanol-induced (0, 0.25, 0.5, 0.75, and 1 g/kg) alterations in social behavior using a modified social interaction test in a familiar environment. Acute restraint stress increased anxiety, as indexed by reduced levels of social investigation at both ages, and decreased social preference among adolescents. These increases in anxiety were dramatically reversed among adolescents by acute ethanol. No anxiolytic-like effects of ethanol emerged following restraint stress in adults. The social suppression seen in response to higher doses of ethanol was reversed by restraint stress in animals of both ages. To the extent that these data are applicable to humans, the results of the present study provide some experimental evidence that stressful life events may increase the attractiveness of alcohol as an anxiolytic agent for adolescents. Copyright © 2011 Elsevier Inc. All rights reserved.

[Effect of Dendrobium officinale granule on long-term-alcohol-induced hypertension rats].

Science.gov (United States)

Lv, Gui-Yuan; Xia, Chao-Qun; Chen, Su-Hong; Su, Jie; Liu, Xiao-Pang; Li, Bo; Gao, Jian-Li

2013-10-01

To observe the effect of Dendrobium officinale granule (DOG) on symptoms, blood pressure and serum biochemical indexes of long-term-alcohol-induced hypertension rats. The alcohol-induced hypertension rat model was established by feeding alcohol drink to normal rats (the alcohol volume fraction increases from 5% to 22%). Since the 4th week, DOG was administered for 32 weeks, once everyday. During the experiment, body weight, kinematic parameters (locomotor activities, grip strength, duration of vertigo) and blood pressures (systolic blood pressure, diastolic blood pressure and mean blood pressure) were detected regularly. On the 28th and 32nd weeks, blood samples were collected to determine serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), uric acid (UA), creatinine (Cr), cholesterol (CH) and triglycerides (TG). (1) Sign: The DOG-administered group showed reduction in the duration of vertigo and increase in appetite, body weight, locomotor activities and grip strength. (2) Blood pressure: The DOG-administered group showed significant decrease in blood pressure since the 8th week. (3) Biochemical indexes: The DOG-administered group showed notable decrease in serum ALT, AST, ALP, Cr, UA, TG level, but without significant change in TC level. The long-term administration of DOG can relieve alcohol-induced hypertension, while alleviating general signs, liver and kidney injuries and abnormal blood fat biochemical indexes.

The effects of moderate alcohol supplementation on estrone sulfate and DHEAS in postmenopausal women in a controlled feeding study

Directory of Open Access Journals (Sweden)

Albanes Demetrius

2004-09-01

Full Text Available Abstract Background We have demonstrated that moderate alcohol consumption (15 g/d, 30 g/d for 8 weeks resulted in significantly increased levels of serum estrone sulfate and DHEAS in 51 postmenopausal women in a randomized, placebo-controlled trial. We now report on the relationships between serum estrone sulfate and dehydroepiandrosterone sulfate (DHEAS levels after 4 weeks of moderate alcohol supplementation, and compare the results to the 8 weeks data to elucidate time-to-effect differences. Methods Postmenopausal women (n = 51 consumed 0 (placebo, 15 (1 drink, and 30 (2 drinks g alcohol (ethanol/ day for 8 weeks as part of a controlled diet in a randomized crossover design. Blood samples were drawn at baseline, at 4 weeks and at 8 weeks. Changes in estrone sulfate and DHEAS levels from placebo to 15 g and 30 g alcohol per day were estimated using linear mixed models. Results and Discussion At week 4, compared to the placebo, estrone sulfate increased an average 6.9% (P = 0.24 when the women consumed 15 g of alcohol per day, and 22.2% (P = 0.0006 when they consumed 30 g alcohol per day. DHEAS concentrations also increased significantly by an average of 8.0% (P Conclusions These data indicate that the hormonal effects due to moderate alcohol consumption are seen early, within 4 weeks of initiation of ingestion.

Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice.

Science.gov (United States)

Zhang, Wenliang; Zhong, Wei; Sun, Qian; Sun, Xinguo; Zhou, Zhanxiang

2017-08-21

Chronic alcohol feeding causes lipid accumulation and apoptosis in the liver. This study investigated the role of bioactive lipid metabolites in alcohol-induced liver damage and tested the potential of targeting arachidonate 15-lipoxygenase (ALOX15) in treating alcoholic liver disease (ALD). Results showed that chronic alcohol exposure induced hepatocyte apoptosis in association with increased hepatic 13-HODE. Exposure of 13-HODE to Hepa-1c1c7 cells induced oxidative stress, ER stress and apoptosis. 13-HODE also perturbed proteins related to lipid metabolism. HODE-generating ALOX15 was up-regulated by chronic alcohol exposure. Linoleic acid, but not ethanol or acetaldehyde, induced ALOX15 expression in Hepa-1c1c7 cells. ALOX15 knockout prevented alcohol-induced liver damage via attenuation of oxidative stress, ER stress, lipid metabolic disorder, and cell death signaling. ALOX15 inhibitor (PD146176) treatment also significantly alleviated alcohol-induced oxidative stress, lipid accumulation and liver damage. These results demonstrated that activation of ALOX15/13-HODE circuit critically mediates the pathogenesis of ALD. This study suggests that ALOX15 is a potential molecular target for treatment of ALD.

Alcohol-induced retrograde memory impairment in rats: prevention by caffeine.

Science.gov (United States)

Spinetta, Michael J; Woodlee, Martin T; Feinberg, Leila M; Stroud, Chris; Schallert, Kellan; Cormack, Lawrence K; Schallert, Timothy

2008-12-01

Ethanol and caffeine are two of the most widely consumed drugs in the world, often used in the same setting. Animal models may help to understand the conditions under which incidental memories formed just before ethanol intoxication might be lost or become difficult to retrieve. Ethanol-induced retrograde amnesia was investigated using a new odor-recognition test. Rats thoroughly explored a wood bead taken from the cage of another rat, and habituated to this novel odor (N1) over three trials. Immediately following habituation, rats received saline, 25 mg/kg pentylenetetrazol (a seizure-producing agent known to cause retrograde amnesia) to validate the test, 1.0 g/kg ethanol, or 3.0 g/kg ethanol. The next day, they were presented again with N1 and also a bead from a new rat's cage (N2). Rats receiving saline or the lower dose of ethanol showed overnight memory for N1, indicated by preferential exploration of N2 over N1. Rats receiving pentylenetetrazol or the higher dose of ethanol appeared not to remember N1, in that they showed equal exploration of N1 and N2. Caffeine (5 mg/kg), delivered either 1 h after the higher dose of ethanol or 20 min prior to habituation to N1, negated ethanol-induced impairment of memory for N1. A combination of a phosphodiesterase-5 inhibitor and an adenosine A(2A) antagonist, mimicking two major mechanisms of action of caffeine, likewise prevented the memory impairment, though either drug alone had no such effect. Binge alcohol can induce retrograde, caffeine-reversible disruption of social odor memory storage or recall.

Hepcidin regulation in wild-type and Hfe knockout mice in response to alcohol consumption: evidence for an alcohol-induced hypoxic response.

Science.gov (United States)

Heritage, Mandy L; Murphy, Therese L; Bridle, Kim R; Anderson, Gregory J; Crawford, Darrell H G; Fletcher, Linda M

2009-08-01

Expression of Hamp1, the gene encoding the iron regulatory peptide hepcidin, is inappropriately low in HFE-associated hereditary hemochromatosis and Hfe knockout mice (Hfe(-/-)). Since chronic alcohol consumption is also associated with disturbances in iron metabolism, we investigated the effects of alcohol consumption on hepcidin mRNA expression in Hfe(-/-) mice. Hfe(-/-) and C57BL/6 (wild-type) mice were pair-fed either an alcohol liquid diet or control diet for up to 8 weeks. The mRNA levels of hepcidin and ferroportin were measured at the mRNA level by RT-PCR and protein expression of hypoxia inducible factor-1 alpha (HIF-1alpha) was measured by western blot. Hamp1 mRNA expression was significantly decreased and duodenal ferroportin expression was increased in alcohol-fed wild-type mice at 8 weeks. Time course experiments showed that the decrease in hepcidin mRNA was not immediate, but was significant by 4 weeks. Consistent with the genetic defect, Hamp1 mRNA was decreased and duodenal ferroportin mRNA expression was increased in Hfe(-/-) mice fed on the control diet compared with wild-type animals and alcohol further exacerbated these effects. HIF-1alpha protein levels were elevated in alcohol-fed wild-type animals compared with controls. Alcohol may decrease Hamp1 gene expression independently of the HFE pathway possibly via alcohol-induced hypoxia.

Evaluation of Moringa oleifera Leaf Extract on Alcohol-induced ...

African Journals Online (AJOL)

induced hepatotoxicity in rats was evaluated. Rats fed alcohol only produced significant increase in the levels of enzyme markers of tissues damage (ALT, AST and ALP), lipid peroxidation (TBARS) and decreased serum vitamin C levels ...

Sida rhomboidea.Roxb extract alleviates pathophysiological changes in experimental in vivo and in vitro models of high fat diet/fatty acid induced non-alcoholic steatohepatitis.

Science.gov (United States)

Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Dandekar, Deven S; Devkar, Ranjitsinh V; Ramachandran, A V

2012-03-01

The present study was aim to evaluate protective role of Sida rhomboidea.Roxb (SR) extract against high fat diet/fatty acid induced pathophysiological alterations in experimental model of non-alcoholic steatohepatitis (NASH). Effect of SR extract on plasma levels of markers of hepatic damage, plasma and hepatic lipids, mitochondrial oxidative stress, status of enzymatic and non-enzymatic antioxidants and histopathological changes in liver tissue were evaluated in high fat diet fed C57BL/6J mice. Also, the effect of SR supplementation on lipid accumulation, lipid peroxidation, cytotoxicity and cell viability were evaluated in oleic acid treated HepG2 cells. Supplementation of NASH mice with SR extract prevented high fat diet induced elevation in plasma marker enzymes of liver damage, plasma and hepatic lipids, mitochondrial oxidative stress and compromised enzymatic and non-enzymatic antioxidant status. Further, addition of SR extract to in vitro HepG2 cells minimized oleic acid induced lipid accumulation, higher lipid peroxidation, cytotoxicity and reduced cell viability. These in vivo and in vitro studies suggest that SR extract has the potential of preventing high fat/fatty acid induced NASH mainly due to its hypolipidemic and antioxidant activities. Copyright © 2010 Elsevier GmbH. All rights reserved.

Clay-Alcohol-Water Dispersions: Anomalous Viscosity Changes Due to Network Formation of Clay Nanosheets Induced by Alcohol Clustering.

Science.gov (United States)

Kimura, Yuji; Haraguchi, Kazutoshi

2017-05-16

Clay-alcohol-water ternary dispersions were compared with alcohol-water binary mixtures in terms of viscosity and optical absorbance. Aqueous clay dispersions to which lower alcohols (ethanol, 1-propanol, 2-propanol, and tert-butanol) were added exhibited significant viscosity anomalies (maxima) when the alcohol content was 30-55 wt %, as well as optical absorbance anomalies (maxima). The maximum viscosity (η max ) depended strongly on the clay content and varied between 300 and 8000 mPa·s, making it remarkably high compared with the viscosity anomalies (2 mPa·s) observed in alcohol-water binary mixtures. The alcohol content at η max decreased as the hydrophobicity of the alcohol increased. The ternary dispersions with viscosity anomalies exhibited thixotropic behaviors. The effects of other hydrophilic solvents (glycols) and other kinds of clays were also clarified. Based on these findings and the average particle size changes, the viscosity anomalies in the ternary dispersions were explained by alcohol-clustering-induced network formation of the clay nanosheets. It was estimated that 0.9, 1.7, and 2.5 H 2 O molecules per alcohol molecule were required to stabilize the ethanol, 2-propanol, and tert-butanol, respectively, in the clay-alcohol-water dispersions.

miR-339-5p inhibits alcohol-induced brain inflammation through regulating NF-κB pathway

International Nuclear Information System (INIS)

Zhang, Yu; Wei, Guangkuan; Di, Zhiyong; Zhao, Qingjie

2014-01-01

Graphical abstract: - Highlights: • Alcohol upregulates miR-339-5p expression. • miR-339-5p inhibits the NF-kB pathway. • miR-339-5p interacts with and blocks activity of IKK-beat and IKK-epsilon. • miR-339-5p modulates IL-1β, IL-6 and TNF-α. - Abstract: Alcohol-induced neuroinflammation is mediated by the innate immunesystem. Pro-inflammatory responses to alcohol are modulated by miRNAs. The miRNA miR-339-5p has previously been found to be upregulated in alcohol-induced neuroinflammation. However, little has been elucidated on the regulatory functions of this miRNA in alcohol-induced neuroinflammation. We investigated the function of miR-339-5p in alcohol exposed brain tissue and isolated microglial cells using ex vivo and in vitro techniques. Our results show that alcohol induces transcription of miR 339-5p, IL-6, IL-1β and TNF-α in mouse brain tissue and isolated microglial cells by activating NF-κB. Alcohol activation of NF-κB allows for nuclear translocation of the NF-κB subunit p65 and expression of pro-inflammatory mediators. miR-339-5p inhibited expression of these pro-inflammatory factors through the NF-κB pathway by abolishing IKK-β and IKK-ε activity

miR-339-5p inhibits alcohol-induced brain inflammation through regulating NF-κB pathway

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yu [Department of Neurology, The First Affiliated School of Harbin Medical University, Harbin 150001 (China); Wei, Guangkuan [Department of Neurology, Heilongjiang Provincial Hospital, Harbin 150036 (China); Di, Zhiyong [Department of Laboratory, Heilongjiang Provincial Hospital, Harbin 150036 (China); Zhao, Qingjie, E-mail: zhaoqingjie2013@163.com [Department of Neurology, The First Affiliated School of Harbin Medical University, Harbin 150001 (China)

2014-09-26

Graphical abstract: - Highlights: • Alcohol upregulates miR-339-5p expression. • miR-339-5p inhibits the NF-kB pathway. • miR-339-5p interacts with and blocks activity of IKK-beat and IKK-epsilon. • miR-339-5p modulates IL-1β, IL-6 and TNF-α. - Abstract: Alcohol-induced neuroinflammation is mediated by the innate immunesystem. Pro-inflammatory responses to alcohol are modulated by miRNAs. The miRNA miR-339-5p has previously been found to be upregulated in alcohol-induced neuroinflammation. However, little has been elucidated on the regulatory functions of this miRNA in alcohol-induced neuroinflammation. We investigated the function of miR-339-5p in alcohol exposed brain tissue and isolated microglial cells using ex vivo and in vitro techniques. Our results show that alcohol induces transcription of miR 339-5p, IL-6, IL-1β and TNF-α in mouse brain tissue and isolated microglial cells by activating NF-κB. Alcohol activation of NF-κB allows for nuclear translocation of the NF-κB subunit p65 and expression of pro-inflammatory mediators. miR-339-5p inhibited expression of these pro-inflammatory factors through the NF-κB pathway by abolishing IKK-β and IKK-ε activity.

Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice

OpenAIRE

Zhang, Wenliang; Zhong, Wei; Sun, Qian; Sun, Xinguo; Zhou, Zhanxiang

2017-01-01

Chronic alcohol feeding causes lipid accumulation and apoptosis in the liver. This study investigated the role of bioactive lipid metabolites in alcohol-induced liver damage and tested the potential of targeting arachidonate 15-lipoxygenase (ALOX15) in treating alcoholic liver disease (ALD). Results showed that chronic alcohol exposure induced hepatocyte apoptosis in association with increased hepatic 13-HODE. Exposure of 13-HODE to Hepa-1c1c7 cells induced oxidative stress, ER stress and apo...

Effect of antioxidant supplementation on exercise-induced cardiac troponin release in cyclists: a randomized trial.

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Lieke J J Klinkenberg

Full Text Available Cardiac troponin is the biochemical gold standard to diagnose acute myocardial infarction. Interestingly however, elevated cardiac troponin concentrations are also frequently observed during and after endurance-type exercise. Oxidative stress associated with prolonged exercise has been proposed to contribute to cardiac troponin release. Therefore, the aim of this study was to assess the effect of 4 week astaxanthin supplementation (a potent cartenoid antioxidant on antioxidant capacity and exercise-induced cardiac troponin release in cyclists.Thirty-two well-trained male cyclists (age 25±5, weight 73±7 kg, maximum O2 uptake 60±5 mL·kg(-1·min(-1, Wmax 5.4±0.5 W·kg(-1; mean ± SD were repeatedly subjected to a laboratory based standardized exercise protocol before and after 4 weeks of astaxanthin (20 mg/day, or placebo supplementation in a double-blind randomized manner. Blood samples were obtained at baseline, at 60 min of cycling and immediately post-exercise (≈ 120 min.The pre-supplementation cycling trial induced a significant rise of median cardiac troponin T concentrations from 3.2 (IQR 3.0-4.2 to 4.7 ng/L (IQR 3.7-6.7, immediately post-exercise (p<0.001. Four weeks of astaxanthin supplementation significantly increased mean basal plasma astaxanthin concentrations from non-detectable values to 175±86 µg·kg(-1. However, daily astaxanthin supplementation had no effect on exercise-induced cardiac troponin T release (p = 0.24, as measured by the incremental area under the curve. Furthermore, the elevation in basal plasma astaxanthin concentrations was not reflected in changes in antioxidant capacity markers (trolox equivalent antioxidant capacity, uric acid, and malondialdehyde. Markers of inflammation (high-sensitivity C-reactive protein and exercise-induced skeletal muscle damage (creatine kinase were equally unaffected by astaxanthin supplementation.Despite substantial increases in plasma astaxanthin concentrations

Sarcopenia in Alcoholic Liver Disease: Clinical and Molecular Advances.

Science.gov (United States)

Dasarathy, Jaividhya; McCullough, Arthur J; Dasarathy, Srinivasan

2017-08-01

Despite advances in treatment of alcohol use disorders that focus on increasing abstinence and reducing recidivism, alcoholic liver disease (ALD) is projected to be the major cause of cirrhosis and its complications. Malnutrition is recognized as the most frequent complication in ALD, and despite the high clinical significance, there are no effective therapies to reverse malnutrition in ALD. Malnutrition is a relatively imprecise term, and sarcopenia or skeletal muscle loss, the major component of malnutrition, is primarily responsible for the adverse clinical consequences in patients with liver disease. It is, therefore, critical to define the specific abnormality (sarcopenia) rather than malnutrition in ALD, so that therapies targeting sarcopenia can be developed. Skeletal muscle mass is maintained by a balance between protein synthesis and proteolysis. Both direct effects of ethanol (EtOH) and its metabolites on the skeletal muscle and the consequences of liver disease result in disturbed proteostasis (protein homeostasis) and consequent sarcopenia. Once cirrhosis develops in patients with ALD, abstinence is unlikely to be effective in completely reversing sarcopenia, as other contributors including hyperammonemia, hormonal, and cytokine abnormalities aggravate sarcopenia and maintain a state of anabolic resistance initiated by EtOH. Cirrhosis is also a state of accelerated starvation, with increased gluconeogenesis that requires amino acid diversion from signaling and substrate functions. Novel therapeutic options are being recognized that are likely to supplant the current "deficiency replacement" approach and instead focus on specific molecular perturbations, given the increasing availability of small molecules that can target specific signaling components. Myostatin antagonists, leucine supplementation, and mitochondrial protective agents are currently in various stages of evaluation in preclinical studies to prevent and reverse sarcopenia, in cirrhosis in

Seizure-induced brain lesions: A wide spectrum of variably reversible MRI abnormalities

International Nuclear Information System (INIS)

Cianfoni, A.; Caulo, M.; Cerase, A.; Della Marca, G.; Falcone, C.; Di Lella, G.M.; Gaudino, S.; Edwards, J.; Colosimo, C.

2013-01-01

Introduction MRI abnormalities in the postictal period might represent the effect of the seizure activity, rather than its structural cause. Material and Methods Retrospective review of clinical and neuroimaging charts of 26 patients diagnosed with seizure-related MR-signal changes. All patients underwent brain-MRI (1.5-Tesla, standard pre- and post-contrast brain imaging, including DWI-ADC in 19/26) within 7 days from a seizure and at least one follow-up MRI, showing partial or complete reversibility of the MR-signal changes. Extensive clinical work-up and follow-up, ranging from 3 months to 5 years, ruled out infection or other possible causes of brain damage. Seizure-induced brain-MRI abnormalities remained a diagnosis of exclusion. Site, characteristics and reversibility of MRI changes, and association with characteristics of seizures were determined. Results MRI showed unilateral (13/26) and bilateral abnormalities, with high (24/26) and low (2/26) T2-signal, leptomeningeal contrast-enhancement (2/26), restricted diffusion (9/19). Location of abnormality was cortical/subcortical, basal ganglia, white matter, corpus callosum, cerebellum. Hippocampus was involved in 10/26 patients. Reversibility of MRI changes was complete in 15, and with residual gliosis or focal atrophy in 11 patients. Reversibility was noted between 15 and 150 days (average, 62 days). Partial simple and complex seizures were associated with hippocampal involvement (p = 0.015), status epilepticus with incomplete reversibility of MRI abnormalities (p = 0.041). Conclusions Seizure or epileptic status can induce transient, variably reversible MRI brain abnormalities. Partial seizures are frequently associated with hippocampal involvement and status epilepticus with incompletely reversible lesions. These seizure-induced MRI abnormalities pose a broad differential diagnosis; increased awareness may reduce the risk of misdiagnosis and unnecessary intervention

Seizure-induced brain lesions: A wide spectrum of variably reversible MRI abnormalities

Energy Technology Data Exchange (ETDEWEB)

Cianfoni, A., E-mail: acianfoni@hotmail.com [Neuroradiology, Neurocenter of Italian Switzerland–Ospedale regionale Lugano, Via Tesserete 46, Lugano, 6900, CH (Switzerland); Caulo, M., E-mail: caulo@unich.it [Department of Neuroscience and Imaging, University of Chieti, Via dei Vestini 33, 6610 Chieti. Italy (Italy); Cerase, A., E-mail: alfonsocerase@gmail.com [Unit of Neuroimaging and Neurointervention NINT, Department of Neurological and Sensorineural Sciences, Azienda Ospedaliera Universitaria Senese, Policlinico “Santa Maria alle Scotte”, V.le Bracci 16, Siena (Italy); Della Marca, G., E-mail: dellamarca@rm.unicatt.it [Neurology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Falcone, C., E-mail: carlo_falc@libero.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Di Lella, G.M., E-mail: gdilella@rm.unicatt.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Gaudino, S., E-mail: sgaudino@sirm.org [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Edwards, J., E-mail: edwardjc@musc.edu [Neuroscience Dept., Medical University of South Carolina, 96J Lucas st, 29425, Charleston, SC (United States); Colosimo, C., E-mail: colosimo@rm.unicatt.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy)

2013-11-01

Introduction MRI abnormalities in the postictal period might represent the effect of the seizure activity, rather than its structural cause. Material and Methods Retrospective review of clinical and neuroimaging charts of 26 patients diagnosed with seizure-related MR-signal changes. All patients underwent brain-MRI (1.5-Tesla, standard pre- and post-contrast brain imaging, including DWI-ADC in 19/26) within 7 days from a seizure and at least one follow-up MRI, showing partial or complete reversibility of the MR-signal changes. Extensive clinical work-up and follow-up, ranging from 3 months to 5 years, ruled out infection or other possible causes of brain damage. Seizure-induced brain-MRI abnormalities remained a diagnosis of exclusion. Site, characteristics and reversibility of MRI changes, and association with characteristics of seizures were determined. Results MRI showed unilateral (13/26) and bilateral abnormalities, with high (24/26) and low (2/26) T2-signal, leptomeningeal contrast-enhancement (2/26), restricted diffusion (9/19). Location of abnormality was cortical/subcortical, basal ganglia, white matter, corpus callosum, cerebellum. Hippocampus was involved in 10/26 patients. Reversibility of MRI changes was complete in 15, and with residual gliosis or focal atrophy in 11 patients. Reversibility was noted between 15 and 150 days (average, 62 days). Partial simple and complex seizures were associated with hippocampal involvement (p = 0.015), status epilepticus with incomplete reversibility of MRI abnormalities (p = 0.041). Conclusions Seizure or epileptic status can induce transient, variably reversible MRI brain abnormalities. Partial seizures are frequently associated with hippocampal involvement and status epilepticus with incompletely reversible lesions. These seizure-induced MRI abnormalities pose a broad differential diagnosis; increased awareness may reduce the risk of misdiagnosis and unnecessary intervention.

Biomarker-Based Approaches for Assessing Alcohol Use Disorders

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Onni Niemelä

2016-01-01

Full Text Available Although alcohol use disorders rank among the leading public health problems worldwide, hazardous drinking practices and associated morbidity continue to remain underdiagnosed. It is postulated here that a more systematic use of biomarkers improves the detection of the specific role of alcohol abuse behind poor health. Interventions should be initiated by obtaining information on the actual amounts of recent alcohol consumption through questionnaires and measurements of ethanol and its specific metabolites, such as ethyl glucuronide. Carbohydrate-deficient transferrin is a valuable tool for assessing chronic heavy drinking. Activities of common liver enzymes can be used for screening ethanol-induced liver dysfunction and to provide information on the risk of co-morbidities including insulin resistance, metabolic syndrome and vascular diseases. Conventional biomarkers supplemented with indices of immune activation and fibrogenesis can help to assess the severity and prognosis of ethanol-induced tissue damage. Many ethanol-sensitive biomarkers respond to the status of oxidative stress, and their levels are modulated by factors of life style, including weight gain, physical exercise or coffee consumption in an age- and gender-dependent manner. Therefore, further attention should be paid to defining safe limits of ethanol intake in various demographic categories and establishing common reference intervals for biomarkers of alcohol use disorders.

The effects of alcohol on mood induced by an emotional film. A study among women

NARCIS (Netherlands)

van Tilburg, M.A.L.; Vingerhoets, A.J.J.M.

2002-01-01

Objective: The present study was designed to investigate the effects of alcohol on women's reactions to a negative mood-inducing stimulus. It is hypothesized that, like in men, alcohol also reduces tension or induces positive mood in women. In addition, we explored whether different mood states were

Reversible Age-Related Phenotypes Induced during Larval Quiescence in C. elegans

Science.gov (United States)

Roux, Antoine E.; Langhans, Kelley; Huynh, Walter; Kenyon, Cynthia

2017-01-01

Summary Cells can enter quiescent states in which cell cycling and growth are suspended. We find that during a long developmental arrest (quiescence) induced by starvation, newly-hatched C. elegans acquire features associated with impaired proteostasis and aging: mitochondrial fission, ROS production, protein aggregation, decreased proteotoxic-stress resistance, and at the organismal level, decline of mobility and high mortality. All signs of aging but one, the presence of protein aggregates, were reversed upon return to development induced by feeding. The endoplasmic reticulum receptor IRE-1 is completely required for recovery, and the downstream transcription factor XBP-1, as well as a protein kinase, KGB-1, are partially required. Interestingly, kgb-1(−) mutants that do recover fail to reverse aging-like mitochondrial phenotypes and have a short adult lifespan. Our study describes the first pathway that reverses phenotypes of aging at the exit of prolonged quiescence. PMID:27304510

First interactions between hydrogen and stress-induced reverse transformation of Ni-Ti superelastic alloy

Science.gov (United States)

Yokoyama, Ken'ichi; Hashimoto, Tatsuki; Sakai, Jun'ichi

2017-11-01

The first dynamic interactions between hydrogen and the stress-induced reverse transformation have been investigated by performing an unloading test on a Ni-Ti superelastic alloy subjected to hydrogen charging under a constant applied strain in the elastic deformation region of the martensite phase. Upon unloading the specimen, charged with a small amount of hydrogen, no change in the behaviour of the stress-induced reverse transformation is observed in the stress-strain curve, although the behaviour of the stress-induced martensite transformation changes. With increasing amount of hydrogen charging, the critical stress for the reverse transformation markedly decreases. Eventually, for a larger amount of hydrogen charging, the reverse transformation does not occur, i.e. there is no recovery of the superelastic strain. The residual martensite phase on the side surface of the unloaded specimen is confirmed by X-ray diffraction. Upon training before the unloading test, the properties of the reverse transformation slightly recover after ageing in air at room temperature. The present study indicates that to change the behaviour of the reverse transformation a larger amount of hydrogen than that for the martensite transformation is necessary. In addition, it is likely that a substantial amount of hydrogen in solid solution more strongly suppresses the reverse transformation than hydrogen trapped at defects, thereby stabilising the martensite phase.

DHEA supplementation in ovariectomized rats reduces impaired glucose-stimulated insulin secretion induced by a high-fat diet

Directory of Open Access Journals (Sweden)

Katherine Veras

2014-01-01

Full Text Available Dehydroepiandrosterone (DHEA and the dehydroepiandrosterone sulfate (DHEA-S are steroids produced mainly by the adrenal cortex. There is evidence from both human and animal models suggesting beneficial effects of these steroids for obesity, diabetes mellitus, hypertension, and osteoporosis, conditions associated with the post-menopausal period. Accordingly, we hypothesized that DHEA supplementation in ovariectomized (OVX female rats fed a high-fat diet would maintain glucose-induced insulin secretion (GSIS and pancreatic islet function. OVX resulted in a 30% enlargement of the pancreatic islets area compared to the control rats, which was accompanied by a 50% reduction in the phosphorylation of AKT protein in the pancreatic islets. However, a short-term high-fat diet induced insulin resistance, accompanied by impaired GSIS in isolated pancreatic islets. These effects were reversed by DHEA treatment, with improved insulin sensitivity to levels similar to the control group, and with increased serine phosphorylation of the AKT protein. These data confirm the protective effect of DHEA on the endocrine pancreas in a situation of diet-induced overweight and low estrogen concentrations, a phenotype similar to that of the post-menopausal period.

Iron supplementation at high altitudes induces inflammation and oxidative injury to lung tissues in rats

Energy Technology Data Exchange (ETDEWEB)

Salama, Samir A., E-mail: salama.3@buckeyemail.osu.edu [High Altitude Research Center, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11751 (Egypt); Department of Pharmacology and GTMR Unit, College of Clinical Pharmacy, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); Omar, Hany A. [Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514 (Egypt); Maghrabi, Ibrahim A. [Department of Clinical Pharmacy, College of Clinical Pharmacy, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); AlSaeed, Mohammed S. [Department of Surgery, College of Medicine, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); EL-Tarras, Adel E. [High Altitude Research Center, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia)

2014-01-01

Exposure to high altitudes is associated with hypoxia and increased vulnerability to oxidative stress. Polycythemia (increased number of circulating erythrocytes) develops to compensate the high altitude associated hypoxia. Iron supplementation is, thus, recommended to meet the demand for the physiological polycythemia. Iron is a major player in redox reactions and may exacerbate the high altitudes-associated oxidative stress. The aim of this study was to explore the potential iron-induced oxidative lung tissue injury in rats at high altitudes (6000 ft above the sea level). Iron supplementation (2 mg elemental iron/kg, once daily for 15 days) induced histopathological changes to lung tissues that include severe congestion, dilatation of the blood vessels, emphysema in the air alveoli, and peribronchial inflammatory cell infiltration. The levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), lipid peroxidation product and protein carbonyl content in lung tissues were significantly elevated. Moreover, the levels of reduced glutathione and total antioxidant capacity were significantly reduced. Co-administration of trolox, a water soluble vitamin E analog (25 mg/kg, once daily for the last 7 days of iron supplementation), alleviated the lung histological impairments, significantly decreased the pro-inflammatory cytokines, and restored the oxidative stress markers. Together, our findings indicate that iron supplementation at high altitudes induces lung tissue injury in rats. This injury could be mediated through excessive production of reactive oxygen species and induction of inflammatory responses. The study highlights the tissue injury induced by iron supplementation at high altitudes and suggests the co-administration of antioxidants such as trolox as protective measures. - Highlights: • Iron supplementation at high altitudes induced lung histological changes in rats. • Iron induced oxidative stress in lung tissues of rats at high altitudes. • Iron

Iron supplementation at high altitudes induces inflammation and oxidative injury to lung tissues in rats

International Nuclear Information System (INIS)

Salama, Samir A.; Omar, Hany A.; Maghrabi, Ibrahim A.; AlSaeed, Mohammed S.; EL-Tarras, Adel E.

2014-01-01

Exposure to high altitudes is associated with hypoxia and increased vulnerability to oxidative stress. Polycythemia (increased number of circulating erythrocytes) develops to compensate the high altitude associated hypoxia. Iron supplementation is, thus, recommended to meet the demand for the physiological polycythemia. Iron is a major player in redox reactions and may exacerbate the high altitudes-associated oxidative stress. The aim of this study was to explore the potential iron-induced oxidative lung tissue injury in rats at high altitudes (6000 ft above the sea level). Iron supplementation (2 mg elemental iron/kg, once daily for 15 days) induced histopathological changes to lung tissues that include severe congestion, dilatation of the blood vessels, emphysema in the air alveoli, and peribronchial inflammatory cell infiltration. The levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), lipid peroxidation product and protein carbonyl content in lung tissues were significantly elevated. Moreover, the levels of reduced glutathione and total antioxidant capacity were significantly reduced. Co-administration of trolox, a water soluble vitamin E analog (25 mg/kg, once daily for the last 7 days of iron supplementation), alleviated the lung histological impairments, significantly decreased the pro-inflammatory cytokines, and restored the oxidative stress markers. Together, our findings indicate that iron supplementation at high altitudes induces lung tissue injury in rats. This injury could be mediated through excessive production of reactive oxygen species and induction of inflammatory responses. The study highlights the tissue injury induced by iron supplementation at high altitudes and suggests the co-administration of antioxidants such as trolox as protective measures. - Highlights: • Iron supplementation at high altitudes induced lung histological changes in rats. • Iron induced oxidative stress in lung tissues of rats at high altitudes. • Iron

Alcohol-induced structural transitions in the acid-denatured Bacillus licheniformis α-amylase

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Adyani Azizah Abd Halim

2017-01-01

Full Text Available Alcohol-induced structural changes in the acid-denatured Bacillus licheniformis α-amylase (BLA at pH 2.0 were studied by far-ultra violet circular dichroism, intrinsic, three-dimensional and 8-anilino-1-naphthalene sulfonic acid (ANS fluorescence, acrylamide quenching and thermal denaturation. All the alcohols used in this study produced partial refolding in the acid-denatured BLA as evident from the increased mean residue ellipticity at 222 nm, increased intrinsic fluorescence and decreased ANS fluorescence. The order of effectiveness of these alcohols to induce a partially folded state of BLA was found to be: 2,2,2-trifluoroethanol/tert-butanol > 1-propanol/2-propanol > 2-chloroethanol > ethanol > methanol. Three-dimensional fluorescence and acrylamide quenching results obtained in the presence of 5.5 M tert-butanol also suggested formation of a partially folded state in the acid-denatured BLA. However, 5.5 M tert-butanol-induced state of BLA showed a non-cooperative thermal transition. All these results suggested formation of a partially folded state of the acid-denatured BLA in the presence of these alcohols. Furthermore, their effectiveness was found to be guided by their chain length, position of methyl groups and presence of the substituents.

Nrf2-mediated antioxidant response by ethanolic extract of Sida cordifolia provides protection against alcohol-induced oxidative stress in liver by upregulation of glutathione metabolism.

Science.gov (United States)

Rejitha, S; Prathibha, P; Indira, M

2015-03-01

Objective The study aimed to evaluate the antioxidant property of ethanolic extract of Sida cordifolia (SAE) on alcohol-induced oxidative stress and to elucidate its mechanism of action. Methods Male albino rats of the Sprague-Dawley strain were grouped into four: (1) control, (2) alcohol (4 g/kg body weight), (3) SAE (50 mg/100 g body weight), and (4) alcohol (4 g/kg body weight) + SAE (50 mg/100 g body weight). Alcohol and SAE were given orally each day by gastric intubation. The duration of treatment was 90 days. Results The activities of toxicity markers in liver and serum increased significantly in alcohol-treated rats and to a lesser extent in the group administered SAE + alcohol. The activity of alcohol dehydrogenase and the reactive oxygen species level were increased significantly in alcohol-treated rats but attenuated in the SAE co-administered group. Oxidative stress was increased in alcohol-treated rats as evidenced by the lowered activities of antioxidant enzymes, decreased level of reduced glutathione (GSH), increased lipid peroxidation products, and decreased expression of γ-glutamyl cysteine synthase in liver. The co-administration of SAE with alcohol almost reversed these changes. The activity of glutathione-S-transferase and translocation of Nrf2 from cytosol to nucleus in the liver was increased in both the alcohol and alcohol + SAE groups, but the maximum changes were observed in the latter group. Discussion The SAE most likely elicits its antioxidant potential by reducing oxidative stress, enhancing the translocation of Nrf2 to nucleus and thereby regulating glutathione metabolism, leading to enhanced GSH content.

Zinc supplementation during pregnancy protects against lipopolysaccharide-induced fetal growth restriction and demise through its anti-inflammatory effect.

Science.gov (United States)

Chen, Yuan-Hua; Zhao, Mei; Chen, Xue; Zhang, Ying; Wang, Hua; Huang, Ying-Ying; Wang, Zhen; Zhang, Zhi-Hui; Zhang, Cheng; Xu, De-Xiang

2012-07-01

LPS is associated with adverse developmental outcomes, including preterm delivery, fetal death, teratogenicity, and intrauterine growth restriction (IUGR). Previous reports showed that zinc protected against LPS-induced teratogenicity. In the current study, we investigated the effects of zinc supplementation during pregnancy on LPS-induced preterm delivery, fetal death and IUGR. All pregnant mice except controls were i.p. injected with LPS (75 μg/kg) daily from gestational day (GD) 15 to GD17. Some pregnant mice were administered zinc sulfate through drinking water (75 mg elemental Zn per liter) throughout the pregnancy. As expected, an i.p. injection with LPS daily from GD15 to GD17 resulted in 36.4% (4/11) of dams delivered before GD18. In dams that completed the pregnancy, 63.2% of fetuses were dead. Moreover, LPS significantly reduced fetal weight and crown-rump length. Of interest, zinc supplementation during pregnancy protected mice from LPS-induced preterm delivery and fetal death. In addition, zinc supplementation significantly alleviated LPS-induced IUGR and skeletal development retardation. Further experiments showed that zinc supplementation significantly attenuated LPS-induced expression of placental inflammatory cytokines and cyclooxygenase-2. Zinc supplementation also significantly attenuated LPS-induced activation of NF-κB and MAPK signaling in mononuclear sinusoidal trophoblast giant cells of the labyrinth zone. It inhibited LPS-induced placental AKT phosphorylation as well. In conclusion, zinc supplementation during pregnancy protects against LPS-induced fetal growth restriction and demise through its anti-inflammatory effect.

Resveratrol Ameliorates Experimental Alcoholic Liver Disease by Modulating Oxidative Stress

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He Peiyuan

2017-01-01

Full Text Available The aim of this study was to investigate the hepatoprotective effects of resveratrol in alcoholic liver disease (ALD. Alcohol was administered to healthy female rats starting from 6% (v/v and gradually increased to 20% (v/v by the fifth week. After 16 weeks of intervention, liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT] were analyzed using a chemistry analyzer, while hepatic antioxidant enzymes, oxidative stress markers, and caspase 3 activity were assessed using ELISA kits. Furthermore, hepatic CYP2E1 protein levels and mRNA levels of antioxidant and inflammation-related genes were determined using western blotting and RT-PCR, respectively. The results showed that resveratrol significantly attenuated alcohol-induced elevation of liver enzymes and improved hepatic antioxidant enzymes. Resveratrol also attenuated alcohol-induced CYP2E1 increase, oxidative stress, and apoptosis (caspase 3 activity. Moreover, genes associated with oxidative stress and inflammation were regulated by resveratrol supplementation. Taken together, the results suggested that resveratrol alleviated ALD through regulation of oxidative stress, apoptosis, and inflammation, which was mediated at the transcriptional level. The data suggests that resveratrol is a promising natural therapeutic agent against chronic ALD.

The Investigation of Strain-Induced Martensite Reverse Transformation in AISI 304 Austenitic Stainless Steel

Science.gov (United States)

Cios, G.; Tokarski, T.; Żywczak, A.; Dziurka, R.; Stępień, M.; Gondek, Ł.; Marciszko, M.; Pawłowski, B.; Wieczerzak, K.; Bała, P.

2017-10-01

This paper presents a comprehensive study on the strain-induced martensitic transformation and reversion transformation of the strain-induced martensite in AISI 304 stainless steel using a number of complementary techniques such as dilatometry, calorimetry, magnetometry, and in-situ X-ray diffraction, coupled with high-resolution microstructural transmission Kikuchi diffraction analysis. Tensile deformation was applied at temperatures between room temperature and 213 K (-60 °C) in order to obtain a different volume fraction of strain-induced martensite (up to 70 pct). The volume fraction of the strain-induced martensite, measured by the magnetometric method, was correlated with the total elongation, hardness, and linear thermal expansion coefficient. The thermal expansion coefficient, as well as the hardness of the strain-induced martensitic phase was evaluated. The in-situ thermal treatment experiments showed unusual changes in the kinetics of the reverse transformation (α' → γ). The X-ray diffraction analysis revealed that the reverse transformation may be stress assisted—strains inherited from the martensitic transformation may increase its kinetics at the lower annealing temperature range. More importantly, the transmission Kikuchi diffraction measurements showed that the reverse transformation of the strain-induced martensite proceeds through a displacive, diffusionless mechanism, maintaining the Kurdjumov-Sachs crystallographic relationship between the martensite and the reverted austenite. This finding is in contradiction to the results reported by other researchers for a similar alloy composition.

A case of posterior reversible encephalopathy syndrome associated with acute pancreatitis and chronic alcoholism.

Science.gov (United States)

Baek, Hyun Seok; Lee, Se-Jin

2015-01-01

Posterior reversible encephalopathy syndrome (PRES) is known to be caused by a variety of clinical disorders. The authors encountered a case of PRES associated with acute pancreatitis and chronic alcoholism. A 49-year-old man presented with altered mental status. Magnetic resonance imaging (MRI) displayed vasogenic edema at the bilateral posterior temporal and parieto-occipital lobes and cerebellum. Laboratory tests and abdominal computed tomography (CT) revealed acute pancreatitis. The patient recovered completely, and follow-up brain MRI and abdominal CT exhibited resolution of the previous lesions. We suggest that acute pancreatitis might be an etiology of PRES. Copyright © 2015 Elsevier Inc. All rights reserved.

Determinants of dietary supplement use - healthy individuals use dietary supplements

DEFF Research Database (Denmark)

Kofoed, Christina L F; Christensen, Jane; Dragsted, Lars Ove

2015-01-01

influence the use of dietary supplements. Only few studies investigating the use of dietary supplements have been conducted in the Danish population. The present cross-sectional study is based on 54 948 Danes, aged 50-64 years, who completed self-administrated questionnaires on diet, dietary supplements...... and lifestyle between 1993 and 1997. A health index including smoking, physical activity, alcohol and diet, and a metabolic risk index including waist circumference, urinary glucose and measured hypertension were constructed. Logistic regression was used to investigate these determinants in relation...... to the intake of dietary supplements. We found that 71 % of the participants were dietary supplement users; female sex, older age groups and higher educated participants were more likely to be users of any dietary supplements. One additional point in the health index was associated with 19, 16 and 9 % higher...

Feasibility of Trace Alcohol Congener Detection and Identification Using Laser-Induced Breakdown Spectroscopy

International Nuclear Information System (INIS)

Zhang Jialiang; Wang Shangmin; Zhao Lixian; Liu Liying; Wang Dezhen

2014-01-01

In this paper, a feasible scheme is reported for the detection and identification of trace alcohol congeners that have identical elemental composition using laser-induced breakdown spectroscopy (LIBS). In the scheme, an intensive pulsed laser is used to break down trace alcohol samples and the optical emission spectra of the induced plasma are collected for the detection and identification of alcohol molecules. In order to prepare trace alcohol samples, pure ethanol or methanol is bubbled by argon carrier gas and then mixed into matrix gases. The key issue for the scheme is to constitute indices from the LIBS data of the alcohol samples. Two indices are found to be suitable for alcohol detection and identification. One is the emission intensity ratio (denoted as H/C) of the hydrogen line (653.3 nm) to the carbon line (247.9 nm) for identification and the other is the ratio of the carbon line (as C/Ar) or the hydrogen line (as H/Ar) to the argon lines (866.7 nm) for quantitative detection. The calibration experiment result shows that the index H/C is specific for alcohol congeners while almost being independent of alcohol concentration. In detail, the H/C keeps a specific constant of 34 and 23 respectively for ethanol and methanol. In the meanwhile, the C/Ar and H/Ar indices respond almost linearly to the alcohol concentration below 1300 ppm, and are therefore competent for concentration measurement. With the indices, trace alcohol concentration measurement achieves a limit of 140 ppm using a laser pulse energy of 300 mJ. (plasma technology)

Supplementation with zinc in rats enhances memory and reverses an age-dependent increase in plasma copper.

Science.gov (United States)

Sandusky-Beltran, Leslie A; Manchester, Bryce L; McNay, Ewan C

2017-08-30

Zinc and copper are essential trace elements. Dyshomeostasis in these two metals has been observed in Alzheimer's disease, which causes profound cognitive impairment. Insulin therapy has been shown to enhance cognitive performance; however, recent data suggest that this effect may be at least in part due to the inclusion of zinc in the insulin formulation used. Zinc plays a key role in regulation of neuronal glutamate signaling, suggesting a possible link between zinc and memory processes. Consistent with this, zinc deficiency causes cognitive impairments in children. The effect of zinc supplementation on short- and long-term recognition memory, and on spatial working memory, was explored in young and adult male Sprague Dawley rats. After behavioral testing, hippocampal and plasma zinc and copper were measured. Age increased hippocampal zinc and copper, as well as plasma copper, and decreased plasma zinc. An interaction between age and treatment affecting plasma copper was also found, with zinc supplementation reversing elevated plasma copper concentration in adult rats. Zinc supplementation enhanced cognitive performance across tasks. These data support zinc as a plausible therapeutic intervention to ameliorate cognitive impairment in disorders characterized by alterations in zinc and copper, such as Alzheimer's disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Magnesium supplement in pregnancy-induced hypertension. A clinicopathological study

DEFF Research Database (Denmark)

Rudnicki, M; Junge, Jette; Frølich, A

1990-01-01

as a double-blind randomized controlled study in which 11 women were allocated to magnesium and 7 to placebo treatment. The treatment comprised a 48-hour intravenous magnesium/placebo infusion followed by daily oral magnesium/placebo intake until one day after delivery. Magnesium supplement increased birth....... There was no significant difference when the magnesium group, the placebo group and the control group were compared separately. The present study suggests that magnesium supplement has a beneficial effect on fetal growth in pregnancy-induced hypertension. With regard to the light and electron microscopic changes we were...... unable to demonstrate any significant difference between the magnesium, placebo and control groups....

Effectiveness of artichoke extract in preventing alcohol-induced hangovers: a randomized controlled trial

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Pittler, Max H.; White, Adrian R.; Stevinson, Clare; Ernst, Edzard

2003-01-01

Background Extract of globe artichoke (Cynara scolymus) is promoted as a possible preventive or cure for alcohol-induced hangover symptoms. However, few rigorous clinical trials have assessed the effects of artichoke extract, and none has examined the effects in relation to hangovers. We undertook this study to test whether artichoke extract is effective in preventing the signs and symptoms of alcohol-induced hangover. Methods We recruited healthy adult volunteers between 18 and 65 years of age to participate in a randomized double-blind crossover trial. Participants received either 3 capsules of commercially available standardized artichoke extract or indistinguishable, inert placebo capsules immediately before and after alcohol exposure. After a 1-week washout period the volunteers received the opposite treatment. Participants predefined the type and amount of alcoholic beverage that would give them a hangover and ate the same meal before commencing alcohol consumption on the 2 study days. The primary outcome measure was the difference in hangover severity scores between the artichoke extract and placebo interventions. Secondary outcome measures were differences between the interventions in scores using a mood profile questionnaire and cognitive performance tests administered 1 hour before and 10 hours after alcohol exposure. Results Fifteen volunteers participated in the study. The mean number (and standard deviation) of alcohol units (each unit being 7.9 g, or 10 mL, of ethanol) consumed during treatment with artichoke extract and placebo was 10.7 (3.1) and 10.5 (2.4) respectively, equivalent to 1.2 (0.3) and 1.2 (0.2) g of alcohol per kilogram body weight. The volume of nonalcoholic drink consumed and the duration of sleep were similar during the artichoke extract and placebo interventions. None of the outcome measures differed significantly between interventions. Adverse events were rare and were mild and transient. Interpretation Our results suggest that

Exercise reverses metabolic syndrome in high-fat diet-induced obese rats.

Science.gov (United States)

Touati, Sabeur; Meziri, Fayçal; Devaux, Sylvie; Berthelot, Alain; Touyz, Rhian M; Laurant, Pascal

2011-03-01

Chronic consumption of a high-fat diet induces obesity. We investigated whether exercise would reverse the cardiometabolic disorders associated with obesity without it being necessary to change from a high- to normal-fat diet. Sprague-Dawley rats were placed on a high-fat (HFD) or control diet (CD) for 12 wk. HFD rats were then divided into four groups: sedentary HFD (HFD-S), exercise trained (motor treadmill for 12 wk) HFD (HFD-Ex), modified diet (HFD to CD; HF/CD-S), and exercise trained with modified diet (HF/CD-Ex). Cardiovascular risk parameters associated with metabolic syndrome were measured, and contents of aortic Akt, phospho-Akt at Ser (473), total endothelial nitric oxide synthase (eNOS), and phospho-eNOS at Ser (1177) were determined by Western blotting. Chronic consumption of HFD induced a metabolic syndrome. Exercise and dietary modifications reduced adiposity, improved glucose and insulin levels and plasma lipid profile, and exerted an antihypertensive effect. Exercise was more effective than dietary modification in improving plasma levels of thiobarbituric acid-reacting substance and in correcting the endothelium-dependent relaxation to acetylcholine and insulin. Furthermore, independent of the diet used, exercise increased Akt and eNOS phosphorylation. Metabolic syndrome induced by HFD is reversed by exercise and diet modification. It is demonstrated that exercise training induces these beneficial effects without the requirement for dietary modification, and these beneficial effects may be mediated by shear stress-induced Akt/eNOS pathway activation. Thus, exercise may be an effective strategy to reverse almost all the atherosclerotic risk factors linked to obesity, particularly in the vasculature.

Effects of Pomegranate peel hydroAlcoholic extract and vitamin E supplementation on Paraoxonase, myeloperoxidase Activities and nitric oxide levels following an exhaustive exercise in rats

Directory of Open Access Journals (Sweden)

Saeid Veiskarami

2017-03-01

Full Text Available Background: free radicals produced as a result of heavy training exercise especially oxygen species (ROS damage to body tissues Which can be prevent from this by consuming antioxidant substances timely. The aim of this study was to evaluate effect of Pomegranate (Punica Granatum peel hydro alcoholic on reduced of oxidative stress induced by an exhaustive exercise. Materials and Methods: Thirty two weight-matched male Wistar rats were evenly divided into: 1 control: received saline (0.2 ml saline/ rat by oral administration via epigastric tube. 2 Received oral administration of 200 mg/kg pomegranate peel hydro alcoholic extract (PPHE200. 3 Received oral administration of 250 mg/kg Pomegranate peel hydro alcoholic extract (PPHE250. 4 Received oral administration of vitamin E (vit E 5 mg/kg. Animals were submitted to swimming exhaustive exercise stress for an 8-week. At the end of the experiment, blood samples were collected for serum. Serum samples were analyzed for paraoxonase-1(PON-1 and myeloperoxidase (MPO activities and nitric oxide levels. Results: Paraoxonase-1 (PON-1 activities serum were significantly increases in PPHE200 (23.03±1.47, PPHE250 (23.59±1.98 and vit E (25.38±2.65 than in the control (18.57±1.380 (p<0.05.In PPHE200 (32.76±9.97 ،PPHE250 (31.45±6.05 and vit E (24.94±4.65 treated animals was determined in serum where myeloperoxidase activities reduced significantly compared with control (40.70±6.14 (p<0.05. Levels of Nitric oxide levels were significantly lower in PPHE 200 (46.59±2.48, PPHE250 (40.27±2.62 and vit E (36.25±3.82 treated than in control (47.18±5.36 (p<0.05. Conclusion: Results indicated that Pomegranate peel hydro alcoholic extract supplementations can strength antioxidant defense system and anti-inflammatory induced by exhaustive exercise.

Opposite variations in maternal and neonatal thyroid function induced by iodine supplementation during pregnancy

DEFF Research Database (Denmark)

Nøhr, S B; Laurberg, P

2000-01-01

pregnancy, and 95 took no artificial iodine supplementation. Iodine supplementation (+I) induced opposite variations in thyroid function in the mother and the fetus. In +I mothers, TSH was 7.6% lower than in mothers with no supplementation (P ... in the +I group (P caused by opposite shifts in TSH frequency distribution in mothers and neonates. The association between iodine supplementation and high serum TSH in the neonates was further substantiated by an inverse correlation between thyroglobulin and TSH in cord blood...

Effect of antioxidant supplementation on exercise-induced cardiac troponin release in cyclists: a randomized trial.

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Klinkenberg, Lieke J J; Res, Peter T; Haenen, Guido R; Bast, Aalt; van Loon, Luc J C; van Dieijen-Visser, Marja P; Meex, Steven J R

2013-01-01

Cardiac troponin is the biochemical gold standard to diagnose acute myocardial infarction. Interestingly however, elevated cardiac troponin concentrations are also frequently observed during and after endurance-type exercise. Oxidative stress associated with prolonged exercise has been proposed to contribute to cardiac troponin release. Therefore, the aim of this study was to assess the effect of 4 week astaxanthin supplementation (a potent cartenoid antioxidant) on antioxidant capacity and exercise-induced cardiac troponin release in cyclists. Thirty-two well-trained male cyclists (age 25±5, weight 73±7 kg, maximum O2 uptake 60±5 mL·kg(-1)·min(-1), Wmax 5.4±0.5 W·kg(-1); mean ± SD) were repeatedly subjected to a laboratory based standardized exercise protocol before and after 4 weeks of astaxanthin (20 mg/day), or placebo supplementation in a double-blind randomized manner. Blood samples were obtained at baseline, at 60 min of cycling and immediately post-exercise (≈ 120 min). The pre-supplementation cycling trial induced a significant rise of median cardiac troponin T concentrations from 3.2 (IQR 3.0-4.2) to 4.7 ng/L (IQR 3.7-6.7), immediately post-exercise (pexercise-induced cardiac troponin T release (p = 0.24), as measured by the incremental area under the curve. Furthermore, the elevation in basal plasma astaxanthin concentrations was not reflected in changes in antioxidant capacity markers (trolox equivalent antioxidant capacity, uric acid, and malondialdehyde). Markers of inflammation (high-sensitivity C-reactive protein) and exercise-induced skeletal muscle damage (creatine kinase) were equally unaffected by astaxanthin supplementation. Despite substantial increases in plasma astaxanthin concentrations, astaxanthin supplementation did not improve antioxidant capacity in well-trained cyclists. Accordingly, exercise-induced cardiac troponin T concentrations were not affected by astaxanthin supplementation. ClinicalTrials.gov NCT01241877.

The protective role of low-concentration alcohol in high-fructose induced adverse cardiovascular events in mice.

Science.gov (United States)

Wu, Xiaoqi; Pan, Bo; Wang, Ying; Liu, Lingjuan; Huang, Xupei; Tian, Jie

2018-01-01

Cardiovascular disease remains a worldwide public health issue. As fructose consumption is dramatically increasing, it has been demonstrated that a fructose-rich intake would increase the risk of cardiovascular disease. In addition, emerging evidences suggest that low concentration alcohol intake may exert a protective effect on cardiovascular system. This study aimed to investigate whether low-concentration alcohol consumption would prevent the adverse effects on cardiovascular events induced by high fructose in mice. From the results of hematoxylin-eosin staining, echocardiography, heart weight/body weight ratio and the expression of hypertrophic marker ANP, we found high-fructose result in myocardial hypertrophy and the low-concentration alcohol consumption would prevent the cardiomyocyte hypertrophy from happening. In addition, we observed low-concentration alcohol consumption could inhibit mitochondria swollen induced by high-fructose. The elevated levels of glucose, triglyceride, total cholesterol in high-fructose group were reduced by low concentration alcohol. Low expression levels of SIRT1 and PPAR-γ induced by high-fructose were significantly elevated when fed with low-concentration alcohol. The histone lysine 9 acetylation (acH3K9) level was decreased in PPAR-γ promoter in high-fructose group but elevated when intake with low concentration alcohol. The binding levels of histone deacetylase SIRT1 were increased in the same region in high-fructose group, while the low concentration alcohol can prevent the increased binding levels. Overall, our study indicates that low-concentration alcohol consumption could inhibit high-fructose related myocardial hypertrophy, cardiac mitochondria damaged and disorders of glucose-lipid metabolism. Furthermore, these findings also provide new insights into histone acetylation-deacetylation mechanisms of low-concentration alcohol treatment that may contribute to the prevention of cardiovascular disease induced by high

Dietary supplementation with Agaricus blazei murill extract prevents diet-induced obesity and insulin resistance in rats.

Science.gov (United States)

Vincent, Mylène; Philippe, Erwann; Everard, Amandine; Kassis, Nadim; Rouch, Claude; Denom, Jessica; Takeda, Yorihiko; Uchiyama, Shoji; Delzenne, Nathalie M; Cani, Patrice D; Migrenne, Stéphanie; Magnan, Christophe

2013-03-01

Dietary supplement may potentially help to fight obesity and other metabolic disorders such as insulin-resistance and low-grade inflammation. The present study aimed to test whether supplementation with Agaricus blazei murill (ABM) extract could have an effect on diet-induced obesity in rats. Wistar rats were fed with control diet (CD) or high-fat diet (HF) and either with or without supplemented ABM for 20 weeks. HF diet-induced body weight gain and increased fat mass compared to CD. In addition HF-fed rats developed hyperleptinemia and insulinemia as well as insulin resistance and glucose intolerance. In HF-fed rats, visceral adipose tissue also expressed biomarkers of inflammation. ABM supplementation in HF rats had a protective effect against body weight gain and all study related disorders. This was not due to decreased food intake which remained significantly higher in HF rats whether supplemented with ABM or not compared to control. There was also no change in gut microbiota composition in HF supplemented with ABM. Interestingly, ABM supplementation induced an increase in both energy expenditure and locomotor activity which could partially explain its protective effect against diet-induced obesity. In addition a decrease in pancreatic lipase activity is also observed in jejunum of ABM-treated rats suggesting a decrease in lipid absorption. Taken together these data highlight a role for ABM to prevent body weight gain and related disorders in peripheral targets independently of effect in food intake in central nervous system. Copyright © 2012 The Obesity Society.

Ethyl Alcohol Extract of Hizikia fusiforme Induces Caspase ...

African Journals Online (AJOL)

Erah

In this study, the role of the ethyl alcohol extract of H. fusiforme (EAHF) in the induction of apoptosis in ... closely related to the induction of apoptosis via the downregulation of IAP family members such as IAP-. 1, IAP-2 ... induces apoptosis in a variety of cancer cells through ... Total cell extracts were prepared using PRO-.

Ethanol up-regulates nucleus accumbens neuronal activity dependent pentraxin (Narp): implications for alcohol-induced behavioral plasticity.

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Ary, Alexis W; Cozzoli, Debra K; Finn, Deborah A; Crabbe, John C; Dehoff, Marlin H; Worley, Paul F; Szumlinski, Karen K

2012-06-01

Neuronal activity dependent pentraxin (Narp) interacts with α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) glutamate receptors to facilitate excitatory synapse formation by aggregating them at established synapses. Alcohol is well-characterized to influence central glutamatergic transmission, including AMPA receptor function. Herein, we examined the influence of injected and ingested alcohol upon Narp protein expression, as well as basal Narp expression in mouse lines selectively bred for high blood alcohol concentrations under limited access conditions. Alcohol up-regulated accumbens Narp levels, concomitant with increases in levels of the GluR1 AMPA receptor subunit. However, accumbens Narp or GluR1 levels did not vary as a function of selectively bred genotype. We next employed a Narp knock-out (KO) strategy to begin to understand the behavioral relevance of alcohol-induced changes in protein expression in several assays of alcohol reward. Compared to wild-type mice, Narp KO animals: fail to escalate daily intake of high alcohol concentrations under free-access conditions; shift their preference away from high alcohol concentrations with repeated alcohol experience; exhibit a conditioned place-aversion in response to the repeated pairing of 3 g/kg alcohol with a distinct environment and fail to exhibit alcohol-induced locomotor hyperactivity following repeated alcohol treatment. Narp deletion did not influence the daily intake of either food or water, nor did it alter any aspect of spontaneous or alcohol-induced motor activity, including the development of tolerance to its motor-impairing effects with repeated treatment. Taken together, these data indicate that Narp induction, and presumably subsequent aggregation of AMPA receptors, may be important for neuroplasticity within limbic subcircuits mediating or maintaining the rewarding properties of alcohol. Published by Elsevier Inc.

Effect of chronic alcohol ingestion on the progression of periodontitis induced in Fisher-344 rats

Directory of Open Access Journals (Sweden)

Éder Ricardo Biasoli

2009-01-01

Full Text Available Objective: Understand the effect of chronic alcohol on the progression of periodontitis induced in Fischer-344 rats.Methods: For the study, 22 Fischer-344 rats, two months old were used, divided into groups: alcohol (n=8, ligature (n=7 and control (n=7. On the first day, the animals in the alcohol group were exposed to ingestion of a water solution containing 20% alcohol (size/size, up to day 90. After thirty days from the beginning of the experiment, the animals in the alcohol group and the ligature group were submitted to the placement of a silk thread around the right maxillary second molar. Nothing was performed on the left side, serving as control. All the groups were submitted to euthanasia 60 days after ligature placement. To assess the destruction of periodontitis, a radiographic exam was used to measure the destruction of bone height. Results: The results of the study showed that on the side in which periodontitis was induced, the group that ingested alcohol suffered an increase in destruction, with statistical differences when compared with the ligature and control groups and increased bone destruction in the ligature group when compared to control. Conclusion: Within the limitations of the study, it was concluded that chronic alcohol consumption by Fischer-344 rats led to greater progression of induced periodontitis.

REM sleep deprivation induces endothelial dysfunction and hypertension in middle-aged rats: Roles of the eNOS/NO/cGMP pathway and supplementation with L-arginine.

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Jiang, Jiaye; Gan, Zhongyuan; Li, Yuan; Zhao, Wenqi; Li, Hanqing; Zheng, Jian-Pu; Ke, Yan

2017-01-01

Sleep loss can induce or aggravate the development of cardiovascular and cerebrovascular diseases. However, the molecular mechanism underlying this phenomenon is poorly understood. The present study was designed to investigate the effects of REM sleep deprivation on blood pressure in rats and the underlying mechanisms of these effects. After Sprague-Dawley rats were subjected to REM sleep deprivation for 5 days, their blood pressures and endothelial function were measured. In addition, one group of rats was given continuous access to L-arginine supplementation (2% in distilled water) for the 5 days before and the 5 days of REM sleep deprivation to reverse sleep deprivation-induced pathological changes. The results showed that REM sleep deprivation decreased body weight, increased blood pressure, and impaired endothelial function of the aortas in middle-aged rats but not young rats. Moreover, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) concentrations as well as endothelial NO synthase (eNOS) phosphorylation in the aorta were decreased by REM sleep deprivation. Supplementation with L-arginine could protect against REM sleep deprivation-induced hypertension, endothelial dysfunction, and damage to the eNOS/NO/cGMP signaling pathway. The results of the present study suggested that REM sleep deprivation caused endothelial dysfunction and hypertension in middle-aged rats via the eNOS/NO/cGMP pathway and that these pathological changes could be inhibited via L-arginine supplementation. The present study provides a new strategy to inhibit the signaling pathways involved in insomnia-induced or insomnia-enhanced cardiovascular diseases.

Betaine supplementation reduces congenital defects after prenatal alcohol exposure (Conference Presentation)

Science.gov (United States)

Karunamuni, Ganga; Gu, Shi; Doughman, Yong Qiu; Sheehan, Megan M.; Ma, Pei; Peterson, Lindsy M.; Linask, Kersti K.; Jenkins, Michael W.; Rollins, Andrew M.; Watanabe, Michiko

2016-03-01

Over 500,000 women per year in the United States drink during pregnancy, and 1 in 5 of this population also binge drink. As high as 20-50% of live-born children with prenatal alcohol exposure (PAE) present with congenital heart defects including outflow and valvuloseptal anomalies that can be life-threatening. Previously we established a model of PAE (modeling a single binge drinking episode) in the avian embryo and used optical coherence tomography (OCT) imaging to assay early-stage cardiac function/structure and late-stage cardiac defects. At early stages, alcohol/ethanol-exposed embryos had smaller cardiac cushions and increased retrograde flow. At late stages, they presented with gross morphological defects in the head and chest wall, and also exhibited smaller or abnormal atrio-ventricular (AV) valves, thinner interventricular septae (IVS), and smaller vessel diameters for the aortic trunk branches. In other animal models, the methyl donor betaine (found naturally in many foods such as wheat bran, quinoa, beets and spinach) ameliorates neurobehavioral deficits associated with PAE but the effects on heart structure are unknown. In our model of PAE, betaine supplementation led to a reduction in gross structural defects and appeared to protect against certain types of cardiac defects such as ventricular septal defects and abnormal AV valvular morphology. Furthermore, vessel diameters, IVS thicknesses and mural AV leaflet volumes were normalized while the septal AV leaflet volume was increased. These findings highlight the importance of betaine and potentially methylation levels in the prevention of PAE-related birth defects which could have significant implications for public health.

Trace elements in the scalp hair of patients with alcohol induced psychosis

International Nuclear Information System (INIS)

Pradeep, A.S.; Nagaraju, G.J.; Sarita, P.

2012-01-01

A number of essential trace elements play a major role in various metabolic pathways and in many diseases like autoimmune, neurological and psychiatric. This study is undertaken with an aim to evaluate the levels of different trace elements in the scalp hair samples of patients suffering from alcohol induced psychosis by particle induced X-ray emission technique (PIXE). It is observed that Fe (p < 0.0005), Cu (p < 0.001) are significantly higher in the hair samples of alcohol induced psychosis patients compared to those in normals while concentrations of Mn (p < 0.005) and Zn (p < 0.0001) are lower. The concentrations of Co and Ni in the hair samples are found to be in consonance with the concentrations in the normals. (author)

Reversible cold-induced abnormalities in myocardial perfusion and function in systemic sclerosis

International Nuclear Information System (INIS)

Alexander, E.L.; Firestein, G.S.; Weiss, J.L.; Heuser, R.R.; Leitl, G.; Wagner, H.N. Jr.; Brinker, J.A.; Ciuffo, A.A.; Becker, L.C.

1986-01-01

The effects of peripheral cold exposure on myocardial perfusion and function were studied in 13 patients with scleroderma without clinically evident myocardial disease. Ten patients had at least one transient, cold-induced, myocardial perfusion defect visualized by thallium-201 scintigraphy, and 12 had reversible, cold-induced, segmental left ventricular hypokinesis by two-dimensional echocardiography. The 10 patients with transient perfusion defects all had anatomically corresponding ventricular wall motion abnormalities. No one in either of two control groups (9 normal volunteers and 7 patients with chest pain and normal coronary arteriograms) had cold-induced abnormalities. This study is the first to show the simultaneous occurrence of cold-induced abnormalities in myocardial perfusion and function in patients with scleroderma. The results suggest that cold exposure in such patients may elicit transient reflex coronary vasoconstriction resulting in reversible myocardial ischemia and dysfunction. Chronic recurrent episodes of coronary spasm may lead to focal myocardial fibrosis

Vitamin K1 (phylloquinone) and K2 (menaquinone-4) supplementation improves bone formation in a high-fat diet-induced obese mice.

Science.gov (United States)

Kim, Misung; Na, Woori; Sohn, Cheongmin

2013-09-01

Several reports suggest that obesity is a risk factor for osteoporosis. Vitamin K plays an important role in improving bone metabolism. This study examined the effects of vitamin K1 and vitamin K2 supplementation on the biochemical markers of bone turnover and morphological microstructure of the bones by using an obese mouse model. Four-week-old C57BL/6J male mice were fed a 10% fat normal diet group or a 45% kcal high-fat diet group, with or without 200 mg/1000 g vitamin K1 (Normal diet + K1, high-fat diet + K1) and 200 mg/1000 g vitamin K2 (Normal diet + K2, high-fat diet + K2) for 12 weeks. Serum levels of osteocalcin were higher in the high-fat diet + K2 group than in the high-fat diet group. Serum OPG level of the high-fat diet group, high-fat diet + K1 group, and high-fat diet + K2 group was 2.31 ± 0.31 ng/ml, 2.35 ± 0.12 ng/ml, and 2.90 ± 0.11 ng/ml, respectively. Serum level of RANKL in the high-fat diet group was significantly higher than that in the high-fat diet + K1 group and high-fat diet + K2 group (p<0.05). Vitamin K supplementation seems to tend to prevent bone loss in high-fat diet induced obese state. These findings suggest that vitamin K supplementation reversed the high fat diet induced bone deterioration by modulating osteoblast and osteoclast activities and prevent bone loss in a high-fat diet-induced obese mice.

Inhibition of Mammary Cancer Progression in Fetal Alcohol Exposed Rats by β-Endorphin Neurons.

Science.gov (United States)

Zhang, Changqing; Franklin, Tina; Sarkar, Dipak K

2016-01-01

Fetal alcohol exposure (FAE) increases the susceptibility to carcinogen-induced mammary cancer progression in rodent models. FAE also decreases β-endorphin (β-EP) level and causes hyperstress response, which leads to inhibition of immune function against cancer. Previous studies have shown that injection of nanosphere-attached dibutyryl cyclic adenosine monophosphate (dbcAMP) into the third ventricle increases the number of β-EP neurons in the hypothalamus. In this study, we assessed the therapeutic potential of stress regulation using methods to increase hypothalamic levels of β-EP, a neuropeptide that inhibits stress axis activity, in treatment of carcinogen-induced mammary cancer in fetal alcohol exposed rats. Fetal alcohol exposed and control Sprague Dawley rats were given a dose of N-Nitroso-N-methylurea (MNU) at postnatal day 50 to induce mammary cancer growth. Upon detection of mammary tumors, the animals were either transplanted with β-EP neurons or injected with dbcAMP-delivering nanospheres into the hypothalamus to increase β-EP peptide production. Spleen cytokines were detected using reverse transcription polymerase chain reaction assays. Metastasis study was done by injecting mammary cancer cells MADB106 into jugular vein of β-EP-activated or control fetal alcohol exposed animals. Both transplantation of β-EP neurons and injection of dbcAMP-delivering nanospheres inhibited MNU-induced mammary cancer growth in control rats, and reversed the effect of FAE on the susceptibility to mammary cancer. Similar to the previously reported immune-enhancing and stress-suppressive effects of β-EP transplantation, injection of dbcAMP-delivering nanospheres increased the levels of interferon-γ and granzyme B and decreased the levels of epinephrine and norepinephrine in fetal alcohol exposed rats. Mammary cancer cell metastasis study also showed that FAE increased incidence of lung tumor retention, while β-EP transplantation inhibited lung tumor growth in

Thermodynamic and fluorescence studies of the underlying factors in benzyl alcohol-induced lipid interdigitated phase.

Science.gov (United States)

Chen, C H; Hoye, K; Roth, L G

1996-09-15

To further investigate factors contributing to the action of alcohol in the solute-induced lipid interdigitation phase, thermodynamic and fluorescence polarization measurements were carried out to study the interaction of benzyl alcohol with dipalmitoyl phosphatidylcholine bilayer vesicles. The obtained results were compared with those previously reported for ethanol and cyclohexanol (L. G. Roth and C-H. Chen, Arch. Biochem. Biophys. 296, 207, 1992). Similar to ethanol, benzyl alcohol was found to exhibit a biphasic effect on the enthalpy (delta Hm) and the temperature (tm) of the lipid-phase transition and the steady-state fluorescence polarization (P) monitored by 1,6-diphenyl-1,3,5-hexatriene. At a total concentration of benzyl alcohol delta Hm and P, which were correlated with the formation of a lipid interdigitated phase, as evidenced by reported X-ray diffraction data. Combining the results with benzyl alcohol and ethanol suggested that simultaneously large changes in delta Hm and P can be used as an indication of the occurrence of a solute-induced lipid interdigitated phase. The overall interacting force in the formation of this lipid phase, as derived from the interactions of the hydroxyl portion of an alcohol with the lipid phosphate head group and the hydrophobic portion of an alcohol with the lipid hydrocarbon chains, may or may not be dominated by hydrophobic interaction. Although lipid/water partition coefficients and the contribution of hydrophobic interaction to the overall interacting force were comparable between benzyl alcohol and cyclohexanol, benzyl alcohol induced lipid interdigitated phase, but not for cyclohexanol. This was due to the ability of benzyl alcohol to be more effective than cyclohexanol in simultaneously interacting with the phosphate head group and the hydrocarbon chains of lipid.

Ellagic acid attenuates high-carbohydrate, high-fat diet-induced metabolic syndrome in rats.

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Panchal, Sunil K; Ward, Leigh; Brown, Lindsay

2013-03-01

Fruits and nuts may prevent or reverse common human health conditions such as obesity, diabetes and hypertension; together, these conditions are referred to as metabolic syndrome, an increasing problem. This study has investigated the responses to ellagic acid, present in many fruits and nuts, in a diet-induced rat model of metabolic syndrome. Eight- to nine-week-old male Wistar rats were divided into four groups for 16-week feeding with cornstarch diet (C), cornstarch diet supplemented with ellagic acid (CE), high-carbohydrate, high-fat diet (H) and high-carbohydrate, high-fat diet supplemented with ellagic acid (HE). CE and HE rats were given 0.8 g/kg ellagic acid in food from week 8 to 16 only. At the end of 16 weeks, cardiovascular, hepatic and metabolic parameters along with protein levels of Nrf2, NF-κB and CPT1 in the heart and the liver were characterised. High-carbohydrate, high-fat diet-fed rats developed cardiovascular remodelling, impaired ventricular function, impaired glucose tolerance, non-alcoholic fatty liver disease with increased protein levels of NF-κB and decreased protein levels of Nrf2 and CPT1 in the heart and the liver. Ellagic acid attenuated these diet-induced symptoms of metabolic syndrome with normalisation of protein levels of Nrf2, NF-κB and CPT1. Ellagic acid derived from nuts and fruits such as raspberries and pomegranates may provide a useful dietary supplement to decrease the characteristic changes in metabolism and in cardiac and hepatic structure and function induced by a high-carbohydrate, high-fat diet by suppressing oxidative stress and inflammation.

Multi-Vitamin B Supplementation Reverses Hypoxia-Induced Tau Hyperphosphorylation and Improves Memory Function in Adult Mice.

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Yu, Lixia; Chen, Yuan; Wang, Weiguang; Xiao, Zhonghai; Hong, Yan

2016-08-04

Hypobaric hypoxia (HH) leads to reduced oxygen delivery to brain. It could trigger cognitive dysfunction and increase the risk of dementia including Alzheimer's disease (AD). The present study was undertaken in order to examine whether B vitamins (B6, B12, folate, and choline) could exert protective effects on hypoxia-induced memory deficit and AD related molecular events in mice. Adult male Kunming mice were assigned to five groups: normoxic control, hypoxic model (HH), hypoxia+vitamin B6/B12/folate (HB), hypoxia+choline (HC), hypoxia+vitamin B6/B12/folate+choline (HBC). Mice in the hypoxia, HB, HC, and HBC groups were exposed to hypobaric hypoxia for 8 h/day for 28 days in a decompression chamber mimicking 5500 meters of high altitude. Spatial and passive memories were assessed by radial arm and step-through passive test, respectively. Levels of tau and glycogen synthase kinase (GSK)-3β phosphorylation were detected by western blot. Homocysteine (Hcy) concentrations were determined using enzymatic cycling assay. Mice in the HH group exhibited significant spatial working and passive memory impairment, increased tau phosphorylation at Thr181, Ser262, Ser202/Thr205, and Ser396 in the cortex and hippocampus, and elevated Hcy levels compared with controls. Concomitantly, the levels of Ser9-phosphorylated GSK-3β were significantly decreased in brain after hypoxic treatment. Supplementations of vitamin B6/B12/folate+choline could significantly ameliorate the hypoxia-induced memory deficits, observably decreased Hcy concentrations in serum, and markedly attenuated tau hyperphosphorylation at multiple AD-related sites through upregulating inhibitory Ser9-phosphorylated GSK-3β. Our finding give further insight into combined neuroprotective effects of vitamin B6, B12, folate, and choline on brain against hypoxia.

Alcohol-Induced Memory Blackouts as an Indicator of Injury Risk among College Drinkers

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Mundt, Marlon P.; Zakletskaia, Larissa I.; Brown, David D.; Fleming, Michael F.

2011-01-01

Objective An alcohol-induced memory blackout represents an amnesia to recall events but does not involve a loss of consciousness. Memory blackouts are a common occurrence among college drinkers, but it is not clear if a history of memory blackouts is predictive of future alcohol-related injury above and beyond the risk associated with heavy drinking episodes. This analysis sought to determine if baseline memory blackouts can prospectively identify college students with alcohol-related injury in the next 24 months after controlling for heavy drinking days. Methods Data were analyzed from the College Health Intervention Project Study (CHIPS), a randomized controlled trial of screening and brief physician intervention for problem alcohol use among 796 undergraduate and 158 graduate students at four university sites in the US and one in Canada, conducted from 2004 to 2009. Multivariate analyses used generalized estimating equations (GEE) with the logit link. Results The overall 24-month alcohol-related injury rate was 25.6%, with no significant difference between males and females (p=.51). Alcohol-induced memory blackouts at baseline exhibited a significant dose-response on odds of alcohol-related injury during follow-up, increasing from 1.57 (95% CI: 1.13–2.19) for subjects reporting 1–2 memory blackouts at baseline to 2.64 (95% CI: 1.65–4.21) for students acknowledging 6+ memory blackouts at baseline. The link between memory blackouts and injury was mediated by younger age, prior alcohol-related injury, heavy drinking, and sensation-seeking disposition. Conclusions Memory blackouts are a significant predictor of future alcohol-related injury among college drinkers after adjusting for heavy drinking episodes. PMID:21708813

Naltrexone Reverses Ethanol Preference and Protein Kinase C Activation in Drosophila melanogaster

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Rajeswari Koyyada

2018-03-01

Full Text Available Alcohol use disorder (AUD is a major health, social and economic problem for which there are few effective treatments. The opiate antagonist naltrexone is currently prescribed clinically with mixed success. We have used naltrexone in an established behavioral assay (CAFE in Drosophila melanogaster that measures the flies' preference for ethanol-containing food. We have confirmed that Drosophila exposed to ethanol develop a preference toward this drug and we demonstrate that naltrexone, in a dose dependant manner, reverses the ethanol-induced ethanol preference. This effect is not permanent, as preference for alcohol returns after discontinuing naltrexone. Additionally, naltrexone reduced the alcohol-induced increase in protein kinase C activity. These findings are of interest because they confirm that Drosophila is a useful model for studying human responses to addictive drugs. Additionally because of the lack of a closely conserved opiate system in insects, our results could either indicate that a functionally related system does exist in insects or that in insects, and potentially also in mammals, naltrexone binds to alternative sites. Identifying such sites could lead to improved treatment strategies for AUD.

Naltrexone Reverses Ethanol Preference and Protein Kinase C Activation in Drosophila melanogaster

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Koyyada, Rajeswari; Latchooman, Nilesh; Jonaitis, Julius; Ayoub, Samir S.; Corcoran, Olivia; Casalotti, Stefano O.

2018-01-01

Alcohol use disorder (AUD) is a major health, social and economic problem for which there are few effective treatments. The opiate antagonist naltrexone is currently prescribed clinically with mixed success. We have used naltrexone in an established behavioral assay (CAFE) in Drosophila melanogaster that measures the flies' preference for ethanol-containing food. We have confirmed that Drosophila exposed to ethanol develop a preference toward this drug and we demonstrate that naltrexone, in a dose dependant manner, reverses the ethanol-induced ethanol preference. This effect is not permanent, as preference for alcohol returns after discontinuing naltrexone. Additionally, naltrexone reduced the alcohol-induced increase in protein kinase C activity. These findings are of interest because they confirm that Drosophila is a useful model for studying human responses to addictive drugs. Additionally because of the lack of a closely conserved opiate system in insects, our results could either indicate that a functionally related system does exist in insects or that in insects, and potentially also in mammals, naltrexone binds to alternative sites. Identifying such sites could lead to improved treatment strategies for AUD. PMID:29593550

Saturation of retinol-binding protein correlates closely to the severity of alcohol-induced liver disease

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Wagnerberger, S.; Schäfer, C.; Bode, C.

2006-01-01

Impaired metabolism of retinol has been shown to occur in alcohol-induced liver disease (ALD). The purpose of the present study was to investigate the saturation of retinol-binding protein (RBP) in 6 patients with different stages of ALD. Hospitalized alcohol consumers (n=118) with different stages......: 43.5+/-6.2%; ALD3: 29.0+/-5.1%). The present study indicates that plasma concentrations of retinol and RBP per se do not correlate to severity of ALD, but rather that the retinol/RBP ratio links to the severity of alcohol-induced liver damage. From these results, a reduced availability of retinol...

Changes in cerebral [18F]-FDG uptake induced by acute alcohol administration in a rat model of alcoholism.

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Gispert, Juan D; Figueiras, Francisca P; Vengeliene, Valentina; Herance, José R; Rojas, Santiago; Spanagel, Rainer

2017-06-01

Several [ 18 F]-FDG positron emission tomography (PET) studies in alcoholics have consistently reported decreases in overall brain glucose metabolism at rest and following acute alcohol administration. However, changes in cerebral glucose utilization associated with the transition to addiction are not well understood and require longitudinal translational imaging studies in animal models of alcoholism. Here, we studied brain glucose uptake in alcohol drinking rats in order to provide convergent evidence to what has previously been reported in human studies. Brain glucose metabolism was measured by [ 18 F]-FDG microPET imaging in different male Wistar rat groups: short-term drinking (three months), long-term drinking (twelve months) and alcohol-naïve. Global and regional cerebral glucose uptake was measured at rest and following acute alcohol administration. We showed that alcohol significantly reduced the whole-brain glucose metabolism. This effect was most pronounced in the parietal cortex and cerebellum. Alcohol-induced decreases in brain [ 18 F]-FDG uptake was most apparent in alcohol-naïve rats, less intense in short-term drinkers and absent in long-term drinkers. The latter finding indicates the occurrence of tolerance to the intoxicating effects of alcohol in long-term drinking individuals. In contrast, some regions, like the ventral striatum and entorhinal cortex, showed enhanced metabolic activity, an effect that did not undergo tolerance during long-term alcohol consumption. Our findings are comparable to those described in human studies using the same methodology. We conclude that [ 18 F]-FDG PET studies in rat models of alcoholism provide good translation and can be used for future longitudinal studies investigating alterations in brain function during different stages of the addiction cycle. Copyright © 2017 Elsevier B.V. All rights reserved.

The effects of diet-induced obesity on hepatocyte insulin signaling pathways and induction of non-alcoholic liver damage

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Sameer Fatani

2011-03-01

intracellular insulin signaling mechanisms, namely IRS-2 and PI 3-kinase, leading to hepatic insulin resistance. Moreover, diet-induced obesity induces fatty liver, an effect which can be reversed by either removal of the source of obesity or treatment with fenofibrate, a peroxisome proliferator-activated receptor alpha agonist.Keywords: obesity, non-alcoholic steatohepatitis, hepatocyte insulin signaling, fenofibrate

Population pharmacokinetic–pharmacodynamic analysis for sugammadex-mediated reversal of rocuronium-induced neuromuscular blockade

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Kleijn, Huub J; Zollinger, Daniel P; van den Heuvel, Michiel W; Kerbusch, Thomas

2011-01-01

AIMS An integrated population pharmacokinetic–pharmacodynamic model was developed with the following aims: to simultaneously describe pharmacokinetic behaviour of sugammadex and rocuronium; to establish the pharmacokinetic–pharmacodynamic model for rocuronium-induced neuromuscular blockade and reversal by sugammadex; to evaluate covariate effects; and to explore, by simulation, typical covariate effects on reversal time. METHODS Data (n = 446) from eight sugammadex clinical studies covering men, women, non-Asians, Asians, paediatrics, adults and the elderly, with various degrees of renal impairment, were used. Modelling and simulation techniques based on physiological principles were applied to capture rocuronium and sugammadex pharmacokinetics and pharmacodynamics and to identify and quantify covariate effects. RESULTS Sugammadex pharmacokinetics were affected by renal function, bodyweight and race, and rocuronium pharmacokinetics were affected by age, renal function and race. Sevoflurane potentiated rocuronium-induced neuromuscular blockade. Posterior predictive checks and bootstrapping illustrated the accuracy and robustness of the model. External validation showed concordance between observed and predicted reversal times, but interindividual variability in reversal time was pronounced. Simulated reversal times in typical adults were 0.8, 1.5 and 1.4 min upon reversal with sugammadex 16 mg kg−1 3 min after rocuronium, sugammadex 4 mg kg−1 during deep neuromuscular blockade and sugammadex 2 mg kg−1 during moderate blockade, respectively. Simulations indicated that reversal times were faster in paediatric patients and slightly slower in elderly patients compared with adults. Renal function did not affect reversal time. CONCLUSIONS Simulations of the therapeutic dosing regimens demonstrated limited impact of age, renal function and sevoflurane use, as predicted reversal time in typical subjects was always <2 min. PMID:21535448

Perillyl alcohol suppresses antigen-induced immune responses in the lung

International Nuclear Information System (INIS)

Imamura, Mitsuru; Sasaki, Oh; Okunishi, Katsuhide; Nakagome, Kazuyuki; Harada, Hiroaki; Kawahata, Kimito; Tanaka, Ryoichi; Yamamoto, Kazuhiko; Dohi, Makoto

2014-01-01

Highlights: •Perillyl alcohol (POH) is an isoprenoid which inhibits the mevalonate pathway. •We examined whether POH suppresses immune responses with a mouse model of asthma. •POH treatment during sensitization suppressed Ag-induced priming of CD4 + T cells. •POH suppressed airway eosinophila and cytokine production in thoracic lymph nodes. -- Abstract: Perillyl alcohol (POH) is an isoprenoid which inhibits farnesyl transferase and geranylgeranyl transferase, key enzymes that induce conformational and functional changes in small G proteins to conduct signal production for cell proliferation. Thus, it has been tried for the treatment of cancers. However, although it affects the proliferation of immunocytes, its influence on immune responses has been examined in only a few studies. Notably, its effect on antigen-induced immune responses has not been studied. In this study, we examined whether POH suppresses Ag-induced immune responses with a mouse model of allergic airway inflammation. POH treatment of sensitized mice suppressed proliferation and cytokine production in Ag-stimulated spleen cells or CD4 + T cells. Further, sensitized mice received aerosolized OVA to induce allergic airway inflammation, and some mice received POH treatment. POH significantly suppressed indicators of allergic airway inflammation such as airway eosinophilia. Cytokine production in thoracic lymph nodes was also significantly suppressed. These results demonstrate that POH suppresses antigen-induced immune responses in the lung. Considering that it exists naturally, POH could be a novel preventive or therapeutic option for immunologic lung disorders such as asthma with minimal side effects

Alcohol consumption in relation to maternal deaths from induced-abortions in Ghana

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Asamoah Benedict O

2012-08-01

Full Text Available Abstract Introduction The fight against maternal deaths has gained attention as the target date for Millennium Development Goal 5 approaches. Induced-abortion is one of the leading causes of maternal deaths in developing countries which hamper this effort. In Ghana, alcohol consumption and unwanted pregnancies are on the ascendancy. We examined the association between alcohol consumption and maternal mortality from induced-abortion. We further analyzed the factors that lie behind the alcohol consumption patterns in the study population. Method The data we used was extracted from the Ghana Maternal Health Survey 2007. This was a national survey conducted across the 10 administrative regions of Ghana. The survey identified 4203 female deaths through verbal autopsy, among which 605 were maternal deaths in the 12 to 49 year-old age group. Analysis was done using Statistical software IBM SPSS Statistics 20. A case control study design was used. Cross-tabulations and logistic regression models were used to investigate associations between the different variables. Results Alcohol consumption was significantly associated with abortion-related maternal deaths. Women who had ever consumed alcohol (OR adjusted 2.6, 95% CI 1.38–4.87, frequent consumers (OR adjusted 2.6, 95% CI 0.89–7.40 and occasional consumers (OR adjusted 2.7, 95% CI 1.29–5.46 were about three times as likely to die from abortion-related causes compared to those who abstained from alcohol. Maternal age, marital status and educational level were found to have a confounding effect on the observed association. Conclusion Policy actions directed toward reducing abortion-related deaths should consider alcohol consumption, especially among younger women. Policy makers in Ghana should consider increasing the legal age for alcohol consumption. We suggest that information on the health risks posed by alcohol and abortion be disseminated to communities in the informal sector where

Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction.

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Kiyatkin, Eugene A; Ren, Suelynn; Wakabayashi, Ken T; Baumann, Michael H; Shaham, Yavin

2016-01-01

MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (>2.5 °C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results.

Folic acid and safflower oil supplementation interacts and protects embryos from maternal diabetes-induced damage.

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Higa, R; Kurtz, M; Mazzucco, M B; Musikant, D; White, V; Jawerbaum, A

2012-05-01

Maternal diabetes increases the risk of embryo malformations. Folic acid and safflower oil supplementations have been shown to reduce embryo malformations in experimental models of diabetes. In this study we here tested whether folic acid and safflower oil supplementations interact to prevent embryo malformations in diabetic rats, and analyzed whether they act through the regulation of matrix metalloproteinases (MMPs), their endogenous inhibitors (TIMPs), and nitric oxide (NO) and reactive oxygen species production. Diabetes was induced by streptozotocin administration prior to mating. From Day 0.5 of pregnancy, rats did or did not receive folic acid (15 mg/kg) and/or a 6% safflower oil-supplemented diet. Embryos and decidua were explanted on Day 10.5 of gestation for further analysis of embryo resorptions and malformations, MMP-2 and MMP-9 activities, TIMP-1 and TIMP-2 levels, NO production and lipid peroxidation. Maternal diabetes induced resorptions and malformations that were prevented by folic acid and safflower oil supplementation. MMP-2 and MMP-9 activities were increased in embryos and decidua from diabetic rats and decreased with safflower oil and folic acid supplementations. In diabetic animals, the embryonic and decidual TIMPs were increased mainly with safflower oil supplementation in decidua and with folic acid in embryos. NO overproduction was decreased in decidua from diabetic rats treated with folic acid alone and in combination with safflower oil. These treatments also prevented increases in embryonic and decidual lipid peroxidation. In conclusion, folic acid and safflower oil supplementations interact and protect the embryos from diabetes-induced damage through several pathways related to a decrease in pro-inflammatory mediators.

Mechanisms of neuroimmune gene induction in alcoholism.

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Crews, Fulton T; Vetreno, Ryan P

2016-05-01

Alcoholism is a primary, chronic relapsing disease of brain reward, motivation, memory, and related circuitry. It is characterized by an individual's continued drinking despite negative consequences related to alcohol use, which is exemplified by alcohol use leading to clinically significant impairment or distress. Chronic alcohol consumption increases the expression of innate immune signaling molecules (ISMs) in the brain that alter cognitive processes and promote alcohol drinking. Unraveling the mechanisms of alcohol-induced neuroimmune gene induction is complicated by positive loops of multiple cytokines and other signaling molecules that converge on nuclear factor kappa-light-chain-enhancer of activated B cells and activator protein-1 leading to induction of additional neuroimmune signaling molecules that amplify and expand the expression of ISMs. Studies from our laboratory employing reverse transcription polymerase chain reaction (RT-PCR) to assess mRNA, immunohistochemistry and Western blot analysis to assess protein expression, and others suggest that ethanol increases brain neuroimmune gene and protein expression through two distinct mechanisms involving (1) systemic induction of innate immune molecules that are transported from blood to the brain and (2) the direct release of high-mobility group box 1 (HMGB1) from neurons in the brain. Released HMGB1 signals through multiple receptors, particularly Toll-like receptor (TLR) 4, that potentiate cytokine receptor responses leading to a hyperexcitable state that disrupts neuronal networks and increases excitotoxic neuronal death. Innate immune gene activation in brain is persistent, consistent with the chronic relapsing disease that is alcoholism. Expression of HMGB1, TLRs, and other ISMs is increased several-fold in the human orbital frontal cortex, and expression of these molecules is highly correlated with each other as well as lifetime alcohol consumption and age of drinking onset. The persistent and

Antioxidant effects of Spirulina supplement against lead acetate-induced hepatic injury in rats

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Walid Hamdy El-Tantawy

2016-10-01

Full Text Available Lead is a toxic metal that induces a wide range of behavioral, biochemical and physiological effects in humans. Oxidative damage has been proposed as a possible mechanism involved in lead toxicity. The current study was carried out to evaluate the antioxidant activities of Spirulina supplement against lead acetate -induced hepatic injury in rats. Five groups of rats were used in this study, Control, Lead acetate (100 mg/kg, Lead acetate (100 mg/kg + 0.5 g/kg Spirulina, Lead acetate (100 mg/kg + 1 g/kg Spirulina and Lead acetate + 25 mg/100 g Vitamin C (reference drug. All experimental groups received the oral treatment by stomach tube once daily for 4 weeks. Lead intoxication resulted in a significant increase in serum alanine transaminae (ALT, aspartate transaminae (AST activities, liver homogenate tumor necrosis factor-α (TNF-α, caspase-3, malondialdehyde (MDA, nitric oxide (NO levels and a significant decline of total serum protein, liver homogenate reduced glutathione (GSH level and superoxide dismutase (SOD activity. Both doses of Spirulina supplement as well as Vitamin C succeeded to improve the biochemical parameters of serum and liver and prevented the lead acetate-induced significant changes on plasma and antioxidant status of the liver. Both doses of Spirulina supplement had the same anti-apoptotic activity and high dose exhibited more antioxidant activity than that of low dose. In conclusion, the results of the present work revealed that Spirulina supplement had protective, antioxidant and anti-apoptotic effects on lead acetate-induced hepatic damage.

Subacute ethanol consumption reverses p-xylene-induced decreases in axonal transport

Energy Technology Data Exchange (ETDEWEB)

Padilla, S.; Lyerly, D.L.; Pope, C.N.

1992-01-01

Organic solvants, as a class, have been implicated as neurotoxic agents in humans and laboratory animals. The study was designed to assess the interaction between subacute ingestion of moderate levels of ethanol and the p-xylene-induced decreases in protein and glycoprotein synthesis and axonal transport in the rat optic system. The results indicated that animals maintained on 10% ethanol as a drinking liquid show less p-xylene-induced neurotoxicity than animals receiving no ethanol supplement.

Colostrum supplementation protects against exercise - induced oxidative stress in skeletal muscle in mice

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Appukutty Mahenderan

2012-11-01

Full Text Available Abstract Background This study examined the effects of bovine colostrum on exercise –induced modulation of antioxidant parameters in skeletal muscle in mice. Adult male BALB/c mice were randomly divided into four groups (control, colostrum alone, exercise and exercise with colostrum and each group had three subgroups (day 0, 21 and 42. Colostrum groups of mice were given a daily oral supplement of 50 mg/kg body weight of bovine colostrum and the exercise group of mice were made to exercise on the treadmill for 30 minutes per day. Total antioxidants, lipid hydroperoxides, xanthine oxidase and super oxide dismutase level was assayed from the homogenate of hind limb skeletal muscle. Results Exercise—induced a significant oxidative stress in skeletal muscles as evidenced by the elevated lipid hydroperoxides and xanthine oxidase levels. There was a significant decrease in skeletal muscle total antioxidants and superoxide dismutase levels. Daily colostrum supplement significantly reduced the lipid hydroperoxides and xanthine oxidase enzyme level and increased the total antioxidant levels in the leg muscle. Conclusion Thus, the findings of this study showed that daily bovine colostrum supplementation was beneficial to skeletal muscle to reduce the oxidant-induced damage during muscular exercise.

Role of Alcohol on the Fracture Resistance of Dentin

Energy Technology Data Exchange (ETDEWEB)

Nalla, Ravi K.; Kinney, John H.; Tomsia, Antoni P.; Ritchie,Robert O.

2006-05-01

Healthy dentin, the mineralized tissue that makes up the bulk of the tooth, is naturally hydrated in vivo; however, it is known that various chemical reagents including acetone and ethanol can induce dehydration and thereby affect its properties. Here, we seek to investigate this in light of the effect alcohol can have on the mechanical properties of dentin, specifically by measuring the stiffness, strength and toughness of dentin in simulated body fluid and scotch whisky. Results indicate that chemical dehydration induced by the whisky has a significant beneficial effect on the elastic modulus, strength and fracture toughness of dentin. Although this makes teeth more resistant to fracture, the change in properties is fully reversible upon rehydration. This effect is considered to be associated with increased cross-linking of the collagen molecules from intermolecular hydrogen-bonding where water is replaced with weaker hydrogen-bond forming solvents such as alcohol.

Effects of betaine supplementation and choline deficiency on folate deficiency-induced hyperhomocysteinemia in rats.

Science.gov (United States)

Liu, Ying; Liu, Yi-qun; Morita, Tatsuya; Sugiyama, Kimio

2012-01-01

The effect of betaine status on folate deficiency-induced hyperhomocysteinemia was investigated to determine whether folate deficiency impairs homocysteine removal not only by the methionine synthase (MS) pathway but also by the betaine-homocysteine S-methyltransferase (BHMT) pathway. For this purpose, we investigated the effect of dietary supplementation with betaine at a high level (1%) in rats fed a folate-deprived 10% casein diet (10C) and 20% casein diet (20C). We also investigated the effect of choline deprivation on folate deficiency-induced hyperhomocysteinemia in rats fed 20C. Supplementation of folate-deprived 10C and 20C with 1% betaine significantly suppressed folate deprivation-induced hyperhomocysteinemia, but the extent of suppression was partial or limited, especially in rats fed 10C, the suppression of plasma homocysteine increment being 48.5% in rats fed 10C and 69.7% in rats fed 20C. Although betaine supplementation greatly increased hepatic betaine concentration and BHMT activity, these increases did not fully explain why the effect of betaine supplementation was partial or limited. Folate deprivation markedly increased the hepatic concentration of N,N-dimethylglycine (DMG), a known inhibitor of BHMT, and there was a significant positive correlation between hepatic DMG concentration and plasma homocysteine concentration, suggesting that folate deficiency increases hepatic DMG concentration and thereby depresses BHMT reaction, leading to interference with the effect of betaine supplementation. Choline deprivation did not increase plasma homocysteine concentration in rats fed 20C, but it markedly enhanced plasma homocysteine concentration when rats were fed folate-deprived 20C. This indicates that choline deprivation reinforced folate deprivation-induced hyperhomocysteinemia. Increased hepatic DMG concentration was also associated with such an effect. These results support the concept that folate deficiency impairs homocysteine metabolism not only

Moderate acute intake of de-alcoholized red wine, but not alcohol, is protective against radiation-induced DNA damage ex vivo -- results of a comparative in vivo intervention study in younger men.

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Greenrod, W; Stockley, C S; Burcham, P; Abbey, M; Fenech, M

2005-12-11

Moderate intake of wine is associated with reduced risk of cardiovascular disease and possibly cancer however it remains unclear whether the potential health benefits of wine intake are due to alcohol or the non-alcoholic fraction of wine. We therefore tested the hypothesis that the non-alcoholic fraction of wine protects against genome damage induced by oxidative stress in a crossover intervention study involving six young adult males aged 21-26 years. The participants adhered to a low plant phenolic compound diet for 48 h prior to consuming 300 mL of complete red wine, de-alcoholized red wine or ethanol on separate occasions 1 week apart. Blood samples were collected 0.5, 1.0 and 2.0 h after beverage consumption. Baseline and radiation-induced genome damage was measured using the cytokinesis-block micronucleus assay and total plasma catechin concentration was measured. Consumption of de-alcoholized red wine significantly decreased the gamma radiation-induced DNA damage at 1 and 2 h post-consumption by 20%. In contrast alcohol tended to increase radiation-induced genome damage and complete wine protected against radiation-induced genome damage relative to alcohol. The observed effects were only weakly correlated with the concentration of total plasma catechin (R=-0.23). These preliminary data suggest that only the non-alcoholic fraction of red wine protects DNA from oxidative damage but this effect cannot be explained solely by plasma catechin.

Alcohol consumption negates estrogen-mediated myocardial repair in ovariectomized mice by inhibiting endothelial progenitor cell mobilization and function.

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Mackie, Alexander R; Krishnamurthy, Prasanna; Verma, Suresh K; Thorne, Tina; Ramirez, Veronica; Qin, Gangjian; Abramova, Tatiana; Hamada, Hiromichi; Losordo, Douglas W; Kishore, Raj

2013-06-21

We have shown previously that estrogen (estradiol, E2) supplementation enhances voluntary alcohol consumption in ovariectomized female rodents and that increased alcohol consumption impairs ischemic hind limb vascular repair. However, the effect of E2-induced alcohol consumption on post-infarct myocardial repair and on the phenotypic/functional properties of endothelial progenitor cells (EPCs) is not known. Additionally, the molecular signaling of alcohol-estrogen interactions remains to be elucidated. This study examined the effect of E2-induced increases in ethanol consumption on post-infarct myocardial function/repair. Ovariectomized female mice, implanted with 17β-E2 or placebo pellets were given access to alcohol for 6 weeks and subjected to acute myocardial infarction. Left ventricular functions were consistently depressed in mice consuming ethanol compared with those receiving only E2. Alcohol-consuming mice also displayed significantly increased infarct size and reduced capillary density. Ethanol consumption also reduced E2-induced mobilization and homing of EPCs to injured myocardium compared with the E2-alone group. In vitro, exposure of EPCs to ethanol suppressed E2-induced proliferation, survival, and migration and markedly altered E2-induced estrogen receptor-dependent cell survival signaling and gene expression. Furthermore, ethanol-mediated suppression of EPC biology was endothelial nitric oxide synthase-dependent because endothelial nitric oxide synthase-null mice displayed an exaggerated response to post-acute myocardial infarction left ventricular functions. These data suggest that E2 modulation of alcohol consumption, and the ensuing EPC dysfunction, may negatively compete with the beneficial effects of estrogen on post-infarct myocardial repair.

Preventive effects of Flos Perariae (Gehua water extract and its active ingredient puerarin in rodent alcoholism models

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Wang Yuqiang

2010-10-01

Full Text Available Abstract Background Radix Puerariae is used in Chinese medicine to treat alcohol addiction and intoxication. The present study investigates the effects of Flos puerariae lobatae water extract (FPE and its active ingredient puerarin on alcoholism using rodent models. Methods Alcoholic animals were given FPE or puerarin by oral intubation prior or after alcohol treatment. The loss of righting reflex (LORR assay was used to evaluate sedative/hypnotic effects. Changes of gama-aminobutyric acid type A receptor (GABAAR subunits induced by alcohol treatment in hippocampus were measured with western blot. In alcoholic mice, body weight gain was monitored throughout the experiments. Alcohol dehydrogenase (ADH levels in liver were measured. Results FPE and puerarin pretreatment significantly prolonged the time of LORR induced by diazepam in acute alcoholic rat. Puerarin increased expression of gama-aminobutyric acid type A receptor alpha1 subunit and decreased expression of alpha4 subunit. In chronic alcoholic mice, puerarin pretreatment significantly increased body weight and liver ADH activity in a dose-dependent manner. Puerarin pretreatment, but not post-treatment, can reverse the changes of gama-aminobutyric acid type A receptor subunit expression and increase ADH activity in alcoholism models. Conclusion The present study demonstrates that FPE and its active ingredient puerarin have preventive effects on alcoholism related disorders.

Polycyclic aromatic hydrocarbon-induced CYP1B1 activity is suppressed by perillyl alcohol in MCF-7 cells

International Nuclear Information System (INIS)

Chan, Nelson L.S.; Wang Huan; Wang Yun; Leung, H.Y.; Leung, Lai K.

2006-01-01

Perillyl alcohol (POH) is a dietary monoterpene with potential applications in chemoprevention and chemotherapy. Although clinical trials are under way, POH's physiological and pharmacological properties are still unclear. In the present study, the effect of POH on polycyclic aromatic hydrocarbon (PAH)-induced genotoxicity, and the related expression were examined in MCF-7 cells. Exposure to environmental toxicant increases the risk of cancer. Many of these compounds are pro-carcinogens and are biotransformed into their ultimate genotoxic structures by xenobiotic metabolizing enzymes. CYP1A1 and 1B1 are enzymes that catalyze the biotransformation of dimethylbenz[a]anthracene (DMBA). Our data revealed that 0.5 μM of POH was effective in blocking DMBA-DNA binding. Ethoxyresorufin-O-deethylase (EROD) assay indicated that the administration of POH inhibited the DMBA-induced enzyme activity in MCF-7 cells. Enzyme kinetic analysis revealed that POH inhibited CYP1B1 but not CYP1A1 activity. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay also demonstrated that the monoterpene reduced CYP1B1 mRNA abundance induced by DMBA. The present study illustrated that POH might inhibit and downregulate CYP1B1, which could protect against PAH-induced carcinogenesis

Alcohol, microbiome, life style influence alcohol and non-alcoholic organ damage.

Science.gov (United States)

Neuman, Manuela G; French, Samuel W; Zakhari, Samir; Malnick, Stephen; Seitz, Helmut K; Cohen, Lawrence B; Salaspuro, Mikko; Voinea-Griffin, Andreea; Barasch, Andrei; Kirpich, Irina A; Thomes, Paul G; Schrum, Laura W; Donohue, Terrence M; Kharbanda, Kusum K; Cruz, Marcus; Opris, Mihai

2017-02-01

This paper is based upon the "8th Charles Lieber's Satellite Symposium" organized by Manuela G. Neuman at the Research Society on Alcoholism Annual Meeting, on June 25, 2016 at New Orleans, Louisiana, USA. The integrative symposium investigated different aspects of alcohol-induced liver disease (ALD) as well as non-alcohol-induced liver disease (NAFLD) and possible repair. We revealed the basic aspects of alcohol metabolism that may be responsible for the development of liver disease as well as the factors that determine the amount, frequency and which type of alcohol misuse leads to liver and gastrointestinal diseases. We aimed to (1) describe the immuno-pathology of ALD, (2) examine the role of genetics in the development of alcoholic hepatitis (ASH) and NAFLD, (3) propose diagnostic markers of ASH and non-alcoholic steatohepatitis (NASH), (4) examine age and ethnic differences as well as analyze the validity of some models, (5) develop common research tools and biomarkers to study alcohol-induced effects, 6) examine the role of alcohol in oral health and colon and gastrointestinal cancer and (7) focus on factors that aggravate the severity of organ-damage. The present review includes pre-clinical, translational and clinical research that characterizes ALD and NAFLD. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD with simple fatty infiltrations and chronic alcoholic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes and cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human deficiency virus were discussed

Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study

DEFF Research Database (Denmark)

Sorgenfrei, Iben F; Norrild, Kathrine; Larsen, Per Bo

2006-01-01

Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block.......Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block....

Oleanolic acid supplement attenuates liquid fructose-induced adipose tissue insulin resistance through the insulin receptor substrate-1/phosphatidylinositol 3-kinase/Akt signaling pathway in rats

Energy Technology Data Exchange (ETDEWEB)

Li, Ying [Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016 (China); Wang, Jianwei, E-mail: wangjianwei1968@gmail.com [Department of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016 (China); Gu, Tieguang [Endocrinology and Metabolism Group, Sydney Institute of Health Sciences, Sydney, NSW 2000 Australia (Australia); Yamahara, Johji [Pharmafood Institute, Kyoto 602-8136 (Japan); Li, Yuhao, E-mail: yuhao@sitcm.edu.au [Endocrinology and Metabolism Group, Sydney Institute of Health Sciences, Sydney, NSW 2000 Australia (Australia)

2014-06-01

Oleanolic acid, a triterpenoid contained in more than 1620 plants including various fruits and foodstuffs, has numerous metabolic effects, such as hepatoprotection. However, its underlying mechanisms remain poorly understood. Adipose tissue insulin resistance (Adipo-IR) may contribute to the development and progress of metabolic abnormalities through release of excessive free fatty acids from adipose tissue. This study investigated the effect of oleanolic acid on Adipo-IR. The results showed that supplement with oleanolic acid (25 mg/kg, once daily, by oral gavage) over 10 weeks attenuated liquid fructose-induced increase in plasma insulin concentration and the homeostasis model assessment of insulin resistance (HOMA-IR) index in rats. Simultaneously, oleanolic acid reversed the increase in the Adipo-IR index and plasma non-esterified fatty acid concentrations during the oral glucose tolerance test assessment. In white adipose tissue, oleanolic acid enhanced mRNA expression of the genes encoding insulin receptor, insulin receptor substrate (IRS)-1 and phosphatidylinositol 3-kinase. At the protein level, oleanolic acid upregulated total IRS-1 expression, suppressed the increased phosphorylated IRS-1 at serine-307, and restored the increased phosphorylated IRS-1 to total IRS-1 ratio. In contrast, phosphorylated Akt to total Akt ratio was increased. Furthermore, oleanolic acid reversed fructose-induced decrease in phosphorylated-Akt/Akt protein to plasma insulin concentration ratio. However, oleanolic acid did not affect IRS-2 mRNA expression. Therefore, these results suggest that oleanolic acid supplement ameliorates fructose-induced Adipo-IR in rats via the IRS-1/phosphatidylinositol 3-kinase/Akt pathway. Our findings may provide new insights into the mechanisms of metabolic actions of oleanolic acid. - Highlights: • Adipose insulin resistance (Adipo-IR) contributes to metabolic abnormalities. • We investigated the effect of oleanolic acid (OA) on adipo-IR in

Oleanolic acid supplement attenuates liquid fructose-induced adipose tissue insulin resistance through the insulin receptor substrate-1/phosphatidylinositol 3-kinase/Akt signaling pathway in rats

International Nuclear Information System (INIS)

Li, Ying; Wang, Jianwei; Gu, Tieguang; Yamahara, Johji; Li, Yuhao

2014-01-01

Oleanolic acid, a triterpenoid contained in more than 1620 plants including various fruits and foodstuffs, has numerous metabolic effects, such as hepatoprotection. However, its underlying mechanisms remain poorly understood. Adipose tissue insulin resistance (Adipo-IR) may contribute to the development and progress of metabolic abnormalities through release of excessive free fatty acids from adipose tissue. This study investigated the effect of oleanolic acid on Adipo-IR. The results showed that supplement with oleanolic acid (25 mg/kg, once daily, by oral gavage) over 10 weeks attenuated liquid fructose-induced increase in plasma insulin concentration and the homeostasis model assessment of insulin resistance (HOMA-IR) index in rats. Simultaneously, oleanolic acid reversed the increase in the Adipo-IR index and plasma non-esterified fatty acid concentrations during the oral glucose tolerance test assessment. In white adipose tissue, oleanolic acid enhanced mRNA expression of the genes encoding insulin receptor, insulin receptor substrate (IRS)-1 and phosphatidylinositol 3-kinase. At the protein level, oleanolic acid upregulated total IRS-1 expression, suppressed the increased phosphorylated IRS-1 at serine-307, and restored the increased phosphorylated IRS-1 to total IRS-1 ratio. In contrast, phosphorylated Akt to total Akt ratio was increased. Furthermore, oleanolic acid reversed fructose-induced decrease in phosphorylated-Akt/Akt protein to plasma insulin concentration ratio. However, oleanolic acid did not affect IRS-2 mRNA expression. Therefore, these results suggest that oleanolic acid supplement ameliorates fructose-induced Adipo-IR in rats via the IRS-1/phosphatidylinositol 3-kinase/Akt pathway. Our findings may provide new insights into the mechanisms of metabolic actions of oleanolic acid. - Highlights: • Adipose insulin resistance (Adipo-IR) contributes to metabolic abnormalities. • We investigated the effect of oleanolic acid (OA) on adipo-IR in

Alteration of BRCA1 expression affects alcohol-induced transcription of RNA Pol III-dependent genes.

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Zhong, Qian; Shi, Ganggang; Zhang, Yanmei; Lu, Lei; Levy, Daniel; Zhong, Shuping

2015-02-01

Emerging evidence has indicated that alcohol consumption is an established risk factor for breast cancer. Deregulation of RNA polymerase III (Pol III) transcription enhances cellular Pol III gene production, leading to an increase in translational capacity to promote cell transformation and tumor formation. We have reported that alcohol intake increases Pol III gene transcription to promote cell transformation and tumor formation in vitro and in vivo. Studies revealed that tumor suppressors, pRb, p53, PTEN and Maf1 repress the transcription of Pol III genes. BRCA1 is a tumor suppressor and its mutation is tightly related to breast cancer development. However, it is not clear whether BRCA1 expression affects alcohol-induced transcription of Pol III genes. At the present studies, we report that restoring BRCA1 in HCC 1937 cells, which is a BRCA1 deficient cell line, represses Pol III gene transcription. Expressing mutant or truncated BRCA1 in these cells does not affect the ability of repression on Pol III genes. Our analysis has demonstrated that alcohol induces Pol III gene transcription. More importantly, overexpression of BRCA1 in estrogen receptor positive (ER+) breast cancer cells (MCF-7) decreases the induction of tRNA(Leu) and 5S rRNA genes by alcohol, whereas reduction of BRCA1 by its siRNA slightly increases the transcription of the class of genes. This suggests that BRCA1 is associated with alcohol-induced deregulation of Pol III genes. These studies for the first time demonstrate the role of BRCA1 in induction of Pol III genes by alcohol and uncover a novel mechanism of alcohol-associated breast cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

21 CFR 582.5580 - D-Pantothenyl alcohol.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false D-Pantothenyl alcohol. 582.5580 Section 582.5580 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5580 D-Pantothenyl alcohol. (a) Product. D-Pantothenyl alcohol. (b) Conditions of use...

Effects of coenzyme Q10 supplementation on the anthropometric variables, lipid profiles and liver enzymes in patients with non-alcoholic fatty liver disease

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Elnaz Jafarvand

2016-03-01

Full Text Available This randomized double-blind placebo-controlled trial was conducted on 41 patients with non-alcoholic fatty liver disease. Patients in intervention group received 100 mg/day coenzyme Q10 (CoQ10 for four weeks. There was a significant reduction in waist circumference and aspartate aminotransferase concentrations after CoQ10 supplementation (p<0.05. Dietary fiber was in negative correlation with change in serum alanine aminotransferase (ALT concentrations (r = -410, p = 0.04, and dietary fat intake was in positive relation with serum triglyceride (r = 463, p = 0.04 and in negative relation with serum high-density lipoprotein cholesterol (HDL-C (r = -533, p = 0.02 in CoQ10-treated group. CoQ10 supplement is able to reduce central obesity and improve liver function in non-alcoholic fatty liver disease. Dietary factors were also significant determinants of change in liver-specific enzyme ALT and lipid profile in these patients. Further trials with higher dose of CoQ10 and longer treatment periods are warranted to better clarify these findings.

Perillyl alcohol suppresses antigen-induced immune responses in the lung

Energy Technology Data Exchange (ETDEWEB)

Imamura, Mitsuru; Sasaki, Oh; Okunishi, Katsuhide; Nakagome, Kazuyuki; Harada, Hiroaki; Kawahata, Kimito; Tanaka, Ryoichi; Yamamoto, Kazuhiko [Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Dohi, Makoto, E-mail: mdohi-tky@umin.ac.jp [Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Institute of Respiratory Immunology, Shibuya Clinic for Respiratory Diseases and Allergology, Tokyo (Japan)

2014-01-03

Highlights: •Perillyl alcohol (POH) is an isoprenoid which inhibits the mevalonate pathway. •We examined whether POH suppresses immune responses with a mouse model of asthma. •POH treatment during sensitization suppressed Ag-induced priming of CD4{sup +} T cells. •POH suppressed airway eosinophila and cytokine production in thoracic lymph nodes. -- Abstract: Perillyl alcohol (POH) is an isoprenoid which inhibits farnesyl transferase and geranylgeranyl transferase, key enzymes that induce conformational and functional changes in small G proteins to conduct signal production for cell proliferation. Thus, it has been tried for the treatment of cancers. However, although it affects the proliferation of immunocytes, its influence on immune responses has been examined in only a few studies. Notably, its effect on antigen-induced immune responses has not been studied. In this study, we examined whether POH suppresses Ag-induced immune responses with a mouse model of allergic airway inflammation. POH treatment of sensitized mice suppressed proliferation and cytokine production in Ag-stimulated spleen cells or CD4{sup +} T cells. Further, sensitized mice received aerosolized OVA to induce allergic airway inflammation, and some mice received POH treatment. POH significantly suppressed indicators of allergic airway inflammation such as airway eosinophilia. Cytokine production in thoracic lymph nodes was also significantly suppressed. These results demonstrate that POH suppresses antigen-induced immune responses in the lung. Considering that it exists naturally, POH could be a novel preventive or therapeutic option for immunologic lung disorders such as asthma with minimal side effects.

Inhibition of protein kinase A and GIRK channel reverses fentanyl-induced respiratory depression.

Science.gov (United States)

Liang, Xiaonan; Yong, Zheng; Su, Ruibin

2018-06-11

Opioid-induced respiratory depression is a major obstacle to improving the clinical management of moderate to severe chronic pain. Opioids inhibit neuronal activity via various pathways, including calcium channels, adenylyl cyclase, and potassium channels. Currently, the underlying molecular pathway of opioid-induced respiratory depression is only partially understood. This study aimed to investigate the mechanisms of opioid-induced respiratory depression in vivo by examining the effects of different pharmacological agents on fentanyl-induced respiratory depression. Respiratory parameters were detected using whole body plethysmography in conscious rats. We show that pre-treatment with the protein kinase A (PKA) inhibitor H89 reversed the fentanyl-related effects on respiratory rate, inspiratory time, and expiratory time. Pre-treatment with the G protein-gated inwardly rectifying potassium (GIRK) channel blocker Tertiapin-Q dose-dependently reversed the fentanyl-related effects on respiratory rate and inspiratory time. A phosphodiesterase 4 (PDE4) inhibitor and cyclic adenosine monophosphate (cAMP) analogs did not affect fentanyl-induced respiratory depression. These findings suggest that PKA and GIRK may be involved in fentanyl-induced respiratory depression and could represent useful therapeutic targets for the treatment of fentanyl-induced ventilatory depression. Copyright © 2018 Elsevier B.V. All rights reserved.

Stress-induced and cue-induced craving for alcohol in heavy drinkers: Preliminary evidence of genetic moderation by the OPRM1 and CRH-BP genes.

Science.gov (United States)

Ray, Lara A

2011-01-01

Neurobiological theories of addiction have highlighted disruption in stress pathways as a central feature of addictive disorders, and pharmacological treatments targeting stress mechanisms hold great promise. This study examines genetic determinants of stress-induced and cue-induced craving in heavy drinkers by testing single-nucleotide polymorphisms (SNPs) of the corticotrophin-releasing hormone binding protein (CRH-BP) gene and the mu-opioid receptor (OPRM1) gene. This study combines guided imagery stress exposure and in vivo alcohol cue exposure in a sample of 64 (23 women) non-treatment-seeking heavy drinkers. Analyses, uncorrected for multiple comparisons, revealed that a tag SNP of the CRH-BP gene (rs10055255) moderated stress-induced craving in this sample. The same SNP predicted greater affective responses to the stress manipulation, including greater levels of subjective tension and negative mood. The Asp40 allele of the OPRM1 was associated with greater cue-induced alcohol craving following the neutral imagery condition. These initial results extend recent preclinical and clinical findings implicating the CRH-BP in stress-related alcoholism and confirm the role of the Asp40 allele of the OPRM1 gene in reward-driven alcohol phenotypes. Human laboratory models of stress and cue-induced craving may be useful in pharmacotherapy development targeting dysregulation of stress systems. Larger studies are needed to validate these preliminary findings, which should also be extended to clinical samples. Copyright © 2010 by the Research Society on Alcoholism.

Lowering the alcohol content of red wine does not alter its cardioprotective properties.

Science.gov (United States)

Lamont, Kim; Blackhurst, Dee; Albertyn, Zulfah; Marais, David; Lecour, Sandrine

2012-05-23

Many epidemiological, clinical and laboratory studies suggest that chronic and moderate consumption of red wine benefits cardiovascular health, because of the alcoholic content or the polyphenols/flavonoids. The antioxidant and cardioprotective properties of a French red wine (cabernet sauvignon, 12% alcohol by volume) were compared with those of the same wine subjected to reverse osmosis for partial removal of alcohol (6% alcohol by volume). Antioxidant capacity was assessed in vitro using the oxygen radical absorbance capacity (ORAC) assay. To test the cardioprotective effect of 12% v. 6% wine, the drinking water of rats used for controls was supplemented with red wine (12% or 6%). After 10 days, hearts were isolated on a Langendorff system and subjected to 30 minutes of global ischaemia plus 30 minutes of reperfusion (I/R). No differences in antioxidant capacity were observed between wine of 12% and 6% alcohol content (n=8 per group). Control hearts subjected to I/R presented a rate pressure product (heart rate x left ventricular developed pressure, expressed as a percentage of baseline value) of 16±4% (mean±standard error). Pretreatment with wine 12% or 6% improved the rate pressure product to 40±6% and 43±6%, respectively (pwine did not alter its antioxidant and cardioprotective properties. Moderate and regular consumption of lower alcohol content wines may confer beneficial effects without the risks associated with traditional wines of higher alcohol content.

Advances and New Concepts in Alcohol-Induced Organelle Stress, Unfolded Protein Responses and Organ Damage

Directory of Open Access Journals (Sweden)

Cheng Ji

2015-06-01

Full Text Available Alcohol is a simple and consumable biomolecule yet its excessive consumption disturbs numerous biological pathways damaging nearly all organs of the human body. One of the essential biological processes affected by the harmful effects of alcohol is proteostasis, which regulates the balance between biogenesis and turnover of proteins within and outside the cell. A significant amount of published evidence indicates that alcohol and its metabolites directly or indirectly interfere with protein homeostasis in the endoplasmic reticulum (ER causing an accumulation of unfolded or misfolded proteins, which triggers the unfolded protein response (UPR leading to either restoration of homeostasis or cell death, inflammation and other pathologies under severe and chronic alcohol conditions. The UPR senses the abnormal protein accumulation and activates transcription factors that regulate nuclear transcription of genes related to ER function. Similarly, this kind of protein stress response can occur in other cellular organelles, which is an evolving field of interest. Here, I review recent advances in the alcohol-induced ER stress response as well as discuss new concepts on alcohol-induced mitochondrial, Golgi and lysosomal stress responses and injuries.

Central administration of the anorexigenic peptide neuromedin U decreases alcohol intake and attenuates alcohol-induced reward in rodents.

Science.gov (United States)

Vallöf, Daniel; Ulenius, Lisa; Egecioglu, Emil; Engel, Jörgen A; Jerlhag, Elisabet

2017-05-01

By investigating the neurochemical mechanisms through which alcohol activates the brain reward systems, novel treatment strategies for alcohol use disorder (AUD), a chronic relapsing disease, can be developed. In contrast to the common view of the function of gut-brain peptides, such as neuromedin U (NMU), to regulate food intake and appetite, a novel role in reinforcement mediation has been implied. The anorexigenic effects of NMU are mediated via NMU2 receptors, preferably in the arcuate nucleus and paraventricular nucleus. The expression of NMU2 receptors is also expressed in several reward-related areas in the brain, suggesting a role in reward regulation. The present experiments were therefore set up to investigate the effect of intracerebroventricular administration of NMU on alcohol-mediated behaviors in rodents. We found that central administration of NMU attenuated alcohol-induced locomotor stimulation, accumbal dopamine release and the expression of conditioned place preference in mice. In addition, NMU dose dependently decreased alcohol intake in high, but not in low, alcohol-consuming rats. Central NMU administration did not alter the blood alcohol concentrations nor change the corticosterone levels in rodents. Given that AUD is a major health-care challenge causing an enormous cost to society and novel treatment strategies are warranted, our data suggest that NMU analogues deserve to be evaluated as novel treatment of AUD in humans. © 2016 The Authors Addiction Biology published by John Wiley & Sons Ltd.

Magnesium supplement in pregnancy-induced hypertension. A clinicopathological study

DEFF Research Database (Denmark)

Rudnicki, M; Junge, Jette; Frølich, A

1990-01-01

The placenta and the umbilical cord obtained from 18 women with pregnancy-induced hypertension were investigated by light microscopy. The umbilical artery was studied by electron microscopy. 10 placentae and umbilical cords from normal pregnancies served as controls. The study was performed...... fibrosis or intervillous fibrin. Ultrastructurally, the endothelial cells of the umbilical arteries from women with pregnancy-induced hypertension showed a significant increase in the amount of dilated endoplasmic reticulum and basal laminae thickness when all 18 cases were compared with the controls....... There was no significant difference when the magnesium group, the placebo group and the control group were compared separately. The present study suggests that magnesium supplement has a beneficial effect on fetal growth in pregnancy-induced hypertension. With regard to the light and electron microscopic changes we were...

Reversible and non-reversible enlargement of cerebral spinal fluid spaces in anorexia nervosa

International Nuclear Information System (INIS)

Artmann, H.; Grau, H.; Adelmann, M.; Schleiffer, R.

1985-01-01

Brain CT studies of 35 patients with anoxia nervosa confirmed the observations of other authors: cerebral dystrophic changes correlate with weight loss and the reversibility of these changes also correlates with the normalization of body weight. Other corroborated facts are: the most numerous and most pronounced enlargements are of the cortical sulci and the interhemispheric fissure, moderate widening affects the ventricles and the rarest and most insignificant changes are those of the cerebellum. The reversibility of the changes showed a parallel to the extent of the changes themselves and to the duration of improvement of the body weight. The reversibility of the enlargement of the cortical sulci and of the distances between the frontal horns of the lateral ventricles was more often significant than that of the abnormal measurements of the cella media. This difference is based on minimal early acquired brain damage which occurs in 60% of our patients. This high incidence of early acquired minimal brain disease in patients with anorexia nervosa is here discussed as a nonspecific predisposing factor. Although there is no exact explanation of the etiology of the reversible enlargement of cerenral spinal fluid (CSF) spaces in anorexia nervosa, the changes resemble those in alcoholics. The mechanisms of brain changes in alcoholism, as shown experimentally, seem to us to throw light on the probable mechanism of reversible dystrophic brain changes in anorexia nervosa. (orig.)

Reversible and non-reversible enlargement of cerebral spinal fluid spaces in anorexia nervosa

Energy Technology Data Exchange (ETDEWEB)

Artmann, H.; Grau, H.; Adelmann, M.; Schleiffer, R.

1985-07-01

Brain CT studies of 35 patients with anoxia nervosa confirmed the observations of other authors: cerebral dystrophic changes correlate with weight loss and the reversibility of these changes also correlates with the normalization of body weight. Other corroborated facts are: the most numerous and most pronounced enlargements are of the cortical sulci and the interhemispheric fissure, moderate widening affects the ventricles and the rarest and most insignificant changes are those of the cerebellum. The reversibility of the changes showed a parallel to the extent of the changes themselves and to the duration of improvement of the body weight. The reversibility of the enlargement of the cortical sulci and of the distances between the frontal horns of the lateral ventricles was more often significant than that of the abnormal measurements of the cella media. This difference is based on minimal early acquired brain damage which occurs in 60% of our patients. This high incidence of early acquired minimal brain disease in patients with anorexia nervosa is here discussed as a nonspecific predisposing factor. Although there is no exact explanation of the etiology of the reversible enlargement of cerenral spinal fluid (CSF) spaces in anorexia nervosa, the changes resemble those in alcoholics. The mechanisms of brain changes in alcoholism, as shown experimentally, seem to us to throw light on the probable mechanism of reversible dystrophic brain changes in anorexia nervosa.

Metronidazole-Induced Encephalopathy in Alcoholic Liver Disease: A Diagnostic and Therapeutic Challenge.

Science.gov (United States)

Sonthalia, Nikhil; Pawar, Sunil V; Mohite, Ashok R; Jain, Samit S; Surude, Ravindra G; Rathi, Pravin M; Contractor, Qais

2016-10-01

Acute encephalopathy in a patient with alcoholic liver disease (ALD) is a commonly encountered emergency situation occurring most frequently due to liver failure precipitated by varying etiologies. Acute reversible cerebellar ataxia with confusion secondary to prolonged metronidazole use has been reported rarely as a cause of encephalopathy in patients with ALD. We describe a decompensated ALD patient with recurrent pyogenic cholangitis associated with hepatolithiasis who presented to the emergency department with sudden-onset cerebellar ataxia with dysarthria and mental confusion after prolonged use of metronidazole. Magnetic resonance imaging (MRI) of the brain was suggestive of bilateral dentate nuclei hyper intensities on T2 and fluid-attenuated inversion recovery sections seen classically in metronidazole-induced encephalopathy (MIE). Decompensated liver cirrhosis resulted in decreased hepatic clearance and increased cerebrospinal fluid concentration of metronidazole leading to toxicity at a relatively low total cumulative dose of 22 g. Both the clinical symptoms and MRI brain changes were reversed at 7 days and 6 weeks, respectively, after discontinuation of metronidazole. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: A patient with ALD presenting with encephalopathy creates a diagnostic dilemma for the emergency physician regarding whether to continue metronidazole and treat for hepatic encephalopathy or to suspect for MIE and withhold the drug. Failure to timely discontinue metronidazole may worsen the associated hepatic encephalopathy in these patients. Liver cirrhosis patients have higher mean concentration of metronidazole and its metabolite in the blood, making it necessary to keep the cumulative dose of metronidazole to < 20 g in them. Copyright © 2016 Elsevier Inc. All rights reserved.

Fatty acid amide supplementation decreases impulsivity in young adult heavy drinkers

Science.gov (United States)

van Kooten, Maria J.; Veldhuizen, Maria G.; de Araujo, Ivan E.; O’Malley, Stephanie; Small, Dana M.

2016-01-01

Compromised dopamine signaling in the striatum has been associated with the expression of impulsive behaviors in addiction, obesity and alcoholism. In rodents, Intragastric infusion of the fatty acid amide oleoylethanolamide increases striatal extracellular dopamine levels via vagal afferent signaling. Here we tested whether supplementation with PhosphoLean™, a dietary supplement that contains the precursor of the fatty acid amide oleoylethanolamide (N-oleyl-phosphatidylethanolamine), would reduce impulsive responding and alcohol use in heavy drinking young adults. Twenty-two individuals were assigned to a three-week supplementation regimen with PhosphoLean™ or placebo. Impulsivity was assessed with self-report questionnaires and behavioral tasks pre- and post-supplementation. Although self-report measures of impulsivity did not change, supplementation with PhosphoLean™, but not placebo, significantly reduced false alarm rate on a Go/No-Go task. In addition, an association was found between improved sensitivity on the Go/No-Go task and reduced alcohol intake. These findings provide preliminary evidence that promoting fatty acid derived gut-brain dopamine communication may have therapeutic potential for reducing impulsivity in heavy drinkers. PMID:26656766

Mouth reversal extinguishes mismatch negativity induced by the McGurk illusion

DEFF Research Database (Denmark)

Eskelund, Kasper; Andersen, Tobias

2013-01-01

The sight of articulatory mouth movements (visual speech) influences auditory speech perception. This is demonstrated by the McGurk illusion in which incongruent visual speech alters the auditory phonetic percept. In behavioral studies, reversal of the vertical mouth direction has been reported...... by visual speech with either upright (unaltered) or vertically reversed mouth area. In a preliminary analysis, we found a Mismatch Negativity component induced by the McGurk illusion for 6 of 17 participants at electrode Cz when the mouth area was upright. In comparison, these participants produced...

Ghrelin knockout mice show decreased voluntary alcohol consumption and reduced ethanol-induced conditioned place preference.

Science.gov (United States)

Bahi, Amine; Tolle, Virginie; Fehrentz, Jean-Alain; Brunel, Luc; Martinez, Jean; Tomasetto, Catherine-Laure; Karam, Sherif M

2013-05-01

Recent work suggests that stomach-derived hormone ghrelin receptor (GHS-R1A) antagonism may reduce motivational aspects of ethanol intake. In the current study we hypothesized that the endogenous GHS-R1A agonist ghrelin modulates alcohol reward mechanisms. For this purpose ethanol-induced conditioned place preference (CPP), ethanol-induced locomotor stimulation and voluntary ethanol consumption in a two-bottle choice drinking paradigm were examined under conditions where ghrelin and its receptor were blocked, either using ghrelin knockout (KO) mice or the specific ghrelin receptor (GHS-R1A) antagonist "JMV2959". We showed that ghrelin KO mice displayed lower ethanol-induced CPP than their wild-type (WT) littermates. Consistently, when injected during CPP-acquisition, JMV2959 reduced CPP-expression in C57BL/6 mice. In addition, ethanol-induced locomotor stimulation was lower in ghrelin KO mice. Moreover, GHS-R1A blockade, using JMV2959, reduced alcohol-stimulated locomotion only in WT but not in ghrelin KO mice. When alcohol consumption and preference were assessed using the two-bottle choice test, both genetic deletion of ghrelin and pharmacological antagonism of the GHS-R1A (JMV2959) reduced voluntary alcohol consumption and preference. Finally, JMV2959-induced reduction of alcohol intake was only observed in WT but not in ghrelin KO mice. Taken together, these results suggest that ghrelin neurotransmission is necessary for the stimulatory effect of ethanol to occur, whereas lack of ghrelin leads to changes that reduce the voluntary intake as well as conditioned reward by ethanol. Our findings reveal a major, novel role for ghrelin in mediating ethanol behavior, and add to growing evidence that ghrelin is a key mediator of the effects of multiple abused drugs. Copyright © 2013 Elsevier Inc. All rights reserved.

Prevention of congenital defects induced by prenatal alcohol exposure (Conference Presentation)

Science.gov (United States)

Sheehan, Megan M.; Karunamuni, Ganga; Pedersen, Cameron J.; Gu, Shi; Doughman, Yong Qiu; Jenkins, Michael W.; Watanabe, Michiko; Rollins, Andrew M.

2017-02-01

Over 500,000 women per year in the United States drink during pregnancy, and 1 in 5 of this population also binge drink. Up to 40% of live-born children with prenatal alcohol exposure (PAE) present with congenital heart defects (CHDs) including life-threatening outflow and valvuloseptal anomalies. Previously we established a PAE model in the avian embryo and used optical coherence tomography (OCT) imaging to assay looping-stage (early) cardiac function/structure and septation-stage (late) cardiac defects. Early-stage ethanol-exposed embryos had smaller cardiac cushions (valve precursors) and increased retrograde flow, while late-stage embryos presented with gross head/body defects, and exhibited smaller atrio-ventricular (AV) valves, interventricular septae, and aortic vessels. However, supplementation with the methyl donor betaine reduced gross defects, prevented cardiac defects such as ventricular septal defects and abnormal AV valves, and normalized cardiac parameters. Immunofluorescent staining for 5-methylcytosine in transverse embryo sections also revealed that DNA methylation levels were reduced by ethanol but normalized by co-administration of betaine. Furthermore, supplementation with folate, another methyl donor, in the PAE model appeared to normalize retrograde flow levels which are typically elevated by ethanol exposure. Studies are underway to correlate retrograde flow numbers for folate with associated cushion volumes. Finally, preliminary findings have revealed that glutathione, a key endogenous antioxidant which also regulates methyl group donation, is particularly effective in improving alcohol-impacted survival and gross defect rates. Current investigations will determine whether glutathione has any positive effect on PAE-related CHDs. Our studies could have significant implications for public health, especially related to prenatal nutrition recommendations.

Protective effect of polysaccharide from maca (Lepidium meyenii) on Hep-G2 cells and alcoholic liver oxidative injury in mice.

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Zhang, Lijun; Zhao, Qingsheng; Wang, Liwei; Zhao, Mingxia; Zhao, Bing

2017-06-01

To study the characterization and hepatoprotective activity of polysaccharide from maca (Lepidium meyenii), the main polysaccharide from maca (MP-1) was obtained by DEAE-52 cellulose column. The average molecular weight of MP-1 was 1067.3kDa and the polysaccharide purity was 91.63%. In order to assess the antioxidant activities of MP-1, four kinds of methods were used, including scavenging hydroxyl radical, DPPH, superoxide anion radical, and FRAP, and the results indicated high antioxidant activities. Furthermore, hepatoprotective activity of MP-1 was studied both in vitro and vivo. In vitro, the alcohol induced Hep-G2 cells model was established to evaluate the protective effect of MP-1, which demonstrated MP-1 can alleviate alcohol damage in Hep-G2 cells. In vivo, the Institute　of　Cancer　Researcch (ICR) mice were used to evaluate hepatoprotecive effects of MP-1 on alcoholic liver disease (ALD). Supplement with MP-1 supressed the triglyceride level both in serum and in hepatic tissue. In addition, MP-1 ameliorated serous transaminases increase induced by alcohol, including aspartate transaminase, alanine aminotransferase, and γ-glutamyl transpeptidase. Moreover, MP-1 also dramatically increased the superoxide dismutase, glutathione peroxidase, and glutathione s-transferase levels in alcoholic mice. Meantime, histopathologic results MP-1 lighten inflammation induced by alcohol. These results indicate that MP-1 possesses hepatoprotective activity against hepatic injury induced by alcohol. Copyright © 2017 Elsevier B.V. All rights reserved.

Determinants of dietary supplement use--healthy individuals use dietary supplements.

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Kofoed, Christina L F; Christensen, Jane; Dragsted, Lars O; Tjønneland, Anne; Roswall, Nina

2015-06-28

The prevalence of dietary supplement use varies largely among populations, and previous studies have indicated that it is high in the Danish population compared with other European countries. The diversity in supplement use across countries indicates that cultural and environmental factors could influence the use of dietary supplements. Only few studies investigating the use of dietary supplements have been conducted in the Danish population. The present cross-sectional study is based on 54,948 Danes, aged 50-64 years, who completed self-administrated questionnaires on diet, dietary supplements and lifestyle between 1993 and 1997. A health index including smoking, physical activity, alcohol and diet, and a metabolic risk index including waist circumference, urinary glucose and measured hypertension were constructed. Logistic regression was used to investigate these determinants in relation to the intake of dietary supplements. We found that 71 % of the participants were dietary supplement users; female sex, older age groups and higher educated participants were more likely to be users of any dietary supplements. One additional point in the health index was associated with 19, 16 and 9 % higher likelihood of being user of any, more common and less common supplements, respectively. In the metabolic risk index, one additional point was associated with 17 and 16 % lower likelihood of being user of any supplement and more common supplements, respectively. No significant association was found for less common supplement use. In conclusion, those with the healthiest lifestyle were more likely to use dietary supplements. Thus, lifestyle and dietary composition should be considered as confounders on supplement use and health outcomes.

Honokiol reverses alcoholic fatty liver by inhibiting the maturation of sterol regulatory element binding protein-1c and the expression of its downstream lipogenesis genes

International Nuclear Information System (INIS)

Yin Huquan; Kim, Youn-Chul; Chung, Young-Suk; Kim, Young-Chul; Shin, Young-Kee; Lee, Byung-Hoon

2009-01-01

Ethanol induces hepatic steatosis via a complex mechanism that is not well understood. Among the variety of molecules that have been proposed to participate in this mechanism, the sterol regulatory element (SRE)-binding proteins (SREBPs) have been identified as attractive targets for therapeutic intervention. In the present study, we evaluated the effects of honokiol on alcoholic steatosis and investigated its possible effect on the inhibition of SREBP-1c maturation. In in vitro studies, H4IIEC3 rat hepatoma cells developed increased lipid droplets when exposed to ethanol, but co-treatment with honokiol reversed this effect. Honokiol inhibited the maturation of SREBP-1c and its translocation to the nucleus, the binding of nSREBP-1c to SRE or SRE-related sequences of its lipogenic target genes, and the expression of genes for fatty acid synthesis. In contrast, magnolol, a structural isomer of honokiol, had no effect on nSREBP-1c levels. Male Wistar rats fed with a standard Lieber-DeCarli ethanol diet for 4 weeks exhibited increased hepatic triglyceride and decreased hepatic glutathione levels, with concomitantly increased serum alanine aminotransferase and TNF-α levels. Daily administration of honokiol (10 mg/kg body weight) by gavage during the final 2 weeks of ethanol treatment completely reversed these effects on hepatotoxicity markers, including hepatic triglyceride, hepatic glutathione, and serum TNF-α, with efficacious abrogation of fat accumulation in the liver. Inhibition of SREBP-1c protein maturation and of the expression of Srebf1c and its target genes for hepatic lipogenesis were also observed in vivo. A chromatin immunoprecipitation assay demonstrated inhibition of specific binding of SREBP-1c to the Fas promoter by honokiol in vivo. These results demonstrate that honokiol has the potential to ameliorate alcoholic steatosis by blocking fatty acid synthesis regulated by SREBP-1c

Separation of mixtures of organic substance using reverse osmosis membranes

Energy Technology Data Exchange (ETDEWEB)

Kimura, Shoji; Nakao, Shin' ichi; Tanimura, Shinobu

1987-12-25

With the arrival of energy crisis, attention has been concentrated on the production of alcohol by means of biomass conversion. Energy-saving concentration method was searched to replace a distillation method as a method of concentrating dilute alcohols, for which a reverse osmosis method was proposed; experimental results have been reported accordingly. One result is that the osmotic pressure method has a limitation of difficulty to exceed more than 15% concentration. For this, the reverse osmosis was reviewed and it was found that wider concentration range should be examined for the area where the reverse osmosis was not experimented. Fils employed were a polyamide film of Nitto Denko Co. and an acrylonitrile film of sumitomo Chemical Co.. The result revealed that alcohol could be concentrated up to rather high concentration in alcohol-water system; even in a non-aqueous system, separation with high selective permeability was possible by the proper selection of film materials. (4 figs, 2 refs)

Alcohol enhances oxysterol-induced apoptosis in human endothelial cells by a calcium-dependent mechanism.

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Spyridopoulos, I; Wischhusen, J; Rabenstein, B; Mayer, P; Axel, D I; Fröhlich, K U; Karsch, K R

2001-03-01

Controversy exists about the net effect of alcohol on atherogenesis. A protective effect is assumed, especially from the tannins and phenolic compounds in red wine, owing to their inhibition of low density lipoprotein (LDL) oxidation. However, increased atherogenesis occurs in subjects with moderate to heavy drinking habits. The purpose of this study was to investigate the influence of alcohol in combination with oxysterols on the endothelium. Cultured human arterial endothelial cells (HAECs) served as an in vitro model to test the cellular effects of various oxysterols. Oxysterols (7beta-hydroxycholesterol, 7-ketocholesterol, and cholesterol-5,6-epoxides), which are assumed to be the most toxic constituents of oxidized LDL, induced apoptosis in HAECs through calcium mobilization followed by activation of caspase-3. Ethanol, methanol, isopropanol, tert-butanol, and red wine all potentiated oxysterol-induced cell death up to 5-fold, paralleled by further induction of caspase-3. The alcohol effect occurred in a dose-dependent manner and reached a plateau at 0.05% concentration. Alcohol itself did not affect endothelial cell viability, nor did other solvents such as dimethyl sulfoxide mimic the alcohol effect. So far as the physiologically occurring oxysterols are concerned, this effect was apparent only for oxysterols oxidized at the steran ring. The possibility of alcohol facilitating the uptake of oxysterols into the cell was not supported by the data from an uptake study with radiolabeled compounds. Finally, alcohol in combination with oxysterols did cause a dramatic increase in cytosolic calcium influx. Blockage of calcium influx by the calcium channel blocker aurintricarboxylic acid or the calcium chelator ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid abrogated the alcohol-mediated enhancement of oxysterol toxicity. We describe for the first time a mechanistic concept explaining possible adverse effects of alcohol in conjunction with

Quaternary naltrexone reverses radiogenic and morphine-induced locomotor hyperactivity

Energy Technology Data Exchange (ETDEWEB)

Mickley, G.A.; Stevens, K.E.; Galbraith, J.A.; White, G.A.; Gibbs, G.L.

1984-04-01

The present study attempted to determine the relative role of the peripheral and central nervous system in the production of morphine-induced or radiation-induced locomotor hyperactivity of the mouse. Toward this end, we used a quaternary derivative of an opiate antagonist (naltrexone methobromide), which presumably does not cross the blood-brain barrier. Quaternary naltrexone was used to challenge the stereotypic locomotor response observed in these mice after either an i.p. injection of morphine or exposure to 1500 rads /sup 60/Co. The quaternary derivative of naltrexone reversed the locomotor hyperactivity normally observed in the C57BL/6J mouse after an injection of morphine. It also significantly attenuated radiation-induced locomotion. The data reported here support the hypothesis of endorphin involvement in radiation-induced and radiogenic behaviors. However, these conclusions are contingent upon further research which more fully evaluates naltrexone methobromide's capacity to cross the blood-brain barrier.

Reversal of haloperidol-induced tardive vacuous chewing movements and supersensitive somatodendritic serotonergic response by imipramine in rats

International Nuclear Information System (INIS)

Samad, N.; Haleem, D.J.

2013-01-01

The study was designed to test the hypothesis that a decrease in the responsiveness of somatodendritic 5-HT-1A receptors by co- administration of imipramine could reverse the induction of VCMs and supersensitivity at 5-HT-IA receptors by haloperidol. Rats treated with haloperidol 0.2mg/rat/day for 2 weeks induced VCMs with twitching of facial musculature that increased in a time dependent manner as the treatment continued to 5 weeks. Co administration of imipramine (5mg/kg/m1) attenuated haloperidol-induced VCMs after 2 weeks and completely reversed it after 5 weeks. The intensity of 8-hydroxy -2-di(n-propyleamino)tetraline (8-OH-DPAT)-induced locomotion and forepaw treading were greater in saline+haloperidol injected but not in imipramine+haloperidol injected animals. 8-OH-DPAT induced decreases of 5-HT metabolism were greater in saline+haloperidol injected animals but not in imipramine+haloperidol injected animals. The mechanism involved in reversal/attenuation of haloperidol-induced tardive dyskinesia by imipramine is discussed. (author)

X-ray irradiation induced reversible resistance change in Pt/TiO2/Pt cells.

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Chang, Seo Hyoung; Kim, Jungho; Phatak, Charudatta; D'Aquila, Kenneth; Kim, Seong Keun; Kim, Jiyoon; Song, Seul Ji; Hwang, Cheol Seong; Eastman, Jeffrey A; Freeland, John W; Hong, Seungbum

2014-02-25

The interaction between X-rays and matter is an intriguing topic for both fundamental science and possible applications. In particular, synchrotron-based brilliant X-ray beams have been used as a powerful diagnostic tool to unveil nanoscale phenomena in functional materials. However, it has not been widely investigated how functional materials respond to the brilliant X-rays. Here, we report the X-ray-induced reversible resistance change in 40-nm-thick TiO2 films sandwiched by Pt top and bottom electrodes, and propose the physical mechanism behind the emergent phenomenon. Our findings indicate that there exists a photovoltaic-like effect, which modulates the resistance reversibly by a few orders of magnitude, depending on the intensity of impinging X-rays. We found that this effect, combined with the X-ray irradiation induced phase transition confirmed by transmission electron microscopy, triggers a nonvolatile reversible resistance change. Understanding X-ray-controlled reversible resistance changes can provide possibilities to control initial resistance states of functional materials, which could be useful for future information and energy storage devices.

Negative mood-induced alcohol-seeking is greater in young adults who report depression symptoms, drinking to cope, and subjective reactivity.

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Hogarth, Lee; Hardy, Lorna; Mathew, Amanda R; Hitsman, Brian

2018-04-01

Acute negative mood powerfully motivates alcohol-seeking behavior, but it remains unclear whether sensitivity to this effect is greater in drinkers who report depression symptoms, drinking to cope, and subjective reactivity. To examine these questions, 128 young adult alcohol drinkers (ages 18-25) completed questionnaires of alcohol use disorder symptoms, depression symptoms, and drinking to cope with negative affect. Baseline alcohol choice was measured by preference to enlarge alcohol versus food thumbnail images in two-alternative forced-choice trials. Negative mood was then induced by depressive statements and music, before alcohol choice was tested. Subjective reactivity was indexed by increased sadness pre- to post-mood induction. Baseline alcohol choice correlated with alcohol dependence symptoms (p = .001), and drinking coping motives (ps ≤ .01). Mood induction increased alcohol choice and subjective sadness overall (ps choice was associated with depression symptoms (p = .007), drinking to cope (ps ≤ .03), and subjective reactivity (p = .007). The relationship between mood-induced alcohol choice and drinking to cope remained significant after covarying for other drinking motives. Furthermore, the three predictors (depression, drinking to cope, and subjective reactivity) accounted for unique variance in mood-induced alcohol choice (ps ≥ .03), and collectively accounted for 18% of the variance (p choice task as sensitive to the relative value of alcohol and acute negative mood. The findings also accord with the core prediction of negative reinforcement theory that sensitivity to the motivational impact of negative mood on alcohol-seeking behavior may be an important mechanism that links depression and alcohol dependence. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Combined effects of radon inhalation and antioxidant vitamin administration on acute alcohol-induced hepatopathy in mice

International Nuclear Information System (INIS)

Etani, Reo; Kataoka, Takahiro; Nishiyama, Yuichi; Takata, Yuji; Yamaoka, Kiyonori

2015-01-01

It has been reported that radon inhalation activates antioxidative functions in liver and has an antioxidative effect against hepatopathy similar to that of the antioxidative effects of ascorbic acid (VC) or α-tocopherol (VE). In this study, we examined the combined effects of radon inhalation and antioxidant vitamin administration on acute alcohol-induced hepatopathy in mice. ICR mice were subjected to intraperitoneal (i.p.) administration of alcohol after pretreating with air only (sham) or radon at a concentration of approximately 2000 Bq/m 3 for 24 hours and i.p. administration of VC (300 mg/kg body weight) or VE (300 mg/kg body weight). In mice injected with alcohol, the combined radon and antioxidant vitamins treatment significantly decreased the activities of glutamic oxaloacetic transaminase in serum compared to not only the alcohol-administered group (sham group), but also the radon inhalation with alcohol administration group or the vitamin and alcohol administration group. In addition, radon inhalation significantly increased the antioxidant level, in such as the catalase activity and the total glutathione content in liver compared to the sham group. These results suggested that the combined radon and antioxidant vitamin treatment could effectively inhibit alcohol-induced hepatopathy in mice without any antagonizing action. (author)

Preventive Effects of Forced Exercise against Alcohol-induced Physical Dependency and Reduction of Pain Perception Threshold

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Majid Motaghinejad

2014-01-01

Full Text Available Background: Treatment of postabstinence syndrome of alcohol is one of the major strategies of alcoholism treatment. Exercise can be modulated major brain pathways such as a reward system and pain perception centers. The aim of this study was to evaluation the effects of forced exercise in the management of alcohol dependence and pain perception alteration which induced by alcoholism. Methods: 72 adult male rats were divided into 2 major groups: (1 40 of them was divided into groups of positive control (alcohol dependent negative control and alcohol dependent groups under treatment by forced exercise, diazepam (0.4 mg/kg and forced exercise in combination with diazepam and alcohol withdrawal signs, and blood cortisols, were measured in this groups. (2 32 rats were divided into control, alcohol dependent (without treatment, and alcohol-dependent groups under treatment by forced exercise or indometacin (5 mg/kg and then pain perception was assessed by using writhing test, tail-flick and hot plate test. Results: Forced exercise, diazepam, and their combinations significantly attenuates withdrawal syndrome to 20 ± 2, 22 ± 1.3 and 16 ± 2 and blood cortisol level to 6.8 ± 1.3,7.9 ± 1.2 and 5.8 ± 1.1, respectively, in comparison with the positive control group (P < 0.05 and P < 0.001. In alcohol dependent animal under treatment by forced exercise, pain response significantly inhibited with 37%, 57% and 38% decreases in writhing test, hot plate, and tail-flick test, respectively, in comparison with alcohol dependent (without treatment group (P < 0.05. Conclusions: This study suggested that forced exercise can be useful as adjunct therapy in alcoholism patient and also can be effective in modulation of pain threshold reduction that was induced by alcohol dependency.

Trauma- and Stress-Induced Response in Veterans with Alcohol Dependence and Comorbid Post-Traumatic Stress Disorder.

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Ralevski, Elizabeth; Southwick, Steven; Jackson, Eric; Jane, Jane Serrita; Russo, Melanie; Petrakis, Ismene

2016-08-01

Alcohol dependence (AD) and post-traumatic stress disorder (PTSD) commonly co-occur, and the co-occurrence is associated with worse prognosis than either disorder absent the other. Craving is an important construct related to relapse, but the relationship between PTSD symptoms, craving, and relapse is not well understood. Several studies have documented the relationship between stress and craving in individuals without comorbid PTSD, but the effect on those with comorbid PTSD is not well known. A small literature suggests that trauma imagery affects craving. This is the first study to explore the effects of trauma-induced and stress-induced scripts on alcohol craving, affect, cardiovascular, and cortisol responses in the laboratory. Veterans (n = 25) diagnosed with AD and PTSD who were participating in a randomized clinical treatment trial took part in this laboratory study. Baseline assessment included PTSD symptoms and drinking quantity and frequency over 3 months before study initiation. In the laboratory, participants were exposed to neutral, stressful, and trauma scripts randomly assigned. Main outcomes included craving, anxiety, mood states, salivary cortisol, and cardiovascular responses. Both stress and trauma scripts produced greater increases in craving, negative affect, and cardiovascular reactivity, compared to neutral scripts. Trauma scripts produced significantly stronger craving for alcohol and greater cardiovascular reactivity than stress scripts. Also, trauma-induced but not stress-induced craving was positively correlated with baseline levels of drinking. There were no changes in cortisol levels from pre- to postexposure of any scripts. The results highlight that trauma cues are more salient in inducing alcohol craving than stress cues and higher reactivity is related to more baseline drinking. This finding is consistent with clinical observations that show an association between PTSD symptoms and alcohol relapse. It also underscores the

Reversal of CRF- and stress-induced anorexia by an ayurvedic formulation

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V. S. Kulkarni

2012-04-01

Full Text Available Trikatu churna is one of the commonly used Ayurvedic formulations in the traditional system of medicine in India for the treatment of agnimandya, i.e. anorexia. Trikatu contains equal amounts of finely powdered rhizomes of Zingiber officinale Roscoe (Zingiberaceae and fruits of Piper longum L. and Piper nigrum L. (Piperaceae. The chief objective of the study was to determine the antianorectic effects of three drugs individually and to compare these effects with the effect of Trikatu. The activity of the drugs was studied after anorexia was induced in rats by (1 physical stress arising from immobilization for 60 min; (2 intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS, 100 μg/kg body weight; and (3 intraperitoneal administration of fluoxetine (8 mg/kg body weight. Similar doses of the extracts were tested on freely feeding rats and on rats that had been deprived of food for 20 h. Corticotrophin-releasing factor (CRF, 0.3 μg/rat can induce anxiogenic-like behavior and reduced food intake. This model was also studied, and the results were compared. The components of Trikatu churna failed to individually reverse the inhibition of feeding. In contrast, Trikatu churna pretreatment reversed stress-, fluoxetine- and CRF-induced anorexia. The study provides strong evidence of the synergistic action of Ayurvedic formulas and also proves the ability of Trikatu churna to reduce stress and CRF-induced anorexia.

Reversal of CRF- and stress-induced anorexia by an ayurvedic formulation

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V. S. Kulkarni

2011-09-01

Full Text Available Trikatu churna is one of the commonly used Ayurvedic formulations in the traditional system of medicine in India for the treatment of agnimandya, i.e. anorexia. Trikatu contains equal amounts of finely powdered rhizomes of Zingiber officinale Roscoe (Zingiberaceae and fruits of Piper longum L. and Piper nigrum L. (Piperaceae. The chief objective of the study was to determine the antianorectic effects of three drugs individually and to compare these effects with the effect of Trikatu. The activity of the drugs was studied after anorexia was induced in rats by (1 physical stress arising from immobilization for 60 min; (2 intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS, 100 μg/kg body weight; and (3 intraperitoneal administration of fluoxetine (8 mg/kg body weight. Similar doses of the extracts were tested on freely feeding rats and on rats that had been deprived of food for 20 h. Corticotrophin-releasing factor (CRF, 0.3 μg/rat can induce anxiogenic-like behavior and reduced food intake. This model was also studied, and the results were compared. The components of Trikatu churna failed to individually reverse the inhibition of feeding. In contrast, Trikatu churna pretreatment reversed stress-, fluoxetine- and CRF-induced anorexia. The study provides strong evidence of the synergistic action of Ayurvedic formulas and also proves the ability of Trikatu churna to reduce stress and CRF-induced anorexia.

The Protective Effect of Cordycepin On Alcohol-Induced Osteonecrosis of the Femoral Head

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Yi-Xuan Chen

2017-08-01

Full Text Available Background: Alcohol abuse is known to be a leading risk factor for atraumatic osteonecrosis of the femoral head (ONFH, in which the suppression of osteogenesis plays a critical role. Cordycepin benefits bone metabolism; however, there has been no study to determine its effect on osteonecrosis. Methods: Human bone mesenchymal stem cells (hBMSCs were identified by multi-lineage differentiation. Alkaline phosphatase (ALP activity, RT-PCR, western blots, immunofluorescent assay and Alizarin red staining of BMSCs were evaluated. A rat model of alcohol-induced ONFH was established to investigate the protective role of cordycepin against ethanol. Hematoxylin & eosin (H&E staining and micro-computerized tomography (micro-CT were performed to observe ONFH. Apoptosis was assessed by TdT-mediated dUTP nick end labeling (TUNEL. Immunohistochemical staining was carried out to detect OCN and COL1. Results: Ethanol significantly suppressed ALP activity, decreased gene expression of OCN and BMP2, lowered levels of RUNX2 protein, and reduced immunofluorescence staining of OCN and COL1 and calcium formation of hBMSCs. However, these inhibitory effects were attenuated by cordycepin co-treatment at concentrations of 1 and 10 µg/mL Moreover, it was revealed that the osteo-protective effect of cordycepin was associated with modulation of the Wnt/β-catenin pathway. In vivo, by micro-CT, TUNEL and immunohistochemical staining of OCN and COL1, we found that cordycepin administration prevented alcohol-induced ONFH. Conclusion: Cordycepin treatment to enhance osteogenesis may be considered a potential therapeutic approach to prevent the development of alcohol-induced ONFH.

Moringa oleifera Supplemented Diets Prevented Nickel-Induced Nephrotoxicity in Wistar Rats

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O. S. Adeyemi

2014-01-01

Full Text Available Background. The Moringa oleifera plant has been implicated for several therapeutic potentials. Objective. To evaluate whether addition of M. oleifera to diet has protective effect against nickel-induced nephrotoxicity in rats. Methodology. Male Wistar rats were assigned into six groups of five. The rats were given oral exposure to 20 mg/kg nickel sulphate (NiSO4 in normal saline and sustained on either normal diet or diets supplemented with Moringa oleifera at different concentrations for 21 days. 24 hours after cessation of treatments, all animals were sacrificed under slight anesthesia. The blood and kidney samples were collected for biochemical and histopathology analyses, respectively. Results. NiSO4 exposure reduced the kidney-to-body weight ratio in rats and caused significant elevation in the levels of plasma creatinine, urea, and potassium. Also, the plasma level of sodium was decreased by NiSO4 exposure. However, addition of M. oleifera to diets averted the nickel-induced alteration to the level of creatinine and urea. The histopathology revealed damaged renal tubules and glomerular walls caused by NiSO4 exposure. In contrast, the damages were ameliorated by the M. oleifera supplemented diets. Conclusion. The addition of M. oleifera to diet afforded significant protection against nickel-induced nephrotoxicity.

Moringa oleifera Supplemented Diets Prevented Nickel-Induced Nephrotoxicity in Wistar Rats

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Adeyemi, O. S.; Elebiyo, T. C.

2014-01-01

Background. The Moringa oleifera plant has been implicated for several therapeutic potentials. Objective. To evaluate whether addition of M. oleifera to diet has protective effect against nickel-induced nephrotoxicity in rats. Methodology. Male Wistar rats were assigned into six groups of five. The rats were given oral exposure to 20 mg/kg nickel sulphate (NiSO4) in normal saline and sustained on either normal diet or diets supplemented with Moringa oleifera at different concentrations for 21 days. 24 hours after cessation of treatments, all animals were sacrificed under slight anesthesia. The blood and kidney samples were collected for biochemical and histopathology analyses, respectively. Results. NiSO4 exposure reduced the kidney-to-body weight ratio in rats and caused significant elevation in the levels of plasma creatinine, urea, and potassium. Also, the plasma level of sodium was decreased by NiSO4 exposure. However, addition of M. oleifera to diets averted the nickel-induced alteration to the level of creatinine and urea. The histopathology revealed damaged renal tubules and glomerular walls caused by NiSO4 exposure. In contrast, the damages were ameliorated by the M. oleifera supplemented diets. Conclusion. The addition of M. oleifera to diet afforded significant protection against nickel-induced nephrotoxicity. PMID:25295181

Specific behavioral and cellular adaptations induced by chronic morphine are reduced by dietary omega-3 polyunsaturated fatty acids.

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Joshua Hakimian

Full Text Available Opiates, one of the oldest known drugs, are the benchmark for treating pain. Regular opioid exposure also induces euphoria making these compounds addictive and often misused, as shown by the current epidemic of opioid abuse and overdose mortalities. In addition to the effect of opioids on their cognate receptors and signaling cascades, these compounds also induce multiple adaptations at cellular and behavioral levels. As omega-3 polyunsaturated fatty acids (n-3 PUFAs play a ubiquitous role in behavioral and cellular processes, we proposed that supplemental n-3 PUFAs, enriched in docosahexanoic acid (DHA, could offset these adaptations following chronic opioid exposure. We used an 8 week regimen of n-3 PUFA supplementation followed by 8 days of morphine in the presence of this diet. We first assessed the effect of morphine in different behavioral measures and found that morphine increased anxiety and reduced wheel-running behavior. These effects were reduced by dietary n-3 PUFAs without affecting morphine-induced analgesia or hyperlocomotion, known effects of this opiate acting at mu opioid receptors. At the cellular level we found that morphine reduced striatal DHA content and that this was reversed by supplemental n-3 PUFAs. Chronic morphine also increased glutamatergic plasticity and the proportion of Grin2B-NMDARs in striatal projection neurons. This effect was similarly reversed by supplemental n-3 PUFAs. Gene analysis showed that supplemental PUFAs offset the effect of morphine on genes found in neurons of the dopamine receptor 2 (D2-enriched indirect pathway but not of genes found in dopamine receptor 1(D1-enriched direct-pathway neurons. Analysis of the D2 striatal connectome by a retrogradely transported pseudorabies virus showed that n-3 PUFA supplementation reversed the effect of chronic morphine on the innervation of D2 neurons by the dorsomedial prefontal and piriform cortices. Together these changes outline specific behavioral and

Dual role of protein tyrosine phosphatase 1B in the progression and reversion of non-alcoholic steatohepatitis

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Águeda González-Rodríguez

2018-01-01

Full Text Available Objectives: Non-alcoholic fatty liver disease (NAFLD is the most common chronic liver disease in Western countries. Protein tyrosine phosphatase 1B (PTP1B, a negative modulator of insulin and cytokine signaling, is a therapeutic target for type 2 diabetes and obesity. We investigated the impact of PTP1B deficiency during NAFLD, particularly in non-alcoholic steatohepatitis (NASH. Methods: NASH features were evaluated in livers from wild-type (PTP1BWT and PTP1B-deficient (PTP1BKO mice fed methionine/choline-deficient diet (MCD for 8 weeks. A recovery model was established by replacing MCD to chow diet (CHD for 2–7 days. Non-parenchymal liver cells (NPCs were analyzed by flow cytometry. Oval cells markers were measured in human and mouse livers with NASH, and in oval cells from PTP1BWT and PTP1BKO mice. Results: PTP1BWT mice fed MCD for 8 weeks exhibited NASH, NPCs infiltration, and elevated Fgf21, Il6 and Il1b mRNAs. These parameters decreased after switching to CHD. PTP1B deficiency accelerated MCD-induced NASH. Conversely, after switching to CHD, PTP1BKO mice rapidly reverted NASH compared to PTP1BWT mice in parallel to the normalization of serum triglycerides (TG levels. Among NPCs, a drop in cytotoxic natural killer T (NKT subpopulation was detected in PTP1BKO livers during recovery, and in these conditions M2 macrophage markers were up-regulated. Oval cells markers (EpCAM and cytokeratin 19 significantly increased during NASH only in PTP1B-deficient livers. HGF-mediated signaling and proliferative capacity were enhanced in PTP1BKO oval cells. In NASH patients, oval cells markers were also elevated. Conclusions: PTP1B elicits a dual role in NASH progression and reversion. Additionally, our results support a new role for PTP1B in oval cell proliferation during NAFLD. Keywords: PTP1B, Steatosis, Steatohepatitis, Inflammation, Oval cells

CHRONIC ALCOHOL NEUROADAPTATION AND STRESS CONTRIBUTE TO SUSCEPTIBILITY FOR ALCOHOL CRAVING AND RELAPSE

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BREESE, GEORGE R.; SINHA, RAJITA; HEILIG, MARKUS

2010-01-01

Alcoholism is a chronic relapsing disorder. Major characteristics observed in alcoholics during an initial period of alcohol abstinence are altered physiological functions and a negative emotional state. Evidence suggests that a persistent, cumulative adaptation involving a kindling/allostasis-like process occurs during the course of repeated chronic alcohol exposures that is critical for the negative symptoms observed during alcohol withdrawal. Basic studies have provided evidence for specific neurotransmitters within identified brain sites being responsible for the negative emotion induced by the persistent cumulative adaptation following intermittent-alcohol exposures. After an extended period of abstinence, the cumulative alcohol adaptation increases susceptibility to stress- and alcohol cue-induced negative symptoms and alcohol seeking, both of which can facilitate excessive ingestion of alcohol. In the alcoholic, stressful imagery and alcohol cues alter physiological responses, enhance negative emotion, and induce craving. Brain fMRI imaging following stress and alcohol cues has documented neural changes in specific brain regions of alcoholics not observed in social drinkers. Such altered activity in brain of abstinent alcoholics to stress and alcohol cues is consistent with a continuing ethanol adaptation being responsible. Therapies in alcoholics found to block responses to stress and alcohol cues would presumably be potential treatments by which susceptibility for continued alcohol abuse can be reduced. By continuing to define the neurobiological basis of the sustained alcohol adaptation critical for the increased susceptibility of alcoholics to stress and alcohol cues that facilitate craving, a new era is expected to evolve in which the high rate of relapse in alcoholism is minimized. 250 PMID:20951730

Modulatory effects of dietary supplementation by Vernonia amygdalina on high-fat-diet-induced obesity in Wistar rats.

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Ekeleme-Egedigwe, Chima A; Ijeh, Ifeoma I; Okafor, Polycarp N

2017-01-01

Obesity is a growing public health problem arising from energy imbalance. The effect of 10% dietary incorporation of Vernonia amygdalina (VA) leaves into high-fat diets on some biological markers of adiposity and dyslipidaemia was investigated. Experimental diets consisted of the following – CD (control diet); HFD (high-fat diet); and HFD- VA (HFD containing 10% Vernonia amygdalina leaves) supplementation. Fifteen male Wistar rats were randomly divided into three groups of five animals each. After twelve weeks of feeding, serum lipid profile, blood glucose concentrations, body weight, adiposity index, feed intake, fecal loss and relative organ weight were investigated. Vernonia amygdalina (VA) inhibited HFD-induced weight gain and adiposity in rats. HFD-induced obese rats showed a significant increase in the levels of serum TG and TC compared to rats on a normal diet. However, the levels of serum TG, TC, LDL-C in HFDVA rats reduced significantly relative to the levels in HFD rats. Our results indicate that HFDVA reversed fatty infiltration leading to decreased body weight and fat tissue mass in the rats. These results suggested that incorporation of Vernonia amygdalina into high-fat diets may have therapeutic potentials for obesity and related metabolic disorders. Further studies to explore its possibility as an alternative pharmacologic agent to treat obesity are warranted.

Carboxylesterase 1 Is Regulated by Hepatocyte Nuclear Factor 4α and Protects Against Alcohol- and MCD diet-induced Liver Injury.

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Xu, Jiesi; Xu, Yang; Li, Yuanyuan; Jadhav, Kavita; You, Min; Yin, Liya; Zhang, Yanqiao

2016-04-14

The liver is a major organ that controls hepatic and systemic homeostasis. Dysregulation of liver metabolism may cause liver injury. Previous studies have demonstrated that carboxylesterase 1 (CES1) regulates hepatic triglyceride metabolism and protects against liver steatosis. In the present study, we investigated whether CES1 played a role in the development of alcoholic liver disease (ALD) and methionine and choline-deficient (MCD) diet-induced liver injury. Both hepatocyte nuclear factor 4α (HNF4α) and CES1 were markedly reduced in patients with alcoholic steatohepatitis. Alcohol repressed both HNF4α and CES1 expression in primary hepatocytes. HNF4α regulated CES1 expression by directly binding to the proximal promoter of CES1. Global inactivation of CES1 aggravated alcohol- or MCD diet-induced liver inflammation and liver injury, likely as a result of increased production of acetaldehyde and reactive oxygen species and mitochondrial dysfunctions. Knockdown of hepatic CES1 exacerbated ethanol-induced steatohepatitis. These data indicate that CES1 plays a crucial role in protection against alcohol- or MCD diet-induced liver injury.

Reversal of aflatoxin induced liver damage by turmeric and curcumin.

Science.gov (United States)

Soni, K B; Rajan, A; Kuttan, R

1992-09-30

The effect of certain food additives on aflatoxin production by Aspergillus parasiticus has been studied in vitro. Extracts of turmeric (Curcuma longa), garlic (Allium sativum) and asafoetida (Ferula asafoetida) inhibited the aflatoxin production considerably (more than 90%) at concentrations of 5-10 mg/ml. Similar results were also seen using butylated hydroxytoluene, butylated hydroxyanisole and ellagic acid at concentration 0.1 mM. Curcumin, the antioxidant principle from Curcuma longa did not have any effect on aflatoxin production. Turmeric and curcumin were also found to reverse the aflatoxin induced liver damage produced by feeding aflatoxin B1 (AFB1) (5 micrograms/day per 14 days) to ducklings. Fatty changes, necrosis and biliary hyperplasia produced by AFB1 were considerably reversed by these food additives.

Ascorbic acid suppresses endotoxemia and NF-κB signaling cascade in alcoholic liver fibrosis in guinea pigs: A mechanistic approach

Energy Technology Data Exchange (ETDEWEB)

Abhilash, P.A.; Harikrishnan, R.; Indira, M., E-mail: indiramadambath@gmail.com

2014-01-15

Alcohol consumption increases the small intestinal bacterial overgrowth (SIBO) and intestinal permeability of endotoxin. The endotoxin mediated inflammatory signaling plays a major role in alcoholic liver fibrosis. We evaluated the effect of ascorbic acid (AA), silymarin and alcohol abstention on the alcohol induced endotoxemia and NF-κB activation cascade pathway in guinea pigs (Cavia porcellus). Guinea pigs were administered ethanol at a daily dose of 4 g/kg b.wt for 90 days. After 90 days, ethanol administration was stopped. The ethanol treated animals were divided into abstention, silymarin (250 mg/kg b.wt) and AA (250 mg/kg b.wt) supplemented groups and maintained for 30 days. The SIBO, intestinal permeability and endotoxin were significantly increased in the ethanol group. The mRNA expressions of intestinal proteins claudin, occludin and zona occludens-1 were significantly decreased in ethanol group. The mRNA levels of inflammatory receptors, activity of IKKβ and the protein expressions of phospho-IκBα, NF-κB, TNF-α, TGF-β{sub 1} and IL-6 were also altered in ethanol group. The expressions of fibrosis markers α-SMA, α{sub 1} (I) collagen and sirius red staining in the liver revealed the induction of fibrosis. But the supplementation of AA could induce greater reduction of ethanol induced SIBO, intestinal barrier defects, NF-κB activation and liver fibrosis than silymarin. The possible mechanism may be the inhibitory effect of AA on SIBO, intestinal barrier defect and IKKβ, which decreased the activation of NF-κB and synthesis of cytokines. This might have led to suppression of HSCs activation and liver fibrosis. - Highlights: • Alcohol increases intestinal bacterial overgrowth and permeability of endotoxin. • Endotoxin mediated inflammation plays a major role in alcoholic liver fibrosis. • Ascorbic acid reduces endotoxemia, NF-κB activation and proinflammatory cytokines. • AA's action is by inhibition of SIBO, IKKβ and alteration of

Hyphal-like extension and pseudohyphal formation in industrial strains of yeasts induced by isoamyl alcohol

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Ceccato-Antonini Sandra Regina

2002-01-01

Full Text Available Yeasts can produce pseudohyphae and hyphal-like extensions under certain growth conditions like isoamyl alcohol (IAA induction, a chief constituent of fusel oil, which is a subproduct from the ethanolic fermentation. The morphology switch from yeast to a filamentous form can be troublesome to the process. In this work it was studied the influence of fusel alcohols, nitrogen sources (ammonium sulphate and leucine and glifosate (a chemical maturator for sugar cane added to a complex medium on some industrial strains of yeasts isolated from the fermentative process. Two industrial strains showed transition to hyphal-like extensions or pseudohyphae (clusters of cells upon addition of IAA from 0.3 to 0.9% /v. The alterations were reversible when the yeasts were reinoculated in YEPD without IAA. Although pseudohyphae are a result of nitrogen-limited medium, we observed them as a result of IAA addition. No influence of the nitrogen source or isopropilic alcohol or glifosate was detected for any strain studied in the concentrations used.

Involvement of delta opioid receptors in alcohol withdrawal-induced mechanical allodynia in male C57BL/6 mice.

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Alongkronrusmee, Doungkamol; Chiang, Terrance; van Rijn, Richard M

2016-10-01

As a legal drug, alcohol is commonly abused and it is estimated that 17 million adults in the United States suffer from alcohol use disorder. Heavy alcoholics can experience withdrawal symptoms including anxiety and mechanical allodynia that can facilitate relapse. The molecular mechanisms underlying this phenomenon are not well understood, which stifles development of new therapeutics. Here we investigate whether delta opioid receptors (DORs) play an active role in alcohol withdrawal-induced mechanical allodynia (AWiMA) and if DOR agonists may provide analgesic relief from AWiMA. To study AWiMA, adult male wild-type and DOR knockout C57BL/6 mice were exposed to alcohol by a voluntary drinking model or oral gavage exposure model, which we developed and validated here. We also used the DOR-selective agonist TAN-67 and antagonist naltrindole to examine the involvement of DORs in AWiMA, which was measured using a von Frey model of mechanical allodynia. We created a robust model of alcohol withdrawal-induced anxiety and mechanical allodynia by orally gavaging mice with 3g/kg alcohol for three weeks. AWiMA was exacerbated and prolonged in DOR knockout mice as well as by pharmacological blockade of DORs compared to control mice. However, analgesia induced by TAN-67 was attenuated during withdrawal in alcohol-gavaged mice. DORs appear to play a protective role in the establishment of AWiMA. Our current results indicate that DORs could be targeted to prevent or reduce the development of AWiMA during alcohol use; however, DORs may be a less suitable target to treat AWiMA during active withdrawal. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Reversal of rocuronium-induced (1.2 mg/kg) profound neuromuscular block by sugammadex: a multicenter, dose-finding and safety study.

NARCIS (Netherlands)

Boer, H.D. de; Driessen, J.J.; Marcus, M.A.; Kerkkamp, H.E.M.; Heeringa, M.; Klimek, M.

2007-01-01

BACKGROUND: Reversal of rocuronium-induced neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a modified gamma-cyclodextrin derivative. This study investigated the efficacy and safety of sugammadex in reversing rocuronium-induced profound neuromuscular

Modification of automatic alcohol-approach tendencies in alcohol-dependent patients with mild or major neurocognitive disorder

NARCIS (Netherlands)

Loijen, A.; Rinck, M.; Walvoort, S.J.W.; Kessels, R.P.C.; Becker, E.S.; Egger, J.I.M.

2018-01-01

Background: To examine the applicability of an alcohol-avoidance training procedure in patients with alcohol dependence and alcohol-induced neurocognitive disorders, we trained two groups that differed in the degree of cognitive impairment: One group fulfilled the DSM-5 criteria for Alcohol-Induced

Supplementation of pyruvate prevents palmitate-induced impairment of glucose uptake in C2 myotubes.

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Jung, Jong Gab; Choi, Sung-E; Hwang, Yoon-Jung; Lee, Sang-A; Kim, Eun Kyoung; Lee, Min-Seok; Han, Seung Jin; Kim, Hae Jin; Kim, Dae Jung; Kang, Yup; Lee, Kwan-Woo

2011-10-15

Elevated fatty acid levels have been thought to contribute to insulin resistance. Repression of the glucose transporter 4 (GLUT4) gene as well as impaired GLUT4 translocation may be a mediator for fatty acid-induced insulin resistance. This study was initiated to determine whether palmitate treatment repressed GLUT4 expression, whether glucose/fatty acid metabolism influenced palmitate-induced GLUT4 gene repression (PIGR), and whether attempts to prevent PIGR restored palmitate-induced impairment of glucose uptake (PIIGU) in C2 myotubes. Not only stimulators of fatty acid oxidation, such as bezafibrate, AICAR, and TOFA, but also TCA cycle substrates, such as pyruvate, leucine/glutamine, and α-ketoisocaproate/monomethyl succinate, significantly prevented PIGR. In particular, supplementing with pyruvate through methyl pyruvate resulted in nearly complete prevention of PIIGU, whereas palmitate treatment reduced the intracellular pyruvate level. These results suggest that pyruvate depletion plays a critical role in PIGR and PIIGU; thus, pyruvate supplementation may help prevent obesity-induced insulin resistance in muscle cells. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

Aldehyde Dehydrogenase-2 (ALDH2) Ameliorates Chronic Alcohol Ingestion-Induced Myocardial Insulin Resistance and Endoplasmic Reticulum Stress

OpenAIRE

Li, Shi-Yan; Gilbert, Sara A.B.; Li, Qun; Ren, Jun

2009-01-01

Chronic alcohol intake leads to insulin resistance and alcoholic cardiomyopathy, which appears to be a result of the complex interaction between genes and environment. This study was designed to examine the impact of aldehyde dehydrogenase-2 (ALDH2) transgenic overexpression on alcohol-induced insulin resistance and myocardial injury. ALDH2 transgenic mice were produced using chicken β-actin promoter. Wild-type FVB and ALDH2 mice were fed a 4% alcohol or control diet for 12 wks. Cell shorteni...

Nicotine Prevents and Reverses Paclitaxel-Induced Mechanical Allodynia in a Mouse Model of CIPN.

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Kyte, S Lauren; Toma, Wisam; Bagdas, Deniz; Meade, Julie A; Schurman, Lesley D; Lichtman, Aron H; Chen, Zhi-Jian; Del Fabbro, Egidio; Fang, Xianjun; Bigbee, John W; Damaj, M Imad; Gewirtz, David A

2018-01-01

Chemotherapy-induced peripheral neuropathy (CIPN), a consequence of peripheral nerve fiber dysfunction or degeneration, continues to be a dose-limiting and debilitating side effect during and/or after cancer chemotherapy. Paclitaxel, a taxane commonly used to treat breast, lung, and ovarian cancers, causes CIPN in 59-78% of cancer patients. Novel interventions are needed due to the current lack of effective CIPN treatments. Our studies were designed to investigate whether nicotine can prevent and/or reverse paclitaxel-induced peripheral neuropathy in a mouse model of CIPN, while ensuring that nicotine will not stimulate lung tumor cell proliferation or interfere with the antitumor properties of paclitaxel. Male C57BL/6J mice received paclitaxel every other day for a total of four injections (8 mg/kg, i.p.). Acute (0.3-0.9 mg/kg, i.p.) and chronic (24 mg/kg per day, s.c.) administration of nicotine respectively reversed and prevented paclitaxel-induced mechanical allodynia. Blockade of the antinociceptive effect of nicotine with mecamylamine and methyllycaconitine suggests that the reversal of paclitaxel-induced mechanical allodynia is primarily mediated by the α 7 nicotinic acetylcholine receptor subtype. Chronic nicotine treatment also prevented paclitaxel-induced intraepidermal nerve fiber loss. Notably, nicotine neither promoted proliferation of A549 and H460 non-small cell lung cancer cells nor interfered with paclitaxel-induced antitumor effects, including apoptosis. Most importantly, chronic nicotine administration did not enhance Lewis lung carcinoma tumor growth in C57BL/6J mice. These data suggest that the nicotinic acetylcholine receptor-mediated pathways may be promising drug targets for the prevention and treatment of CIPN. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Role of Hypothalamic-Pituitary-Adrenal axis and corticotropin-releasing factor stress system on cue-induced relapse to alcohol seeking.

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Galesi, Fernanda L; Ayanwuyi, Lydia O; Mijares, Miriam Garcia; Cippitelli, Andrea; Cannella, Nazzareno; Ciccocioppo, Roberto; Ubaldi, Massimo

2016-10-05

A large body of evidence has shown that the Corticotropin Releasing Factor (CRF) system, which plays a key role in stress modulation, is deeply involved in relapse to alcohol seeking induced by exposure to stressful events such as foot shock or yohimbine injections. Exposure to environmental cues is also known to be a trigger for alcohol relapse, nevertheless, the relationship between the relapse evoked by the cue-induced model and the CRF stress systems remains unclear. The purpose of this study was to evaluate, in male Wistar rats, the involvement of the CRF system and Hypothalamic-Pituitary-Adrenal (HPA) axis in relapse induced by environmental cues. Antalarmin, a selective CRF1 receptor antagonist, Metyrapone, a corticosterone (CORT) synthesis inhibitor and CORT were evaluated for their effects on the reinstatement test in a cue-induced relapse model. Antalarmin (20mg/kg) blocked relapse to alcohol seeking induced by environmental cues. Metyrapone (50 and 100mg/kg) also blocked relapse in Wistar rats but only at the highest dose (100mg/kg). Corticosterone had no effect on relapse at the doses tested. The results obtained from this study suggest that the CRF stress system and the HPA axis are involved in cue-induced alcohol relapse. Copyright © 2016 Elsevier B.V. All rights reserved.

The effects of resveratrol supplementation on cardiovascular risk factors in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study.

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Faghihzadeh, Forouzan; Adibi, Payman; Hekmatdoost, Azita

2015-09-14

Non-alcoholic fatty liver disease (NAFLD) is usually associated with insulin resistance, central obesity, reduced glucose tolerance, type 2 diabetes mellitus and hypertriacylglycerolaemia. The beneficial effects of resveratrol on metabolic disorders have been shown previously. The aim of this study was to evaluate the effects of resveratrol supplementation on cardiovascular risk factors in patients with NAFLD. In this randomised double-blinded placebo-controlled clinical trial, fifty NAFLD patients were supplemented with either a 500-mg resveratrol capsule or a placebo capsule for 12 weeks. Both groups were advised to follow an energy-balanced diet and physical activity recommendations. resveratrol supplementation reduced alanine aminotransferase (ALT) and hepatic steatosis significantly more than placebo (P0·05). There were no significant changes in blood pressure, insulin resistance markers and TAG in either group (P>0·05). Our data have shown that 12-week supplementation of 500 mg resveratrol does not have any beneficial effect on anthropometric measurements, insulin resistance markers, lipid profile and blood pressure; however, it reduced ALT and hepatic steatosis in patients with NAFLD.

Reversal of alcohol dependence-induced deficits in cue-guided behavior via mGluR2/3 signaling in mice.

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Barker, Jacqueline M; Lench, Daniel H; Chandler, L Judson

2016-01-01

Alcohol use disorders are associated with deficits in adaptive behavior. While some behavioral impairments that are associated with alcohol use disorders may predate exposure to drugs of abuse, others may result directly from exposure to drugs of abuse, including alcohol. Identifying a causal role for how alcohol exposure leads to these impairments will enable further investigation of the neurobiological mechanisms by which it acts to dysregulate adaptive behavior. In the present study, we examined the effects of chronic intermittent ethanol exposure (CIE) on the use of reward-paired cues to guide consummatory behaviors in a mouse model, and further, how manipulations of mGluR2/3 signaling-known to be dysregulated after chronic alcohol exposure-may alter the expression of this behavior. Adult male C57B/6J mice were trained to self-administer 10 % ethanol and exposed to CIE via vapor inhalation. After CIE exposure, mice were trained in a Pavlovian task wherein a cue (tone) was paired with the delivery of a 10 % sucrose unconditioned stimulus. The use of the reward-paired cue to guide licking behavior was determined across training. The effect of systemic mGluR2/3 manipulation on discrimination between cue-on and cue-off intervals was assessed by administration of the mGluR2/3 agonist LY379268 or the antagonist LY341495 prior to a testing session. Exposure to CIE resulted in reductions in discrimination between cue-on and cue-off intervals, with CIE-exposed mice exhibiting significantly lower consummatory behavior during reward-paired cues than air controls. In addition, systemic administration of an mGluR2/3 agonist restored the use of reward-paired cues in CIE-exposed animals without impacting behavior in air controls. Conversely, administration of an mGluR2/3 antagonist mimicked the effects of CIE on cue-guided licking behavior, indicating that mGluR2/3 signaling can bidirectionally regulate the ability to use reward-paired cues to guide behavior. Together

Cholecalciferol attenuates perseverative behavior associated with developmental alcohol exposure in rats in a dose-dependent manner.

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Idrus, N M; Happer, J P; Thomas, J D

2013-07-01

Alcohol is a known teratogen that is estimated to affect 2-5% of the births in the U.S. Prenatal alcohol exposure can produce physical features such as facial dysmorphology, physiological alterations such as cell loss in the central nervous system (CNS), and behavioral changes that include hyperactivity, cognitive deficits, and motor dysfunction. The range of effects associated with prenatal alcohol exposure is referred to as fetal alcohol spectrum disorders (FASD). Despite preventative measures, some women continue to drink while pregnant. Therefore, identifying interventions that reduce the severity of FASD is critical. This study investigated one such potential intervention, vitamin D3, a nutrient that exerts neuroprotective properties. The present study determined whether cholecalciferol, a common vitamin D3 nutritional supplement, could serve as a means of mitigating alcohol-related learning deficits. Using a rat model of FASD, cholecalciferol was given before, during, and after 3rd trimester equivalent alcohol exposure. Three weeks after cholecalciferol treatment, subjects were tested on a serial spatial discrimination reversal learning task. Animals exposed to ethanol committed significantly more errors compared to controls. Cholecalciferol treatment reduced perseverative behavior that is associated with developmental alcohol exposure in a dose-dependent manner. These data have important implications for the treatment of FASD and suggest that cholecalciferol may reduce some aspects of FASD. This article is part of a Special Issue entitled 'Vitamin D Workshop'. Copyright © 2012 Elsevier Ltd. All rights reserved.

Voluntary Ingestion of Natural Cocoa Extenuated Hepatic Damage in Rats with Experimentally Induced Chronic Alcoholic Toxicity

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Godwin Sokpor

2012-05-01

Full Text Available Background: Chronic ethanol ingestion causes hepatic damage imputable to an increasedoxidative stress engendered by alcoholic toxicity. Polyphenols in cocoa have antioxidant properties, and natural cocoa powder (NCP contains the highest levels of total antioxidant capacity when compared to all other kinds of edible cocoa products. This study tested the hypothesis that dietary supplementation with NCP mitigates hepatic injury resulting from chronic ethanol consumption. Three groups of eight randomized Sprague-Dawley rats were fed standardrat food and treated daily for 12 weeks as follows: (i the Ethanol-water group was given unrestricted access to 40% (v/v ethanol for 12 hours (at night followed by water for the remaining 12 hours (daytime, (ii the Ethanol-cocoa group had similarly unrestricted access to 40% ethanol for 12 hours followed by 2% (w/v NCP for 12 hours, and (iii the control group was not given alcohol and had unrestricted access to only water which was synchronously replenished every 12 hours as it was for the ethanol treated animals.Results: Qualitative structural liver damage evidenced by hepatocyte cytoplasmic fatty accumulation, nuclear alterations, and disruption of general liver micro-architecture, was severe in the ethanol-water group when compared with the ethanol-cocoa group of rats. Design-based stereologic assessment yielded a significantly greater volume (Tukey’s HSD, p = 0.0005 ofundamaged hepatocytes (9.61 ml, SD 2.18 ml in the ethanol-cocoa group as opposed to theethanol-water group of rats (2.34 ml, SD 1.21 ml. Control rats had 10.34 ml (SD 1.47 ml of undamaged hepatocytes, and that was not significantly greater (Tukey’s HSD, p=0.659 than the value for the ethanol-cocoa group of rats. Relative to controls, therefore, histomorphometryFunctional Foods in Health and Disease 2012, 2(5:166- 187 showed 93% hepatocyte preservation from alcoholic injury in rats that voluntarily imbibed NCP suspension compared with 23% in

Sugammadex, a new reversal agent for neuromuscular block induced by rocuronium in the anaesthetized Rhesus monkey.

NARCIS (Netherlands)

Boer, H.D. de; Egmond, J. van; Pol, F. van de; Bom, A.; Booij, L.H.D.J.

2006-01-01

BACKGROUND: Binding of the steroidal molecule of rocuronium by a cyclodextrin is a new concept for reversal of neuromuscular block. The present study evaluated the ability of Sugammadex Org 25969, a synthetic gamma-cyclodextrin derivative, to reverse constant neuromuscular block of about 90% induced

Comparative effects of curcumin and its analog on alcohol- and polyunsaturated fatty acid-induced alterations in circulatory lipid profiles.

Science.gov (United States)

Rukkumani, Rajagopalan; Aruna, Kode; Varma, Penumathsa Suresh; Rajasekaran, Kallikat Narayanan; Menon, Venugopal P

2005-01-01

Excessive alcohol intake induces hyperlipidemia. Studies suggest that natural principles and their analogs are known to possess anti-hyperlipidemic properties. In the present work we tested the effect of curcumin, an active principle of turmeric (Curcuma longa), and a curcumin analog on alcohol- and thermally oxidized polyunsaturated fatty acid (deltaPUFA)- induced hyperlipidemia. Male albino Wistar rats were used for the experimental study. Anti-hyperlipidemic activity of curcumin and curcumin analog was evaluated by analyzing the levels of cholesterol, triglycerides (TGs), phospholipids (PLs), and free fatty acids (FFAs). The results showed that the levels of cholesterol, TGs, PLs, and FFAs were increased significantly in alcohol-, deltaPUFA-, and alcohol + deltaPUFA-treated groups, which were brought down significantly on treatment with either of the curcuminoids. Curcumin analog treatment was found to be more effective than curcumin treatment. From the results obtained, we conclude that both curcumin and its analog effectively protect the system against alcohol- and deltaPUFA-induced hyperlipidemia and are possible candidates for the treatment of hyperlipidemia.

Effects of spin-polarized current on pulse field-induced precessional magnetization reversal

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Guang-fu Zhang

2012-12-01

Full Text Available We investigate effects of a small DC spin-polarized current on the pulse field-induced precessional magnetization reversal in a thin elliptic magnetic element by micromagnetic simulations. We find that the spin-polarized current not only broadens the time window of the pulse duration, in which a successful precessional reversal is achievable, but also significantly suppresses the magnetization ringing after the reversal. The pulse time window as well as the decay rate of the ringing increase with increasing the current density. When a spin-polarized current with 5 MA/cm2 is applied, the time window increases from 80 ps to 112 ps, and the relaxation time of the ringing decreases from 1.1 ns to 0.32 ns. Our results provide useful information to achieve magnetic nanodevices based on precessional switching.

Reversal of haloperidol induced motor deficits in rats exposed to repeated immobilization stress.

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Shireen, Erum; Pervez, Sidra; Masroor, Maria; Ali, Wafa Binte; Rais, Qudsia; Khalil, Samira; Tariq, Anum; Haleem, Darakshan Jabeen

2014-09-01

Stress is defined as a non specific response of body to any physiological and psychological demand. Preclinical studies have shown that an uncontrollable stress condition produces neurochemical and behavioral deficits. The present study was conducted to test the hypothesis that a decrease in the responsiveness of somatodendritic 5-hydroxytryptamine (5-HT)-1A receptors following adaptation to stress could attenuate haloperidol induced acute parkinsonian like effect. Results showed that single exposure (2h) to immobilization stress markedly decreased food intake, growth rate and locomotor activity but these stress-induced behavioral deficits were not observed following repeated (2h/day for 5 days) exposure of immobilization stress suggesting behavioral tolerance occurs to similar stress. An important finding of present study is a reversal of haloperidol-induced motor deficits in animals exposed to repeated immobilization stress than respective control animals. It is suggested that stress induced possible desensitization of somatodendritic 5-HT-1A as well as 5-HT-2C receptors could release dopamine system from the inhibitory influence of serotonin. On the other hand, an increase in the effectiveness of postsynaptic 5-HT-1A receptors elicits a direct stimulatory influence on the activity of dopaminergic neuron and is possibly involved in the reversal of haloperidol-induced parkinsonian like symptoms in repeatedly immobilized rats.

Suplementação de vitamina C em rações para reversão sexual da tilápia do Nilo Vitamin C diet supplementation for sex reversal of the Nile tilapia

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Glaucio Nogueira Toyama

2000-06-01

Full Text Available O estudo avaliou o efeito da suplementação de vitamina C: 0; 50; 100; 200; 400; 600; 800; 1000 mg kg-1 na dieta de reversão sexual da tilápia do Nilo (Oreochromis niloticus. Foram avaliados o ganho de peso e incremento em comprimento aos 0, 10, 20 e 30 dias de tratamento; porcentagem da sobrevivência final (S% e porcentagem de reversão sexual (RS% de pós-larvas estocadas em "hapas" de 0,08 m³. A partir do 20º dia, foram observadas diferenças (PThe effects of vitamin C supplementation (0; 50; 100; 200; 400; 600; 800; 1,000 mg kg-1 of diet on diets for sex reversal of the Nile tilapia, Oreochromis niloticus, were evaluated on groups of 600 larvae stocked in 0.08 m³ hapas and fed for 30 days with hormone-treated feeds containing different supplementation levels (n=3. Weight gain and total length increment were evaluated after days 0, 10, 20 and 30. Survival rate (S% and sex reversal rate (SR% were determined at the end of the experimental period. Weight gain and total length became significantly different only after day 20 (P<0.0001. Best results for weight gain were attained with dietary vitamin C levels above 800 mg kg-1, while the best results for growth in length were attained with dietary vitamin C levels above 400 mg kg-1. Levels of supplementation higher than 200 mg kg-1 did not lead to better survival rates. SR% values were not significantly affected by vitamin C supplementation of sex reversal diets (P<0.9993. Optimal values for vitamin C supplementation of sex reversal diets for the Nile tilapia, derived from polinomial regression analysis procedures, were: weight gain 859.5 mg; growth in length 765.0 mg, and for survival rate 685.7 mg.

Garlic Supplementation Ameliorates UV-Induced Photoaging in Hairless Mice by Regulating Antioxidative Activity and MMPs Expression.

Science.gov (United States)

Kim, Hye Kyung

2016-01-08

UV exposure is associated with oxidative stress and is the primary factor in skin photoaging. UV-induced reactive oxygen species (ROS) cause the up-regulation of metalloproteinase (MMPs) and the degradation of dermal collagen and elastic fibers. Garlic and its components have been reported to exert antioxidative effects. The present study investigated the protective effect of garlic on UV-induced photoaging and MMPs regulation in hairless mice. Garlic was supplemented in the diet, and Skh-1 hairless mice were exposed to UV irradiation five days/week for eight weeks. Mice were divided into four groups; Non-UV, UV-irradiated control, UV+1% garlic powder diet group, and UV+2% garlic powder diet group. Chronic UV irradiation induced rough wrinkling of the skin with hyperkeratosis, and administration of garlic diminished the coarse wrinkle formation. UV-induced dorsal skin and epidermal thickness were also ameliorated by garlic supplementation. ROS generation, skin and serum malondialdehyde levels were significantly increased by UV exposure and were ameliorated by garlic administration although the effects were not dose-dependent. Antioxidant enzymes such as superoxide dismutase and catalase activities in skin tissues were markedly reduced by UV irradiation and garlic treatment increased these enzyme activities. UV-induced MMP-1 and MMP-2 protein levels were suppressed by garlic administration. Furthermore, garlic supplementation prevented the UV-induced increase of MMP-1 mRNA expression and the UV-induced decrease of procollagen mRNA expression. These results suggest that garlic may be effective for preventing skin photoaging accelerated by UV irradiation through the antioxidative system and MMP regulation.

Treatment with pioglitazone induced significant, reversible mitral regurgitation.

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Dorkhan, Mozhgan; Dencker, Magnus; Frid, Anders

2008-04-30

There has in recent years been great concern about possible cardiac side effects of thiazolidinediones (TZDs). We present a case-report of a 60 year-old male who developed significant mitral regurgitation during six months treatment with pioglitazone in parallel with laboratory indications of fluid retention. Echocardiography six months after discontinuation of medication showed regression of mitral regurgitation and the laboratory parameters were also normalized. It is noteworthy that six months treatment with pioglitazone could induce significant valve dysfunction, which was reversible, and this underlines the importance of carefully monitoring patients when placing them on treatment with TZDs.

Treatment with pioglitazone induced significant, reversible mitral regurgitation

Directory of Open Access Journals (Sweden)

Frid Anders

2008-04-01

Full Text Available Abstract There has in recent years been great concern about possible cardiac side effects of thiazolidinediones (TZDs. We present a case-report of a 60 year-old male who developed significant mitral regurgitation during six months treatment with pioglitazone in parallel with laboratory indications of fluid retention. Echocardiography six months after discontinuation of medication showed regression of mitral regurgitation and the laboratory parameters were also normalized. It is noteworthy that six months treatment with pioglitazone could induce significant valve dysfunction, which was reversible, and this underlines the importance of carefully monitoring patients when placing them on treatment with TZDs.

AMPK Activation Prevents and Reverses Drug-Induced Mitochondrial and Hepatocyte Injury by Promoting Mitochondrial Fusion and Function.

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Sun Woo Sophie Kang

Full Text Available Mitochondrial damage is the major factor underlying drug-induced liver disease but whether conditions that thwart mitochondrial injury can prevent or reverse drug-induced liver damage is unclear. A key molecule regulating mitochondria quality control is AMP activated kinase (AMPK. When activated, AMPK causes mitochondria to elongate/fuse and proliferate, with mitochondria now producing more ATP and less reactive oxygen species. Autophagy is also triggered, a process capable of removing damaged/defective mitochondria. To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac. In the absence of AMPK activation, the drugs caused hepatocytes to lose polarized morphology and have significantly decreased ATP levels and viability. At the subcellular level, mitochondria underwent fragmentation and had decreased membrane potential due to decreased expression of the mitochondrial fusion proteins Mfn1, 2 and/or Opa1. Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects. The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology. In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1. AMPK activation also stimulated autophagy/mitophagy, most significantly in acetaminophen-treated cells. These results suggest that activation of AMPK prevents/reverses drug-induced mitochondrial and hepatocellular damage through regulation of mitochondrial fusion and autophagy, making it a potentially valuable approach for treatment of drug-induced liver injury.

AMPK Activation Prevents and Reverses Drug-Induced Mitochondrial and Hepatocyte Injury by Promoting Mitochondrial Fusion and Function

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Taniane, Caitlin; Farrell, Geoffrey; Arias, Irwin M.; Lippincott-Schwartz, Jennifer; Fu, Dong

2016-01-01

Mitochondrial damage is the major factor underlying drug-induced liver disease but whether conditions that thwart mitochondrial injury can prevent or reverse drug-induced liver damage is unclear. A key molecule regulating mitochondria quality control is AMP activated kinase (AMPK). When activated, AMPK causes mitochondria to elongate/fuse and proliferate, with mitochondria now producing more ATP and less reactive oxygen species. Autophagy is also triggered, a process capable of removing damaged/defective mitochondria. To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac. In the absence of AMPK activation, the drugs caused hepatocytes to lose polarized morphology and have significantly decreased ATP levels and viability. At the subcellular level, mitochondria underwent fragmentation and had decreased membrane potential due to decreased expression of the mitochondrial fusion proteins Mfn1, 2 and/or Opa1. Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects. The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology. In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1. AMPK activation also stimulated autophagy/mitophagy, most significantly in acetaminophen-treated cells. These results suggest that activation of AMPK prevents/reverses drug-induced mitochondrial and hepatocellular damage through regulation of mitochondrial fusion and autophagy, making it a potentially valuable approach for treatment of drug-induced liver injury. PMID:27792760

5-HT1A receptor-dependent modulation of emotional and neurogenic deficits elicited by prolonged consumption of alcohol.

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Belmer, Arnauld; Patkar, Omkar L; Lanoue, Vanessa; Bartlett, Selena E

2018-02-01

Repeated episodes of binge-like alcohol consumption produce anxiety, depression and various deleterious effects including alterations in neurogenesis. While the involvement of the serotonin receptor 1 A (5-HT 1A ) in the regulation of anxiety-like behavior and neurogenesis is well documented, its contribution to alcohol withdrawal-induced anxiety and alcohol-induced deficits in neurogenesis is less documented. Using the Drinking-In-the-Dark (DID) paradigm to model chronic long-term (12 weeks) binge-like voluntary alcohol consumption in mice, we show that the selective partial activation of 5-HT 1A receptors by tandospirone (3 mg/kg) prevents alcohol withdrawal-induced anxiety in a battery of behavioral tests (marble burying, elevated-plus-maze, open-field), which is accompanied by a robust decrease in binge-like ethanol intake (1 and 3 mg/kg). Furthermore, using triple immunolabelling of proliferation and neuronal differentiation markers, we show that long-term DID elicits profound deficits in neurogenesis and neuronal fate specification in the dorsal hippocampus that are entirely reversed by a 2-week chronic treatment with the 5-HT 1A partial agonist tandospirone (3 mg/kg/day). Together, our results confirm previous observations that 5-HT 1A receptors play a pivotal role in alcohol drinking behavior and the associated emotional and neurogenic impairments, and suggest that 5-HT 1A partial agonists represent a promising treatment strategy for alcohol abuse.

Impact of TLR4 on behavioral and cognitive dysfunctions associated with alcohol-induced neuroinflammatory damage.

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Pascual, María; Baliño, Pablo; Alfonso-Loeches, Silvia; Aragón, Carlos M G; Guerri, Consuelo

2011-06-01

Toll-like receptors (TLRs) play an important role in the innate immune response, and emerging evidence indicates their role in brain injury and neurodegeneration. Our recent results have demonstrated that ethanol is capable of activating glial TLR4 receptors and that the elimination of these receptors in mice protects against ethanol-induced glial activation, induction of inflammatory mediators and apoptosis. This study was designed to assess whether ethanol-induced inflammatory damage causes behavioral and cognitive consequences, and if behavioral alterations are dependent of TLR4 functions. Here we show in mice drinking alcohol for 5months, followed by a 15-day withdrawal period, that activation of the astroglial and microglial cells in frontal cortex and striatum is maintained and that these events are associated with cognitive and anxiety-related behavioral impairments in wild-type (WT) mice, as demonstrated by testing the animals with object memory recognition, conditioned taste aversion and dark and light box anxiety tasks. Mice lacking TLR4 receptors are protected against ethanol-induced inflammatory damage, and behavioral associated effects. We further assess the possibility of the epigenetic modifications participating in short- or long-term behavioral effects associated with neuroinflammatory damage. We show that chronic alcohol treatment decreases H4 histone acetylation and histone acetyltransferases activity in frontal cortex, striatum and hippocampus of WT mice. Alterations in chromatin structure were not observed in TLR4(-/-) mice. These results provide the first evidence of the role that TLR4 functions play in the behavioral consequences of alcohol-induced inflammatory damage and suggest that the epigenetic modifications mediated by TLR4 could contribute to short- or long-term alcohol-induced behavioral or cognitive dysfunctions. Copyright © 2011 Elsevier Inc. All rights reserved.

Choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and MEK expression in mice

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Zhang, Jianhai; Zhang, Yufang; Liang, Chen; Wang, Nasui; Zheng, Heping; Wang, Jundong

2016-01-01

Fluoride is known to cause male reproductive toxicity, and the elucidation of its underlying mechanisms is an ongoing research focus in reproductive toxicology and epidemiology. Choline, an essential nutrient, has been extensively studied for its benefits in nervous system yet was rarely discussed for its prospective effect in male reproductive system. This study aims to explore the potential protective role of choline against NaF-induced male reproductive toxicity via MAPK pathway. The male mice were administrated by 150 mg/L NaF in drinking water, 5.75 g/kg choline in diet, and their combination respectively from maternal gestation to postnatal 15 weeks. The results showed that fluoride exposure reduced body weight growth, lowered sperm count and survival percentages, altered testicular histology, down-regulated the mRNA expressions of NGF, Ras, Raf, and MEK genes in testes, as well as significantly decreased the expressions of both NGF and phosphor-MEK proteins in testes. Examination of data from choline-treated mice revealed that choline supplementation ameliorated these fluoride-induced changes. Taken together, our findings suggest that choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and phosphor-MEK expression. The suitable dosage and supplementation periods of choline await further exploration. - Highlights: • Fluoride exposure altered the growth and development, sperm count and sperm survival percentages, testicular histology • Fluoride exposure decreased NGF, Ras, and Mek mRNA and NGF and p-MEK protein expressions in testis of mice. • Choline supplementation diminishes fluoride-induced testicular toxicity.

Choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and MEK expression in mice

Energy Technology Data Exchange (ETDEWEB)

Zhang, Jianhai [Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801 (China); Zhang, Yufang [Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801 (China); Veterinary Station in Chen Villages of Lin Country, Linxian, Shanxi 033200 (China); Liang, Chen [Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801 (China); Wang, Nasui [Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia, Charlottesville, VA 22908 (United States); Division of Endocrinology and Metabolism, Department of Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou (China); Zheng, Heping [Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908 (United States); Wang, Jundong, E-mail: wangjd53@outlook.com [Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801 (China)

2016-11-01

Fluoride is known to cause male reproductive toxicity, and the elucidation of its underlying mechanisms is an ongoing research focus in reproductive toxicology and epidemiology. Choline, an essential nutrient, has been extensively studied for its benefits in nervous system yet was rarely discussed for its prospective effect in male reproductive system. This study aims to explore the potential protective role of choline against NaF-induced male reproductive toxicity via MAPK pathway. The male mice were administrated by 150 mg/L NaF in drinking water, 5.75 g/kg choline in diet, and their combination respectively from maternal gestation to postnatal 15 weeks. The results showed that fluoride exposure reduced body weight growth, lowered sperm count and survival percentages, altered testicular histology, down-regulated the mRNA expressions of NGF, Ras, Raf, and MEK genes in testes, as well as significantly decreased the expressions of both NGF and phosphor-MEK proteins in testes. Examination of data from choline-treated mice revealed that choline supplementation ameliorated these fluoride-induced changes. Taken together, our findings suggest that choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and phosphor-MEK expression. The suitable dosage and supplementation periods of choline await further exploration. - Highlights: • Fluoride exposure altered the growth and development, sperm count and sperm survival percentages, testicular histology • Fluoride exposure decreased NGF, Ras, and Mek mRNA and NGF and p-MEK protein expressions in testis of mice. • Choline supplementation diminishes fluoride-induced testicular toxicity.

5-Aza-2'-deoxycytidine in the medial prefrontal cortex regulates alcohol-related behavior and Ntf3-TrkC expression in rats.

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Xiaomeng Qiao

Full Text Available Recent studies have indicated that DNA methylation plays an important role in the development of alcohol abuse. 5-Aza-2'-deoxycytidine (5-Aza-dc, an inhibitor of DNA methyltransferases, was FDA approved for myelodysplastic syndrome treatment. However, it is unclear whether 5-Aza-dc is involved in alcohol abuse. In this study, using a chronic alcohol exposure model in rats, 5-Aza-dc was injected into the medial prefrontal cortex (mPFC. Alcohol-drinking behavior and the anxiety related behavior were evaluated by two-bottle choice and open field test. We found that 5-Aza-dc injection into the mPFC significantly decreased alcohol consumption and alcohol preference in alcohol-exposure rats, corresponding to the reduced blood alcohol levels. Although 5-Aza-dc potentiated the anxiety-like behavior of alcohol-exposure rats, it had no effect on the locomotor activity. Moreover, both of the mRNA and protein levels of DNA Methyltransferase 3A (DNMT3A and DNMT3B in the mPFC were upregulated after 35 days of alcohol exposure and this upregulation could be reversed by 5-Aza-dc treatment. Additionally, 5-Aza-dc reversed the alcohol-induced downregulation of neurotrophin-3 (Ntf3, correspondingly the expression of its receptor-TrkC was reduced. These findings identified a functional role of 5-Aza-dc in alcohol-related behavioral phenotypes and one of the potential target genes, Ntf3. We also provide novel evidence for DNA methyltransferases as potential therapeutic targets in alcohol abuse.

TNF α is involved in neuropathic pain induced by nucleoside reverse transcriptase inhibitor in rats

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Zheng, Xuexing; Ouyang, Handong; Liu, Shue; Mata, Marina; Fink, David J.; Hao, Shuanglin

2011-01-01

In patients with HIV/AIDS, neuropathic pain is a common neurological complication. Infection with the HIV itself may lead to neuropathic pain, and painful symptoms are enhanced when patients are treated with nucleoside reverse transcriptase inhibitors (NRTI). The mechanisms by which NRTIs contribute to the development of neuropathic pain are not known. In the current studies, we tested the role of TNFα in antiretroviral drug-induced neuropathic pain. We administered 2′,3′-dideoxycytidine (ddC, one of the NRTIs) systemically to induce mechanical allodynia. We found that ddC induced overexpression of both mRNA and proteins of GFAP and TNFα in the spinal dorsal horn. TNFα was colocalized with GFAP in the spinal dorsal horn and with NeuN in the DRG. Knockdown of TNFα with siRNA blocked the mechanical allodynia induced by ddC. Intrathecal administration of glial inhibitor or recombinant TNF soluble receptor, reversed mechanical allodynia induced by ddC. These results suggest that TNFα is involved in NRTI-induced neuropathic pain. PMID:21741472

The effects of cocaine, alcohol and cocaine/alcohol combinations in conditioned taste aversion learning.

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Busse, Gregory D; Verendeev, Andrey; Jones, Jermaine; Riley, Anthony L

2005-09-01

We have recently reported that alcohol attenuates cocaine place preferences. Although the basis for this effect is unknown, alcohol may attenuate cocaine reward by potentiating its aversive effects. To examine this possibility, these experiments assessed the effects of alcohol on cocaine-induced taste aversions under conditions similar to those that resulted in attenuated place preferences. Specifically, Experiments 1 and 2 assessed the effects of alcohol (0.5 g/kg) on taste aversions induced by 20, 30 and 40 mg/kg cocaine. Experiment 3 examined the role of intertrial interval in the effects of alcohol (0.5 g/kg) on cocaine (30 mg/kg) taste aversions. In Experiments 1 and 2, cocaine was effective at conditioning aversions. Alcohol produced no measurable effect. Combining cocaine and alcohol produced no greater aversion than cocaine alone (and, in fact, weakened aversions at the lowest dose of cocaine). In Experiment 3, varying the intertrial interval from 3 days (as in the case of Experiments 1 and 2) to 1 day (a procedure identical to that in which alcohol attenuated cocaine place preferences) resulted in significant alcohol- and cocaine-induced taste aversions. Nonetheless, alcohol remained ineffective in potentiating cocaine aversions. Thus, under these conditions alcohol does not potentiate cocaine's aversiveness. These results were discussed in terms of their implication for the effects of alcohol on cocaine-induced place preferences. Further, the effects of alcohol on place preferences conditioned by cocaine were discussed in relation to other assessments of the effects of alcohol on the affective properties of cocaine and the implications of these interactions for alcohol and cocaine co-use.

Metabolic response of Candida albicans to phenylethyl alcohol under hyphae-inducing conditions.

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Han, Ting-Li; Tumanov, Sergey; Cannon, Richard D; Villas-Boas, Silas G

2013-01-01

Phenylethyl alcohol was one of the first quorum sensing molecules (QSMs) identified in C. albicans. This extracellular signalling molecule inhibits the hyphal formation of C. albicans at high cell density. Little is known, however, about the underlying mechanisms by which this QSM regulates the morphological switches of C. albicans. Therefore, we have applied metabolomics and isotope labelling experiments to investigate the metabolic changes that occur in C. albicans in response to phenylethyl alcohol under defined hyphae-inducing conditions. Our results showed a global upregulation of central carbon metabolism when hyphal development was suppressed by phenylethyl alcohol. By comparing the metabolic changes in response to phenylethyl alcohol to our previous metabolomic studies, we were able to short-list 7 metabolic pathways from central carbon metabolism that appear to be associated with C. albicans morphogenesis. Furthermore, isotope-labelling data showed that phenylethyl alcohol is indeed taken up and catabolised by yeast cells. Isotope-labelled carbon atoms were found in the majority of amino acids as well as in lactate and glyoxylate. However, isotope-labelled carbon atoms from phenylethyl alcohol accumulated mainly in the pyridine ring of NAD(+)/NADH and NADP(-/)NADPH molecules, showing that these nucleotides were the main products of phenylethyl alcohol catabolism. Interestingly, two metabolic pathways where these nucleotides play an important role, nitrogen metabolism and nicotinate/nicotinamide metabolism, were also short-listed through our previous metabolomics works as metabolic pathways likely to be closely associated with C. albicans morphogenesis.

Restoration of hippocampal growth hormone reverses stress-induced hippocampal impairment

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Caitlin M. Vander Weele

2013-06-01

Full Text Available Though growth hormone (GH is synthesized by hippocampal neurons, where its expression is influenced by stress exposure, its function is poorly characterized. Here, we show that a regimen of chronic stress that impairs hippocampal function in rats also leads to a profound decrease in hippocampal GH levels. Restoration of hippocampal GH in the dorsal hippocampus via viral-mediated gene transfer completely reversed stress-related impairment of two hippocampus-dependent behavioral tasks, auditory trace fear conditioning and contextual fear conditioning, without affecting hippocampal function in unstressed control rats. GH overexpression reversed stress-induced decrements in both fear acquisition and long-term fear memory. These results suggest that loss of hippocampal GH contributes to hippocampal dysfunction following prolonged stress and demonstrate that restoring hippocampal GH levels following stress can promote stress resilience.

Reversal of metabolic disorders by pharmacological activation of bile acid receptors TGR5 and FXR

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Kavita Jadhav

2018-03-01

Full Text Available Objectives: Activation of the bile acid (BA receptors farnesoid X receptor (FXR or G protein-coupled bile acid receptor (GPBAR1; TGR5 improves metabolic homeostasis. In this study, we aim to determine the impact of pharmacological activation of bile acid receptors by INT-767 on reversal of diet-induced metabolic disorders, and the relative contribution of FXR vs. TGR5 to INT-767's effects on metabolic parameters. Methods: Wild-type (WT, Tgr5−/−, Fxr−/−, Apoe−/− and Shp−/− mice were used to investigate whether and how BA receptor activation by INT-767, a semisynthetic agonist for both FXR and TGR5, could reverse diet-induced metabolic disorders. Results: INT-767 reversed HFD-induced obesity dependent on activation of both TGR5 and FXR and also reversed the development of atherosclerosis and non-alcoholic fatty liver disease (NAFLD. Mechanistically, INT-767 improved hypercholesterolemia by activation of FXR and induced thermogenic genes via activation of TGR5 and/or FXR. Furthermore, INT-767 inhibited several lipogenic genes and de novo lipogenesis in the liver via activation of FXR. We identified peroxisome proliferation-activated receptor γ (PPARγ and CCAAT/enhancer-binding protein α (CEBPα as novel FXR-regulated genes. FXR inhibited PPARγ expression by inducing small heterodimer partner (SHP whereas the inhibition of CEBPα by FXR was SHP-independent. Conclusions: BA receptor activation can reverse obesity, NAFLD, and atherosclerosis by specific activation of FXR or TGR5. Our data suggest that, compared to activation of FXR or TGR5 only, dual activation of both FXR and TGR5 is a more attractive strategy for treatment of common metabolic disorders. Keywords: Farnesoid X receptor, TGR5, Atherosclerosis, Obesity, NAFLD

Antioxidant Supplementation Reduces Genomic Aberrations in Human Induced Pluripotent Stem Cells

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Junfeng Ji

2014-01-01

Full Text Available Somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs using oncogenic transcription factors. However, this method leads to genetic aberrations in iPSCs via unknown mechanisms, which may limit their clinical use. Here, we demonstrate that the supplementation of growth media with antioxidants reduces the genome instability of cells transduced with the reprogramming factors. Antioxidant supplementation did not affect transgene expression level or silencing kinetics. Importantly, iPSCs made with antioxidants had significantly fewer de novo copy number variations, but not fewer coding point mutations, than iPSCs made without antioxidants. Our results suggest that the quality and safety of human iPSCs might be enhanced by using antioxidants in the growth media during the generation and maintenance of iPSCs.

Intrinsic torque reversals induced by magnetic shear effects on the turbulence spectrum in tokamak plasmas

Energy Technology Data Exchange (ETDEWEB)

Lu, Z. X.; Tynan, G. [Center for Energy Research and Department of Mechanical and Aerospace Engineering, University of California at San Diego, San Diego, California 92093 (United States); Center for Momentum Transport and Flow Organization and Center for Astrophysics and Space Science, University of California, San Diego, California 92093 (United States); Wang, W. X.; Ethier, S. [Princeton Plasma Physics Laboratory, Princeton, New Jersey 08540 (United States); Diamond, P. H. [Center for Momentum Transport and Flow Organization and Center for Astrophysics and Space Science, University of California, San Diego, California 92093 (United States); Gao, C.; Rice, J. [Plasma Science and Fusion Center, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 (United States)

2015-05-15

Intrinsic torque, which can be generated by turbulent stresses, can induce toroidal rotation in a tokamak plasma at rest without direct momentum injection. Reversals in intrinsic torque have been inferred from the observation of toroidal velocity changes in recent lower hybrid current drive (LHCD) experiments. This work focuses on understanding the cause of LHCD-induced intrinsic torque reversal using gyrokinetic simulations and theoretical analyses. A new mechanism for the intrinsic torque reversal linked to magnetic shear (s{sup ^}) effects on the turbulence spectrum is identified. This reversal is a consequence of the ballooning structure at weak s{sup ^}. Based on realistic profiles from the Alcator C-Mod LHCD experiments, simulations demonstrate that the intrinsic torque reverses for weak s{sup ^} discharges and that the value of s{sup ^}{sub crit} is consistent with the experimental results s{sup ^}{sub crit}{sup exp}≈0.2∼0.3 [Rice et al., Phys. Rev. Lett. 111, 125003 (2013)]. The consideration of this intrinsic torque feature in our work is important for the understanding of rotation profile generation at weak s{sup ^} and its consequent impact on macro-instability stabilization and micro-turbulence reduction, which is crucial for ITER. It is also relevant to internal transport barrier formation at negative or weakly positive s{sup ^}.

Brain-specific inactivation of the Crhr1 gene inhibits post-dependent and stress-induced alcohol intake, but does not affect relapse-like drinking

DEFF Research Database (Denmark)

Molander, Anna; Vengeliene, Valentina; Heilig, Markus

2012-01-01

, a conditional brain-specific Crhr1-knockout (Crhr1(NestinCre)) and a global knockout mouse line were studied for basal alcohol drinking, stress-induced alcohol consumption, deprivation-induced intake, and escalated alcohol consumption in the post-dependent state. In a second set of experiments, we tested CRHR1...... not affect relapse-like drinking after a deprivation period in rats. We conclude that CRH/CRHR1 extra-HPA and HPA signaling may have opposing effects on stress-related alcohol consumption. CRHR1 does not have a role in basal alcohol intake or relapse-like drinking situations with a low stress load.......Corticotropin-releasing hormone (CRH) and its receptor, CRH receptor-1 (CRHR1), have a key role in alcoholism. Especially, post-dependent and stress-induced alcohol intake involve CRH/CRHR1 signaling within extra-hypothalamic structures, but a contribution of the hypothalamic-pituitary-adrenal (HPA...

76 FR 17140 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

Science.gov (United States)

2011-03-28

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... Alcohol Abuse and Alcoholism Special Emphasis Panel; RFA-AA-11-02 Alcohol Induced Metabolic and Hepatic...: Philippe Marmillot, PhD, Scientific Review Officer, National Institute on Alcohol Abuse and Alcoholism...

IgA against gut-derived endotoxins: does it contribute to suppression of hepatic inflammation in alcohol-induced liver disease?

DEFF Research Database (Denmark)

Parlesak, Alexandr; Schäfer, C.; Bode, C.

2002-01-01

Endotoxins of intestinal origin are supposed to play an important role in the development of alcoholic hepatitis in man. To estimate the role of immunoglobulin response to gut-derived endotoxin in the development of alcohol-induced liver disease, serum levels of IgA and IgG against fecal endotoxin......, endotoxin, and acute-phase proteins were measured in patients with different stages of alcoholic liver disease and in healthy controls. Antibodies of type IgA, but not IgG, against fecal endotoxins were significantly increased in patients with alcohol-induced liver disease. IgA antibodies against fecal...... endotoxin were found to be closely correlated with the plasma concentrations of alanine aminotransferase, gamma-glutamyl transferase, and C-reactive protein in patients with alcoholic liver disease. In conclusion, as IgA located in body tissue was shown to suppress the inflammatory process, enhanced...

27 CFR 19.918 - Information already on file and supplemental information.

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2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Information already on file and supplemental information. 19.918 Section 19.918 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS DISTILLED SPIRITS PLANTS Distilled Spirits For Fuel Use Permits § 19.918...

The role of medial prefrontal cortex in extinction and reinstatement of alcohol-seeking in rats.

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Willcocks, Andrea L; McNally, Gavan P

2013-01-01

The prelimbic (PL) and infralimbic (IL) medial prefrontal cortex (mPFC) are thought to play opposing roles in drug-seeking behaviour. Specifically, the PL promotes drug-seeking whereas the IL is necessary for the inhibition of drug-seeking during extinction. We studied the roles of the PL, IL and dorsal peduncular PFC (DP) in the expression of context-induced reinstatement, reacquisition and extinction of alcoholic beer-seeking. In context-induced reinstatement (renewal), animals were trained to nosepoke for alcoholic beer (context A), extinguished (context B) and then tested in context A and B. In reacquisition, animals received the same instrumental training and extinction without any contextual manipulation. On test, alcoholic beer was again available and responding was compared with naive controls. Just prior to the test, rats received bilateral infusion of baclofen/muscimol into the PL, IL or DP. Reversible inactivation of the PL attenuated ABA renewal but augmented reacquisition. Reversible inactivation of IL had no effect on the reinstatement or reacquisition of alcoholic beer-seeking and had no effect on extinction expression (ABB and AAA). IL inactivation did, however, increase the latencies with which animals responded on test but only when animals were tested in the extinction context. DP inactivation had no effect on reinstatement or reacquisition. These studies are inconsistent with the view that PL and IL exert opposing effects on drug-seeking. Rather, they support the view that PL is important for retrieval of drug-seeking contingency information and that the use of contextual information is enhanced with IL manipulation. © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

[Alcohol intake--a two-edged sword. Part 1: metabolism and pathogenic effects of alcohol].

Science.gov (United States)

Ströhle, Alexander; Wolters, Maike; Hahn, Andreas

2012-08-01

From the biomedical point of view alcohol is a Janus-faced dietary component with a dose-dependent effect varying from cardiovascular protection to cytotoxicity. Alcohol is absorbed in the upper gastrointestinal tract by passive diffusion, is quickly distributed throughout body water and is mostly eliminated through oxidation. The enzymatically-catalyzed oxidative degradation to acetaldehyde and further to acetate is primarily localized in the liver. In case of a low blood alcohol concentration (0.5 per thousand) are increasingly oxidized by the microsomal ethanoloxidizing system (MEOS). Alcohol consumption induces several metabolic reactions as well as acute effects on the central nervous system. Chronic alcohol consumption to some extent irreparably damages nearly every organ with the liver being particularly concerned. There are three stages of alcohol-induced liver disease (fatty liver, alcohol hepatitis, liver cirrhosis) and the liver damages mainly result from reaction products of alcohol degradation (acetaldehyde, NADH and reactive oxygen species). An especially dreaded clinical complication of the alcohol-induced liver disease is the hepatic encephalopathy. Its pathogenesis is a multifactorial and self-perpetuating process with the swelling of astrocytes being a crucial point. Swollen astrocytes induce several reactions such as oxidative/nitrosative stress, impaired signal transduction, protein modifications and a modified gene expression profile. The swelling of astrocytes and the change in neuronal activity are attributed to several neurotoxins, especially ammonia and aromatic amino acids. In alcohol addicted subjects multiple micronutrient deficiencies are common. The status of folic acid, thiamine, pyridoxine and zinc is especially critical.

Nutritional supplementation with arginine protects radiation-induced effects: an experimental study

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Pinto, Flavia Cristina Morone, E-mail: fcmorone@gmail.com [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil); Campos-Silva, Pamella; Souza, Diogo Benchimol de; Costa, Waldemar Silva; Sampaio, Francisco Jose Barcellos [Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ (Brazil)

2016-10-15

Purpose: To investigate the protective effect of L-arginine on the prostate (nonneoplasic) of rats with radiation-induced injury. Methods: Twenty-nine Wistar rats, male adult, allocated into three groups: Control group (C) was not exposed to irradiation (n=10); Radiated group (R) had undergone pelvic irradiation (n=10); Supplemented and radiated group (R+S) had undergone pelvic irradiation plus L-arginine supplementation (n=9). The animals were observed for signs of toxicity. After euthanization, the prostate was dissected under magnification and stained by hematoxylin and eosin to study acinar structures and stained with Picrosirius red for collagen analysis. Results: After radiation exposure, all animals presented diarrhea, but supplementation with L-arginine reduced this effect. The weight gain in the R+S group was significantly higher than in the C and R groups. In the R+S group the collagen density and the prostate acinar area was similar to the R and C groups. Epithelial height was significantly reduced in group R compared with group C (p<0.0001). When comparing the group R+S with R, a statistical difference was observed to be present (p<0.0001). Conclusions: Pelvic radiation promotes systemic effects and some structural modifications in the ventral prostate of rats. These modifications can be prevented by oral supplementation with L-arginine. (author)

Reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia: sugammadex versus neostigmine.

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Lemmens Hendrikus JM

2010-09-01

Full Text Available Abstract Background Acetylcholinesterase inhibitors cannot rapidly reverse profound neuromuscular block. Sugammadex, a selective relaxant binding agent, reverses the effects of rocuronium and vecuronium by encapsulation. This study assessed the efficacy of sugammadex compared with neostigmine in reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia. Methods Patients aged ≥18 years, American Society of Anesthesiologists class 1-4, scheduled to undergo surgery under general anesthesia were enrolled in this phase III, multicenter, randomized, safety-assessor blinded study. Sevoflurane anesthetized patients received vecuronium 0.1 mg/kg for intubation, with maintenance doses of 0.015 mg/kg as required. Patients were randomized to receive sugammadex 4 mg/kg or neostigmine 70 μg/kg with glycopyrrolate 14 μg/kg at 1-2 post-tetanic counts. The primary efficacy variable was time from start of study drug administration to recovery of the train-of-four ratio to 0.9. Safety assessments included physical examination, laboratory data, vital signs, and adverse events. Results Eighty three patients were included in the intent-to-treat population (sugammadex, n = 47; neostigmine, n = 36. Geometric mean time to recovery of the train-of-four ratio to 0.9 was 15-fold faster with sugammadex (4.5 minutes compared with neostigmine (66.2 minutes; p Conclusions Recovery from profound vecuronium-induced block is significantly faster with sugammadex, compared with neostigmine. Neostigmine did not rapidly reverse profound neuromuscular block (Trial registration number: NCT00473694.

Magnetic field induced flow pattern reversal in a ferrofluidic Taylor-Couette system.

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Altmeyer, Sebastian; Do, Younghae; Lai, Ying-Cheng

2015-12-21

We investigate the dynamics of ferrofluidic wavy vortex flows in the counter-rotating Taylor-Couette system, with a focus on wavy flows with a mixture of the dominant azimuthal modes. Without external magnetic field flows are stable and pro-grade with respect to the rotation of the inner cylinder. More complex behaviors can arise when an axial or a transverse magnetic field is applied. Depending on the direction and strength of the field, multi-stable wavy states and bifurcations can occur. We uncover the phenomenon of flow pattern reversal as the strength of the magnetic field is increased through a critical value. In between the regimes of pro-grade and retrograde flow rotations, standing waves with zero angular velocities can emerge. A striking finding is that, under a transverse magnetic field, a second reversal in the flow pattern direction can occur, where the flow pattern evolves into pro-grade rotation again from a retrograde state. Flow reversal is relevant to intriguing phenomena in nature such as geomagnetic reversal. Our results suggest that, in ferrofluids, flow pattern reversal can be induced by varying a magnetic field in a controlled manner, which can be realized in laboratory experiments with potential applications in the development of modern fluid devices.

Reversible catecholamine-induced cardiomyopathy due to pheochromocytoma: case report.

Science.gov (United States)

Satendra, Milan; de Jesus, Cláudia; Bordalo e Sá, Armando L; Rosário, Luís; Rocha, José; Bicha Castelo, Henrique; Correia, Maria José; Nunes Diogo, António

2014-03-01

Pheochromocytoma is a tumor originating from chromaffin tissue. It commonly presents with symptoms and signs of catecholamine excess, such as hypertension, tachycardia, headache and sweating. Cardiovascular manifestations include catecholamine-induced cardiomyopathy, which may present as severe left ventricular dysfunction and congestive heart failure. We report a case of pheochromocytoma which was diagnosed following investigation of dilated cardiomyopathy. We highlight the dramatic symptomatic improvement and reversal of cardiomyopathy, with recovery of left ventricular function after treatment. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Saturation of retinol-binding protein correlates closely to the severity of alcohol-induced liver disease

DEFF Research Database (Denmark)

Wagnerberger, S.; Schäfer, C.; Bode, C.

2006-01-01

Impaired metabolism of retinol has been shown to occur in alcohol-induced liver disease (ALD). The purpose of the present study was to investigate the saturation of retinol-binding protein (RBP) in 6 patients with different stages of ALD. Hospitalized alcohol consumers (n=118) with different stages...... chromatography and enzyme-linked immunosorbent assay methods, respectively. No differences were noted in daily retinol intake, but subjects with ALD had significantly lower concentrations of retinol in plasma (ALD1: 1.81+/-0.17 micromol/l [mean+/-S.E.M.]; ALD2: 1.95+/-0.24 micromol/l; ALD3: 0.67+/-0.13 micromol......: 43.5+/-6.2%; ALD3: 29.0+/-5.1%). The present study indicates that plasma concentrations of retinol and RBP per se do not correlate to severity of ALD, but rather that the retinol/RBP ratio links to the severity of alcohol-induced liver damage. From these results, a reduced availability of retinol...

Effect of Dietary Cocoa Tea (Camellia ptilophylla Supplementation on High-Fat Diet-Induced Obesity, Hepatic Steatosis, and Hyperlipidemia in Mice

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Xiao Rong Yang

2013-01-01

Full Text Available Recent studies suggested that green tea has the potential to protect against diet-induced obesity. The presence of caffeine within green tea has caused limitations. Cocoa tea (Camellia ptilophylla is a naturally decaffeinated tea plant. To determine whether cocoa tea supplementation results in an improvement in high-fat diet-induced obesity, hyperlipidemia and hepatic steatosis, and whether such effects would be comparable to those of green tea extract, we studied six groups of C57BL/6 mice that were fed with (1 normal chow (N; (2 high-fat diet (21% butterfat + 0.15% cholesterol, wt/wt (HF; (3 a high-fat diet supplemented with 2% green tea extract (HFLG; (4 a high-fat diet supplemented with 4% green tea extract (HFHG; (5 a high-fat diet supplemented with 2% cocoa tea extract (HFLC; and (6 a high-fat diet supplemented with 4% cocoa tea extract (HFHC. From the results, 2% and 4% dietary cocoa tea supplementation caused a dose-dependent decrease in (a body weight, (b fat pad mass, (c liver weight, (d total liver lipid, (e liver triglyceride and cholesterol, and (f plasma lipids (triglyceride and cholesterol. These data indicate that dietary cocoa tea, being naturally decaffeinated, has a beneficial effect on high-fat diet-induced obesity, hepatomegaly, hepatic steatosis, and elevated plasma lipid levels in mice, which are comparable to green tea. The present findings have provided the proof of concept that dietary cocoa tea might be of therapeutic value and could therefore provide a safer and cost effective option for patients with diet-induced metabolic syndrome.

Distinct cellular responses differentiating alcohol- and hepatitis C virus-induced liver cirrhosis

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Boix Loreto

2006-11-01

Full Text Available Abstract Background Little is known at the molecular level concerning the differences and/or similarities between alcohol and hepatitis C virus induced liver disease. Global transcriptional profiling using oligonucleotide microarrays was therefore performed on liver biopsies from patients with cirrhosis caused by either chronic alcohol consumption or chronic hepatitis C virus (HCV. Results Global gene expression patterns varied significantly depending upon etiology of liver disease, with a greater number of differentially regulated genes seen in HCV-infected patients. Many of the gene expression changes specifically observed in HCV-infected cirrhotic livers were expectedly associated with activation of the innate antiviral immune response. We also compared severity (CTP class of cirrhosis for each etiology and identified gene expression patterns that differentiated ethanol-induced cirrhosis by class. CTP class A ethanol-cirrhotic livers showed unique expression patterns for genes implicated in the inflammatory response, including those related to macrophage activation and migration, as well as lipid metabolism and oxidative stress genes. Conclusion Stages of liver cirrhosis could be differentiated based on gene expression patterns in ethanol-induced, but not HCV-induced, disease. In addition to genes specifically regulating the innate antiviral immune response, mechanisms responsible for differentiating chronic liver damage due to HCV or ethanol may be closely related to regulation of lipid metabolism and to effects of macrophage activation on deposition of extracellular matrix components.

Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor Subunits

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Liu, Xiao; Li, Jitao; Guo, Chunmei; Wang, Hongli; Sun, Yaxin; Wang, Han; Su, Yun-Ai; Li, Keqing; Si, Tianmei

2018-01-01

Cognitive dysfunction constitutes an essential component in schizophrenia for its early presence in the pathophysiology of the disease and close relatedness to life quality of patients. To develop effective treatment of cognitive deficits, it is important to understand their neurobiological causes and to identify potential therapeutic targets. In this study, adopting repeated MK-801 treatment as an animal model of schizophrenia, we investigated whether antipsychotic drugs, olanzapine and haloperidol, can reverse MK-801-induced cognitive deficits and how the reversal processes recruited proteins involved in glutamate neurotransmission in rat medial prefrontal cortex (mPFC) and hippocampus. We found that low-dose chronic MK-801 treatment impaired object-in-context recognition memory and reversal learning in the Morris water maze, leaving reference memory relatively unaffected, and that these cognitive deficits can be partially reversed by olanzapine, not haloperidol, treatment. At the molecular level, chronic MK-801 treatment resulted in the reduction of multiple N-methyl-D-aspartate (NMDA) receptor subunits in rat mPFC and olanzapine, not haloperidol, treatment restored the levels of GluN1 and phosphorylated GluN2B in this region. Taken together, MK-801-induced cognitive deficits may be associated with region-specific changes in NMDA receptor subunits and the reversal of specific NMDA receptor subunits may underlie the cognition-enhancing effects of olanzapine. PMID:29375333

Fucoidan from Fucus vesiculosus Protects against Alcohol-Induced Liver Damage by Modulating Inflammatory Mediators in Mice and HepG2 Cells

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Jung Dae Lim

2015-02-01

Full Text Available Fucoidan is an l-fucose-enriched sulfated polysaccharide isolated from brown algae and marine invertebrates. In this study, we investigated the protective effect of fucoidan from Fucus vesiculosus on alcohol-induced murine liver damage. Liver injury was induced by oral administration of 25% alcohol with or without fucoidan (30 mg/kg or 60 mg/kg for seven days. Alcohol administration increased serum aspartate aminotransferase and alanine aminotransferase levels, but these increases were suppressed by the treatment of fucoidan. Transforming growth factor beta 1 (TGF-β1, a liver fibrosis-inducing factor, was highly expressed in the alcohol-fed group and human hepatoma HepG2 cell; however, the increase in TGF-β1 expression was reduced following fucoidan administration. Treatment with fucoidan was also found to significantly reduce the production of inflammation-promoting cyclooygenase-2 and nitric oxide, while markedly increasing the expression of the hepatoprotective enzyme, hemeoxygenase-1, on murine liver and HepG2 cells. Taken together, the antifibrotic and anti-inflammatory effects of fucoidan on alcohol-induced liver damage may provide valuable insights into developing new therapeutics or interventions.

Dexamethasone Does Not Inhibit Sugammadex Reversal After Rocuronium-Induced Neuromuscular Block.

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Buonanno, Pasquale; Laiola, Anna; Palumbo, Chiara; Spinelli, Gianmario; Servillo, Giuseppe; Di Minno, Raffaele Maria; Cafiero, Tullio; Di Iorio, Carlo

2016-06-01

Sugammadex is a relatively new molecule that reverses neuromuscular block induced by rocuronium. The particular structure of sugammadex traps the cyclopentanoperhydrophenanthrene ring of rocuronium in its hydrophobic cavity. Dexamethasone shares the same steroidal structure with rocuronium. Studies in vitro have demonstrated that dexamethasone interacts with sugammadex, reducing its efficacy. In this study, we investigated the clinical relevance of this interaction and its influence on neuromuscular reversal. In this retrospective case-control study, we analyzed data from 45 patients divided into 3 groups: dexamethasone after induction group (15 patients) treated with 8 mg dexamethasone as an antiemetic drug shortly after induction of anesthesia; dexamethasone before reversal group (15 patients) treated with dexamethasone just before sugammadex injection; and control group (15 patients) treated with 8 mg ondansetron. All groups received 0.6 mg/kg rocuronium at induction, 0.15 mg/kg rocuronium at train-of-four ratio (TOF) 2 for neuromuscular relaxation, and 2 mg/kg sugammadex for reversal at the end of the procedure at TOF2. Neuromuscular relaxation was monitored with a TOF-Watch® system. The control group had a recovery time of 154 ± 54 seconds (mean ± SD), the dexamethasone after induction group 134 ± 55 seconds, and the dexamethasone before reversal group 131 ± 68 seconds. The differences among groups were not statistically significant (P = 0.5141). Our results show that the use of dexamethasone as an antiemetic drug for the prevention of postoperative nausea and vomiting does not interfere with reversal of neuromuscular blockade with sugammadex in patients undergoing elective surgery with general anesthesia in contrast to in vitro studies that support this hypothesis.

EFFECTS OF PALM VITAMIN E SUPPLEMENTATION ON EXERCISE-INDUCED OXIDATIVE STRESS AND ENDURANCE PERFORMANCE IN THE HEAT

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Chen Chee Keong

2006-12-01

Full Text Available This study investigates the effects of tocotrienol-rich palm vitamin E supplementation on exercise-induced lipid peroxidation and endurance performance in the heat. In a double blind, cross-over study, eighteen healthy, male recreational athletes completed two endurance running trials, until exhaustion, on a motorized treadmill at 70% VO2max on two separate occasions following a 6-week supplementation regimen of either tocotrienol-rich palm vitamin E (E or placebo (P. Both trials were conducted in the heat (31oC, 70% relative humidity. During the trials, rectal temperature (Trec, ratings of perceived exertion (RPE and oxygen uptake (VO2 were recorded. Blood samples were collected for the determination of plasma volume changes (PVC, malondialdehyde (MDA, creatine kinase (CK, total antioxidant status (TAS and vitamin E. After the supplementation regimen, serum alpha-tocopherol increased ~33% but serum concentrations of tocotrienols were negligible. No significant differences were evident in mean Trec, RPE, VO2 or in the time to exhaustion between the E-supplemented and the placebo- supplemented groups. Similarly, mean PVC, CK and TAS were also not different between the two groups. Resting plasma mean MDA concentration in the E-supplemented group was significantly lower than that in the placebo-supplemented group. At exhaustion, plasma mean MDA was higher than the resting values in both groups. Although tocotrienol-rich palm vitamin E supplementation decreased lipid peroxidation at rest and, to some extent, during exercise in the heat, as evident from the lower MDA levels, it however did not enhance endurance running performance or prevent exercise-induced muscle damage or influenced body core temperature or plasma volume changes during exercise in the heat

Lactobacillus rhamnosus CCFM1107 treatment ameliorates alcohol-induced liver injury in a mouse model of chronic alcohol feeding.

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Tian, Fengwei; Chi, Feifei; Wang, Gang; Liu, Xiaoming; Zhang, Qiuxiang; Chen, Yongquan; Zhang, Hao; Chen, Wei

2015-12-01

Lactobacillus rhamnosus CCFM1107 was screened for high antioxidative activity from 55 lactobacilli. The present study attempted to explore the protective properties of L. rhamnosus CCFM1107 in alcoholic liver injury. A mouse model was induced by orally feeding alcohol when simultaneously treated with L. rhamnosus CCFM1107, the drug Hu-Gan- Pian (HGP), L. rhamnosus GG (LGG), and L. plantarum CCFM1112 for 3 months. Biochemical analysis was performed for both serum and liver homogenate. Detailed intestinal flora and histological analyses were also carried out. Our results indicated that the administration of L. rhamnosus CCFM1107 significantly inhibited the increase in the levels of serum aminotransferase and endotoxin, as well as the levels of triglyceride (TG) and cholesterol (CHO) in the serum and in the liver. Glutathione (GSH), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were elevated while the levels of malondialdehyde (MDA) were decreased. The enteric dysbiosis caused by alcohol was restored by increasing the numbers of both lactobacilli and bifidobacteria and decreasing the numbers of both enterococci and enterobacter. Histological analysis confirmed the protective effect of L. rhamnosus CCFM1107. Compared with the other lactobacilli and to the drug Hu-Gan-Pian, there is a high chance that L. rhamnosus CCFM1107 provides protective effects on alcoholic liver injury by reducing oxidative stress and restoring the intestinal flora.

Dietary polyphenol supplementation prevents alterations of spatial navigation in middle-aged mice

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Julien eBensalem

2016-02-01

Full Text Available Spatial learning and memory deficits associated with hippocampal synaptic plasticity impairments are commonly observed during aging. Besides, the beneficial role of dietary polyphenols has been suggested as potential functional food candidates to prevent this memory decline. Indeed, polyphenols could potentiate the signaling pathways of synaptic plasticity underlying learning and memory. In this study, spatial learning deficits of middle-aged mice were first highlighted and characterized according to navigation patterns in the Morris water maze task. An eight-week polyphenol-enriched diet, containing a polyphenol-rich extract from grape and blueberry (PEGB (from the Neurophenols Consortium with high contents of flavonoids, stilbenes and phenolic acids, was then successful in reversing these age-induced effects. The use of spatial strategies was indeed delayed with aging whereas a polyphenol supplementation could promote the occurrence of spatial strategies. These behavioral results were associated with neurobiological changes: while the expression of hippocampal CaMKII mRNA levels was reduced in middle-aged animals, the polyphenol-enriched diet could rescue them. Besides, an increased expression of NGF mRNA levels was also observed in supplemented adult and middle-aged mice. Thus these data suggest that supplementation with polyphenols could be an efficient nutritional way to prevent age-induced cognitive decline.

Association Between Alcohol Sports Sponsorship and Consumption: A Systematic Review

OpenAIRE

Brown, Katherine

2016-01-01

Aim Concerns have been raised about the impact of alcohol sports sponsorship on harmful consumption, with some countries banning this practice or considering a ban. We review evidence on the relationship between exposure to alcohol sports sponsorship and alcohol consumption. Methods Search of electronic databases (PubMed, Cochrane Library, Google Scholar and International Alcohol Information Database) supplemented by hand searches of references and conference proceedings to locate studies pro...

Prenatal choline supplementation attenuates MK-801-induced deficits in memory, motor function, and hippocampal plasticity in adult male rats.

Science.gov (United States)

Nickerson, Chelsea A; Brown, Alexandra L; Yu, Waylin; Chun, Yoona; Glenn, Melissa J

2017-10-11

Choline is essential to the development and function of the central nervous system and supplemental choline during development is neuroprotective against a variety of insults, including neurotoxins like dizocilpine (MK-801). MK-801 is an NMDA receptor antagonist that is frequently used in rodent models of psychological disorders, particularly schizophrenia. At low doses, it causes cognitive impairments, and at higher doses it induces motor deficits, anhedonia, and neuronal degeneration. The primary goals of the present study were to investigate whether prenatal choline supplementation protects against the cognitive impairments, motor deficits, and neuropathologies that are precipitated by MK-801 administration in adulthood. Adult male Sprague-Dawley rats were fed a standard or supplemented choline diet prenatally. Using the novelty preference test of object recognition, we found that only prenatal standard-fed rats displayed memory consolidation deficits induced by low-dose MK-801 administered immediately following study of sample objects; all other groups, including prenatal choline supplemented rats given MK-801, showed intact memory. Following high-dose MK-801, prenatal choline supplementation significantly alleviated rats' motor response to MK-801, particularly ataxia. Using doublecortin and Ki67 to mark neurogenesis and cell division, respectively, in the hippocampus, we found that prenatal choline supplementation, in the face of MK-801 toxicity, protected against reduced hippocampal plasticity. Taken together, the current findings suggest that prenatal choline supplementation protects against a variety of behavioral and neural pathologies induced by the neurotoxin, MK-801. This research contributes to the growing body of evidence supporting the robust neuroprotective capacity of choline. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Sugammadex 4.0 mg kg-1 reversal of deep rocuronium-induced neuromuscular blockade

DEFF Research Database (Denmark)

Yu, Buwei; Wang, Xiangrui; Hansen, Søren Helbo

2014-01-01

Objective: Maintenance of deep Neuro Muscular Blockade (NMB) until the end of surgery may be beneficial in some surgical procedures. The selective relaxant binding agent sugammadex rapidly reverses deep levels of rocuronium-induced NMB. The purpose of this study was to evaluate the efficacy...... and safety of sugammadex 4.0 mg kg-1 for reversal of deep rocuronium-induced NMB in Chinese and Caucasian patients. Methods: This was an open-label, multicenter, prospective Phase III efficacy study in adult American Society of Anesthesiologists Class 1-3 patients scheduled for surgery under general...... anesthesia and requiring deep NMB. All patients received intravenous propofol and opioids for induction and maintenance of anesthesia, and a single intubation dose of rocuronium 0.6 mg/kg, with maintenance doses of 0.1-0.2 mg/kg as required. Sugammadex 4.0 mg/kg was administered after the last dose...

Reversible photo-induced trap formation in mixed-halide hybrid perovskites for photovoltaics.

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Hoke, Eric T; Slotcavage, Daniel J; Dohner, Emma R; Bowring, Andrea R; Karunadasa, Hemamala I; McGehee, Michael D

2015-01-01

We report on reversible, light-induced transformations in (CH 3 NH 3 )Pb(Br x I 1- x ) 3 . Photoluminescence (PL) spectra of these perovskites develop a new, red-shifted peak at 1.68 eV that grows in intensity under constant, 1-sun illumination in less than a minute. This is accompanied by an increase in sub-bandgap absorption at ∼1.7 eV, indicating the formation of luminescent trap states. Light soaking causes a splitting of X-ray diffraction (XRD) peaks, suggesting segregation into two crystalline phases. Surprisingly, these photo-induced changes are fully reversible; the XRD patterns and the PL and absorption spectra revert to their initial states after the materials are left for a few minutes in the dark. We speculate that photoexcitation may cause halide segregation into iodide-rich minority and bromide-enriched majority domains, the former acting as a recombination center trap. This instability may limit achievable voltages from some mixed-halide perovskite solar cells and could have implications for the photostability of halide perovskites used in optoelectronics.

Effects of large volume injection of aliphatic alcohols as sample diluents on the retention of low hydrophobic solutes in reversed-phase liquid chromatography.

Science.gov (United States)

David, Victor; Galaon, Toma; Aboul-Enein, Hassan Y

2014-01-03

Recent studies showed that injection of large volume of hydrophobic solvents used as sample diluents could be applied in reversed-phase liquid chromatography (RP-LC). This study reports a systematic research focused on the influence of a series of aliphatic alcohols (from methanol to 1-octanol) on the retention process in RP-LC, when large volumes of sample are injected on the column. Several model analytes with low hydrophobic character were studied by RP-LC process, for mobile phases containing methanol or acetonitrile as organic modifiers in different proportions with aqueous component. It was found that starting with 1-butanol, the aliphatic alcohols can be used as sample solvents and they can be injected in high volumes, but they may influence the retention factor and peak shape of the dissolved solutes. The dependence of the retention factor of the studied analytes on the injection volume of these alcohols is linear, with a decrease of its value as the sample volume is increased. The retention process in case of injecting up to 200μL of upper alcohols is dependent also on the content of the organic modifier (methanol or acetonitrile) in mobile phase. Copyright © 2013 Elsevier B.V. All rights reserved.

Choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and MEK expression in mice.

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Zhang, Jianhai; Zhang, Yufang; Liang, Chen; Wang, Nasui; Zheng, Heping; Wang, Jundong

2016-11-01

Fluoride is known to cause male reproductive toxicity, and the elucidation of its underlying mechanisms is an ongoing research focus in reproductive toxicology and epidemiology. Choline, an essential nutrient, has been extensively studied for its benefits in nervous system yet was rarely discussed for its prospective effect in male reproductive system. This study aims to explore the potential protective role of choline against NaF-induced male reproductive toxicity via MAPK pathway. The male mice were administrated by 150mg/L NaF in drinking water, 5.75g/kg choline in diet, and their combination respectively from maternal gestation to postnatal 15weeks. The results showed that fluoride exposure reduced body weight growth, lowered sperm count and survival percentages, altered testicular histology, down-regulated the mRNA expressions of NGF, Ras, Raf, and MEK genes in testes, as well as significantly decreased the expressions of both NGF and phosphor-MEK proteins in testes. Examination of data from choline-treated mice revealed that choline supplementation ameliorated these fluoride-induced changes. Taken together, our findings suggest that choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and phosphor-MEK expression. The suitable dosage and supplementation periods of choline await further exploration. Copyright © 2016 Elsevier Inc. All rights reserved.

Progressive myopia or hyperopia can be induced in chicks and reversed by manipulation of the chromaticity of ambient light.

Science.gov (United States)

Foulds, Wallace S; Barathi, Veluchamy A; Luu, Chi D

2013-12-09

To determine whether progressive ametropia can be induced in chicks and reversed by manipulation of the chromaticity of ambient light. One-day-old chicks were raised in red light (90% red, 10% yellow-green) or in blue light (85% blue, 15% green) with a 12 hour on/off cycle for 14 to 42 days. Refraction was determined by streak retinoscopy, and by automated infrared photoretinoscopy and ocular biometry by A-scan ultrasonography. Red light induced progressive myopia (mean refraction ± SD at 28 days, -2.83 ± 0.25 diopters [D]). Progressive hyperopia was induced by blue light (mean refraction at 28 days, +4.55 ± 0.21 D). The difference in refraction between the groups was highly significant at P light (-2.21 ± 0.21 D) was reversed to hyperopia (+2.50 ± 0.29 D) by subsequent 21 days of blue light. Hyperopia induced by 21 days of blue light (+4.21 ± 0.19 D) was reversed to myopia (-1.23 ± 0.12 D) by 21 days of red light. Rearing chicks in red light caused progressive myopia, while rearing in blue light caused progressive hyperopia. Light-induced myopia or hyperopia in chicks can be reversed to hyperopia or myopia, respectively, by an alteration in the chromaticity of ambient light. Manipulation of chromaticity may be applicable to the management of human childhood myopia.

THYROID HORMONE REVERSES AGING-INDUCED MYOCARDIAL FATTY ACID OXIDATION DEFECTS AND IMPROVES THE RESPONSE TO ACUTELY INCREASED AFTERLOAD

Energy Technology Data Exchange (ETDEWEB)

Ledee, Dolena; Portman, Michael A.; Kajimoto, Masaki; Isern, Nancy G.; Olson, Aaron

2013-06-07

Background: Subclinical hypothyroidism occurs during aging in humans and mice and may contribute to development of heart failure. Aging also impairs myocardial fatty acid oxidation, causing increased reliance on flux through pyruvate dehydrogenase (PDH) to maintain function. We hypothesize that the metabolic changes in aged hearts make them less tolerant to acutely increased work and that thyroid hormone reverses these defects. Methods: Studies were performed on young (Young, 4-6 months) and aged (Old, 22-24 months) C57/BL6 mice at standard (50 mmHg) and high afterload (80 mmHg). Another aged group received thyroid hormone for 3 weeks (Old-TH, high afterload only). Function was measured in isolated working hearts along with substrate fractional contributions (Fc) to the citric acid cycle (CAC) using perfusate with 13C labeled lactate, pyruvate, glucose and unlabeled palmitate and insulin. Results: Cardiac function was similar between Young and Old mice at standard afterload. Palmitate Fc was reduced but no individual carbohydrate contributions differed. CAC and individual substrate fluxes decreased in aged. At high afterload, -dP/dT was decreased in Old versus Young. Similar to low afterload, palmitate Fc was decreased in Old. Thyroid hormone reversed aging-induced changes in palmitate Fc and flux while significantly improving cardiac function. Conclusion: The aged heart shows diminished ability to increase cardiac work due to substrate limitations, primarily impaired fatty acid oxidation. The heart accommodates slightly by increasing efficiency through oxidation of carbohydrate substrates. Thyroid hormone supplementation in aged mice significantly improves cardiac function potentially through restoration of fatty acid oxidation.

Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation through activating the NR2B subunits of NMDA receptors

Energy Technology Data Exchange (ETDEWEB)

Shi, Wen-Zhu [Anesthesia and Operation Center, Hainan Branch of Chinese PLA General Hospital, Hainan 572013 (China); Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853 (China); Miao, Yu-Liang [Department of Anesthesiology, PLA No. 306 Hospital, Beijing 100101 (China); Guo, Wen-Zhi [Department of Anesthesiology, Beijing Military General Hospital of Chinese People’s Liberation Army, Beijing 100700 (China); Wu, Wei, E-mail: wwzwgk@163.com [Department of Head and Neck Surgery of Otolaryngology, PLA No. 306 Hospital, Beijing 100101 (China); Li, Bao-Wei [Department of Head and Neck Surgery of Otolaryngology, PLA No. 306 Hospital, Beijing 100101 (China); An, Li-Na [Department of Anesthesiology, Armed Police General Hospital, Beijing 100039 (China); Fang, Wei-Wu [Department of Anesthesiology, PLA No. 306 Hospital, Beijing 100101 (China); Mi, Wei-Dong, E-mail: elite2005gg@163.com [Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853 (China)

2014-04-25

Highlights: • Leptin promotes the proliferation of neural stem cells isolated from embryonic mouse hippocampus. • Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation. • The effects of leptin are partially mediated by upregulating NR2B subunits. - Abstract: Corticosterone inhibits the proliferation of hippocampal neural stem cells (NSCs). The removal of corticosterone-induced inhibition of NSCs proliferation has been reported to contribute to neural regeneration. Leptin has been shown to regulate brain development, improve angiogenesis, and promote neural regeneration; however, its effects on corticosterone-induced inhibition of NSCs proliferation remain unclear. Here we reported that leptin significantly promoted the proliferation of hippocampal NSCs in a concentration-dependent pattern. Also, leptin efficiently reversed the inhibition of NSCs proliferation induced by corticosterone. Interestingly, pre-treatment with non-specific NMDA antagonist MK-801, specific NR2B antagonist Ro 25-6981, or small interfering RNA (siRNA) targeting NR2B, significantly blocked the effect of leptin on corticosterone-induced inhibition of NSCs proliferation. Furthermore, corticosterone significantly reduced the protein expression of NR2B, whereas pre-treatment with leptin greatly reversed the attenuation of NR2B expression caused by corticosterone in cultured hippocampal NSCs. Our findings demonstrate that leptin reverses the corticosterone-induced inhibition of NSCs proliferation. This process is, at least partially mediated by increased expression of NR2B subunits of NMDA receptors.

Reversal with sugammadex for rocuronium-induced deep neuromuscular block after pretreatment of magnesium sulfate in rabbits.

Science.gov (United States)

Kang, Woon Seok; Kim, Kyo Sang; Song, Shin Mi

2017-04-01

Magnesium sulfate (MgSO 4 ) has been used in the treatment of pre-eclampsia, hypertension and arrhythmia. Magnesium enhances the neuromuscular block of rocuronium. This study has been conducted to evaluate the reversal efficacy of sugammadex from deep rocuronium-induced neuromuscular block (NMB) during consistent pretreatment of MgSO 4 in rabbits. Twenty-eight rabbits were randomly assigned to four groups, a control group or study groups (50% MgSO 4 150-200 mg/kg and 25 mg/kg/h IV), and received rocuronium 0.6 mg/kg. When post-tetanic count 1-2 appeared, sugammadex 2, 4, and 8 mg/kg was administered in the 2-mg group, control and 4-mg group, and 8-mg group, respectively. The recovery course after reversal of sugammadex administration was evaluated in each group. The mean serum concentration of magnesium was maintained at more than 2 mmol/L in the study groups, and the total dose of MgSO 4 was more than 590 mg. The reversal effect of sugammadex on rocuronium-induced NMB in pretreated MgSO 4 was not different from that in the group without MgSO 4 . The recovery time to train-of-four ratio 0.9 after sugammadex administration in the 2-mg group was longer than in the other groups (P rocuronium-induced NMB during large pretreatment of MgSO 4 was not affected. However, we should consider that the reversal effect of sugammadex varied depending on the dose.

Benefits of dietary phytochemical supplementation on eccentric exercise-induced muscle damage: Is including antioxidants enough?

Science.gov (United States)

Pereira Panza, Vilma Simões; Diefenthaeler, Fernando; da Silva, Edson Luiz

2015-09-01

The purpose of this review was to critically discuss studies that investigated the effects of supplementation with dietary antioxidant phytochemicals on recovery from eccentric exercise-induced muscle damage. The performance of physical activities that involve unaccustomed eccentric muscle actions-such as lowering a weight or downhill walking-can result in muscle damage, oxidative stress, and inflammation. These events may be accompanied by muscle weakness and delayed-onset muscle soreness. According to the current evidences, supplementation with dietary antioxidant phytochemicals appears to have the potential to attenuate symptoms associated with eccentric exercise-induced muscle damage. However, there are inconsistencies regarding the relationship between muscle damage and blood markers of oxidative stress and inflammation. Furthermore, the effectiveness of strategies appear to depend on a number of aspects inherent to phytochemical compounds as well as its food matrix. Methodological issues also may interfere with the proper interpretation of supplementation effects. Thus, the study may contribute to updating professionals involved in sport nutrition as well as highlighting the interest of scientists in new perspectives that can widen dietary strategies applied to training. Copyright © 2015 Elsevier Inc. All rights reserved.

Surfactant self-assembly in alcohol-rich solutions

International Nuclear Information System (INIS)

Bouguerra, N.; Jebari, M.M.; Gomati, R.; Gharbi, A.

2005-01-01

Ionic conductivity and viscosity measurements are achieved along alcohol dilution lines of a single-isotropic phase domain, which extends from the alcohol corner to sponge phase domain to brine corner, of an alcohol-surfactant-brine phase diagram. The results are discussed in terms of amphiphilic self-assembly which leads to stable mixtures of the slightly miscible alcohol and brine used. We show the formation of reverse micelles, whose cores are either dry or charged of brine according to the samples composition, and whose sizes remain small near the sponge phase structure

Role of Creatine Supplementation on Exercise-Induced Cardiovascular Function and Oxidative Stress

Directory of Open Access Journals (Sweden)

Michael I. C. Kingsley

2009-01-01

Full Text Available Many degenerative diseases are associated with increased oxidative stress. Creatine has the potential to act as an indirect and direct antioxidant; however, limited data exist to evaluate the antioxidant capabilities of creatine supplementation within in vivo human systems. This study aimed to investigate the effects of oral creatine supplementation on markers of oxidative stress and antioxidant defenses following exhaustive cycling exercise. Following preliminary testing and two additional familiarization sessions, 18 active males repeated two exhaustive incremental cycling trials (T1 and T2 separated by exactly 7 days. The subjects were assigned, in a double-blind manner, to receive either 20 g of creatine (Cr or a placebo (P for the 5 days preceding T2. Breath-by-breath respiratory data and heart rate were continually recorded throughout the exercise protocol and blood samples were obtained at rest (preexercise, at the end of exercise (postexercise, and the day following exercise (post24 h. Serum hypdroperoxide concentrations were elevated at postexercise by 17 ± 5% above preexercise values (p = 0.030. However, supplementation did not influence lipid peroxidation (serum hypdroperoxide concentrations, resistance of low density lipoprotein to oxidative stress (t1/2max LDL oxidation and plasma concentrations of non-enzymatic antioxidants (retinol, α-carotene, β-carotene, α-tocopherol, γ-tocopherol, lycopene and vitamin C. Heart rate and oxygen uptake responses to exercise were not affected by supplementation. These findings suggest that short-term creatine supplementation does not enhance non-enzymatic antioxidant defence or protect against lipid peroxidation induced by exhaustive cycling in healthy males.

Early reversal of profound rocuronium-induced neuromuscular blockade by sugammadex in a randomized multicenter study - Efficacy, safety, and pharmacokinetics

NARCIS (Netherlands)

Sparr, Harald J.; Vermeyen, Karel M.; Beaufort, Anton M.; Rietbergen, Henk; Proost, Johannes H.; Saldien, Vera; Velik-Salchner, Corinna; Wierda, J. Mark K. H.

Background: Sugammadex reverses the neuromuscular blocking effects of rocuronium by chemical encapsulation. The efficacy, safety, and pharmacokinetics of sugammadex for reversal of profound rocuronium-induced neuromuscular blockade were evaluated. Methods: Ninety-eight male adult patients were

Deficiency of insulin-like growth factor 1 reduces vulnerability to chronic alcohol intake-induced cardiomyocyte mechanical dysfunction: role of AMPK.

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Ge, Wei; Li, Qun; Turdi, Subat; Wang, Xiao-Ming; Ren, Jun

2011-08-01

Circulating insulin-like growth factor I (IGF-1) levels are closely associated with cardiac performance although the role of IGF-1 in alcoholic cardiac dysfunction is unknown. This study was designed to evaluate the impact of severe liver IGF-1 deficiency (LID) on chronic alcohol-induced cardiomyocyte contractile and intracellular Ca(2+) dysfunction. Adult male C57 and LID mice were placed on a 4% alcohol diet for 15 weeks. Cardiomyocyte contractile and intracellular Ca(2+) properties were evaluated including peak shortening (PS), maximal velocity of shortening/relengthening (±dL/dt), time-to-relengthening (TR(90) ), change in fura-fluorescence intensity (ΔFFI) and intracellular Ca(2+) decay. Levels of apoptotic regulators caspase-3, Bcl-2 and c-Jun NH2-terminal kinase (JNK), the ethanol metabolizing enzyme mitochondrial aldehyde dehydrogenase (ALDH2), as well as the cellular fuel gauge AMP-activated protein kinase (AMPK) were evaluated. Chronic alcohol intake enlarged myocyte cross-sectional area, reduced PS, ± dL/dt and ΔFFI as well as prolonged TR(90) and intracellular Ca(2+) decay, the effect of which was greatly attenuated by IGF-1 deficiency. The beneficial effect of LID against alcoholic cardiac mechanical defect was ablated by IGF-1 replenishment. Alcohol intake increased caspase-3 activity/expression although it down-regulated Bcl-2, ALDH2 and pAMPK without affecting JNK and AMPK. IGF-1 deficiency attenuated alcoholism-induced responses in all these proteins with the exception of Bcl-2. In addition, the AMPK agonist 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside abrogated short-term ethanol incubation-elicited cardiac mechanical dysfunction. Taken together, these data suggested that IGF-1 deficiency may reduce the sensitivity to ethanol-induced myocardial mechanical dysfunction. Our data further depicted a likely role of Caspase-3, ALDH2 and AMPK activation in IGF-1 deficiency induced 'desensitization' of alcoholic cardiomyopathy. © 2011 The

Schisandra sphenanthera extract (Wuzhi Tablet protects against chronic-binge and acute alcohol-induced liver injury by regulating the NRF2-ARE pathway in mice

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Xuezhen Zeng

2017-09-01

Full Text Available Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available. Wuzhi Tablet (WZ, a preparation of extract from Schisandra sphenanthera that is a traditional hepato-protective herb, exerted a significant protective effect against acetaminophen-induced liver injury in our recent studies, but whether WZ can alleviate alcohol-induced toxicity remains unclear. This study aimed to investigate the contribution of WZ to alcohol-induced liver injury by using chronic-binge and acute models of alcohol feeding. The activities of ALT and AST in serum were assessed as well as the level of GSH and the activity of SOD in the liver. The expression of CYP2E1 and proteins in the NRF2-ARE signaling pathway including NRF2, GCLC, GCLM, HO-1 were measured, and the effect of WZ on NRF2 transcriptional activity was determined. We found that both models resulted in liver steatosis accompanied by increased transaminase activities, but that liver injury was significantly attenuated by WZ. WZ administration also inhibited CYP2E1 expression induced by alcohol, and elevated the level of GSH and the activity of SOD in the liver. Moreover, the NRF2-ARE signaling pathway was activated by WZ and the target genes were all upregulated. Furthermore, WZ significantly activated NRF2 transcriptional activity. Collectively, our study demonstrates that WZ protected against alcohol-induced liver injury by reducing oxidative stress and improving antioxidant defense, possibly by activating the NRF2-ARE pathway.

Protective Effects of Tinospora cordifolia on Hepatic and Gastrointestinal Toxicity Induced by Chronic and Moderate Alcoholism.

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Sharma, Bhawana; Dabur, Rajesh

2016-01-01

Heavy alcohol intake depletes the plasma vitamins due to hepatotoxicity and decreased intestinal absorption. However, moderate alcohol intake is often thought to be healthy. Therefore, effects of chronic moderate alcohol intake on liver and intestine were studied using urinary vitamin levels. Furthermore, effects of Tinospora cordifolia water extract (TCE) (hepatoprotective) on vitamin excretion and intestinal absorption were also studied. In the study, asymptomatic moderate alcoholics (n = 12) without chronic liver disease and healthy volunteers (n = 14) of mean age 39 ± 2.2 (mean ± SD) were selected and divided into three groups. TCE treatment was performed for 14 days. The blood and urine samples were collected on Day 0 and 14 after treatment with TCE and analyzed. In alcoholics samples, a significant increase in the levels of gamma-glutamyl transferase, aspartate transaminase, alanine transaminase, Triglyceride, Cholesterol, HDL and LDL (P alcoholic samples; however, TCE intervention restored the CA and biotin levels. Vitamin metabolism biomarkers, i.e. homocysteine and xanthurenic acid, were also normalized after TCE intervention. Overall data depict that moderate alcohol intake is also hepatotoxic and decreases intestinal absorption. However, TCE treatment effectively increased the intestinal absorption and retaining power of liver that regulated alcohol-induced multivitamin deficiency. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Heat-Killed Lactobacillus salivarius and Lactobacillus johnsonii Reduce Liver Injury Induced by Alcohol In Vitro and In Vivo.

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Chuang, Cheng-Hung; Tsai, Cheng-Chih; Lin, En-Shyh; Huang, Chin-Shiu; Lin, Yun-Yu; Lan, Chuan-Ching; Huang, Chun-Chih

2016-10-31

The aim of the present study was to determine whether Lactobacillus salivarius (LS) and Lactobacillus johnsonii (LJ) prevent alcoholic liver damage in HepG2 cells and rat models of acute alcohol exposure. In this study, heat-killed LS and LJ were screened from 50 Lactobacillus strains induced by 100 mM alcohol in HepG2 cells. The severity of alcoholic liver injury was determined by measuring the levels of aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (γ-GT), lipid peroxidation, triglyceride (TG) and total cholesterol. Our results indicated that heat-killed LS and LJ reduced AST, ALT, γ-GT and malondialdehyde (MDA) levels and outperformed other bacterial strains in cell line studies. We further evaluated these findings by administering these strains to rats. Only LS was able to reduce serum AST levels, which it did by 26.2%. In addition LS significantly inhibited serum TG levels by 39.2%. However, both strains were unable to inhibit ALT levels. In summary, we demonstrated that heat-killed LS and LJ possess hepatoprotective properties induced by alcohol both in vitro and in vivo.

Heat-Killed Lactobacillus salivarius and Lactobacillus johnsonii Reduce Liver Injury Induced by Alcohol In Vitro and In Vivo

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Cheng-Hung Chuang

2016-10-01

Full Text Available The aim of the present study was to determine whether Lactobacillus salivarius (LS and Lactobacillus johnsonii (LJ prevent alcoholic liver damage in HepG2 cells and rat models of acute alcohol exposure. In this study, heat-killed LS and LJ were screened from 50 Lactobacillus strains induced by 100 mM alcohol in HepG2 cells. The severity of alcoholic liver injury was determined by measuring the levels of aspartate transaminase (AST, alanine transaminase (ALT, gamma-glutamyl transferase (γ-GT, lipid peroxidation, triglyceride (TG and total cholesterol. Our results indicated that heat-killed LS and LJ reduced AST, ALT, γ-GT and malondialdehyde (MDA levels and outperformed other bacterial strains in cell line studies. We further evaluated these findings by administering these strains to rats. Only LS was able to reduce serum AST levels, which it did by 26.2%. In addition LS significantly inhibited serum TG levels by 39.2%. However, both strains were unable to inhibit ALT levels. In summary, we demonstrated that heat-killed LS and LJ possess hepatoprotective properties induced by alcohol both in vitro and in vivo.

Reversion of thyrotoxic atrial fibrillation in hypothyroid state after radioiodine treatment

International Nuclear Information System (INIS)

Yamamoto, Makiko; Saito, Shintaro; Sakurada, Toshiro; Yoshida, Katsumi; Kaise, Kazuro; Kaise, Nobuko; Fukazawa, Hiroshi; Itagaki, Yoichi; Yoshinaga, Kaoru

1992-01-01

Twenty patients with thyrotoxic Basedow's disease complicated by atrial fibrillation lasting more than one month despite treatment with antithyroidal drugs were treated with radioiodine supplemented with an antithyroidal drug or inorganic iodine. We classified the 20 patients on the basis of strial fibrillation reversion into two groups, one with reversion (group I) and the other without reversion (group II). In all 12 patients in group I, T 4 and T 3 decreased to hypothyroid levels in 3.2±1.3 months, and one month later all patients had their sinus rhythm restored while T 4 and T 3 also remained below normal (2.6±1.1 μg/dl and 77.9±34.4 ng/dl, respectively). Although T 4 and T 3 also decreased within 3.5±1.8 months in all 8 patients in group II, one month later, atrial fibrillation persisted while T 4 and T 3 (10.4±5.3 μg/dl and 157.7±67.5 ng/dl, respectively) rose significantly compared to those in group I (p<0.001 and p<0.01, respectively). For reversion of atrial fibrillation it is important that the onset of hypothyroidism is rapidly induced by radioiodine and that hypothyroidism continues for at least one month. (author)

Inhibition of Drp-1 dependent mitochondrial fission augments alcohol-induced cardiotoxicity via dysregulated Akt signaling

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Anusha Sivakumar

2017-10-01

Full Text Available Cardiovascular disorders (CVDs still claim high mortality in spite of advancements in prognosis and treatment strategies. Alcohol is one of the most commonly consumed drugs globally and chronic/binge consumption (BAC 0.08 g/dL in 2 hours is a risk factor for CVDs. However, the aetiology and pathophysiological mechanisms of alcohol induced cardiotoxicity are still poorly understood. Mitochondria are the prime site for the ATP demands of the heart and also ethanol metabolism. These subcellular organelles depict dynamic fusion and fission events that are vital for structure and functional integrity. While fused mitochondrial improve ATP production and cell survival, increased fragmentation can be the cause or result of apoptosis. In this study, we proposed to analyze the mechanism of mitochondrial fission protein Drp-1-dependent apoptosis during alcohol toxicity. Male Wistar rats (220-250 kg body weight were given isocaloric sucrose or ethanol for 45 days, orally, via drinking water and intermittent gavage twice a week. Histopathological examination of the heart displayed hypertrophy with mild inflammation. Drp-1 immunoblotting showed over-expression of the protein during ethanol treatment. We next hypothesized that inhibiting Drp-1 could attenuate alcohol-induced cardiotoxicity. Interestingly, silencing Drp-1 with siRNA in-vitro augmented cytotoxicity. Also, crude mitochondrial fraction showed increased Bak aggregation, reduced cytochrome c release but increased SMAC/DIABLO. We analyzed the Akt cell survival signaling and found that PTEN showed over-expression at both transcriptional and translational level with no significant change in total Akt but down-regulation of p-Akt (Ser473. In conclusion, we have shown that inhibition of Drp-1 dependent mitochondrial fission is not cardioprotective against alcohol-induced apoptotic signaling and augments the cytotoxicity. To our knowledge, this study is the first to interlink cell survival AKT signaling

Roux-en-Y gastric bypass reverses the effects of diet-induced obesity to inhibit the responsiveness of central vagal motoneurones.

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Browning, Kirsteen N; Fortna, Samuel R; Hajnal, Andras

2013-05-01

Diet-induced obesity (DIO) has been shown to alter the biophysical properties and pharmacological responsiveness of vagal afferent neurones and fibres, although the effects of DIO on central vagal neurones or vagal efferent functions have never been investigated. The aims of this study were to investigate whether high-fat diet-induced DIO also affects the properties of vagal efferent motoneurones, and to investigate whether these effects were reversed following weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Whole-cell patch-clamp recordings were made from rat dorsal motor nucleus of the vagus (DMV) neurones in thin brainstem slices. The DMV neurones from rats exposed to high-fat diet for 12-14 weeks were less excitable, with a decreased membrane input resistance and decreased ability to fire action potentials in response to direct current pulse injection. The DMV neurones were also less responsive to superfusion with the satiety neuropeptides cholecystokinin and glucagon-like peptide 1. Roux-en-Y gastric bypass reversed all of these DIO-induced effects. Diet-induced obesity also affected the morphological properties of DMV neurones, increasing their size and dendritic arborization; RYGB did not reverse these morphological alterations. Remarkably, independent of diet, RYGB also reversed age-related changes of membrane properties and occurrence of charybdotoxin-sensitive (BK) calcium-dependent potassium current. These results demonstrate that DIO also affects the properties of central autonomic neurones by decreasing the membrane excitability and pharmacological responsiveness of central vagal motoneurones and that these changes were reversed following RYGB. In contrast, DIO-induced changes in morphological properties of DMV neurones were not reversed following gastric bypass surgery, suggesting that they may be due to diet, rather than obesity. These findings represent the first direct evidence for the plausible effect of RYGB to improve vagal

Landolphia owariensis Attenuates Alcohol-induced Cerebellar Neurodegeneration: Significance of Neurofilament Protein Alteration in the Purkinje Cells

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Oyinbo Charles A.

2016-12-01

Full Text Available Background: Alcohol-induced cerebellar neurodegeneration is a neuroadaptation that is associated with chronic alcohol abuse. Conventional drugs have been largely unsatisfactory in preventing neurodegeneration. Yet, multimodal neuro-protective therapeutic agents have been hypothesised to have high therapeutic potential for the treatment of CNS conditions; there is yet a dilemma of how this would be achieved. Contrarily, medicinal botanicals are naturally multimodal in their mechanism of action.

Fiber-Optic Bio-sniffer (Biochemical Gas Sensor) Using Reverse Reaction of Alcohol Dehydrogenase for Exhaled Acetaldehyde.

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Iitani, Kenta; Chien, Po-Jen; Suzuki, Takuma; Toma, Koji; Arakawa, Takahiro; Iwasaki, Yasuhiko; Mitsubayashi, Kohji

2018-02-23

Volatile organic compounds (VOCs) exhaled in breath have huge potential as indicators of diseases and metabolisms. Application of breath analysis for disease screening and metabolism assessment is expected since breath samples can be noninvasively collected and measured. In this research, a highly sensitive and selective biochemical gas sensor (bio-sniffer) for gaseous acetaldehyde (AcH) was developed. In the AcH bio-sniffer, a reverse reaction of alcohol dehydrogenase (ADH) was employed for reducing AcH to ethanol and simultaneously consuming a coenzyme, reduced form of nicotinamide adenine dinucleotide (NADH). The concentration of AcH can be quantified by fluorescence detection of NADH that was consumed by reverse reaction of ADH. The AcH bio-sniffer was composed of an ultraviolet light-emitting diode (UV-LED) as an excitation light source, a photomultiplier tube (PMT) as a fluorescence detector, and an optical fiber probe, and these three components were connected with a bifurcated optical fiber. A gas-sensing region of the fiber probe was developed with a flow-cell and an ADH-immobilized membrane. In the experiment, after optimization of the enzyme reaction conditions, the selectivity and dynamic range of the AcH bio-sniffer were investigated. The AcH bio-sniffer showed a short measurement time (within 2 min) and a broad dynamic range for determination of gaseous AcH, 0.02-10 ppm, which encompassed a typical AcH concentration in exhaled breath (1.2-6.0 ppm). Also, the AcH bio-sniffer exhibited a high selectivity to gaseous AcH based on the specificity of ADH. The sensor outputs were observed only from AcH-contained standard gaseous samples. Finally, the AcH bio-sniffer was applied to measure the concentration of AcH in exhaled breath from healthy subjects after ingestion of alcohol. As a result, a significant difference of AcH concentration between subjects with different aldehyde dehydrogenase type 2 (ALDH2) phenotypes was observed. The AcH bio-sniffer can be

Photoreactivation reverses ultraviolet radition induced premutagenic lesions leading to frameshift mutations in Escherichia coli

International Nuclear Information System (INIS)

Yamamoto, Kazuo

1985-01-01

The effect of photoreactivation of the ultraviolet radiation induced reversion of a trpE9777 frameshift mutation was studied in a uvr A6 derivative of Escherichia coli K12. Two different photoreactivation treatments were used, one providing a single flash of photoreactivating light and another providing 10 min of light from fluorescent lamps. The reversion frequency of the trpE9777 frameshift mutation was strongly reduced when subsueqently exposed to visible light. The dose modification factor (the ratio of equally effective doses), for cells challenged with single-flash photoreactivation, for survival and induction of reversion to Trp + was 3.6 and 3.4, respectively. UV induction of RecA protein synthesis was not reversed by a single flash of photoreactivation. The dose modification factor for 10 min of fluorescent lamp photoreactivation for survival and for induction of reversion to Trp + was 6.5 and 6.3, respectively. The dose modification factor for 10 min of photoreactivation for induction of RecA protein was 1.7-2.5. Photoreactivation decreased the reversion of trpE9777 and increased survival to the same extent. We concluded that cyclobutyl pyrimidine dimers are the premutagenic lesions of UV mutagenesis of the trpE9777 allele in a uvr A6 background. (orig.)

Local Peltier-effect-induced reversible metal–insulator transition in VO2 nanowires

International Nuclear Information System (INIS)

Takami, Hidefumi; Kanki, Teruo; Tanaka, Hidekazu

2016-01-01

We report anomalous resistance leaps and drops in VO 2 nanowires with operating current density and direction, showing reversible and nonvolatile switching. This event is associated with the metal–insulator phase transition (MIT) of local nanodomains with coexistence states of metallic and insulating phases induced by thermoelectric cooling and heating effects. Because the interface of metal and insulator domains has much different Peltier coefficient, it is possible that a significant Peltier effect would be a source of the local MIT. This operation can be realized by one-dimensional domain configuration in VO 2 nanowires because one straight current path through the electronic domain-interface enables theoretical control of thermoelectric effects. This result will open a new method of reversible control of electronic states in correlated electron materials.

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

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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

Reversal of rocuronium-induced (1.2 mg kg-1) profound neuromuscular block by accidental high dose of sugammadex (40 mg kg-1).

NARCIS (Netherlands)

Molina, A.L.; Boer, H.D. de; Klimek, M.; Heeringa, M.; Klein, J.

2007-01-01

Sugammadex is the first selective relaxant binding agent and reverses rocuronium-induced neuromuscular block. A case is reported in which a patient accidentally received a high dose of sugammadex (40 mg kg-1) to reverse a rocuronium-induced (1.2 mg kg-1) profound neuromuscular block. A fast and

Pituitary Adenylate Cyclase-Activating Polypeptide Reverses Ammonium Metavanadate-Induced Airway Hyperresponsiveness in Rats

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Mounira Tlili

2015-01-01

Full Text Available The rate of atmospheric vanadium is constantly increasing due to fossil fuel combustion. This environmental pollution favours vanadium exposure in particular to its vanadate form, causing occupational bronchial asthma and bronchitis. Based on the well admitted bronchodilator properties of the pituitary adenylate cyclase-activating polypeptide (PACAP, we investigated the ability of this neuropeptide to reverse the vanadate-induced airway hyperresponsiveness in rats. Exposure to ammonium metavanadate aerosols (5 mg/m3/h for 15 minutes induced 4 hours later an array of pathophysiological events, including increase of bronchial resistance and histological alterations, activation of proinflammatory alveolar macrophages, and increased oxidative stress status. Powerfully, PACAP inhalation (0.1 mM for 10 minutes alleviated many of these deleterious effects as demonstrated by a decrease of bronchial resistance and histological restoration. PACAP reduced the level of expression of mRNA encoding inflammatory chemokines (MIP-1α, MIP-2, and KC and cytokines (IL-1α and TNF-α in alveolar macrophages and improved the antioxidant status. PACAP reverses the vanadate-induced airway hyperresponsiveness not only through its bronchodilator activity but also by counteracting the proinflammatory and prooxidative effects of the metal. Then, the development of stable analogs of PACAP could represent a promising therapeutic alternative for the treatment of inflammatory respiratory disorders.

Age-Related Macular Degeneration: Pathogenesis, Genetic Background, and the Role of Nutritional Supplements

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Marilita M. Moschos

2014-01-01

Full Text Available Age-related macular degeneration (ARMD is the leading cause of severe vision loss and blindness worldwide, mainly affecting people over 65 years old. Dry and wet ARDM are the main types of the disease, which seem to have a multifactorial background. The aim of this review is to summarize the mechanisms of ARMD pathogenesis and exhibit the role of diet and nutritional supplements in the onset and progression of the disease. Environmental factors, such as smoking, alcohol, and, diet appear to interact with mutations in nuclear and mitochondrial DNA, contributing to the pathogenesis of ARMD. Inflammatory mediators and oxidative stress, induced by the daily exposure of retina to high pressure of oxygen and light radiation, have been also associated with ARMD lesions. Other than medical and surgical therapies, nutritional supplements hold a significant role in the prevention and treatment of ARMD, eliminating the progression of macular degeneration.

Phosphorus Supplementation Recovers the Blunted Diet-Induced Thermogenesis of Overweight and Obese Adults: A Pilot Study

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Maya S. Bassil

2016-12-01

Full Text Available Diet-induced thermogenesis (DIT is believed to be largely related to ATP production, which is dependent on phosphorus (P availability. We aimed to test the effect of P addition on DIT of lean and overweight/obese healthy subjects. DIT was measured with or without P in 10 lean and 13 overweight/obese adults in a double-blind randomized cross-over pilot study with one week washout period. After 10 h overnight fast, resting metabolic rate, respiratory quotient, and substrate utilization were measured at fasting and every 30 min for 3 h after subjects drank a standardized glucose solution, with P (500 mg or placebo pills. Subjective ratings of hunger and satiety were assessed before and after the end of each experiment using validated visual analogue scale (VAS questionnaires. Overweight/obese subjects had a blunted DIT with placebo, while P supplementation induced a 23% increase in their DIT area under the curve (p < 0.05, which was associated with a significant increase in carbohydrate oxidation. Subjects had lower appetite following P supplementation, which was expressed as a significantly (p = 0.02 lower desire to eat a meal (4.0 ± 0.7 cm compared with placebo (5.8 ± 0.9 cm. P supplementation recovers the blunted diet-induced thermogenesis in overweight and obese subjects and enhances their postprandial satiety.

Visualization of alcohol-induced rhabdomyolysis: a correlative radiotracer, histochemical, and electron-microscopic study

International Nuclear Information System (INIS)

Silberstein, E.B.; Bove, K.E.

1979-01-01

Technetium-99m diphosphonate was used to visualize the extent of alcohol-induced rhabdomyolysis and its resolution. Transient secondary hyperparathyroidism was documented. Histological and biochemical analyses of skeletal muscle obtained at biopsy 6 days postscan and 9 days after the onset of the illness did not show abnormal calcium content

Intestinal flora imbalance promotes alcohol-induced liver fibrosis by the TGFβ/smad signaling pathway in mice.

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Zhang, Dong; Hao, Xiuxian; Xu, Lili; Cui, Jing; Xue, Li; Tian, Zibin

2017-10-01

Intestinal flora performs a crucial role in human health and its imbalance may cause numerous pathological changes. The liver can also affect the intestinal function through bile secretion via the enterohepatic cycle. The pathophysiological association between the gut and the liver is described as the gut-liver axis. The present study investigated the role of intestinal flora in alcohol-induced liver fibrosis. A total of 36 C57 mice were randomly and equally divided into 3 different dietary regimes: Group I (alcohol injury; received alcohol); group II (alcohol injury with flora imbalance; received alcohol plus lincomycin hydrochloride) and group III (alcohol injury with corrected flora imbalance; received alcohol, lincomycin hydrochloride and extra probiotics). The present study then investigated several indicators of liver damage. Alkaline phosphatase (ALP) levels, aspartate aminotransferase (AST) levels and alanine aminotransferase (ALT) levels in mice serum were studied. Masson staining and Annexin V-fluorescein isothiocyanate/propidium iodide double staining was also performed, and the expression of mothers against decapentaplegic homolog (smad) 3 and smad4 proteins in hepatic stellate cells (HSCs) of the mice was examined using western blot analysis. The levels of serum ALP, AST and ALT were the highest in group II mice, and all 3 levels decreased in group III mice compared with those from group II. The degree of liver fibrosis was aggravated in group II mice compared with group I mice. The apoptosis of HSCs was significantly inhibited in group II mice, but was increased in group III mice. The HSCs in group II mice exhibited higher expression of smad3 and smad4, whilst group III mice (with corrected intestinal flora imbalance) exhibited downregulated expression of smad3 and smad4. The present data indicates that the intestinal flora perform a significant role in maintaining liver homeostasis. Furthermore, an imbalance of intestinal flora can exacerbate alcohol-induced

Effects of Various Drugs on Alcohol-induced Oxidative Stress in the Liver

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Svetlana Trivic

2008-09-01

Full Text Available The major aim of this work was to investigate how alcohol-induced oxidative stress in combined chemotherapy changes the metabolic function of the liver in experimental animals. This research was conducted to establish how bromocriptine, haloperidol and azithromycin, applied to the experimental model, affected the antioxidative status of the liver. The following parameters were determined: reduced glutathione, activities of glutathione peroxidase, glutathione reductase, peroxidase, catalase, xanthine oxidase and lipid peroxidation intensity. Alanine transaminase was measured in serum. Alcohol stress (AO group reduced glutathione and the activity of xanthine oxidase and glutathione peroxidase, but increased catalase and alanine transaminase activity. The best protective effect was achieved with the bromocriptine (AB1 group, while other groups had similar effects on the studied parameters.

Genetic Etiology for Alcohol-Induced Cardiac Toxicity.

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Ware, James S; Amor-Salamanca, Almudena; Tayal, Upasana; Govind, Risha; Serrano, Isabel; Salazar-Mendiguchía, Joel; García-Pinilla, Jose Manuel; Pascual-Figal, Domingo A; Nuñez, Julio; Guzzo-Merello, Gonzalo; Gonzalez-Vioque, Emiliano; Bardaji, Alfredo; Manito, Nicolas; López-Garrido, Miguel A; Padron-Barthe, Laura; Edwards, Elizabeth; Whiffin, Nicola; Walsh, Roddy; Buchan, Rachel J; Midwinter, William; Wilk, Alicja; Prasad, Sanjay; Pantazis, Antonis; Baski, John; O'Regan, Declan P; Alonso-Pulpon, Luis; Cook, Stuart A; Lara-Pezzi, Enrique; Barton, Paul J; Garcia-Pavia, Pablo

2018-05-22

Alcoholic cardiomyopathy (ACM) is defined by a dilated and impaired left ventricle due to chronic excess alcohol consumption. It is largely unknown which factors determine cardiac toxicity on exposure to alcohol. This study sought to evaluate the role of variation in cardiomyopathy-associated genes in the pathophysiology of ACM, and to examine the effects of alcohol intake and genotype on dilated cardiomyopathy (DCM) severity. The authors characterized 141 ACM cases, 716 DCM cases, and 445 healthy volunteers. The authors compared the prevalence of rare, protein-altering variants in 9 genes associated with inherited DCM. They evaluated the effect of genotype and alcohol consumption on phenotype in DCM. Variants in well-characterized DCM-causing genes were more prevalent in patients with ACM than control subjects (13.5% vs. 2.9%; p = 1.2 ×10 -5 ), but similar between patients with ACM and DCM (19.4%; p = 0.12) and with a predominant burden of titin truncating variants (TTNtv) (9.9%). Separately, we identified an interaction between TTN genotype and excess alcohol consumption in a cohort of DCM patients not meeting ACM criteria. On multivariate analysis, DCM patients with a TTNtv who consumed excess alcohol had an 8.7% absolute reduction in ejection fraction (95% confidence interval: -2.3% to -15.1%; p ACM patients. TTNtv represent a prevalent genetic predisposition for ACM, and are also associated with a worse left ventricular ejection fraction in DCM patients who consume alcohol above recommended levels. Familial evaluation and genetic testing should be considered in patients presenting with ACM. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Neutrophil depletion improves diet-induced non-alcoholic fatty liver disease in mice.

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Ou, Rongying; Liu, Jia; Lv, Mingfen; Wang, Jingying; Wang, Jinmeng; Zhu, Li; Zhao, Liang; Xu, Yunsheng

2017-07-01

Non-alcoholic fatty liver disease is highly associated with morbidity and mortality in population. Although studies have already demonstrated that the immune response plays a pivotal role in the development of non-alcoholic fatty liver disease, the comprehensive regulation is unclear. Therefore, present study was carried out to investigate the non-alcoholic fatty liver disease development under neutrophil depletion. To achieve the aim of the study, C57BL/6 J mice were fed with high fat diet for 6 weeks before treated with neutrophil deplete antibody 1A8 or isotype control (200 μg/ mouse every week) for another 4 weeks. Treated with 1A8 antibody, obese mice exhibited better whole body metabolic parameters, including reduction of body weight gain and fasting blood glucose levels. Neutrophil depletion also effectively reduced hepatic structural disorders, dysfunction and lipid accumulation. Lipid β-oxidative markers, phosphorylated-AMP-activated protein kinase α and phosphorylated-acetyl-CoA carboxylase levels were increased in 1A8 antibody-treated obese mouse group. The mitochondrial number and function were also reversed after 1A8 antibody treatment, including increased mitochondrial number, reduced lipid oxidative damage and enhanced mitochondrial activity. Furthermore, the expression of inflammatory cytokines, tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1 were obviously reduced after neutrophil depletion, accompanied with decreased F4/80 mRNA level and macrophage percentage in liver. The decreased NF-κB signaling activity was also involved in the beneficial effect of neutrophil depletion. Taken together, neutrophil depletion could attenuate metabolic syndromes and hepatic dysfunction.

Alcoholic epilepsy. A definition and a description of other convulsions related to alcoholism.

Science.gov (United States)

Yamane, H; Katoh, N

1981-01-01

The role of alcohol intake and withdrawal in so-called alcoholic epilepsy is discussed and illustrated by case reports. A classification is made which includes definitions of withdrawal convulsions, tetany-like withdrawal convulsions and alcohol-induced epileptic fits, with or without predisposing features.

Childhood sexual abuse history and role reversal in parenting.

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Alexander, P C; Teti, L; Anderson, C L

2000-06-01

This study explored the main and interactive effects of sexual abuse history and relationship satisfaction on self-reported parenting, controlling for histories of physical abuse and parental alcoholism. The community sample consisted of 90 mothers of 5- to 8-year-old children. The sample was limited to those mothers currently in an intimate relationship, 19 of whom reported a history of childhood sexual abuse. Participants completed the Child Behavior Checklist, the Parenting Stress Inventory, the Family Cohesion Index, and questions assessing parent-child role reversal, history of abuse and parental alcoholism, and current relationship satisfaction. Results of analyses and multivariate analyses of covariance suggested that sexual abuse survivors with an unsatisfactory intimate relationship were more likely than either sexual abuse survivors with a satisfactory relationship or nonabused women to endorse items on a questionnaire of role reversal (defined as emotional overdependence upon one's child). Role reversal was not significantly predicted by histories of physical abuse or parental alcoholism or child's gender. While parenting stress was inversely predicted by the significant main effect of relationship satisfaction, neither parenting stress nor child behavior problems were predicted by the main effect of sexual abuse history or by the interaction between sexual abuse history and relationship satisfaction. These results suggest the unique relevance of sexual abuse history and relationship satisfaction in the prediction of a specific type of parent-child role reversal--namely, a mother's emotional overdependence upon her child.

Long-term trends in alcohol policy attitudes in Norway.

Science.gov (United States)

Rossow, Ingeborg; Storvoll, Elisabet E

2014-05-01

The aim of this study was to describe trends in attitudes to alcohol control policies in Norway over a period of 50 years and to discuss how these trends relate to developments in alcohol policy. Survey data from 17 national population surveys, national statistics and previous publications were applied to describe trends in attitudes to alcohol control polices (access to alcohol and price) and changes in these policies over the period 1962 to 2012. From 1962 to 1999, an increasing proportion of the population reported that regulations on availability of alcohol were too strict and that alcohol prices were too high, whereas in the 2000s this trend was reversed and support for existing control policies increased. Although the pillars of Norwegian alcohol policy--high prices, restricted access and a state monopoly on retail sales-remained, control policies were gradually relaxed throughout the entire period. Relaxation of strict alcohol control policies in Norway in the first four decades were probably, in part, the result of increasingly liberal public opinion. The subsequent reversed trend in opinions with increasing support for control policies may be due to several factors, for example, consumer-oriented changes in the monopoly system, increased availability and affordability, increased awareness of alcohol-related harm and the effectiveness of control policies. Thus, the dynamics of policies and attitudes may well change over time. © 2013 Australasian Professional Society on Alcohol and other Drugs.

Opposite effects of alcohol in regulating stress-induced changes in body weight between the two mouse lines with enhanced or low opioid system activity.

Science.gov (United States)

Sacharczuk, Mariusz; Sadowski, Bogdan; Jaszczak, Kazimierz; Lipkowski, Andrzej W; Swiergiel, Artur H

2010-04-19

Considering the involvement of the opioid system in alcoholism, depression and metabolism - known risk factors in human obesity, we studied the effects of chronic mild stress (CMS) and alcohol intake on body weight in two mouse lines selected for high (HA-high analgesia) or low (LA-low analgesia) swim stress-induced analgesia. In comparison to LA mice, HA mice exhibit an upregulation of opioid receptor system function, different depression-like behavior and reduced energy expenditure in stress. LA animals showed enhanced basal and CMS-induced alcohol drinking versus HA. Now we report different effects of alcohol under no stress (control) and CMS conditions on food intake and body weight between the lines. CMS in animals with no access to alcohol increased body weight in both HA and LA mice, with no effect of CMS on food intake in either line and without differences between the lines. In LA mice alcohol reduced body weight under both conditions although significantly more under the control than CMS conditions. In contrast, in HA mice alcohol increased body weight more under the CMS than under control conditions. The results suggest that opioid system may modulate effects of alcohol on stress -induced changes in body weight. (c) 2010 Elsevier Inc. All rights reserved.

A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota.

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Watson, Henry; Mitra, Suparna; Croden, Fiona C; Taylor, Morag; Wood, Henry M; Perry, Sarah L; Spencer, Jade A; Quirke, Phil; Toogood, Giles J; Lawton, Clare L; Dye, Louise; Loadman, Paul M; Hull, Mark A

2017-09-26

Omega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal carcinogenesis. Dietary omega-3 PUFAs alter the mouse intestinal microbiome compatible with antineoplastic activity. Therefore, we investigated the effect of omega-3 PUFA supplements on the faecal microbiome in middle-aged, healthy volunteers (n=22). A randomised, open-label, cross-over trial of 8 weeks' treatment with 4 g mixed eicosapentaenoic acid/docosahexaenoic acid in two formulations (soft-gel capsules and Smartfish drinks), separated by a 12-week 'washout' period. Faecal samples were collected at five time-points for microbiome analysis by 16S ribosomal RNA PCR and Illumina MiSeq sequencing. Red blood cell (RBC) fatty acid analysis was performed by liquid chromatography tandem mass spectrometry. Both omega-3 PUFA formulations induced similar changes in RBC fatty acid content, except that drinks were associated with a larger, and more prolonged, decrease in omega-6 PUFA arachidonic acid than the capsule intervention (p=0.02). There were no significant changes in α or β diversity, or phyla composition, associated with omega-3 PUFA supplementation. However, a reversible increased abundance of several genera, including Bifidobacterium , Roseburia and Lactobacillus was observed with one or both omega-3 PUFA interventions. Microbiome changes did not correlate with RBC omega-3 PUFA incorporation or development of omega-3 PUFA-induced diarrhoea. There were no treatment order effects. Omega-3 PUFA supplementation induces a reversible increase in several short-chain fatty acid-producing bacteria, independently of the method of administration. There is no simple relationship between the intestinal microbiome and systemic omega-3 PUFA exposure. ISRCTN18662143. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless

Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in Mice

OpenAIRE

Hao, Lijun; Xie, Yuxi; Wu, Guikai; Cheng, Aibin; Liu, Xiaogang; Zheng, Rongjuan; Huo, Hong; Zhang, Junwei

2015-01-01

We investigated the effects of Hericium erinaceus (HEM) on liver injury induced by acute alcohol administration in mice. Mice received ethanol (5?g/kg?BW) by gavage every 12?hrs for a total of 3 doses. HEM (200?mg/kg?BW) was gavage before ethanol administration. Subsequent serum alanine aminotransferase (ALT) level, aspartate aminotransaminase (AST) level, Maleic dialdehyde (MDA) level, hepatic total antioxidant status (TAOS), and activated nuclear factor kappa-light-chain-enhancer of activat...

Alcohol abuse and docosahexaenoic acid: Effects on cerebral circulation and neurosurvival

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Michael A Collins

2015-01-01

Full Text Available Alcohol abuse and alcoholism are major and yet surprisingly unacknowledged worldwide causes of brain damage, cognitive impairment, and dementia. Chronic abuse of alcohol is likely to elicit significant changes in essential polyenoic fatty acids and the membrane phospholipids (PLs that covalently contain them in brain membranes. Among the fatty acids of the omega-3 polyenoic class, docosahexaenoic acid (DHA, which is relatively concentrated in mammalian brain, has proven particularly important for proper brain development as well as neurosurvival and protection. DHA losses in brains of chronic alcohol-treated animals may contribute to alcohol′s neuroinflammatory and neuropathological sequelae; indeed, DHA supplementation has beneficial effects, including the possibility that its documented augmenting effects on cerebral circulation could be important. The neurochemical mechanisms by which DHA exerts its effects encompass several signaling routes involving both the membrane PLs in which DHA is esterified as well as unique neuroactive metabolites of the free fatty acid itself. In view of indications that brain DHA deficits are a deleterious outcome of human alcoholism, increasing brain DHA via supplementation during detoxification of alcoholics could potentially fortify against dependence-related neuroinjury.

[Comparison of neostigmine induced reversal of rocuronium in different age children].

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Liu, Jinzhu; Cheng, Zhaoyu

2016-03-15

To compare the effectiveness of neostigmine induced reversal of rocuronium in neonates, infants, young children and children. One hundred and sixty ASA I or II pediatric patients undergoings elective surgical procedures under total intravenous anesthesia were enrolled during July 2014 to April 2015 in Tianjin Children's Hospital. The patients were divided into four groups according to ages: neonate group, infant group, young children group and children group.Then control subgroup and neostigmine reversal subgroup including twenty patients were randomly selected from every different age groups by the method of random number table. After induction of anesthesia, 0.6 mg/kg rocuronium was administered, and 0.2 mg/kg maintenance doses given as required during period of operation. Neuromuscular block was monitored using acceleromyographic train of four (TOF). When T1/control returned to 15%, 0.03 mg/kg neostigmine and 0.01 mg/kg atropine were given to patients of reversal subgroups, and saline 0.1 ml/kg was given to patients of control subgroups. The recovery time of T25, T75, TR0.7, recovery index, blood pressure, heart rate and adverse reactions were observed and recorded. In control subgroups, the recovery time of T75 for neonates, infants, young children and children were (27.10±8.72), (16.70±6.35), (13.05±1.96), (14.40±3.08) min, respectively (F=25.052, P0.05). But the recovery time of T75, TR0.7 and recovery index in neonate group were longer than other age groups (all Procuronium are comparable in infant, young children and children. There are obviously reversal effects in all of age groups when neostigmine is given to antagonize rocuronium. Either spontaneous recovery time or reversal recovery time of neostigmine to rocuronium is longer for neonates than other age's children.

Effects of symbiotic and vitamin E supplementation on blood pressure, nitric oxide and inflammatory factors in non-alcoholic fatty liver disease.

Science.gov (United States)

Ekhlasi, Golnaz; Zarrati, Mitra; Agah, Shahram; Hosseini, Agha Fatemeh; Hosseini, Sharieh; Shidfar, Shahrzad; Soltani Aarbshahi, Seyed Soroush; Razmpoosh, Elham; Shidfar, Farzad

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) has been suggested to be well correlated with altered blood pressure. This study was conducted to determine the effects of symbiotic and vitamin E supplementation on blood pressure and inflammatory indices of patients with NAFLD. This randomized, double-blind, placebo-controlled trial was performed among 60 NAFLD patients aged 25 to 64 years old. Participants were randomly divided into four groups to receive a 400 IU alpha-tocopherol and 2 × 10 8 CFU/g symbiotic supplement for 8 weeks. The anthropometric parameters, systolic blood pressure (SBP) and diastolic blood pressure (DBP), serum malondialdehyde (MDA), nitric oxide (NO) and tumor necrosis factor α (TNFα) were assessed at baseline and after 8 weeks of intervention. After 8 weeks of intervention, combined symbiotic and alpha-tocopherol, symbiotic and alpha-tocopherol alone administration, compared with the placebo, resulted in significant decreases in SBP (-17.07±2.1, -16.07±3.56, -1.73±2.25 and -1.55±3.01 mmHg, P=0.01), serum MDA (-1.19±0.5, -0.12±0.65, 0.14 ± 0.64 and 0.16±0.34 nmol/mL, Psymbiotic supplementation among patients with NAFLD resulted in decreased SBP, serum MDA, TNFα levels and enzymes liver; however, they did not affect DBP and serum NO concentration.

Mediterranean Diet and Multi-Ingredient-Based Interventions for the Management of Non-Alcoholic Fatty Liver Disease

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Manuel Suárez

2017-09-01

Full Text Available Non-alcoholic fatty liver disease (NAFLD comprises a wide spectrum of hepatic disorders, from simple steatosis to hepatic necro-inflammation leading to non-alcoholic steatohepatitis (NASH. Although the prevalence of these multifactorial pathologies is continuously increasing in the population, there is still not an established methodology for their treatment other than weight loss and a change in lifestyle habits, such as a hypocaloric diet and physical exercise. In this framework, there is increasing evidence that several food bioactives and dietary patterns are effective for reversing and preventing the onset of these pathologies. Some studies have claimed that better responses are obtained when treatments are performed under a multifaceted approach, using different bioactive compounds that act against complementary targets. Thus, in this work, current strategies for treating NAFLD and NASH based on multi-ingredient-based supplements or the Mediterranean diet, a dietary pattern rich in bioactive compounds, are reviewed. Furthermore, the usefulness of omics techniques to design effective multi-ingredient nutritional interventions and to predict and monitor their response against these disorders is also discussed.

Mediterranean Diet and Multi-Ingredient-Based Interventions for the Management of Non-Alcoholic Fatty Liver Disease

Science.gov (United States)

Suárez, Manuel; Boqué, Noemí; del Bas, Josep M.; Arola, Lluís; Caimari, Antoni

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) comprises a wide spectrum of hepatic disorders, from simple steatosis to hepatic necro-inflammation leading to non-alcoholic steatohepatitis (NASH). Although the prevalence of these multifactorial pathologies is continuously increasing in the population, there is still not an established methodology for their treatment other than weight loss and a change in lifestyle habits, such as a hypocaloric diet and physical exercise. In this framework, there is increasing evidence that several food bioactives and dietary patterns are effective for reversing and preventing the onset of these pathologies. Some studies have claimed that better responses are obtained when treatments are performed under a multifaceted approach, using different bioactive compounds that act against complementary targets. Thus, in this work, current strategies for treating NAFLD and NASH based on multi-ingredient-based supplements or the Mediterranean diet, a dietary pattern rich in bioactive compounds, are reviewed. Furthermore, the usefulness of omics techniques to design effective multi-ingredient nutritional interventions and to predict and monitor their response against these disorders is also discussed. PMID:28937599

PROTECTIVE EFFECTS OF HYPOTHALAMIC BETA-ENDORPHIN NEURONS AGAINST ALCOHOL-INDUCED LIVER INJURIES AND LIVER CANCERS IN RAT ANIMAL MODELS

Science.gov (United States)

Murugan, Sengottuvelan; Boyadjieva, Nadka; Sarkar, Dipak K.

2014-01-01

Background Recently, retrograde tracing has provided evidence for an influence of hypothalamic β-endorphin (BEP) neurons on the liver, but functions of these neurons are not known. We evaluated the effect of BEP neuronal activation on alcohol-induced liver injury and hepatocellular cancer. Methods Male rats received either BEP neuron transplants or control transplants in the hypothalamus and randomly assigned to feeding alcohol-containing liquid diet or control liquid diet for 8 weeks or to treatment of a carcinogen diethylnitrosamine (DEN). Liver tissues of these animals were analyzed histochemically and biochemically for tissue injuries or cancer. Results Alcohol-feeding increased liver weight and induced several histopathological changes such as prominent microvesicular steatosis and hepatic fibrosis. Alcohol feeding also increased protein levels of triglyceride, hepatic stellate cell activation factors and catecholamines in the liver and endotoxin levels in the plasma. However, these effects of alcohol on the liver were reduced in animals with BEP neuron transplants. BEP neuron transplants also suppressed carcinogen-induced liver histopathologies such as extensive fibrosis, large focus of inflammatory infiltration, hepatocelluar carcinoma, collagen deposition, numbers of preneoplastic foci, levels of hepatic stellate cell activation factors and catecholamines, as well as inflammatory milieu and the levels of NK cell cytotoxic factors in the liver. Conclusion These findings are the first evidence for a role of hypothalamic BEP neurons in influencing liver functions. Additionally, the data identify that BEP neuron transplantation prevents hepatocellular injury and hepatocellular carcinoma formation possibly via influencing the immune function. PMID:25581653

Antihypertensive Effect of Radix Paeoniae Alba in Spontaneously Hypertensive Rats and Excessive Alcohol Intake and High Fat Diet Induced Hypertensive Rats

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Chen Su-Hong

2015-01-01

Full Text Available Radix Paeoniae Alba (Baishao, RPA has long been used in traditional Chinese medicine formulation to treat hypertension by repression the hyperfunction of liver. However, whether the RPA itself has the antihypertensive effect or not is seldom studied. This study was to evaluate the protective effect of RPA on hypertensive rats. Alcohol in conjunction with a high fat diet- (ACHFD- induced hypertensive rats and spontaneously hypertensive rats (SHR was constantly received either RPA extract (25 or 75 mg/kg or captopril (15 mg/kg all along the experiments. As a result, RPA extract (75 mg/kg could significantly reduce systolic blood pressure of both ACHFD-induced hypertensive rats and SHR after 9-week or 4-week treatment. In ACHFD-induced hypertensive rats, the blood pressure was significantly increased and the lipid profiles in serum including triglyceride, total cholesterol, LDL-cholesterol, and HDL-cholesterol were significantly deteriorated. Also, hepatic damage was manifested by a significant increase in alanine transaminase (ALT and aspartate transaminase (AST in serum. The RPA extract significantly reversed these parameters, which revealed that it could alleviate the liver damage of rats. In SHR, our result suggested that the antihypertensive active of RPA extract may be related to its effect on regulating serum nitric oxide (NO and endothelin (ET levels.

Protective role of ginkgo Biloba extract against gamma radiation and alcohol induced liver damage in albino rats

International Nuclear Information System (INIS)

Fahmy, N. M.; Mohamed, E.T.; Mansour, H.H; Hafez, H.F.

2007-01-01

Ginkgo biloba extract (EGb 761) is a standardized extract of Ginkgo biloba leaves that promotes vasodilatation and improves blood flow through arteries, veins and capillaries and has antioxidant properties as a tree radical scavenger. This study was designed to evaluate the protective efficacy of EGb 761 against gamma radiation and/ or alcohol induced disorders in the liver of male albino rats. EGb 761 was given orally at a dose level of 100 mg/ kg body wt for 4 days, absolute alcohol was administered orally at a dose level of 1ml/ rat for 4 days and the dose of gamma radiation was 6.5 Gy. All animals were subjected to the following investigations: nitric oxide (NO), superoxide dismutase (SOD), malonaldehyde (MDA). reduced glutathion (GSH) and glutathione peroxidase (GSHPx) in the liver tissue. In irradiated and/ or alcoholic animal groups, there was a highly significant decrease in liver NO and GSH content and in the activities of GSHPx and SOD. On the other hand, significant increase in MDA content was observed. Treatment with EGb 761 before irradiation and/or alcohol causes significant increase in NO and GSH content and in the activities of GSHPx and SOD and significant decrease in MDA content compared to the irradiated and/ or alcoholic groups. Based on these observations, one could conclude that pre-treatment of rats with EGb 761 could partly protect liver from gamma rays and/ or absolute alcohol injurious and this protection may be induced, at least partly, through antioxidant mechanisms

Phosphatidylcholine reverses ethanol-induced increase in transepithelial endotoxin permeability and abolishes transepithelial leukocyte activation

DEFF Research Database (Denmark)

Mitscherling, K.; Volynets, V.; Parlesak, Alexandr

2009-01-01

BACKGROUND: Chronic alcohol abuse increases both intestinal bacterial overgrowth and intestinal permeability to macromolecules. Intestinal permeability of endotoxin, a component of the outer cell membrane of Gram-negative bacteria, plays a crucial role in the development of alcohol-induced liver...... disease (ALD). As impaired bile flow leads to endotoxemia and the bile component phosphatidylcholine (PC) is therapeutically active in ALD, we tested the hypothesis that conjugated primary bile salts (CPBS) and PC inhibit ethanol-enhanced transepithelial permeability of endotoxin and the subsequent...... transepithelial activation of human leukocytes. METHODS: For this purpose, we used a model in which intestinal epithelial cells (Caco-2) were basolaterally cocultivated with mononuclear leukocytes. Cells were challenged apically with endotoxin from Escherichia coli K12 and were incubated with or without...

Pathological mechanisms of alcohol-induced hepatic portal hypertension in early stage fibrosis rat model.

Science.gov (United States)

Li, Jian; Niu, Jian-Zhao; Wang, Ji-Feng; Li, Yu; Tao, Xiao-Hua

2005-11-07

To study the role of hepatic sinusoidal capillarization and perisinusoidal fibrosis in rats with alcohol-induced portal hypertension and to discuss the pathological mechanisms of alcohol-induced hepatic portal hypertension. Fifty SD rats were divided into control group (n=20) and model group (n=30). Alcoholic liver fibrosis rat model was induced by intragastric infusion of a mixture containing alcohol, corn oil and pyrazole (1 000:250:3). Fifteen rats in each group were killed at wk 16. The diameter and pressure of portal vein were measured. Plasma hyaluronic acid (HA), type IV collagen (CoIV) and laminin (LN) were determined by radioimmunoassay. Liver tissue was fixed in formalin (10%) and 6-mum thick sections were routinely stained with Mallory and Sirius Red. Liver tissue was treated with rabbit polyclonal antibody against LN and ColIV. Hepatic non-parenchymal cells were isolated, total protein was extracted and separated by SDS-PAGE. MMP-2 and TIMP-1 protein expression was estimated by Western blotting. The diameter (2.207+/-0.096 vs 1.528+/-0.054 mm, Pportal vein were significantly higher in model group than those in the control group. Plasma HA (129.97+/-16.10 vs 73.09+/-2.38 ng/mL, Pmodel group. Abundant collagen deposited around the central vein of lobules, hepatic sinusoids and hepatocytes in model group. ColI and ColIII increased remarkably and perisinusoids were almost surrounded by ColIII. Immunohistochemical staining showed that ColIV protein level (0.130+/-0.007 vs 0.032+/-0.004, Pprotein level (0.152+/-0.005 vs 0.029+/-0.005, Pmodel group. MMP-2 protein expression (2.306+/-1.089 vs 0.612+/-0.081, Pprotein expression (3.015+/-1.364 vs 0.446+/-0.009, Pmodel group and TIMP-1 protein expression was evidently higher than MMP-2 protein expression (2.669+/-0.170 vs 1.695+/-0.008, Pportal hypertension in rats.

Lactobacillus rhamnosus strain JB-1 reverses restraint stress-induced gut dysmotility.

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West, C; Wu, R Y; Wong, A; Stanisz, A M; Yan, R; Min, K K; Pasyk, M; McVey Neufeld, K-A; Karamat, M I; Foster, J A; Bienenstock, J; Forsythe, P; Kunze, W A

2017-01-01

Environmental stress affects the gut with dysmotility being a common consequence. Although a variety of microbes or molecules may prevent the dysmotility, none reverse the dysmotility. We have used a 1 hour restraint stress mouse model to test for treatment effects of the neuroactive microbe, L. rhamnosus JB-1 ™ . Motility of fluid-filled ex vivo gut segments in a perfusion organ bath was recorded by video and migrating motor complexes measured using spatiotemporal maps of diameter changes. Stress reduced jejunal and increased colonic propagating contractile cluster velocities and frequencies, while increasing contraction amplitudes for both. Luminal application of 10E8 cfu/mL JB-1 restored motor complex variables to unstressed levels within minutes of application. L. salivarius or Na.acetate had no treatment effects, while Na.butyrate partially reversed stress effects on colonic frequency and amplitude. Na.propionate reversed the stress effects for jejunum and colon except on jejunal amplitude. Our findings demonstrate, for the first time, a potential for certain beneficial microbes as treatment of stress-induced intestinal dysmotility and that the mechanism for restoration of function occurs within the intestine via a rapid drug-like action on the enteric nervous system. © 2016 John Wiley & Sons Ltd.

Dietary L-carnitine supplementation in obese cats alters carnitine metabolism and decreases ketosis during fasting and induced hepatic lipidosis.

Science.gov (United States)

Blanchard, Géraldine; Paragon, Bernard M; Milliat, Fabien; Lutton, Claude

2002-02-01

This study was designed to determine whether dietary carnitine supplement could protect cats from ketosis and improve carnitine and lipid metabolism in experimental feline hepatic lipidosis (FHL). Lean spayed queens received a diet containing 40 (CL group, n = 7) or 1000 (CH group, n = 4) mg/kg of L-carnitine during obesity development. Plasma fatty acid, beta-hydroxybutyrate and carnitine, and liver and muscle carnitine concentrations were measured during experimental induction of FHL and after treatment. In control cats (CL group), fasting and FHL increased the plasma concentrations of fatty acids two- to threefold (P 10-fold (from a basal 0.22 +/- 0.03 to 1.70 +/- 0.73 after 3 wk fasting and 3.13 +/- 0.49 mmol/L during FHL). In carnitine-supplemented cats, these variables increased significantly (P < 0.0001) only during FHL (beta-hydroxybutyrate, 1.42 +/- 0.17 mmol/L). L-Carnitine supplementation significantly increased plasma, muscle and liver carnitine concentrations. Liver carnitine concentration increased dramatically from the obese state to FHL in nonsupplemented cats, but not in supplemented cats, which suggests de novo synthesis of carnitine from endogenous amino acids in control cats and reversible storage in supplemented cats. These results demonstrate the protective effect of a dietary L-carnitine supplement against fasting ketosis during obesity induction. Increasing the L-carnitine level of diets in cats with low energy requirements, such as after neutering, and a high risk of obesity could therefore be recommended.

Protective effect of pineapple (Ananas cosmosus peel extract on alcohol-induced oxidative stress in brain tissues of male albino rats

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Ochuko L Erukainure

2011-03-01

Full Text Available Objective: To investigate the ability of pineapple peels to protect against alcohol-induced oxidative stress in brain tissues using male albino rat models. Methods: Response surface methodology (RSM was used to design a series of experiments to optimize treatment conditions with the aim of investigating the protective effect of pineapple peel extract on alcohol-induced oxidative stress in brain tissues. Oxidative stress was induced by oral administration of ethanol (20% w/v at a dosage of 5 mL/kg bw. The treatment lasted for 28 days. At the end of the treatment, the rats were fasted overnight and sacrificed by cervical dislocation. Tissue homogenates were used for the assessment of protein concentration, reduced glutathione (GSH content, catalase, and SOD. Results: Alcohol administration caused a significant decrease (P>0.05 in GSH level in the group which was only fed alcohol. Treatment with pineapple peel extracts caused increase in GSH level in alcohol fed groups. No significant difference (P<0.05 was observed in SOD levels of the negative control and group fed on only pineapple peel extract. Elevated level of catalase was observed in the negative control but pineapple peel extract significantly reduced the levels. Conclusions: This study indicates the protective effect of pineapple peel against alcoholinduced oxidative stress in brain tissues.

Rapid development of non-alcoholic steatohepatitis in Psammomys obesus (Israeli sand rat.

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Briana Spolding

Full Text Available BACKGROUND AND AIMS: A major impediment to establishing new treatments for non-alcoholic steatohepatitis is the lack of suitable animal models that accurately mimic the biochemical and metabolic characteristics of the disease. The aim of this study was to explore a unique polygenic animal model of metabolic disease as a model of non-alcoholic steatohepatitis by determining the effects of 2% dietary cholesterol supplementation on metabolic and liver endpoints in Psammomys obesus (Israeli sand rat. METHODS: P. obesus were provided ad libitum access to either a standard rodent diet (20% kcal/fat or a standard rodent diet supplemented with 2% cholesterol (w/w for 4 weeks. Histological sections of liver from animals on both diets were examined for key features of non-alcoholic steatohepatitis. The expression levels of key genes involved in hepatic lipid metabolism were measured by real-time PCR. RESULTS: P. obesus fed a cholesterol-supplemented diet exhibited profound hepatomegaly and steatosis, and higher plasma transaminase levels. Histological analysis identified extensive steatosis, inflammation, hepatocyte injury and fibrosis. Hepatic gene expression profiling revealed decreased expression of genes involved in delivery and uptake of lipids, and fatty acid and triglyceride synthesis, and increased expression of genes involved in very low density lipoprotein cholesterol synthesis, triglyceride and cholesterol export. CONCLUSIONS: P. obesus rapidly develop non-alcoholic steatohepatitis when fed a cholesterol-supplemented diet that appears to be histologically and mechanistically similar to patients.

Whole brain radiation-induced impairments in learning and memory are time-sensitive and reversible by systemic hypoxia.

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Junie P Warrington

Full Text Available Whole brain radiation therapy (WBRT is commonly used for treatment of primary and metastatic brain tumors; however, cognitive impairment occurs in 40-50% of brain tumor survivors. The etiology of the cognitive impairment following WBRT remains elusive. We recently reported that radiation-induced cerebrovascular rarefaction within hippocampal subregions could be completely reversed by systemic hypoxia. However, the effects of this intervention on learning and memory have not been reported. In this study, we assessed the time-course for WBRT-induced impairments in contextual and spatial learning and the capacity of systemic hypoxia to reverse WBRT-induced deficits in spatial memory. A clinical fractionated series of 4.5Gy WBRT was administered to mice twice weekly for 4 weeks, and after various periods of recovery, behavioral analyses were performed. To study the effects of systemic hypoxia, mice were subjected to 11% (hypoxia or 21% oxygen (normoxia for 28 days, initiated 1 month after the completion of WBRT. Our results indicate that WBRT induces a transient deficit in contextual learning, disruption of working memory, and progressive impairment of spatial learning. Additionally, systemic hypoxia completely reversed WBRT-induced impairments in learning and these behavioral effects as well as increased vessel density persisted for at least 2 months following hypoxia treatment. Our results provide critical support for the hypothesis that cerebrovascular rarefaction is a key component of cognitive impairment post-WBRT and indicate that processes of learning and memory, once thought to be permanently impaired after WBRT, can be restored.

Is nutrient intake a gender-specific cause for enhanced susceptibility to alcohol-induced liver disease in women?

DEFF Research Database (Denmark)

Wagnerberger, S.; Schäfer, C.; Schwarz, E.

2008-01-01

AIM: Women have a higher susceptibility to alcohol-induced liver disease (ALD) than men. Gender-related differences in food preference were described in previous studies for several populations, but not in alcohol abusers. As certain micronutrients are reported to take influence on the development......, the data of calculated daily macro- and micronutrient intake do not suggest any explicit influence of gender-specific nutrition in the development of ALD....

Taurine supplementation attenuates delayed increase in exercise-induced arterial stiffness.

Science.gov (United States)

Ra, Song-Gyu; Choi, Youngju; Akazawa, Nobuhiko; Ohmori, Hajime; Maeda, Seiji

2016-06-01

There is a delayed increase in arterial stiffness after eccentric exercise that is possibly mediated by the concurrent delayed increase in circulating oxidative stress. Taurine has anti-oxidant action, and taurine supplementation may be able to attenuate the increase in oxidative stress after exercise. The purpose of the present study was to investigate whether taurine supplementation attenuates the delayed increase in arterial stiffness after eccentric exercise. In the present double-blind, randomized, and placebo-controlled trial, we divided 29 young, healthy men into 2 groups. Subjects received either 2.0 g of placebo (n = 14) or taurine (n = 15) 3 times per day for 14 days prior to the exercise, on the day of exercise, and the following 3 days. The exercise consisted of 2 sets of 20 maximal-effort eccentric repetitions with the nondominant arm only. On the morning of exercise and for 4 days thereafter, we measured serum malondialdehyde (MDA) and carotid-femoral pulse wave velocity (cfPWV) as indices of oxidative stress and arterial stiffness, respectively. On the third and fourth days after exercise, both MDA and cfPWV significantly increased in the placebo group. However, these elevations were significantly attenuated in the taurine group. The increase in MDA was associated with an increase in cfPWV from before exercise to 4 days after exercise (r = 0.597, p taurine group. Our results suggest that delayed increase in arterial stiffness after eccentric exercise was probably affected by the exercise-induced oxidative stress and was attenuated by the taurine supplementation.

Alcohol-induced blackout as a criminal defense or mitigating factor: an evidence-based review and admissibility as scientific evidence.

Science.gov (United States)

Pressman, Mark R; Caudill, David S

2013-07-01

Alcohol-related amnesia--alcohol blackout--is a common claim of criminal defendants. The generally held belief is that during an alcohol blackout, other cognitive functioning is severely impaired or absent. The presentation of alcohol blackout as scientific evidence in court requires that the science meets legal reliability standards (Frye, FRE702/Daubert). To determine whether "alcohol blackout" meets these standards, an evidence-based analysis of published scientific studies was conducted. A total of 26 empirical studies were identified including nine in which an alcohol blackout was induced and directly observed. No objective or scientific method to verify the presence of an alcoholic blackout while it is occurring or to confirm its presence retrospectively was identified. Only short-term memory is impaired and other cognitive functions--planning, attention, and social skills--are not impaired. Alcoholic blackouts would not appear to meet standards for scientific evidence and should not be admissible. © 2013 American Academy of Forensic Sciences.

Comparative effects of curcumin and an analog of curcumin on alcohol and PUFA induced oxidative stress.

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Rukkumani, Rajagopalan; Aruna, Kode; Varma, Penumathsa Suresh; Rajasekaran, Kallikat Narayanan; Menon, Venugopal Padmanabhan

2004-08-20

Alcoholic liver disease is a major medical complication of alcohol abuse and a common liver disease in western countries. Increasing evidence demonstrates that oxidative stress plays an important etiologic role in the development of alcoholic liver disease. Alcohol alone or in combination with high fat is known to cause oxidative injury. The present study therefore aims at evaluating the protective role of curcumin, an active principle of turmeric and a synthetic analog of curcumin (CA) on alcohol and thermally oxidised sunflower oil (DeltaPUFA) induced oxidative stress. Male albino Wistar rats were used for the experimental study. The liver marker enzymes: gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), the lipid peroxidative indices: thiobarbituric acid reactive substances (TBARS) and hydroperoxides (HP) and antioxidants such as vitamin C, vitamin E, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) were used as biomarkers for testing the antioxidant potential of the drugs. The liver marker enzymes and lipid peroxidative indices were increased significantly in alcohol, DeltaPUFA and alcohol + DeltaPUFA groups. Administration of curcumin and CA abrograted this effect. The antioxidant status which was decreased in alcohol, DeltaPUFA and alcohol + DeltaPUFA groups was effectively modulated by both curcumin and CA treatment. However, the reduction in oxidative stress was more pronounced in CA treatment groups compared to curcumin. In conclusion, these observations show that CA exerts its protective effect by decreasing the lipid peroxidation and improving antioxidant status, thus proving itself as an effective antioxidant.

DRUG REACTION WITH HERBAL SUPPLEMENT: A POSSIBLE CASE OF DRUG INDUCED LUPUS ERYTHEMATOSUS

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AZIZ NA

2010-01-01

Full Text Available A 24-year-old lady presented with four days history of fever, non-pruritic rash, ankle pain and swelling. She had consumed herbal supplement five days before the onset of symptoms. Examinations revealed erythematous maculo-papular lesions of varying sizes on sun exposed areas. Patient was suspected to have Drug Induced Lupus Erythematosus (DILE and subsequently symptoms subsided rapidly on withholding the herbal medication.

Cysteine Supplementation May be Beneficial in a Subgroup of Mitochondrial Translation Deficiencies.

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Bartsakoulia, Marina; Mϋller, Juliane S; Gomez-Duran, Aurora; Yu-Wai-Man, Patrick; Boczonadi, Veronika; Horvath, Rita

2016-08-30

Mitochondrial encephalomyopathies are severe, relentlessly progressive conditions and there are very few effective therapies available to date. We have previously suggested that in two rare forms of reversible mitochondrial disease (reversible infantile respiratory chain deficiency and reversible infantile hepatopathy) supplementation with L-cysteine can improve mitochondrial protein synthesis, since cysteine is required for the 2-thiomodification of mitochondrial tRNAs. We studied whether supplementation with L-cysteine or N-acetyl-cysteine (NAC) results in any improvement of the mitochondrial function in vitro in fibroblasts of patients with different genetic forms of abnormal mitochondrial translation. We studied in vitro in fibroblasts of patients carrying the common m.3243A>G and m.8344A>G mutations or autosomal recessive mutations in genes affecting mitochondrial translation, whether L-cysteine or N-acetyl-cysteine supplementation have an effect on mitochondrial respiratory chain function. Here we show that supplementation with L-cysteine, but not with N-acetyl-cysteine partially rescues the mitochondrial translation defect in vitro in fibroblasts of patients carrying the m.3243A>G and m.8344A>G mutations. In contrast, N-acetyl-cysteine had a beneficial effect on mitochondrial translation in TRMU and MTO1 deficient fibroblasts. Our results suggest that L-cysteine or N-acetyl-cysteine supplementation may be a potential treatment for selected subgroups of patients with mitochondrial translation deficiencies. Further studies are needed to explore the full potential of cysteine supplementation as a treatment for patients with mitochondrial disease.

Speman®, A Proprietary Ayurvedic Formulation, Reverses Cyclophosphamide-Induced Oligospermia In Rats.

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Mohd. Azeemuddin Mukram

2013-04-01

Full Text Available Background: This investigation was aimed to evaluate the effect of Speman®, a well known ayurvedic proprietary preparation, in an experimental model of cyclophosphamide-(CP induced oligospermia in rats.Materials and Methods: Thirty male rats were randomized in to five, equally-sized groups. Rats in group 1 served as a normal control; group 2 served as an untreated positive control; groups 3, 4, 5 received  Speman® granules  at doses of 300, 600, and 900mg/kg body weight p.o. respectively, once daily for 13 days. On day four, one hour after the respective treatment, oligospermia was induced by administering a single dose of CP (100mg/kg body weight p.o.  to all the groups except group1. At the end of the study period the rats were euthanised and accessory reproductive organs were weighed and subjected to histopathological examination. The semen samples were subject to enumeration of sperms.  Weight of the reproductive organs, histopathological examination of the tissues, and sperm count were the parameters studied to understand the effect of Speman® on rats with CP-induced oligospermia.Results: Changes that occurred due to the administration of CP at a dose of 100 mg/kg body weight were dose dependently reversed with Speman® at a dose of 300, 600, and 900 mg/kg body weight. There was a statistically significant increase in sperm count and the weight of the seminal vesicle, epididymis, and prostate.Conclusion: Findings of this investigation indicate that Speman® dose dependently reversed the CP-induced derangement of various parameters pertaining to the reproductive system.  This could explain the total beneficial actions of Speman® reported in several other clinical trials.

A Comparison Study of Quetiapine and Risperidone's Effectiveness and Safety on Treating Alcohol-induced Mental Disorder.

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Lv, Bei; Duan, Haishui

2016-08-25

Compared with Risperidone, Quetiapine's effectiveness and safety on treating alcohol-induced mental disorder is still unclear. To investigate the clinical effectiveness and safety of Quetiapine on treating alcohol-induced mental disorder. One hundred and forty-eight patients with alcohol-induced mental disorder were divided into the experimental group (75 patients) and the control group (73 patients) by the treatments they received. The patients in the experimental group were treated with Quetiapine by taking it three times per day orally. The mean (sd) maintenance dose was 151.2(27.3) mg/d, and the treatment cycle was 6 weeks. Patients in the control group received Risperidone once per day orally with a mean (sd) maintenance dose being 2.3(0.9) mg/d, and the treatment cycle was 6 weeks as well. The PANSS scale was used to assess patients' before and after treatment. The researchers also observed any adverse reactions in both treatment strategies and evaluated the effectiveness and safety of both treatment strategies. The mean (sd) PANSS scale score of the experimental group after two weeks of treatment was 71.9 (10.2), which was clearly better than the mean (sd) score before treatment (82.6 [11.4]), and was significantly better than the control group's mean (sd) score after two weeks (76.5[12.8]). Also, the experimental group's scores after 4 weeks of treatment and 6 weeks of treatment were significantly better than the control group. The experimental group's efficacy rate (94.7%) was higher than the control group's (90.4%); the cure rate of the experimental group (33.3%) was higher than that of the control group (24.7%), and the difference was statistically significant. The rates of adverse reactions in the experimental and control groups were 13.3% and 19.2% respectively, and they were significantly different from each other. Treating alcohol-induced mental disorder with Quetiapine is more effective than treating it with Risperidone. Quetiapine can improve

Reversal of sodium pump inhibitor induced vascular smooth muscle contraction with digibind. Stoichiometry and its implications.

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Krep, H H; Graves, S W; Price, D A; Lazarus, M; Ensign, A; Soszynski, P A; Hollenberg, N K

1996-01-01

The possibility that a circulating sodium pump inhibitor contributes to the pathogenesis of volume-dependent hypertension via an action on vascular smooth muscle (VSM) is supported by multiple lines of investigation, but remains controversial. We had two goals in this study. The first was to compare the pattern of contractile response of rabbit aorta induced by two candidates, ouabain and a labile sodium pump inhibitor that we have identified in the peritoneal dialysate of volume-expanded hypertensive patients with chronic renal failure. Our second goal was to examine the ability of Digibind, a Fab fragment of antisera directed against digoxin, to reverse VSM contraction induced by both agents. Ouabain induced a concentration-dependent contraction, which was delayed in onset, was gradual, and reached a stable plateau after many hours. The labile sodium pump inhibitor induced a qualitatively similar series of responses. Digibind rapidly reversed the contractile responses to both sodium pump inhibitors, with a rate of relaxation that matched that induced by physical removal of the pump inhibitor from the bath. For ouabain, the Digibind:ouabain stoichiometry was highly predictable. When Digibind was present in a molar concentration equivalent to that of ouabain, or less, it had no effect. When the Digibind concentration was twice that of ouabain, complete relaxation occurred. Although the concentration:VSM response relationship for ouabain was steep, the concentration:effect interaction with Digibind was even more steep. The molar concentration of Digibind required to reverse the effects of the labile endogenous inhibitor from peritoneal dialysate was consistently lower than that for ouabain, which is compatible with either greater potency of the labile factor in VSM or greater affinity for Digibind. These findings are compatible with a role for one or more endogenous sodium pump inhibitors as the determinant of vascular smooth muscle tone in the volume

Alcohol induced osteopenia

International Nuclear Information System (INIS)

Keck, E.; Bremer, G.; Franck, H.

1986-01-01

There is a clear evidence of a propensity to fractures and the development of osteomalacia, osteoporosis, and mixed forms in chronic alcoholics. Osteomalacia is associated with impaired vitamin D status, probably due to enzyme induction in liver and kidney and development of a secondary intestinal hyperparathyroidism. The development of osteoporosis is multifactorial, but seems to arise mainly through reduction in bone formation and reduced dietary protein and calcium intake. Low testosterone levels may also contribute to osteoporosis. (orig.) [de

Alcohol induced osteopenia

Energy Technology Data Exchange (ETDEWEB)

Keck, E.; Bremer, G.; Franck, H.

1986-12-01

There is a clear evidence of a propensity to fractures and the development of osteomalacia, osteoporosis, and mixed forms in chronic alcoholics. Osteomalacia is associated with impaired vitamin D status, probably due to enzyme induction in liver and kidney and development of a secondary intestinal hyperparathyroidism. The development of osteoporosis is multifactorial, but seems to arise mainly through reduction in bone formation and reduced dietary protein and calcium intake. Low testosterone levels may also contribute to osteoporosis.

Striatal modulation of BDNF expression using microRNA124a-expressing lentiviral vectors impairs ethanol-induced conditioned-place preference and voluntary alcohol consumption.

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Bahi, Amine; Dreyer, Jean-Luc

2013-07-01

Alcohol abuse is a major health, economic and social concern in modern societies, but the exact molecular mechanisms underlying ethanol addiction remain elusive. Recent findings show that small non-coding microRNA (miRNA) signaling contributes to complex behavioral disorders including drug addiction. However, the role of miRNAs in ethanol-induced conditioned-place preference (CPP) and voluntary alcohol consumption has not yet been directly addressed. Here, we assessed the expression profile of miR124a in the dorsal striatum of rats upon ethanol intake. The results show that miR124a was downregulated in the dorso-lateral striatum (DLS) following alcohol drinking. Then, we identified brain-derived neurotrophic factor (BDNF) as a direct target of miR124a. In fact, BDNF mRNA was upregulated following ethanol drinking. We used lentiviral vector (LV) gene transfer technology to further address the role of miR124a and its direct target BDNF in ethanol-induced CPP and alcohol consumption. Results reveal that stereotaxic injection of LV-miR124a in the DLS enhances ethanol-induced CPP as well as voluntary alcohol consumption in a two-bottle choice drinking paradigm. Moreover, miR124a-silencer (LV-siR124a) as well as LV-BDNF infusion in the DLS attenuates ethanol-induced CPP as well as voluntary alcohol consumption. Importantly, LV-miR124a, LV-siR124a and LV-BDNF have no effect on saccharin and quinine intake. Our findings indicate that striatal miR124a and BDNF signaling have crucial roles in alcohol consumption and ethanol conditioned reward. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Reversion of thyrotoxic atrial fibrillation in hypothyroid state after radioiodine treatment

Energy Technology Data Exchange (ETDEWEB)

Yamamoto, Makiko; Saito, Shintaro; Sakurada, Toshiro; Yoshida, Katsumi; Kaise, Kazuro; Kaise, Nobuko; Fukazawa, Hiroshi; Itagaki, Yoichi; Yoshinaga, Kaoru [Tohoku Univ., Sendai (Japan). School of Medicine

1992-06-01

Twenty patients with thyrotoxic Basedow's disease complicated by atrial fibrillation lasting more than one month despite treatment with antithyroidal drugs were treated with radioiodine supplemented with an antithyroidal drug or inorganic iodine. We classified the 20 patients on the basis of strial fibrillation reversion into two groups, one with reversion (group I) and the other without reversion (group II). In all 12 patients in group I, T{sub 4} and T{sub 3} decreased to hypothyroid levels in 3.2{+-}1.3 months, and one month later all patients had their sinus rhythm restored while T{sub 4} and T{sub 3} also remained below normal (2.6{+-}1.1 {mu}g/dl and 77.9{+-}34.4 ng/dl, respectively). Although T{sub 4} and T{sub 3} also decreased within 3.5{+-}1.8 months in all 8 patients in group II, one month later, atrial fibrillation persisted while T{sub 4} and T{sub 3} (10.4{+-}5.3 {mu}g/dl and 157.7{+-}67.5 ng/dl, respectively) rose significantly compared to those in group I (p<0.001 and p<0.01, respectively). For reversion of atrial fibrillation it is important that the onset of hypothyroidism is rapidly induced by radioiodine and that hypothyroidism continues for at least one month. (author).

Reversion of thyrotoxic atrial fibrillation in hypothyroid state after radioiodine treatment

Energy Technology Data Exchange (ETDEWEB)

Yamamoto, Makiko; Saito, Shintaro; Sakurada, Toshiro; Yoshida, Katsumi; Kaise, Kazuro; Kaise, Nobuko; Fukazawa, Hiroshi; Itagaki, Yoichi; Yoshinaga, Kaoru (Tohoku Univ., Sendai (Japan). School of Medicine)

1992-06-01

Twenty patients with thyrotoxic Basedow's disease complicated by atrial fibrillation lasting more than one month despite treatment with antithyroidal drugs were treated with radioiodine supplemented with an antithyroidal drug or inorganic iodine. We classified the 20 patients on the basis of strial fibrillation reversion into two groups, one with reversion (group I) and the other without reversion (group II). In all 12 patients in group I, T{sub 4} and T{sub 3} decreased to hypothyroid levels in 3.2{+-}1.3 months, and one month later all patients had their sinus rhythm restored while T{sub 4} and T{sub 3} also remained below normal (2.6{+-}1.1 {mu}g/dl and 77.9{+-}34.4 ng/dl, respectively). Although T{sub 4} and T{sub 3} also decreased within 3.5{+-}1.8 months in all 8 patients in group II, one month later, atrial fibrillation persisted while T{sub 4} and T{sub 3} (10.4{+-}5.3 {mu}g/dl and 157.7{+-}67.5 ng/dl, respectively) rose significantly compared to those in group I (p<0.001 and p<0.01, respectively). For reversion of atrial fibrillation it is important that the onset of hypothyroidism is rapidly induced by radioiodine and that hypothyroidism continues for at least one month. (author).

Phosphatidylcholine Reverses Ethanol-Induced Increase in Transepithelial Endotoxin Permeability and Abolishes Transepithelial Leukocyte Activation

DEFF Research Database (Denmark)

Mitzscherling, Katja; Volynets, Valentina; Parlesak, Alexandr

2009-01-01

Chronic alcohol abuse increases both intestinal bacterial overgrowth and intestinal permeability to macromolecules. Intestinal permeability of endotoxin, a component of the outer cell membrane of Gram-negative bacteria, plays a crucial role in the development of alcohol-induced liver disease (ALD......). As impaired bile flow leads to endotoxemia and the bile component phosphatidylcholine (PC) is therapeutically active in ALD, we tested the hypothesis that conjugated primary bile salts (CPBS) and PC inhibit ethanol-enhanced transepithelial permeability of endotoxin and the subsequent transepithelial...... activation of human leukocytes. For this purpose, we used a model in which intestinal epithelial cells (Caco-2) were basolaterally cocultivated with mononuclear leukocytes. Cells were challenged apically with endotoxin from Escherichia coli K12 and were incubated with or without the addition of CPBS (1.5 m...

Antivenom reversal of biochemical alterations induced by black scorpion Heterometrus fastigiousus Couzijn venom in mice

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MK Chaubey

2009-01-01

Full Text Available In the present study, Heterometrus fastigiousus venom (HFV was employed as antigen to produce species-specific scorpion antivenom (SAV in albino mice (NIH strain. To determine SAV efficacy, it was pre-incubated with 10 LD50 of HFV and then injected subcutaneously into mice. Subsequently, mortality was observed after 24 hours. Minimum effective dose (MED was 12.5 LD50 of HFV/mL of SAV. SAV effectiveness to reverse HFV-induced biochemical alterations in mice was analyzed by challenge method. Simultaneously, mice received subcutaneously 40% of 24-hour-LD50 of HFV and intravenously SAV. After four hours, changes in serum glucose, free amino acids, uric acids, pyruvic acid, cholesterol, total protein, alkaline phosphatase, acid phosphatase, lactic dehydrogenase and glutamate-pyruvate transaminase enzyme level were determined. Treatment with species-specific SAV resulted in the reversal of HFV-induced biochemical alterations.

The Impaired Function of Macrophages Induced by Strenuous Exercise Could Not Be Ameliorated by BCAA Supplementation.

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Xiao, Weihua; Chen, Peijie; Liu, Xiaoguang; Zhao, Linlin

2015-10-21

The aim of this study was to evaluate the effect of strenuous exercise on the functions of peritoneal macrophages in rats and to test the hypothesis that branched-chain amino acid (BCAA) supplementation will be beneficial to the macrophages of rats from strenuous exercise. Forty male Wistar rats were randomly divided into five groups: (C) Control, E) Exercise, (E1) Exercise with one week to recover, (ES) Exercise + Supplementation and (ES1) Exercise + Supplementation with 1 week to recover. All rats except those of the sedentary control were subjected to four weeks of strenuous exercise. Blood hemoglobin, serum testosterone and BCAA levels were tested. Peritoneal macrophages functions were also determined at the same time. The data showed that hemoglobin, testosterone, BCAA levels, and body weight in group E decreased significantly as compared with that of group C. Meanwhile, phagocytosis capacity (decreased by 17.07%, p = 0.031), reactive oxygen species (ROS) production (decreased by 26%, p = 0.003) and MHC II mRNA (decreased by 22%, p = 0.041) of macrophages decreased in the strenuous exercise group as compared with group C. However, the chemotaxis of macrophages did not change significantly. In addition, BCAA supplementation could slightly increase the serum BCAA levels of rats from strenuous exercise (increased by 6.70%, p > 0.05). Moreover, the body weight, the blood hemoglobin, the serum testosterone and the function of peritoneal macrophages in group ES did not change significantly as compared with group E. These results suggest that long-term intensive exercise impairs the function of macrophages, which is essential for microbicidal capability. This may represent a novel mechanism of immunosuppression induced by strenuous exercise. Moreover, the impaired function of macrophage induced by strenuous exercise could not be ameliorated by BCAA supplementation in the dosing and timing used for this study.

The Impaired Function of Macrophages Induced by Strenuous Exercise Could Not Be Ameliorated by BCAA Supplementation

Directory of Open Access Journals (Sweden)

Weihua Xiao

2015-10-01

Full Text Available The aim of this study was to evaluate the effect of strenuous exercise on the functions of peritoneal macrophages in rats and to test the hypothesis that branched-chain amino acid (BCAA supplementation will be beneficial to the macrophages of rats from strenuous exercise. Forty male Wistar rats were randomly divided into five groups: (C Control, E Exercise, (E1 Exercise with one week to recover, (ES Exercise + Supplementation and (ES1 Exercise + Supplementation with 1 week to recover. All rats except those of the sedentary control were subjected to four weeks of strenuous exercise. Blood hemoglobin, serum testosterone and BCAA levels were tested. Peritoneal macrophages functions were also determined at the same time. The data showed that hemoglobin, testosterone, BCAA levels, and body weight in group E decreased significantly as compared with that of group C. Meanwhile, phagocytosis capacity (decreased by 17.07%, p = 0.031, reactive oxygen species (ROS production (decreased by 26%, p = 0.003 and MHC II mRNA (decreased by 22%, p = 0.041 of macrophages decreased in the strenuous exercise group as compared with group C. However, the chemotaxis of macrophages did not change significantly. In addition, BCAA supplementation could slightly increase the serum BCAA levels of rats from strenuous exercise (increased by 6.70%, p > 0.05. Moreover, the body weight, the blood hemoglobin, the serum testosterone and the function of peritoneal macrophages in group ES did not change significantly as compared with group E. These results suggest that long-term intensive exercise impairs the function of macrophages, which is essential for microbicidal capability. This may represent a novel mechanism of immunosuppression induced by strenuous exercise. Moreover, the impaired function of macrophage induced by strenuous exercise could not be ameliorated by BCAA supplementation in the dosing and timing used for this study.

Anemia Offers Stronger Protection Than Sickle Cell Trait Against the Erythrocytic Stage of Falciparum Malaria and This Protection Is Reversed by Iron Supplementation.

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Goheen, M M; Wegmüller, R; Bah, A; Darboe, B; Danso, E; Affara, M; Gardner, D; Patel, J C; Prentice, A M; Cerami, C

2016-12-01

Iron deficiency causes long-term adverse consequences for children and is the most common nutritional deficiency worldwide. Observational studies suggest that iron deficiency anemia protects against Plasmodium falciparum malaria and several intervention trials have indicated that iron supplementation increases malaria risk through unknown mechanism(s). This poses a major challenge for health policy. We investigated how anemia inhibits blood stage malaria infection and how iron supplementation abrogates this protection. This observational cohort study occurred in a malaria-endemic region where sickle-cell trait is also common. We studied fresh RBCs from anemic children (135 children; age 6-24months; hemoglobin Anemia substantially reduced the invasion and growth of both laboratory and field strains of P. falciparum in vitro (~10% growth reduction per standard deviation shift in hemoglobin). The population level impact against erythrocytic stage malaria was 15.9% from anemia compared to 3.5% for sickle-cell trait. Parasite growth was 2.4 fold higher after 49days of iron supplementation relative to baseline (panemia protects African children against falciparum malaria, an effect that is substantially greater than the protection offered by sickle-cell trait. Iron supplementation completely reversed the observed protection and hence should be accompanied by malaria prophylaxis. Lower hemoglobin levels typically seen in populations of African descent may reflect past genetic selection by malaria. National Institute of Child Health and Development, Bill and Melinda Gates Foundation, UK Medical Research Council (MRC) and Department for International Development (DFID) under the MRC/DFID Concordat. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Sugammadex for reversal of rocuronium-induced neuromuscular blockade in pediatric patients

Science.gov (United States)

Won, Young Ju; Lim, Byung Gun; Lee, Dong Kyu; Kim, Heezoo; Kong, Myoung Hoon; Lee, Il Ok

2016-01-01

Abstract Background: Previous studies have shown that sugammadex, a modified γ-cyclodextrin, is a well-tolerated agent for the reversal of neuromuscular blockade (NMB) induced by a steroidal neuromuscular blocking drug in adult patients. However, its use has not been reviewed in pediatric patients. The aim of this meta-analysis was to evaluate the efficacy and safety of sugammadex in the reversal of rocuronium-induced NMB during surgery under general anesthesia in pediatric patients. Methods: A literature search was performed using the Pubmed, EMBASE: Drugs and pharmacology, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. Analysis was conducted using RevMan 5.3. Data collected from different trials were pooled; the weighted mean difference or the pooled risk ratio and the corresponding 95% confidence interval (CI) were used for analysis, and heterogeneity (I2) assessment was performed. Results: Six randomized controlled trials comparing 253 pediatric patients (age range, 2–18 years) were included in the final analysis. The mean time taken to reach a train-of-four ratio of ≥0.9 was significantly shorter in the sugammadex groups (2 and 4 mg/kg) than in the control group (neostigmine or placebo), although the heterogeneity was high. The weighted mean differences of the 2 and 4 mg/kg sugammadex groups were −7.15 (95% CI: −10.77 to −3.54; I2 = 96%; P = 0.0001) and −17.32 (95% CI: −29.31 to −5.32; I2 = 98%; P = 0.005), respectively. The extubation time in the sugammadex group was shorter than that in the control group; the weighted mean difference of the sugammadex group was −6.00 (95% CI: −11.46 to −0.53; I2 = 99%; P = 0.03). There was no significant difference between the groups in terms of the incidence of postanesthetic adverse events; the pooled risk ratio was 0.67 (95% CI: 0.27–1.71; I2 = 59%; P = 0.41). Conclusion: We suggest that sugammadex is fast and

Inducing sex reversal of the urogenital system of marsupials.

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Renfree, Marilyn B; Chew, Keng Yih; Shaw, Geoff

2014-01-01

Marsupials differ from eutherian mammals in their reproductive strategy of delivering a highly altricial young after a short gestation. The young, with its undeveloped organ systems completes its development post-natally, usually within a pouch. The young is dependent on milk with a composition that varies through lactation to support its growth and changing needs as it matures over a lengthy period. Gonadal differentiation occurs after birth, providing a unique opportunity to examine the effects of hormonal manipulations on its sexual differentiation of the highly accessible young. In marsupials a difference in the migration of the urinary ducts around the genital ducts from eutherian mammals results in the unique tammar reproductive tract which has three vaginae and two cervices, and two distinctly separate uteri. In the tammar wallaby, a small member of the kangaroo family, we showed that virilisation of the Wolffian duct, prostate and phallus depends on an alternate androgen pathway, which has now been shown to be important for virilisation in humans. Through hormonal manipulations over differing time periods we have achieved sex reversal of both ovaries and testes, germ cells, genital ducts, prostate and phallus. Whilst we understand many of the mechanisms behind sexual differentiation there are still many lessons to be learned from understanding how sex reversal is achieved by using a model such as the tammar wallaby. This will help guide investigations into the major questions of how and why sex determination is achieved in other species. This review discusses the control and development of the marsupial urogenital system, largely drawn from our studies in the tammar wallaby and our ability to manipulate this system to induce sex reversal. Copyright © 2013 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Long working hours and alcohol use

DEFF Research Database (Denmark)

Virtanen, Marianna; Jokela, Markus; Nyberg, Solja T

2015-01-01

OBJECTIVE: To quantify the association between long working hours and alcohol use. DESIGN: Systematic review and meta-analysis of published studies and unpublished individual participant data. DATA SOURCES: A systematic search of PubMed and Embase databases in April 2014 for published studies......, supplemented with manual searches. Unpublished individual participant data were obtained from 27 additional studies. REVIEW METHODS: The search strategy was designed to retrieve cross sectional and prospective studies of the association between long working hours and alcohol use. Summary estimates were...... countries. The pooled maximum adjusted odds ratio for the association between long working hours and alcohol use was 1.11 (95% confidence interval 1.05 to 1.18) in the cross sectional analysis of published and unpublished data. Odds ratio of new onset risky alcohol use was 1.12 (1.04 to 1...

Reproductive toxicity of chromium in adult bonnet monkeys (Macaca radiata Geoffrey). Reversible oxidative stress in the semen

International Nuclear Information System (INIS)

Subramanian, Senthivinayagam; Rajendiran, Gopalakrishnan; Sekhar, Pasupathi; Gowri, Chandrahasan; Govindarajulu, Pera; Aruldhas, Mariajoseph Michael

2006-01-01

The present study was designed to test the hypothesis that oxidative stress mediates chromium-induced reproductive toxicity. Monthly semen samples were collected from adult monkeys (Macaca radiata), which were exposed to varying doses (50, 100, 200 and 400 ppm) of chromium (as potassium dichromate) for 6 months through drinking water. Chromium treatment decreased sperm count, sperm forward motility and the specific activities of antioxidant enzymes, superoxide dismutase and catalase, and the concentration of reduced glutathione in both seminal plasma and sperm in a dose- and duration-dependent manner. On the other hand, the quantum of hydrogen peroxide in the seminal plasma/sperm from monkeys exposed to chromium increased with increasing dose and duration of chromium exposure. All these changes were reversed after 6 months of chromium-free exposure period. Simultaneous supplementation of vitamin C (0.5 g/L; 1.0 g/L; 2.0 g/L) prevented the development of chromium-induced oxidative stress. Data support the hypothesis and show that chronic chromium exposure induces a reversible oxidative stress in the seminal plasma and sperm by creating an imbalance between reactive oxygen species and antioxidant system, leading to sperm death and reduced motility of live sperm

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.

Addictions Neuroclinical Assessment: A reverse translational approach.

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Kwako, Laura E; Momenan, Reza; Grodin, Erica N; Litten, Raye Z; Koob, George F; Goldman, David

2017-08-01

Incentive salience, negative emotionality, and executive function are functional domains that are etiologic in the initiation and progression of addictive disorders, having been implicated in humans with addictive disorders and in animal models of addictions. Measures of these three neuroscience-based functional domains can capture much of the effects of inheritance and early exposures that lead to trait vulnerability shared across different addictive disorders. For specific addictive disorders, these measures can be supplemented by agent specific measures such as those that access pharmacodynamic and pharmacokinetic variation attributable to agent-specific gatekeeper molecules including receptors and drug-metabolizing enzymes. Herein, we focus on the translation and reverse translation of knowledge derived from animal models of addiction to the human condition via measures of neurobiological processes that are orthologous in animals and humans, and that are shared in addictions to different agents. Based on preclinical data and human studies, measures of these domains in a general framework of an Addictions Neuroclinical Assessment (ANA) can transform the assessment and nosology of addictive disorders, and can be informative for staging disease progression. We consider next steps and challenges for implementation of ANA in clinical care and research. This article is part of the Special Issue entitled "Alcoholism". Published by Elsevier Ltd.

[The catalase inhibitor aminotriazole alleviates acute alcoholic liver injury].

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Ai, Qing; Ge, Pu; Dai, Jie; Liang, Tian-Cai; Yang, Qing; Lin, Ling; Zhang, Li

2015-02-25

In this study, the effects of catalase (CAT) inhibitor aminotriazole (ATZ) on alcohol-induced acute liver injury were investigated to explore the potential roles of CAT in alcoholic liver injury. Acute liver injury was induced by intraperitoneal injection of alcohol in Sprague Dawley (SD) rats, and various doses of ATZ (100-400 mg/kg) or vehicle were administered intraperitoneally at 30 min before alcohol exposure. After 24 h of alcohol exposure, the levels of aspartate transaminase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) in plasma were determined. The degree of hepatic histopathological abnormality was observed by HE staining. The activity of hepatic CAT, hydrogen peroxide (H₂O₂) level and malondialdehyde (MDA) content in liver tissue were measured by corresponding kits. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in plasma were determined by ELISA method. The results showed that treatment with ATZ dose-dependently suppressed the elevation of ALT, AST and LDH levels induced by alcohol exposure, and that ATZ alleviated alcohol-induced histopathological alterations. Furthermore, ATZ inhibited the activity of CAT, reduced hepatic levels of H₂O₂and MDA in alcohol exposed rats. ATZ also decreased the levels of plasma TNF-α and IL-6 in rats with alcohol exposure. These results indicated that ATZ attenuated alcohol-induced acute liver injury in rats, suggesting that CAT might play important pathological roles in the pathogenesis of alcoholic liver injury.

ALCOHOL AND HEART RHYTHM DISORDERS

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A. O. Yusupova

2015-01-01

Full Text Available Alcohol abuse and particularly extension of alcohol consumption in alcohol diseas increases the risk of cardiac arrhythmias development and aggravates existing arrhythmias. Patients do not always receive the necessary specific treatment due to lack of detection of the ethanol genesis of these arrhythmias. Management of patients with alcohol abuse and alcohol dependence, including its cardiac complications among other cardiac arrhythmias should use both antiarrhythmic and anti-alcohol drugs and antidepressants. Such issues as diagnosis and management of patients with alcohol-induced cardiac arrhythmias are presented.

Moderate alcohol consumption increases cholesterol efflux mediated by ABCA1

NARCIS (Netherlands)

Beulens, J.W.J.; Sierksma, A.; Tol, A. van; Fournier, N.; Gent, T. van; Paul, J.L.; Hendriks, H.F.J.

2004-01-01

Moderate alcohol consumption increases HDL cholesterol, which is involved in reverse cholesterol transport (RCT). The aim of this study was to investigate the effect of moderate alcohol consumption on cholesterol efflux, using J774 mouse macrophages and Fu5AH cells, and on other parameters in the

Efficacy of anti-inflammatory, antibiotic and pleiotropic agents in reversing nitrogen mustard-induced injury in ex vivo cultured rabbit cornea.

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Goswami, Dinesh G; Kant, Rama; Tewari-Singh, Neera; Agarwal, Rajesh

2018-09-01

Vesicating agent, Sulfur mustard (SM), causes devastating eye injury; however, there are no effective antidotes available. Using nitrogen mustard (NM), a bi-functional analog of SM, we have earlier reported that NM-induced corneal injury in ex vivo rabbit cornea organ culture model parallels corneal injury reported with SM. Using this model, we have demonstrated the therapeutic efficacy of dexamethasone (DEX), doxycycline (DOX) and silibinin (SB) in reversing NM (2h exposure)-induced corneal injuries when added immediately after washing NM. In the present study, we further examined the efficacy of similar/higher doses of these agents when added immediately, 2, or 4h after washing NM following its 2h exposure. All three treatment agents caused a reversal in established NM-induced injury biomarkers when added immediately or 2h after washing NM following its 2h exposure; however, when treatments were carried out 4h after washing NM, there was no significant effect. Together, our results further show the beneficial effect of these agents in reversing NM-induced corneal injury and indicate the time window for effective treatment. This could be useful towards future development of targeted therapeutics against vesicant-induced ocular injury. Copyright © 2017 Elsevier B.V. All rights reserved.

Extremely low-frequency magnetic fields can impair spermatogenesis recovery after reversible testicular damage induced by heat.

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Tenorio, Bruno Mendes; Ferreira Filho, Moisés Bonifacio Alves; Jimenez, George Chaves; de Morais, Rosana Nogueira; Peixoto, Christina Alves; Nogueira, Romildo de Albuquerque; da Silva Junior, Valdemiro Amaro

2014-06-01

Male infertility is often related to reproductive age couples experiencing fertility-related issues. Men may have fertility problems associated with reversible testicular damage. Considering that men have been increasingly exposed to extremely low-frequency magnetic fields generated by the production, distribution and use of electricity, this study analyzed whether 60 Hz and 1 mT magnetic field exposure may impair spermatogenesis recovery after reversible testicular damage induced by heat shock using rats as an experimental model. Adult male rats were subjected to a single testicular heat shock (HS, 43 °C for 12 min) and then exposed to the magnetic field for 15, 30 and 60 d after HS. Magnetic field exposure during the spermatogenesis recovery induced changes in testis components volume, cell ultrastructure and histomorphometrical parameters. Control animals had a reestablished and active spermatogenesis at 60 d after heat shock, while animals exposed to magnetic field still showed extensive testicular degeneration. Magnetic field exposure did not change the plasma testosterone. In conclusion, extremely low-frequency magnetic field may be harmful to fertility recovery in males affected by reversible testicular damage.

Lactobacillus GG and tributyrin supplementation reduce antibiotic-induced intestinal injury.

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Cresci, Gail; Nagy, Laura E; Ganapathy, Vadivel

2013-11-01

Antibiotic therapy negatively alters the gut microbiota. Lactobacillus GG (LGG) decreases antibiotic-associated diarrhea (AAD) symptoms, but the mechanisms are unknown. Butyrate has beneficial effects on gut health. Altered intestinal gene expression occurs in the absence of gut microbiota. We hypothesized that antibiotic-induced changes in gut microbiota reduce butyrate production, varying genes involved with gut barrier integrity and water and electrolyte absorption, lending to AAD, and that simultaneous supplementation with LGG and/or tributyrin would prevent these changes. C57BL/6 mice aged 6-8 weeks received a chow diet while divided into 8 treatment groups (± saline, ± LGG, ± tributyrin, or both). Mice received treatments orally for 7 days with ± broad-spectrum antibiotics. Water intake was recorded daily and body weight was measured. Intestine tissue samples were obtained and analyzed for expression of genes and proteins involved with water and electrolyte absorption, butyrate transport, and gut integrity via polymerase chain reaction and immunohistochemistry. Antibiotics decreased messenger RNA (mRNA) expression (butyrate transporter and receptor, Na(+)/H(+) exchanger, Cl(-)/HCO3 (-), and a water channel) and protein expression (butyrate transporter, Na(+)/H(+) exchanger, and tight junction proteins) in the intestinal tract. LGG and/or tributyrin supplementation maintained intestinal mRNA expression to that of the control animals, and tributyrin maintained intestinal protein intensity expression to that of control animals. Broad-spectrum antibiotics decrease expression of anion exchangers, butyrate transporter and receptor, and tight junction proteins in mouse intestine. Simultaneous oral supplementation with LGG and/or tributyrin minimizes these losses. Optimizing intestinal health with LGG and/or tributyrin may offer a preventative therapy for AAD.

Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801-induced behavioral impairments and enhances associative learning in rodents

DEFF Research Database (Denmark)

Bubser, Michael; Bridges, Thomas M; Dencker, Ditte

2014-01-01

PAMs, enabling a more extensive characterization of M4 actions in rodent models. We used VU0467154 to test the hypothesis that selective potentiation of M4 receptor signaling could ameliorate the behavioral, cognitive, and neurochemical impairments induced by the noncompetitive NMDAR antagonist MK-801....... VU0467154 produced a robust dose-dependent reversal of MK-801-induced hyperlocomotion and deficits in preclinical models of associative learning and memory functions, including the touchscreen pairwise visual discrimination task in wild-type mice, but failed to reverse these stimulant...

Negative Pressure Pulmonary Edema after Reversing Rocuronium-Induced Neuromuscular Blockade by Sugammadex

Directory of Open Access Journals (Sweden)

Manzo Suzuki

2014-01-01

Full Text Available Negative pressure pulmonary edema (NPPE is a rare complication that accompanies general anesthesia, especially after extubation. We experienced a case of negative pressure pulmonary edema after tracheal extubation following reversal of rocuronium-induced neuromuscular blockade by sugammadex. In this case, the contribution of residual muscular block on the upper airway muscle as well as large inspiratory forces created by the respiratory muscle which has a low response to muscle relaxants, is suspected as the cause.

Cue-induced reinstatement of ethanol seeking in Sardinian alcohol-preferring rats.

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Maccioni, Paola; Orrú, Alessandro; Korkosz, Agnieszka; Gessa, Gian Luigi; Carai, Mauro A M; Colombo, Giancarlo; Bienkowski, Przemyslaw

2007-02-01

The purpose of the present study was to characterize cue-induced reinstatement of ethanol seeking in selectively bred Sardinian alcohol-preferring (sP) rats trained to lever press for ethanol in 30-min self-administration sessions. Four responses on an "active" lever led to presentation of 0.1 ml of 15% (vol/vol) ethanol by a liquid dipper and concurrent activation of a set of discrete light and auditory cues. In a 70-min extinction/reinstatement session, responding was first extinguished for 60 min. Subsequently, different stimuli were delivered in a noncontingent manner and reinstatement of nonreinforced responding was assessed. Fifteen presentations of the ethanol-predictive stimulus complex, including the dipper cup containing 5 or 15% ethanol, potently reinstated responding on the previously active lever. The magnitude of reinstatement increased with the number of stimulus presentations and concentration of ethanol presented by the dipper cup. Fifteen presentations of the ethanol-predictive stimulus complex, including the dipper cup filled with water (0% ethanol), did not produce any reinstatement. These results indicate that (1) noncontingent presentations of the ethanol-predictive stimulus complex may reinstate ethanol seeking in sP rats and (2) the orosensory properties of ethanol may play an important role in reinstatement of ethanol seeking in sP rats. The latter finding concurs with clinical observations that odor and taste of alcoholic beverages elicit immediate craving responses in abstinent alcoholics.

Selective Inducible Nitric Oxide Synthase Inhibitor Reversed Zinc Chloride-Induced Spatial Memory Impairment via Increasing Cholinergic Marker Expression.

Science.gov (United States)

Tabrizian, Kaveh; Azami, Kian; Belaran, Maryam; Soodi, Maliheh; Abdi, Khosrou; Fanoudi, Sahar; Sanati, Mehdi; Mottaghi Dastjerdi, Negar; Soltany Rezaee-Rad, Mohammad; Sharifzadeh, Mohammad

2016-10-01

Zinc, an essential micronutrient and biochemical element of the human body, plays structural, catalytic, and regulatory roles in numerous physiological functions. In the current study, the effects of a pretraining oral administration of zinc chloride (10, 25, and 50 mg/kg) for 14 consecutive days and post-training bilateral intra-hippocampal infusion of 1400W as a selective inducible nitric oxide synthase (iNOS) inhibitor (10, 50, and 100 μM/side), alone and in combination, on the spatial memory retention in Morris water maze (MWM) were investigated. Animals were trained for 4 days and tested 48 h after completion of training. Also, the molecular effects of these compounds on the expression of choline acetyltransferase (ChAT), as a cholinergic marker in the CA1 region of the hippocampus and medial septal area (MSA), were evaluated. Behavioral and molecular findings of this study showed that a 2-week oral administration of zinc chloride (50 mg/kg) impaired spatial memory retention in MWM and decreased ChAT expression. Immunohistochemical analysis of post-training bilateral intra-hippocampal infusion of 1400W revealed a significant increase in ChAT immunoreactivity. Furthermore, post-training bilateral intra-hippocampal infusion of 1400W into the CA1 region of the hippocampus reversed zinc chloride-induced spatial memory impairment in MWM and significantly increased ChAT expression in comparison with zinc chloride-treated animals. Taken together, these results emphasize the role of selective iNOS inhibitors in reversing zinc chloride-induced spatial memory deficits via modulation of cholinergic marker expression.

Increased anxiety, voluntary alcohol consumption and ethanol-induced place preference in mice following chronic psychosocial stress.

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Bahi, Amine

2013-07-01

Stress exposure is known to be a risk factor for alcohol use and anxiety disorders. Comorbid chronic stress and alcohol dependence may lead to a complicated and potentially severe treatment profile. To gain an understanding of the interaction between chronic psychosocial stress and drug exposure, we studied the effects of concomitant chronic stress exposure on alcohol reward using two-bottle choice and ethanol-conditioned place preference (CPP). The study consisted of exposure of the chronic subordinate colony (CSC) mice "intruders" to an aggressive "resident" mouse for 19 consecutive days. Control mice were single housed (SHC). Ethanol consumption using two-bottle choice paradigm and ethanol CPP acquisition was assessed at the end of this time period. As expected, CSC exposure increased anxiety-like behavior and reduced weight gain as compared to SHC controls. Importantly, in the two-bottle choice procedure, CSC mice showed higher alcohol intake than SHC. When testing their response to ethanol-induced CPP, CSC mice achieved higher preference for the ethanol-paired chamber. In fact, CSC exposure increased ethanol-CPP acquisition. Taken together, these data demonstrate the long-term consequences of chronic psychosocial stress on alcohol intake in male mice, suggesting chronic stress as a risk factor for developing alcohol consumption and/or anxiety disorders.

Regulation of Alcohol Extinction and Cue-Induced Reinstatement by Specific Projections among Medial Prefrontal Cortex, Nucleus Accumbens, and Basolateral Amygdala.

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Keistler, Colby R; Hammarlund, Emma; Barker, Jacqueline M; Bond, Colin W; DiLeone, Ralph J; Pittenger, Christopher; Taylor, Jane R

2017-04-26

The ability to inhibit drinking is a significant challenge for recovering alcoholics, especially in the presence of alcohol-associated cues. Previous studies have demonstrated that the regulation of cue-guided alcohol seeking is mediated by the basolateral amygdala (BLA), nucleus accumbens (NAc), and medial prefrontal cortex (mPFC). However, given the high interconnectivity between these structures, it is unclear how mPFC projections to each subcortical structure, as well as projections between BLA and NAc, mediate alcohol-seeking behaviors. Here, we evaluate how cortico-striatal, cortico-amygdalar, and amygdalo-striatal projections control extinction and relapse in a rat model of alcohol seeking. Specifically, we used a combinatorial viral technique to express diphtheria toxin receptors in specific neuron populations based on their projection targets. We then used this strategy to create directionally selective ablations of three distinct pathways after acquisition of ethanol self-administration but before extinction and reinstatement. We demonstrate that ablation of mPFC neurons projecting to NAc, but not BLA, blocks cue-induced reinstatement of alcohol seeking and neither pathway is necessary for extinction of responding. Further, we show that ablating BLA neurons that project to NAc disrupts extinction of alcohol approach behaviors and attenuates reinstatement. Together, these data provide evidence that the mPFC→NAc pathway is necessary for cue-induced reinstatement of alcohol seeking, expand our understanding of how the BLA→NAc pathway regulates alcohol behavior, and introduce a new methodology for the manipulation of target-specific neural projections. SIGNIFICANCE STATEMENT The vast majority of recovering alcoholics will relapse at least once and understanding how the brain regulates relapse will be key to developing more effective behavior and pharmacological therapies for alcoholism. Given the high interconnectivity of cortical, striatal, and limbic

Parkinson’s disease managing reversible neurodegeneration

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Hinz, Marty; Stein, Alvin; Cole, Ted; McDougall, Beth; Westaway, Mark

2016-01-01

Traditionally, the Parkinson’s disease (PD) symptom course has been classified as an irreversible progressive neurodegenerative disease. This paper documents 29 PD and treatment-induced systemic depletion etiologies which cause and/or exacerbate the seven novel primary relative nutritional deficiencies associated with PD. These reversible relative nutritional deficiencies (RNDs) may facilitate and accelerate irreversible progressive neurodegeneration, while other reversible RNDs may induce previously undocumented reversible pseudo-neurodegeneration that is hiding in plain sight since the symptoms are identical to the symptoms being experienced by the PD patient. Documented herein is a novel nutritional approach for reversible processes management which may slow or halt irreversible progressive neurodegenerative disease and correct reversible RNDs whose symptoms are identical to the patient’s PD symptoms. PMID:27103805

Two-cell embryos are more sensitive than blastocysts to AMPK-dependent suppression of anabolism and stemness by commonly used fertility drugs, a diet supplement, and stress.

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Bolnick, Alan; Abdulhasan, Mohammed; Kilburn, Brian; Xie, Yufen; Howard, Mindie; Andresen, Paul; Shamir, Alexandra M; Dai, Jing; Puscheck, Elizabeth E; Secor, Eric; Rappolee, Daniel A

2017-12-01

This study tests whether metformin or diet supplement BR-DIM-induced AMP-activated protein kinase (AMPK) mediated effects on development are more pronounced in blastocysts or 2-cell mouse embryos. Culture mouse zygotes to two-cell embryos and test effects after 0.5-1 h AMPK agonists' (e.g., Met, BR-DIM) exposure on AMPK-dependent ACCser79P phosphorylation and/or Oct4 by immunofluorescence. Culture morulae to blastocysts and test for increased ACCser79P, decreased Oct4 and for AMPK dependence by coculture with AMPK inhibitor compound C (CC). Test whether Met or BR-DIM decrease growth rates of morulae cultured to blastocyst by counting cells. Aspirin, metformin, and hyperosmotic sorbitol increased pACC ser79P ~ 20-fold, and BR-DIM caused a ~ 30-fold increase over two-cell embryos cultured for 1 h in KSOMaa but only 3- to 6-fold increase in blastocysts. We previously showed that these stimuli decreased Oct4 40-85% in two-cell embryos that was ~ 60-90% reversible by coculture with AMPK inhibitor CC. However, Oct4 decreased only 30-50% in blastocysts, although reversibility of loss by CC was similar at both embryo stages. Met and BR-DIM previously caused a near-complete cell proliferation arrest in two-cell embryos and here Met caused lower CC-reversible growth decrease and AMPK-independent BR-DIM-induced blastocyst growth decrease. Inducing drug or diet supplements decreased anabolism, growth, and stemness have a greater impact on AMPK-dependent processes in two-cell embryos compared to blastocysts.

Reversal of dexamethasone induced insulin resistance in 3T3L1 adipocytes by 3β-taraxerol of Mangifera indica.

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Sangeetha, K N; Shilpa, K; Jyothi Kumari, P; Lakshmi, B S

2013-02-15

The present study investigates the efficacy of Mangifera indica ethyl acetate extract (MIEE) and its bioactive compound, 3β-taraxerol in the reversal of dexamethasone (DEX) induced insulin resistance in 3T3L1 adipocytes. MIEE and 3β-taraxerol were evaluated for their ability to restore impaired glucose uptake and, expression of molecular markers in the insulin signaling pathway induced by DEX in 3T3L1 adipocytes using 2-deoxy-D-[1-(3)H] glucose uptake assay and ELISA. An insulin resistant model has been developed using a glucocorticoid, DEX on 3T3L1 adipocytes. Insulin resistant condition was observed at 24h of DEX induction wherein a maximum degree of resistance of about 50% was measured based on inhibition of glucose uptake, which was confirmed using cytotoxicity analysis. The developed model of insulin resistance was studied in comparison to positive control rosiglitazone. DEX induced inhibition of glucose uptake and the expression of insulin signaling markers GLUT4 and PI3K were found to be restored by 3β-taraxerol and MIEE, thus delineating its mechanism of action in the reversal of insulin resistance. 3β-Taraxerol effectively restored DEX induced desensitization via restoration of PI3K and GLUT4 expression. To conclude, since 3β-taraxerol exhibits significant effect in reversing insulin resistance it can be further investigated as an insulin resistance reversal agent. Copyright © 2012 Elsevier GmbH. All rights reserved.