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Liquid Diet (liquid + diet)
Kinds of Liquid Diet Terms modified by Liquid Diet Selected AbstractsRepeated withdrawal from ethanol impairs acquisition but not expression of conditioned fearEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2003T. L. Ripley Abstract Repeated withdrawal from ethanol impairs acquisition of conditioned fear [Stephens, D.N., Brown, G., Duka, T. & Ripley, T.L. (2001) Eur. J. Neurosci., 14, 2023,2031]. This study further examined the effect of repeated withdrawal from ethanol on the expression and acquisition of fear conditioning. Following training, presentation of a cue associated with footshock (CS+) resulted in a suppression of operant responding for food reinforcement. In different groups, shock thresholds were manipulated to give weak or severe behavioural suppression. Rats were subsequently chronically treated with ethanol-containing liquid diet either continuously (single withdrawal) or with three withdrawal periods (repeated withdrawal). Ethanol treatment and withdrawal had no effect on conditioned suppression of responding tested 2 weeks after the final withdrawal, at either shock intensity. Nevertheless, extinction of conditioned fear was impaired in the repeated withdrawal group exposed to the higher shock intensity. In the high intensity group, the stimulus,shock association was then reversed, so that the previously neutral conditioned stimulus (CS,) became the CS+. Acquisition of suppression to the new CS+ was significantly less in the animals previously given repeated experience of withdrawal, confirming our previous finding. Thus, repeated withdrawal from ethanol lead to disruption in the acquisition of fear conditioning but had no effect on retrieval of an association formed prior to the ethanol-withdrawal experiences. [source] Impaired fear conditioning but enhanced seizure sensitivity in rats given repeated experience of withdrawal from alcoholEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2001D. N. Stephens Abstract Repeated experience of withdrawal from chronic alcohol treatment increases sensitivity to seizures. It has been argued by analogy that negative affective consequences of withdrawal also sensitize, but repeated experience of withdrawal from another sedative-hypnotic drug, diazepam, results in amelioration of withdrawal anxiety and aversiveness. We tested whether giving rats repeated experience of withdrawal from alcohol altered their ability to acquire a conditioned emotional response (CER). Male Hooded Lister rats were fed a nutritionally complete liquid diet as their only food source. Different groups received control diet, or diet containing 7% ethanol. Rats receiving ethanol diet were fed for either 24 days (Single withdrawal, SWD), or 30 days, with two periods of 3 days, starting at day 11, and 21, in which they received control diet (Repeated withdrawal, RWD). All rats were fed lab chow at the end of their liquid diet feeding period. Starting 12 days after the final withdrawal, groups of Control, SWD and RWD rats were given pentylenetetrazole (PTZ; 30 mg/kg, i.p.) three times a week, and scored for seizures. The occurrence of two successive Stage 5 seizures was taken as the criterion for full PTZ kindling. Other groups of control, SWD and RWD rats were trained to operate levers to obtain food, and were then exposed, in a fully counterbalanced design, to light and tone stimuli which predicted unavoidable footshock (CS+), or which had no consequences (CS,). Rats consumed approximately 17.5 g/kg/day of ethanol, resulting in blood alcohol levels of approximately 100 mg/dL. Repeated administration of PTZ resulted in increasing seizure scores. RWD rats achieved kindling criterion faster than either Control or SWD rats. No differences were seen in the groups in flinch threshold to footshock (0.3 mA). At a shock intensity of 0.35 mA, Control, but not RWD or SWD rats showed significant suppression to the CS+ CS, presentation did not affect response rates. The three groups differed in their response to pairing the CS+ with increasing shock levels, the Controls remaining more sensitive to the CS+. SWD rats showed significant suppression of lever pressing during CS+ presentations only at 0.45 and 0.5 mA, and RWD rats only at 0.5 mA. Giving rats repeated experience of withdrawal from chronic ethanol results in increased sensitivity to PTZ kindling, but reduces their ability to acquire a CER. Withdrawal kindling of sensitivity to anxiogenic events does not seem to occur under circumstances which give rise to kindling of seizure sensitivity. [source] Effects of venlafaxine on ethanol withdrawal syndrome in ratsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2004Esra Sa Abstract The present study was designed to investigate the effects of venlafaxine, a serotonin and noradrenaline reuptake inhibitor (SNRI), on ethanol withdrawal syndrome in rats. Adult male Wistar rats (187,319 g) were used for the study. Ethanol (7.2%, v/v) was given to rats by a liquid diet for 21 days. Control rats were pair-fed an isocaloric liquid diet containing sucrose as a caloric substitute to ethanol. Venlafaxine (5, 10, 20 and 40 mg/kg) and saline were injected to rats intraperitoneally just before ethanol withdrawal. After the 2nd, 4th and 6th hour of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs that included locomotor hyperactivity, agitation, stereotyped behaviour and wet dog shakes were recorded or rated. A second series of injections was given at the 6th hour after the first one, and rats were then tested for audiogenic seizures. Venlafaxine produced some inhibitory effects on locomotor hyperactivity, stereotypic behaviours and wet dog shakes. However, a two-way anova of the data did not indicate any significant effect. It reduced the incidence of the audiogenic seizures at the 6th hour of ethanol withdrawal. Venlafaxine (20 mg/kg) also prolonged the latency of the seizures significantly. Our results suggest that acute venlafaxine treatment has limited beneficial effects on ethanol withdrawal syndrome in rats. [source] Alcohol-induced free radicals in mice: Direct toxicants or signaling molecules?HEPATOLOGY, Issue 5 2001Ming Yin Tumor necrosis factor , (TNF-,) and free radicals are produced in early alcohol-induced liver injury. Recently, pathology caused by alcohol was blocked nearly completely in tumor necrosis factor , receptor 1 (TNF-R1) knockout mice. With this model, it is now possible to evaluate whether free radicals are directly toxic or act as redox regulators of TNF-, production. Specifically, if free radicals were directly toxic, a parallel decrease in free radicals and pathology in TNF-R1 knockout mice would be predicted. If they only affect TNF-, production, radicals would be expected to remain high while pathology is diminished. Accordingly, free radical production in TNF-R1 knockout mice was studied here. The enteral alcohol delivery model used mice lacking TNF-R1 (p55) and wild-type control C57Bl/6J mice. Animals received a liquid diet continuously with either ethanol or isocaloric maltose-dextrin as control for 4 weeks. Urine ethanol levels fluctuated from 10 to 500 mg/dL in a cyclic pattern in mice receiving ethanol. Ethanol elevated liver:body weight ratios, serum alanine transaminase (ALT) levels, and pathology scores in wild-type mice. These parameters were blunted nearly completely in TNF-R1 knockout mice. Ethanol treatment increased free radical production in wild-type mice compared with animals fed a high-fat control diet. There were no differences in intensity of free radical signals regardless of the presence or absence of TNF-R1; however, pathology differed markedly between these groups. These findings are consistent with the hypothesis that free radicals act as redox signals for TNF-, production and do not directly damage cells in early alcohol-induced hepatic injury. [source] ,Cross-section gastroenterostomy' in patients with irresectable periampullary carcinomaHPB, Issue 2 2001O Horstmann Background The most frequent complication following gastroenterostomy (GE) for gastric outlet obstruction is delayed gastric emptying (DGE), which occurs in roughly 20% of patients. There is evidence that DGE may be linked to the longitudinal incision of the jejunum and that a transverse incision (cross-section GE) may decrease the incidence of DGE following GE. Patients and methods In contrast to the orthodox GE, the jejunum is severed transversely up to a margin of 1.5 cm at the mesenteric border and the anastomosis is created with a single running suture. A Braun anastomosis is added 20,30 cm distally to the GE. Patients were followed prospectively with special regard to the occurrence of DGE. Results Between 1 August 1994 and 1 August 1998, 25 patients underwent cross-section GE, mostly because of an irresectable periampullary carcinoma. Eight patients exhibited clinical signs of gastric outlet obstruction preoperatively, while in 17 the GE was performed on a prophylactic basis. A biliary bypass was added in 15 patients. There was no disruption of the GE, but one patient died in hospital (4%). The nasogastric tube was withdrawn on the first postoperative day (range 0,6 days), a liquid diet was started on the fifth day (range 2,7 days) and a full regular diet was tolerated at a median of 9 days (6,14 days). The incidence of DGE was 4%: only the single patient who died fulfilled the formal criteria for DGE. Discussion In contrast to orthodox GE, DGE seems to be of minor clinical importance following cross-section GE. As the technique is easy to perform, is free of specific complications and leads to a low incidence of DGE, it should be considered as an alternative to conventional GE. [source] The role of a liquid diet in the management of small bowel Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 1 2000Burton I. Korelitz M.D. No abstract is available for this article. [source] Fruit fly liquid larval diet technology transfer and updateJOURNAL OF APPLIED ENTOMOLOGY, Issue 3 2009C. L. Chang Abstract Since October 2006, the US Department of Agriculture,Agricultural Research Service (USDA,ARS) has been implementing a fruit fly liquid larval diet technology transfer, which has proceeded according to the following steps: (1) recruitment of interested groups through request; (2) establishment of the Material Transfer Agreement with agricultural research service; (3) fruit fly liquid larval diet starter kit sent to the requestor for preliminary evaluation; (4) problem-solving through email or onsite demonstration; (5) assessment on feedback from the participants to decide whether to continue the project. Up to date, the project has involved 35 participants from 29 countries and 26 species of fruit flies. Fourteen participants have concluded their evaluation of the process, and 11 of these 14, have deemed it to be successful. One participant has decided to implement the project on a larger scale. The 14 participants were, Argentina (Ceratitis capitata and Anastrepha fraterculus), Bangladesh (Bactrocera cucurbitae, C. capitata, and Bactrocera dorsalis), China (Fujia province) (B. dorsalis), Italy (C. capitata), Fiji (Bactrocera passiflorae), Kenya (Bactrocera invadens, Ceratitis cosyra), Mauritius (Bactrocera zonata and B. cucurbitae), Mexico (Anastrepha species), Philippines (Bactrocera philippinese), Thailand (Bactrocera correcta), Austria (C. capitata, Vienna 8 and A. fraterculus), Israel (Dacus ciliatus and C. capitata), South Africa (C. capitata, Vienna 8) and Australia (C. capitata). The Stellenbosch medfly mass-rearing facility in South Africa and the CDFA in Hawaii were two mass-scale rearing facilities that allowed us to demonstrate onsite rearing in a larger scale. Demonstrations were performed in CDFA in 2007, and in Stellenbosch, South Africa in 2008; both were found to be successful. The Stellenbosch medfly mass-rearing facility in South Africa decided to adopt the technology and is currently evaluating the quality control of the flies that were reared as larvae on a liquid diet. [source] Experimental acute alcohol pancreatitis-related liver damage and endotoxemia: synbiotics but not metronidazole have a protective effectJOURNAL OF DIGESTIVE DISEASES, Issue 4 2005F MAROTTA OBJECTIVE: The aim of this study was to test the effect of gut manipulation by either novel synbiotics or by metronidazole on either endotoxemia or the severity of liver damage in the course of acute pancreatitis from alcohol ingestion. METHODS: Sprague,Dawley rats were fed for 1 week through an intragastric tube a liquid diet with either: (i) 1 mL t.i.d. of a mixture of synbiotics (Lactobacillus acidophilus, Lactobacillus helveticus and Bifidobacterium in an enriched medium); (ii) 20 mg/kg t.i.d. metronidazole; or (iii) standard diet. Then, acute pancreatitis was induced by caerulein and when the disease was full-blown, rats were fed an alcohol-rich diet. Synbiotic and metronidazole treatment was given for a further 2 weeks. Transaminase and endotoxemia levels were measured before treatment, after 6 h, after 24 h and 2 weeks later, at the time the rats were killed. Liver samples were obtained for histological analysis. RESULTS: Synbiotics but not metronidazole improved the acute pancreatitis-induced increase in endotoxemia and transaminase levels. The addition of alcohol worsened these variables to a limited extent in the synbiotic-treated group, while metronidazole had a negative effect on liver damage. CONCLUSIONS: Gut flora pretreatment with synbiotics was able to effectively protect against endotoxin/bacterial translocation, as well as liver damage in the course of acute pancreatitis and concomitant heavy alcohol consumption. The beneficial effect of synbiotics on liver histology seems to be correlated with endotoxemia. Metronidazole did not produce such a beneficial effect; in fact, it further worsened liver damage when alcohol was added to the background of ongoing acute pancreatic inflammation. [source] Nutrients, not caloric restriction, extend lifespan in Queensland fruit flies (Bactrocera tryoni)AGING CELL, Issue 5 2009Benjamin G. Fanson Summary Caloric restriction (CR) has been widely accepted as a mechanism explaining increased lifespan (LS) in organisms subjected to dietary restriction (DR), but recent studies investigating the role of nutrients have challenged the role of CR in extending longevity. Fuelling this debate is the difficulty in experimentally disentangling CR and nutrient effects due to compensatory feeding (CF) behaviour. We quantified CF by measuring the volume of solution imbibed and determined how calories and nutrients influenced LS and fecundity in unmated females of the Queensland fruit fly, Bactocera tryoni (Diptera: Tephritidae). We restricted flies to one of 28 diets varying in carbohydrate:protein (C:P) ratios and concentrations. On imbalanced diets, flies overcame dietary dilutions, consuming similar caloric intakes for most dilutions. The response surface for LS revealed that increasing C:P ratio while keeping calories constant extended LS, with the maximum LS along C:P ratio of 21:1. In general, LS was reduced as caloric intake decreased. Lifetime egg production was maximized at a C:P ratio of 3:1. When given a choice of separate sucrose and yeast solutions, each at one of five concentrations (yielding 25 choice treatments), flies regulated their nutrient intake to match C:P ratio of 3:1. Our results (i) demonstrate that CF can overcome dietary dilutions; (ii) reveal difficulties with methods presenting fixed amounts of liquid diet; (iii) illustrate the need to measure intake to account for CF in DR studies and (iv) highlight nutrients rather than CR as a dominant influence on LS. [source] Efficacy of prepackaged, low residual test meals with 4L polyethylene glycol versus a clear liquid diet with 4L polyethylene glycol bowel preparation: A randomized trialJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2009Dong Il Park Abstract Background and study aims:, A prepackaged low residue one-day diet (breakfast, lunch and dinner) has been recently developed to improve patient tolerance for bowel preparation prior to colonoscopy. The aims of this study were to evaluate the efficacy and tolerability of bowel preparation protocols based on a low residue diet and 4L polyethylene glycol (PEG) solution, and to compare these new options with the traditional liquid diet and the PEG 4L lavage. Methods:, A total of 214 patients (mean age: 54.1 years; 120 male, 94 female) from four university hospitals were included in the analysis. Patients were randomized to receive a clear liquid diet and the PEG 4L regimen (106 patients) or the low residue test meals and the PEG 4L regimen (TM-PEG 4L, 108 patients). The colon cleansing efficacy of the different preparations was rated using the Ottawa bowel preparation scale. Results:, No significant differences were observed between the treatment groups according to the Ottawa cleansing scale findings (PEG 4L: 2.97 vs TM-PEG 4L: 2.46, P = 0.063). The overall tolerability was higher in the TM-PEG 4L group than in the PEG 4L group (P = 0.036). No difference was found when the two groups were compared with regard to adverse events (P = 0.599). Conclusions:, A prepackaged low residue one-day diet provided cleansing efficacy similar to that of a clear liquid diet and offered the benefit of improved tolerability compared to the conventional PEG 4L regimen. [source] An audit designed to assess the need for planned pretreatment PEG placement in patients with stage III & stage IV oral cancerJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 6 2004F.R. Dawson Background:, Nutritional support is a crucial and challenging part of treatment for patients with oral cancer. The aim of this audit was to assess the need for planned pretreatment percutaneous endoscopic gastrostomy (PEG) placement in this group of patients and to assess diet consistency as a predictor of poor outcomes. Method:, This was a retrospective study of 77 consecutive patients with stage III and IV squamous cell carcinoma of the oral cavity treated by radical surgery and post-operative radiotherapy between January 1999 and December 2001. Information was taken from dietitians' records. Patients were divided into two groups according to survival: group 1 (40 patients) comprised nonsurvivors and group 2 (37 patients), survivors. All patients were enterally fed post-operatively. After approximately 10 days, swallowing was assessed and, if deemed competent, patients progressed to a fluid diet. Tube feeding was gradually reduced and then stopped when oral nutrition was sufficient to maintain weight. Patients progressed to soft diet as they were able. During radiotherapy, liquid diet or tube feeding was instigated as required. Results:, In group 1, 65% required tube feeding for less than 30 days (mean 17 days), 20% for 31,100 days (mean 51 days) and 15% for over 100 days (mean 231 days). The overall mean length of tube feeding was 97 days. Thirty-eight per cent of nonsurvivors developed recurrence and went on to subsequent operations necessitating further tube feeding for an average of 129 days. In group 2, 70% were tube fed for less than 30 days (mean 11 days), 14% for between 31,100 days (mean 43 days), and 17% for more than 100 days. The overall mean length of tube feeding was 72 days. The dietary consistency of nonsurvivors was worse than survivors throughout treatment. At first presentation, only 37% of nonsurvivors managed a normal diet, 8% managed a near normal diet and 3% required tube feeding, whereas 48% of survivors managed a normal diet and 16% a near normal diet. At 1 year, there was a significant difference between the two groups' diets. No patients in group 1 managed a normal or near normal diet, whilst 62% required tube feeding. In group 2, 12 and 32% managed a normal and near normal diet, respectively and only 9% required or wished to remain on tube feeding to supplement their diet. Five per cent of patients in this group remained nil by mouth due to fistula. Conclusion:, Deciding whether a patient has a naso-gastric tube, PEG or radiologically inserted gastrostomy tube placed can be a difficult decision. However, a gastrostomy should be considered prior to treatment in patients whose diet is of poor consistency at presentation or who have an inadequate oral intake to maintain or increase weight and in those with a fistula, expected slow recovery of swallowing function, for example, pharyngeal tumour or undergoing brachytherapy or chemoradiotherapy. [source] Pathological Role of Aquaporin-2 in Impaired Water Excretion and HyponatremiaJOURNAL OF NEUROENDOCRINOLOGY, Issue 4 2004S. Ishikawa Abstract In the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), inappropriately elevated secretion of vasopressin can result in a reduction of antidiuretic efficacy: a phenomenon known as ,vasopressin escape'. We compared experimental SIADH with 1-deamino-8- d -arginine vasopressin (dDAVP)-excess rats, where both groups received continuous subcutaneous administration of dDAVP by osmotic minipump but the SIADH rats also received a liquid diet that induced hyponatraemia. The SIADH rats, but not the dDAVP excess rats, showed a marked attenuation of urinary concentrating ability. Vasopressin V2 receptor binding capacity and mRNA expression were similar between the two groups, but the SIADH rats showed a diminished up-regulation of aquaporin-2 (AQP-2) mRNA and protein expression. These findings indicate the presence of tonicity-response regions in the AQP-2 promoter gene, and that either hypervolemia or hypotonicity may attenuate the postreceptor signalling of vasopressin in renal collecting duct cells in SIADH rats. [source] The Interaction of Gestational and Postnatal Ethanol Experience on the Adolescent and Adult Odor-Mediated Responses to Ethanol in Observer and Demonstrator RatsALCOHOLISM, Issue 10 2010Amber M. Eade Background:, Gestational ethanol exposure enhances the adolescent reflexive sniffing response to ethanol odor. Postnatal exposures of naïve animals as either an observer (i.e., conspecific) or demonstrator (i.e., intoxicated peer) using a social transmission of food odor preference paradigm also yields enhanced odor-mediated responses. Studies on the interaction of fetal and postnatal exposures using the social transmission paradigm have been limited to the responses of observers. When combined, the enhanced response is greater than either form of exposure alone and, in observer females, yields adult persistence. The absence of a male effect is noteworthy, given that chemosensory mechanisms are suggested to be an important antecedent factor in the progression of ethanol preference. Observers gain odor information on the breath of the demonstrator through social interaction. Demonstrators experience the pharmacologic properties of ethanol along with retronasal and hematogenic olfaction. Thus, we tested whether augmentation of the fetal ethanol-induced behavioral response with postnatal exposure as a demonstrator differed from that as an observer. We also examined whether re-exposure as a demonstrator yields persistence in both sexes. Methods:, Pregnant dams were fed an ethanol containing or control liquid diet throughout gestation. Progeny received four ethanol or water exposures: one every 48 hours through either intragastric infusion or social interaction with the infused peer beginning on P29. The reflexive behavioral sniffing response to ethanol odor was tested at postnatal (P) day 37 or P90, using whole-body plethysmography. Results:, When tested in either adolescence or adulthood - fetal ethanol exposed adolescent ethanol observers and demonstrators significantly differed in their odor-mediated response to ethanol odor both between themselves and from their respective water controls. Nonetheless, adolescent ethanol re-exposure as a demonstrator, like an observer, enhanced the reflexive sniffing response to ethanol odor at both testing ages by augmenting the known effects of prior fetal ethanol experience. At each age, the magnitude of the enhanced odor response in demonstrators was similar to that of observers. Interestingly, only re-exposure as a demonstrator resulted in persistence of the behavioral response into adulthood in both sexes. Conclusions:, The method of ethanol re-exposure plays an important role in prolonging the odor-mediated effects of fetal exposure. While ethanol odor-specific exposure through social interaction is important, additional factors such as the pairing of retronasal and hematogenic olfaction with ethanol's intoxicating properties appear necessary to achieve persistence in both sexes. [source] QT Interval Dispersion and Cardiac Sympathovagal Balance Shift in Rats With Acute Ethanol WithdrawalALCOHOLISM, Issue 2 2010Seiko Shirafuji Background:, Dysregulation of autonomic nervous system function and impaired homogeneity of myocardial repolarization are 2 important mechanisms for the genesis of ventricular arrhythmias in nonalcoholic subjects. Our previous study suggested that acute ethanol withdrawal promoted the shift of cardiac sympathovagal balance toward sympathetic predominance and reduced the vagal tone, which were related to a higher incidence of ventricular arrhythmia and related death. However, the homogeneity of myocardial repolarization and its relation with the cardiac sympathovagal balance are unknown, especially in alcoholic subjects. The aim of the present study was to clarify these points. Methods:, Male Wistar rats were treated with a continuous ethanol liquid diet for 49 days, and then subjected to 1-day withdrawal and 1-day withdrawal with 7-day carvedilol (can block the sympathetic nervous system completely via ,1, ,2, and , adrenergic receptors) pretreatment. The cardiac sympathovagal balance and homogeneity of myocardial repolarization were evaluated based on the heart rate variability (HRV) and QT interval dispersion (QTd: dynamic changes in QT interval duration). Results:, The increase in QTd was observed only in rats at 1-day withdrawal, but not in nonalcoholic, continuous ethanol intake, and 1-day withdrawal with 7-day carvedilol pretreatment rats. At 1-day withdrawal, the low-frequency power/high-frequency power (LF/HF) ratio in HRV was elevated and correlated with the QTd. The increased QTd and elevated LF/HF ratio were normalized by the 7-day carvedilol pretreatment in rats at 1-day ethanol withdrawal. Conclusions:, In rats with an abrupt termination of the chronic continuous ethanol intake, the homogeneity of myocardial repolarization impaired and correlated with the cardiac sympathovagal balance. Carvedilol pretreatment is associated with a reduction in both the QTd and LF/HF ratio, raising the possibility that the cardiac sympathovagal balance shift may be responsible for the impaired homogeneity of myocardial repolarization, and that ,-blocker pretreatment may decrease the mortality risk during alcoholic withdrawal. [source] Abrupt Termination of an Ethanol Regimen Provokes Ventricular Arrhythmia and Enhances Susceptibility to the Arrhythmogenic Effects of Epinephrine in RatsALCOHOLISM, Issue 2010Jinyao Liu Background:, Pathologists examining victims of sudden unexpected death encounter alcoholics more often than expected; alcohol may play a role in sudden arrhythmic death. Here we determine whether a pattern of alcohol consumption, chronic ethanol intake, and withdrawal increases the incidence of malignant ventricular arrhythmia and modulates susceptibility to the arrhythmogenic potential of sympathetic stimulation from an epinephrine test in rats. Methods:, Male Wistar rats were treated with a continuous ethanol liquid diet for 7 weeks, and then subjected to 1-day withdrawal or 21-day abstinence. Ventricular ectopy was evaluated by 24-hour electrocardiographic telemetry recording; whole-body sympathetic activation, cardiac sympathovagal balance, and susceptibility to ventricular arrhythmia induced by sympathetic stimulation were evaluated based on blood noradrenalin metabolite concentrations, heart rate variability, and a 3-step epinephrine test. Results:, Ventricular arrhythmia and related death were observed only in rats at 1 day of withdrawal, but not in nonalcoholic, continuous ethanol intake or 21-day abstinence rats. One-day withdrawal after a 7-week continuous ethanol regimen elevated circulating noradrenalin metabolite levels and induced cardiac sympathovagal imbalance. Deaths related to the epinephrine test and ventricular arrhythmia induced by low doses of epinephrine were observed only in 1-day withdrawal rats. However, all anomalies were normalized by 21-day abstinence. Conclusions:, Abrupt termination of a 7-week continuous ethanol regimen is sufficient to enhance the whole-body sympathetic activation and cardiac sympathovagal imbalance that contribute to ventricular arrhythmia and sudden death in alcoholic rats. Those providing medical care for alcoholics, including in cases of legal imprisonment, should be aware of the possibility of enhanced susceptibility to sudden arrhythmic death due to the abrupt termination of a chronic ethanol regimen. [source] Operant Behavior and Alcohol Levels in Blood and Brain of Alcohol-Dependent RatsALCOHOLISM, Issue 12 2009Nicholas W. Gilpin Background:, The purpose of the present investigation was to more clearly define blood-alcohol parameters associated with alcohol dependence produced by alcohol vapor inhalation and alcohol-containing liquid diet. Methods:, Alcohol levels in blood and brain were compared during and after 4 hours of acute alcohol vapor exposure; also, brain-alcohol levels were assessed in alcohol-exposed (14-day alcohol vapor) and alcohol-naïve rats during and after 4 hours of acute alcohol vapor exposure. A separate group of rats were implanted with i.v. catheters, made dependent on alcohol via vapor inhalation, and tested for operant alcohol responding; blood-alcohol levels (BALs) were measured throughout operant alcohol drinking sessions during alcohol withdrawal. A final group of rats consumed an alcohol-liquid diet until they were dependent, and those rats were then tested for operant behavior at various withdrawal time points; BALs were measured at different withdrawal time points and after operant sessions. Results:, Blood- and brain-alcohol levels responded similarly to vapor, but brain-alcohol levels peaked at a higher point and more slowly returned to zero in alcohol-naïve rats relative to alcohol-exposed rats. Alcohol vapor exposure also produced an upward shift in subsequent operant alcohol responding and resultant BALs. Rats consumed large quantities of alcohol-liquid diet, most of it during the dark cycle, sufficient to produce high blood-alcohol levels and elevated operant alcohol responding when tested during withdrawal from liquid diet. Conclusions:, These results emphasize that the key determinants of excessive alcohol drinking behavior are the BAL range and pattern of chronic high-dose alcohol exposure. [source] Short-Term Alcohol Administration Alters KiSS-1 Gene Expression in the Reproductive Hypothalamus of Prepubertal Female RatsALCOHOLISM, Issue 9 2009Vinod K. Srivastava Background:, Kisspeptins bind to the G-protein-coupled receptor (GPR54) to activate hypothalamic luteinizing hormone releasing hormone (LHRH) secretion at the time of puberty. Alcohol (ALC) causes depressed prepubertal LHRH release, resulting in depressed luteinizing hormone (LH) secretion and delayed puberty. Because KiSS-1 and GPR54 are important to the onset of puberty, we assessed the effects of chronic ALC administration on basal expression of these puberty-related genes within the reproductive hypothalamus, as well as hormones and transduction signaling pathways contributing to their activity. Methods:, Immature female rats were fed a liquid diet containing ALC for 6 days beginning when 27 days old. Controls received either companion isocaloric liquid diet or rat chow and water. Animals were decapitated on day 33, in the late juvenile stage of development. Blood was collected for the assessment of serum hormone levels. Brain tissues containing the anteroventral periventricular (AVPV) and arcuate (ARC) nuclei were obtained for assessing expression of specific puberty-related genes and proteins. Results:,KiSS-1 mRNA levels in the AVPV and ARC nuclei were suppressed (p < 0.001) in the ALC-treated rats. GPR54 gene and protein expressions were both modestly increased (p < 0.05) in AVPV nucleus, but not in ARC nucleus. Alcohol exposure also resulted in suppressed serum levels of insulin-like growth factor-1 (IGF-1), LH, and estradiol (E2). As IGF-1, in the presence of E2, can induce expression of the KiSS-1 gene, we assessed the potential for ALC to alter IGF-1 signaling in the reproductive hypothalamus. IGF-1 receptor gene and protein expressions were not altered. However, protein expression of phosphorylated Akt, a transduction signal used by IGF-1, was suppressed in the AVPV (p < 0.05) and ARC (p < 0.01) nuclei. Conclusions:, Alcohol causes suppressed KiSS-1 gene expression in the reproductive hypothalamus; hence, contributing to this drug's ability to cause suppressed LHRH secretion and disruption of the pubertal process. We suggest that this action, at least in part, is through altered IGF-1 signaling. [source] Hepcidin Regulation in Wild-Type and Hfe Knockout Mice in Response to Alcohol Consumption: Evidence for an Alcohol-Induced Hypoxic ResponseALCOHOLISM, Issue 8 2009Mandy L. Heritage Background,/Aims:, 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. Methods:,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-1,) was measured by western blot. Results:,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-1, protein levels were elevated in alcohol-fed wild-type animals compared with controls. Conclusion:, Alcohol may decrease Hamp1 gene expression independently of the HFE pathway possibly via alcohol-induced hypoxia. [source] Preclinical Evaluation of Riluzole: Assessments of Ethanol Self-Administration and Ethanol Withdrawal SymptomsALCOHOLISM, Issue 8 2009Joyce Besheer Background:, Many of the neurobehavioral effects of ethanol are mediated by inhibition of excitatory N -methyl- d -aspartate (NMDA) and enhancement of inhibitory ,-amino-butyric-acid (GABA) receptor systems. There is growing interest in drugs that alter these systems as potential medications for problems associated with alcoholism. The drug riluzole, approved for treatment of amyotrophic lateral sclerosis (ALS), inhibits NMDA and enhances GABAA receptor system activity. This study was designed to determine the preclinical efficacy of riluzole to modulate ethanol self-administration and withdrawal. Methods:, Male C57BL/6J mice were trained to lever press on a concurrent fixed-ratio 1 schedule of ethanol (10% v/v) versus water reinforcement during daily 16-hour sessions. Riluzole (1 to 40 mg/kg, IP) was evaluated on ethanol self-administration after acute and chronic (2 week) treatment. To determine if riluzole influences ethanol withdrawal-associated seizures, mice were fed an ethanol-containing or control liquid diet for 18 days. The effects of a single injection of riluzole (30 mg/kg) were examined on handling-induced convulsions after ethanol withdrawal. Results:, Acute riluzole (30 and 40 mg/kg) reduced ethanol self-administration during the first 4 hours of the session, which corresponds to the known pharmacokinetics of this drug. Ethanol self-administration was also reduced by riluzole after chronic treatment. Riluzole (30 mg/kg) significantly decreased the severity of ethanol-induced convulsions 2 hours after ethanol withdrawal. Conclusions:, These results demonstrate that riluzole decreases ethanol self-administration and may reduce ethanol withdrawal severity in mice. Thus, riluzole may have utility in the treatment of problems associated with alcoholism. [source] S-Adenosyl-L-Methionine Co-administration Prevents the Ethanol-Elicited Dissociation of Hepatic Mitochondrial Ribosomes in Male RatsALCOHOLISM, Issue 1 2009Peter Sykora Background:, Chronic ethanol feeding to male rats has been shown to result in decreased mitochondrial translation, depressed respiratory complex levels and mitochondrial respiration rates. In addition, ethanol consumption has been shown to result in an increased dissociation of mitoribosomes. S-adenosyl-L-methionine (SAM) is required for the assembly and subsequent stability of mitoribosomes and is depleted during chronic ethanol feeding. The ability of dietary SAM co-administration to prevent these ethanol-elicited lesions was investigated. Methods:, Male Sprague-Dawley rats were fed a nutritionally adequate liquid diet with ethanol comprising 36% of the calories according to a pair-fed design for 28 days. For some animals, SAM was supplemented in the diet at 200 mg/l. Liver mitochondria were prepared and mitoribosomes isolated. Respiration rates, ATP levels, respiratory complex levels, and the extent of mitoribosome dissociation were determined. Results:, Twenty-eight days of ethanol feeding were found to result in decreased SAM content, depressed respiration, and increased mitoribosome dissociation. No changes in mitochondrial protein content; levels of respiratory complexes I, III, and V; complex I activities; and ATP levels were detected. Co-administration of SAM in the diet was found to prevent ethanol-induced SAM depletion, respiration decreases and mitoribosome dissociation. Conclusions:, Taken together, these findings suggest (1) that mitoribosome dissociation precedes respiratory complex depressions in alcoholic animals and (2) that dietary supplementation of SAM prevents some of the early mitochondrial lesions associated with chronic ethanol consumption. [source] Sex Differences in Ethanol-Induced Hypothermia in Ethanol-Naïve and Ethanol-Dependent/Withdrawn RatsALCOHOLISM, Issue 1 2009Anna N. Taylor Background:, Human and animal findings indicate that males and females display major differences in risk for and consequences of alcohol abuse and alcoholism. These differences are in large part mediated by sex-specific hormonal environments. Gonadal and adrenal secretory products are known to modulate the neurobehavioral responses of ethanol (EtOH) dependence and withdrawal. However, the effects of these steroids on physiological adaptations, such as thermoregulation, are less well established. To study the role of sex-related hormones in mediating sex differences in the hypothermic response to acute challenge with EtOH, we compared the EtOH-induced hypothermic responses of EtOH-naïve male and female rats and EtOH-dependent (on the third day of withdrawal) male and female rats before (intact) and after depletion of all gonadal and adrenal steroids by gonadectomy (GDX) with or without adrenalectomy (ADX). Methods:, Intact and GDX male and female rats, with or without ADX, were fed an EtOH-containing liquid diet for 15 days while control (EtOH-naïve) rats were pairfed the isocaloric liquid diet without EtOH or fed normal rat chow and water. On the third day of withdrawal from the EtOH diet we tested the hypothermic response to EtOH challenge (1.5 g/kg BWt, ip). Blood alcohol content (BAC) and corticosterone (CORT) content were analyzed in a separate series of intact and GDX males and females with and without ADX in response to the EtOH challenge. Results:, Ethanol-induced hypothermia was significantly greater and its duration significantly longer in intact males than females when subjects were EtOH-naïve. EtOH-induced hypothermia was significantly greater in intact females than males by the third day of withdrawal from EtOH dependence. GDX in males significantly shortened the duration of the hypothermic response and tended to blunt EtOH-induced hypothermia while response duration was significantly extended by GDX in females that tended to enhance EtOH-hypothermia. EtOH-induced hypothermia was significantly enhanced and its duration significantly lengthened by combined GDX and ADX in EtOH-naïve and -withdrawn males and by combined GDX and ADX in EtOH-naïve but not EtOH-withdrawn females. These differential EtOH-induced hypothermic responses did not appear to be caused by differences in EtOH handling among the groups. The absence of adrenal activation by EtOH in the GDX,ADX males and females contributes to their enhanced EtOH-induced hypothermic responses. Conclusions:, These results implicate the direct and indirect effects of removal of gonadal and adrenal secretory products as mediators of the thermoregulatory actions of EtOH. [source] Effects of the Glucocorticoid Antagonist, Mifepristone, on the Consequences of Withdrawal From Long Term Alcohol ConsumptionALCOHOLISM, Issue 12 2008Catherine Jacquot Background:, Studies were carried out to test the hypothesis that administration of a glucocorticoid Type II receptor antagonist, mifepristone (RU38486), just prior to withdrawal from chronic alcohol treatment, would prevent the consequences of the alcohol consumption and withdrawal in mice. Materials and Methods:, The effects of administration of a single intraperitoneal dose of mifepristone were examined on alcohol withdrawal hyperexcitability. Memory deficits during the abstinence phase were measured using repeat exposure to the elevated plus maze, the object recognition test, and the odor habituation/discrimination test. Neurotoxicity in the hippocampus and prefrontal cortex was examined using NeuN staining. Results:, Mifepristone reduced, though did not prevent, the behavioral hyperexcitability seen in TO strain mice during the acute phase of alcohol withdrawal (4 hours to 8 hours after cessation of alcohol consumption) following chronic alcohol treatment via liquid diet. There were no alterations in anxiety-related behavior in these mice at 1 week into withdrawal, as measured using the elevated plus maze. However, changes in behavior during a second exposure to the elevated plus maze 1 week later were significantly reduced by the administration of mifepristone prior to withdrawal, indicating a reduction in the memory deficits caused by the chronic alcohol treatment and withdrawal. The object recognition test and the odor habituation and discrimination test were then used to measure memory deficits in more detail, at between 1 and 2 weeks after alcohol withdrawal in C57/BL10 strain mice given alcohol chronically via the drinking fluid. A single dose of mifepristone given at the time of alcohol withdrawal significantly reduced the memory deficits in both tests. NeuN staining showed no evidence of neuronal loss in either prefrontal cortex or hippocampus after withdrawal from chronic alcohol treatment. Conclusions:, The results suggest mifepristone may be of value in the treatment of alcoholics to reduce their cognitive deficits. [source] Ethanol Decreases Rat Hepatic Arylsulfatase A Activity LevelsALCOHOLISM, Issue 11 2006Smith Jean Background: Arylsulfatase A (ASA) is an enzyme that catalyzes the degradation of sulfatides, a glycosphingolipid found in many tissues, but predominantly in myelin and kidney. Arylsulfatase A is 1 member of a family of sulfatases that is activated by a required co- or posttranslational modification with the oxidation of cysteine to formylglycine. This conversion requires a novel oxygenase mechanism that can be inhibited by reactive oxygen species. Ethanol is known to cause an increase in reactive oxygen species in the liver. Because of its effect on the levels of hepatic reactive oxygen species, we hypothesized that ethanol would cause a specific decrease of rat hepatic ASA activity levels. Methods: Male Sprague,Dawley rats received ethanol-containing, Lieber,DeCarli liquid diets for 15 days, and control rats were pair-fed a liquid diet in which dextrose was isocalorically substituted for ethanol. Results: Arylsulfatase A activity levels decreased in livers of animals receiving alcohol compared with control animals. No significant changes in ASA activity levels were observed in the cerebral cortex and kidney. Furthermore, ethanol did not have any significant effect on hexosaminidase activity in any of the tissues examined. Conclusion: Ethanol caused a tissue-specific decrease in hepatic ASA activity levels, but not hexosaminidase activity levels. [source] Maternal Oral Intake Mouse Model for Fetal Alcohol Spectrum Disorders: Ocular Defects as a Measure of EffectALCOHOLISM, Issue 10 2006Scott E. Parnell Background: This work was conducted in an effort to establish an oral intake model system in which the effects of ethanol insult that occur during early stages of embryogenesis can be easily examined and in which agents that may modulate ethanol's teratogenicity can be readily tested in vivo. The model system described utilizes the alcohol deprivation effect to obtain teratogenic levels of maternal ethanol intake on days 7 and 8 of pregnancy in C57Bl/6J mice. Ocular defects including microphthalmia and uveal coloboma, which have previously been shown to result from ethanol administered by gavage or via intraperitoneal injection on these days, served as the developmental end point for this study. The ocular defects are readily identifiable and their degree of severity is expected to correlate with concurrently developing defects of the central nervous system (CNS). Methods: Female C57Bl/6J mice were maintained on an ethanol-containing (4.8% v/v) liquid diet for 14 days and then mated during a subsequent abstinence period. Mice were then reexposed to ethanol on days 7 and 8 of pregnancy only. Control as well as ethanol-exposed dams were killed on their 14th day of pregnancy. Fetuses were then weighed, measured for crown rump length, photographed, and analyzed for ocular abnormalities. Globe size, palpebral fissure length, and pupil size and shape were noted for both the right and left eyes of all fetuses and informative comparisons were made. Results: This exposure paradigm resulted in peak maternal blood alcohol concentrations that ranged from 170 to 220 mg/dL on gestational day (GD) 8. Compared with the GD 14 fetuses from the normal control group, the pair-fed, acquisition controls, as well as the ethanol-exposed fetuses, were developmentally delayed and had reduced weights. Confirming previous studies, comparison of similarly staged control and treated GD 8 embryos illustrated reductions in the size of the forebrain in the latter. Subsequent ocular malformations were noted in 33% of the right eyes and 25% of the left eyes of the 103 GD 14 ethanol-exposed fetuses examined. This incidence of defects is twice that observed in the control groups. Additionally, it was found that the palpebral fissure length is directly correlated with globe size. Conclusions: The high incidence of readily identifiable ocular malformations produced by oral ethanol intake in this model and their relevance to human fetal alcohol spectrum disorders (FASD) makes this an excellent system for utilization in experiments involving factors administered to the embryo that might alter ethanol's teratogenic effects. Additionally, the fact that early ethanol insult yields ocular and forebrain abnormalities that are developmentally associated allows efficient specimen selection for subsequent detailed analyses of CNS effects in this in vivo mammalian FASD model. [source] Fetal Ethanol Exposure Disrupts the Daily Rhythms of Splenic Granzyme B, IFN- ,, and NK Cell Cytotoxicity in AdulthoodALCOHOLISM, Issue 6 2006Alvaro Arjona Background: Circadian (and daily) rhythms are physiological events that oscillate with a 24-hour period. Circadian disruptions may hamper the immune response against infection and cancer. Several immune mechanisms, such as natural killer (NK) cell function, follow a daily rhythm. Although ethanol is known to be a potent toxin for many systems in the developing fetus, including the immune system, the long-term effects of fetal ethanol exposure on circadian immune function have not been explored. Methods: Daily rhythms of cytotoxic factors (granzyme B and perforin), interferon- , (IFN- ,), and NK cell cytotoxic activity were determined in the spleens of adult male rats obtained from mothers who were fed during pregnancy with chow food or an ethanol-containing liquid diet or pair-fed an isocaloric liquid diet. Results: We found that adult rats exposed to ethanol during their fetal life showed a significant alteration in the physiological rhythms of granzyme B and IFN- , that was associated with decreased NK cell cytotoxic activity. Conclusion: These data suggest that fetal ethanol exposure causes a permanent alteration of specific immune rhythms that may in part underlie the immune impairment observed in children prenatally exposed to alcohol. [source] Differential Adaptations in GABAergic and Glutamatergic Systems During Ethanol Withdrawal in Male and Female RatsALCOHOLISM, Issue 6 2005P E. Alele Background: There are significant and consistent sex differences in recovery from ethanol withdrawal in our animal model of ethanol dependence. We have also observed significant and varied sex differences in subunit protein levels of ,-aminobutyric acid A (GABAA) and the N-metheyl-D-aspartate subtype of glutamate receptors occurring with ethanol dependence and withdrawal. Considering the major role of these two systems as targets of ethanol, we wanted to explore additional possible mechanisms underlying changes in GABAergic and glutamatergic responses after chronic ethanol exposure. Therefore, the objective of the present study was to examine GABAergic- and glutamatergic-associated proteins at three days of ethanol withdrawal, when female rats appear to have largely recovered but male rats still display robust signs of withdrawal. Methods: Male and female rats were fed 6% ethanol in a nutritionally complete liquid diet for 14 days according to a pair-fed design; withdrawal was initiated by replacement of the diet with chow. At three days of withdrawal, the cerebral cortex and hippocampus were dissected for use in Western blot analysis. The paired design was maintained throughout all experimental procedures. Results: At three days of ethanol withdrawal, we found region-specific and sex-selective alterations in levels of GAD (glutamic acid decarboxylase, GABA synthetic enzyme), GABA and glutamate transporters, and the synapse-associated proteins HSP70, PSD-95, and synaptophysin. There were also several significant differences in transporter function at this time that varied between males and females. Conclusions: Taken together, these findings show differential adaptations of GABAergic and glutamatergic neurotransmission between female and male rats that are associated with withdrawal recovery. This suggests that selective withdrawal-induced neuroadaptations in regulation of these systems' activities underlie, at least in part, sex differences in withdrawal recovery between male and female rats. [source] Chronic Ethanol-Induced Subtype- and Subregion-Specific Decrease in the mRNA Expression of Metabotropic Glutamate Receptors in Rat HippocampusALCOHOLISM, Issue 9 2004Agnes Simonyi Background: Chronic ethanol consumption is known to induce adaptive changes in the hippocampal glutamatergic transmission and alter NMDA receptor binding and subunit expression. Metabotropic glutamate (mGlu) receptors have been shown to function as modulators of neuronal excitability and can fine tune glutamatergic transmission. This study was aimed to determine whether chronic ethanol treatment could change the messenger RNA (mRNA) expression of mGlu receptors in the hippocampus. Methods: Male Sprague Dawley® rats were fed a Lieber-DeCarli liquid diet with 5% (w/v) ethanol or isocaloric amount of maltose for 2 months. Quantitative in situ hybridization was carried out using coronal brain sections through the hippocampus. Results: The results revealed decreases in mRNA expression of several mGlu receptors in different subregions of the hippocampus. In the dentate gyrus, mGlu3 and mGlu5 receptor mRNA levels were significantly lower in the ethanol-treated rats than in the control rats. In the CA3 region, the mRNA expression of mGlu1, mGlu5, and mGlu7 receptors showed substantial decreases after ethanol exposure. The mGlu7 receptor mRNA levels were also declined in the CA1 region and the polymorph layer of the dentate gyrus. No changes were found in mRNA expression of mGlu2, mGlu4, and mGlu8 receptors. Conclusions: Considering the involvement of hippocampal mGlu receptors in learning and memory processes as well as in neurotoxicity and seizure production, the reduced expression of these receptors might contribute to ethanol withdrawal-induced seizures and also may play a role in cognitive deficits and brain damage caused by long-term ethanol consumption. [source] Dose-Dependent Effects of Prenatal Ethanol Exposure on Synaptic Plasticity and Learning in Mature OffspringALCOHOLISM, Issue 11 2002Daniel D. Savage Background We have observed profound deficits in hippocampal synaptic plasticity and one-trial learning in offspring whose mothers drank moderate quantities of ethanol during pregnancy. In the present study, we examined the question of whether lower maternal blood ethanol concentrations (BECs) could produce functional deficits in offspring. Methods Rat dams consumed either a 2%, 3%, or 5% ethanol liquid diet throughout gestation. Three other groups of dams were pair-fed a 0% ethanol liquid diet, and a seventh group consumed lab chow ad libitum. Adult offspring from each diet group were assigned either to studies of evoked [3H]-D-aspartate (D-ASP) release from hippocampal slices or spatial learning studies using the Morris Water Task. Results Consumption of the 2%, 3%, and 5% ethanol liquid diets produced mean peak maternal BECs of 7, 30 and 83 mg/dL, respectively. Consumption of these ethanol diets had no effect on offspring birthweight, litter size or neonatal mortality. Likewise, evoked D-ASP release from hippocampal slices and performance on a standard version of the Morris Water Task were not affected by prenatal ethanol exposure. By contrast, activity-dependent potentiation of evoked D-ASP release from slices and one-trial learning on a "moving platform" version of the Morris Water Task were markedly reduced in offspring whose mothers consumed the 5% ethanol liquid diet. Intermediate deficits in these two parameters were observed in offspring from the 3% ethanol diet group, whereas offspring from the 2% ethanol diet group were not statistically different than controls. Conclusions We conclude that the threshold for eliciting subtle, yet significant learning deficits in offspring prenatally exposed to ethanol is less than 30 mg/dL. This BEC is roughly equivalent to drinking 1 to 1.5 ounces of ethanol per day. [source] Grape Polyphenols Inhibit Chronic Ethanol-Induced COX-2 mRNA Expression in Rat BrainALCOHOLISM, Issue 3 2002Agnes Simonyi Background: Chronic ethanol has been shown to increase oxidative stress leading to neurodegenerative changes in the brain. Oxidative stress may up-regulate extracellular signal regulated kinases (ERK1/2) and, subsequently, the arachidonic acid cascade mediated by phospholipase A2 (PLA2) and cyclooxygenase (COX-2). Our earlier study showed that grape polyphenols (GP) could ameliorate oxidative damage to synaptic membrane proteins due to chronic ethanol treatment. This study was aimed at examining the effects of GP on mRNA expression of ERK1/2, cytosolic PLA2 (cPLA2), and COX-2 in different brain regions after chronic ethanol treatment. Methods: Male Sprague-Dawley rats were fed a Lieber-DeCarli liquid diet with ethanol or isocaloric amount of maltose, with or without GP for 2 months. In situ hybridization was carried out using coronal brain sections through the hippocampus. Results: Quantitative in situ hybridization showed no changes in ERK1 and cPLA2 mRNA levels in cortical areas and hippocampus after ethanol and/or GP administration. However, a decrease in ERK2 and an increase in COX-2 mRNA level was found in the hippocampus of ethanol-treated animals. GP completely inhibited the increase in COX-2 due to ethanol treatment. Conclusion: Increase in COX-2 expression may be an underlying mechanism for the increase in oxidative stress induced by chronic ethanol administration. Dietary supplementation of GP may have a beneficial role in inhibiting certain alcohol effects. [source] Inhibition of Caspases In Vivo Protects the Rat Liver Against Alcohol-Induced Sensitization to Bacterial LipopolysaccharideALCOHOLISM, Issue 6 2001Ion V. Deaciuc Background: The mechanisms of liver sensitization by alcohol to Gram-negative bacterial lipopolysaccharide (LPS) remain elusive. The purpose of this study was two-fold: (1) to test the hypothesis that alcohol-enhanced liver apoptosis may be a sensitizing mechanism for LPS and (2) to further characterize the liver apoptotic response to alcohol. Methods: Rats were fed a high-fat, alcohol-containing liquid diet for 14 weeks, treated with LPS (1.0 mg/kg of body weight, intravenously) or saline, followed by injection of a pan-caspase inhibitor {IDN1965;N -[(1,3-dimethylindole-2-carbonyl)-valinyl]-3-amino-4-oxo-5-fluoropentanoic acid; 10 mg/kg of body weight, intraperitoneally} or vehicle, and killed. The following parameters were assessed: plasma aspartate: 2-oxoglutarate aminotransferase activity (AST); liver histology and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) response; caspase-3, ,8, and ,9 activity; and mRNA and protein expression for two apoptosis-signaling molecules: Fas receptor and Fas ligand; and three apoptosis adaptors: Bax, Bcl-XL, and Bcl-2. Results: Alcohol-feeding-induced liver steatosis, slightly increased caspases' activity, the number of TUNEL-positive nuclei, and facilitated the LPS necrotic effect without affecting mRNA expression of apoptosis signals and adaptors. LPS induced a significant increase in AST and the number of TUNEL-positive nuclei, both effects being more pronounced in alcohol-treated rats. LPS produced hepatic necrosis only in alcohol-treated rats. LPS effects were associated with up-regulation of mRNA expression for both apoptosis adaptors and signaling molecules. IDN1965 administration 3 hr after LPS injection strongly inhibited caspases' activity, particularly that of caspase-3. IDN1965 also abolished the increase in TUNEL-positive nuclei, reversed the effect of LPS on plasma AST in alcohol-treated rats, and prevented LPS-induced necrosis. Conclusions: (1) Alcohol-enhanced liver apoptosis may not involve regulatory steps at the transcriptional level. LPS-induced liver apoptosis seems to involve transcriptional regulation of several apoptosis adaptors. Therefore, alcohol and LPS may enhance liver apoptosis through different mechanisms. (2) Alcohol-enhanced liver apoptosis precedes and may facilitate the hepatic effects of LPS. LPS superimposed on alcohol further elevates the rate of apoptosis in the liver. This may exceed the phagocytosing capacity of the liver so that all the apoptotic cells are not phagocytosed, but rather die of necrosis. [source] | |||||||||||||