Effects Of Chronic Alcohol Intake Research Articles

Alpha-lipoic Acid Protects Against Chronic Alcohol Consumption-induced Cardiac Damage by the Aldehyde Dehydrogenase 2-associated PINK/Parkin Pathway.

Chronic alcohol intake contributes to high mortality rates due to ethanol-induced cardiac hypertrophy and contractile dysfunction, which are accompanied by increased oxidative stress and disrupted mitophagy. Alpha-lipoic acid (α-LA), a well-known antioxidant, has been shown to protect against cardiac hypertrophy and inflammation. However, little is known about its role and mechanism in the treatment of alcoholic cardiomyopathy. Here, we evaluated the role of α-LA in alcohol-induced cardiac damage by feeding mice a 4.8% (v/v) alcohol diet with or without α-LA for 6 w. Our results suggested that chronic alcohol consumption increased mortality, blood alcohol concentrations, and serum aldehyde levels, but a-LA attenuated the elevations in mortality and aldehydes. Chronic alcohol intake also induced cardiac dysfunction, including enlarged left ventricles, reduced left ventricular ejection fraction, enhanced cardiomyocyte size, and increased serum levels of brain natriuretic peptide, lactate dehydrogenase, and creatine kinase myocardial isoenzyme. Moreover, alcohol intake led to the accumulation of collagen fiber and mitochondrial dysfunction, the effects of which were alleviated by α-LA. In addition, α-LA intake also prevented the increase in reactive oxygen species production and the decrease in mitochondrial number that were observed after alcohol consumption. Chronic alcohol exposure activated PINK1/Parkin-mediated mitophagy. These effects were diminished by α-LA intake by the activation of aldehyde dehydrogenase 2. Our data indicated that α-LA helps protect cardiac cells against the effects of chronic alcohol intake, likely by inhibiting PINK1/Parkin-related mitophagy through the activation of aldehyde dehydrogenase 2.

Effect of chronic alcohol intake on the expression of muscle atrophy-related proteins in growing rats.

In this study, the effect of chronic alcohol intake for 4 weeks on the muscular atrophy factors of rat skeletal muscle was studied using 6-week-old growing Sprague-Dawley rats. Experimental animals were classified into a control group and an alcohol intake group. The alcohol intake group consumed alcohol orally at a concentration of 3-g/kg body weight every day for 4 weeks. The control group consumed tap water in the same way. After 4 weeks alcohol ingestion, glucose, total cholesterol, triglyceride, and high-density lipoprotein cholesterol in serum levels were measured. Western blot was performed to detect the expressions of muscle RING-finger protein-1 (MuRF1), protein kinase B (Akt), phosphorylated Akt (p-Akt), forkhead box O (FoxO), phosphorylated FoxO (p-FoxO), p38, and phosphorylated p38 (p-p38). Results of this experiment showed that chronic alcohol intake enhanced triglyceride concentration. Chronic alcohol intake increased MuRF1 expression to promote muscle proteolysis and decreased p-Akt/Akt ratio and p-FoxO/FoxO ratio to inhibit skeletal muscle growth. Therefore, alcohol consumption has been shown to cause muscle atrophy.

Alcoholic neuropathy associated with chronic alcohol intake

Alcoholic neuropathy (AN), a debilitating condition that mainly affects chronic alcohol drinkers, is thought to cause lesions in the peripheral nervous system leading to sensory, autonomic, and motor dysfunctions. Despite many studies, the pathogenesis of these lesions is still not completely understood. We investigated few aspects on the development of alcohol-induced peripheral neuropathy, by assessing sensory, motor and autonomic functions, as well as stereological analysis of axonal fibers and myelin sheath of the sciatic nerve. Twelve male Wistar rats were divided into Control group and Alcohol group that was submitted to Two Bottle-Choice Paradigm of intermittent and voluntary alcohol solution intake (20%; v/v) during eight weeks. At the end of treatment, three different sensorium-motor tests were applied - Tactile Sensitivity, Thermal Sensitivity, and Functional Observational Battery (FOB). Quantitative morphometric analysis of sciatic nerve structures was performed by stereological method. Alcohol concentration in the blood was measured to analyze possible correlation between availability of alcohol in the blood and the magnitude of the peripheral nerve lesion. Our data showed a peripheral effect of chronic alcohol intake associated with hyperalgesia and a process of demyelination with a strong correlation with alcohol consumption. This process was associated with increased tactile sensitivity, with behavioral reflexes such as locomotor hyperactivity, changes in gait and balance, and autonomic reflexes such as piloerection.

Effect of chronic alcohol consumption on brain structure in males with alcohol use disorder without a familiar history of alcoholism

Structural brain damages caused by chronic alcohol consumption have been extensively reported. However, the neuroimaging findings in people with alcohol use disorder (AUD) are relatively inconsistent. This inconsistency may be due to the influence of different variables that are not always considered, such as the presence of a family history of alcoholism (FHA). The main aim of this research is to study the gray (GM) and white matter (WM) volumes in male participants with AUD without FHA compared to healthy control males (HC) without FHA. For this study, we included 19 participants with AUD without FHA and 18 HC males without FHA. T1-weighted images were acquired with a General Electric Signa Exite 1.5 T scanner. GM and WM tissues were calculated using Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra (DARTEL). All analyses were controlled for age and total brain volume. The statistical threshold was calculated with AlphaSim and further adjusted to account for the non-isotropic smoothness of structural images, according to Hayasaka et al. (2004). The obtained main results showed that, relative to the HC group, the participants with AUD without FHA had significantly lower GM in several brain structures, reflecting relatively purely the effects of chronic alcohol intake on brain volume. GM structure integrity is relevant for the efficient functioning of low and high-order cognitive processes used in everyday life, and its damage seems to be related to the severity/intensity/chronicity of the AUD. As such, it becomes relevant to assess and follow brain structural changes through the dependence course.

Effects of graded increases in ethanol consumption on biochemical markers of bone turnover in young adult male cynomolgus macaques.

Chronic heavy alcohol use is often associated with reduced bone mineral density and altered bone turnover. However, the dose response effects of ethanol on bone turnover have not been established. This study examined the effects of graded increases of ethanol consumption on biochemical markers of bone turnover in young adult male cynomolgus macaques (Macaca fascicularis). For this study, 6.6-year-old (95% CI: 6.5, 6.7) male macaques were subjected to three 30-day sessions of increased ethanol intake over a 90-day interval. During the first 30 days, the monkeys drank a predetermined volume of ethanol corresponding to 0.5g/kg/day, followed by 1.0g/kg/day and 1.5g/kg/day. Osteocalcin, a marker of bone formation, and carboxyterminal cross-linking telopeptide of type 1 collagen (CTX), a marker of resorption, were measured during each 30-day session. In addition, the ratio of osteocalcin to CTX was determined as a surrogate measure of global turnover balance. Mean osteocalcin decreased by 2.6ng/mL (1.8, 3.5) for each one-half unit (0.5g/kg/day) increase in dose (p<0.001). Mean CTX decreased by 0.13ng/mL (0.06, 0.20) for each one-half unit increase in dose (p<0.001). Furthermore, there was an inverse relationship between dose and the ratio of osteocalcin to CTX, such that the mean ratio decreased by 0.9 (0.3, 1.5) for each one-half unit increase in dose (p=0.01). In summary, male cynomolgus macaques had decreased blood osteocalcin and CTX, and osteocalcin to CTX ratio during the 90-day interval of graded increases in ethanol consumption, indicative of reduced bone turnover and negative turnover balance, respectively. These findings suggest that over the range ingested, ethanol resulted in a linear decrease in bone turnover. Furthermore, the negative bone turnover balance observed is consistent with reported effects of chronic alcohol intake on the skeleton.

Effect of chronic alcohol intake on motor functions on the elderly

Alcohol use disorder (AUD) is a chronic and progressive disease influenced by genetic, psychosocial, and environmental factors. The consequences of alcohol consumption involve alterations in neural circuits of emotion and cognition, as well as in the motor planning circuit. Furthermore, during the natural aging process, several biochemical and functional alterations are also observed with neurological consequences. Thus, considering the consequences of chronic alcohol consumption on neural systems and natural aging process, we aimed to analyze the degree of motor and functional impairment in elderly with chronic alcohol consumption. Sixty elderly underwent an analysis of alcohol consumption profile (Alcohol Use Disorders Identification Test – AUDIT) that divided them into a control group (CON) and an alcohol group (ALC). The analysis of quality of life was performed using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), the analysis of motor function was performed using the Borg Scale, the Six-Minute Walk Test (6MWT) and the Motor Scale for Elderly (MSE). We were able to conclude that the misuse of alcohol by the elderly promotes significant physical limitations. These limitations result in a worsening of functional capacity of walking and various dimensions of motor ability: fine motor skill, global coordination, balance, body scheme, spatial organization, temporal organization, and general motor aptitude. Besides the physical limitations caused by alcohol use, the quality of life in their physical, mental, and social aspects was reduced. Thus, actions are required to help the elderly understand these losses and exercise control over alcohol misuse.

Possible ameliorative role of green tea on chronic alcohol mediated renal toxicity of STZ -induced diabetic rats

Summary This research was planned to assess the protective effect of aqueous green tea extract (AGTE) in alcohol treated diabetic rats. This study was examined, whether 20% v/v of 5 g/kg.b.w alcohol intake exacerbates diabetes-induced renal damage associated with an escalated nitroxidative stress and glucose homeostasis in comparison with diabetic condition alone. The present study is primarily focused to investigate the possible toxic effects of chronic alcohol intake on kidney of streptozotocin (STZ)-induced diabetic rats. Forty albino male Wistar rats were used and randomly allocated into five groups. Diabetes was induced by a single intraperitoneal injection of STZ (50 mg/kg) in rats. Alcohol was administered through orogastric tube once daily for a period of 60 days. Impact of chronic alcohol treatment on renal function and selected metabolites of catecholamines and antioxidant metabolisms have been investigated in the kidney of STZ-induced diabetic rats. Biochemical analysis of kidneys demonstrated that chronic alcohol induced alterations in vitro gluconeogenesis, significant decrease in the body weight, and activities of antioxidant enzymes in diabetic rats. A significant increase in the levels of epinephrine and sertonine was observed between alcohol treated, diabetic control and alcohol treated diabetic rat groups. Further, excessive chronic alcohol treatment caused additive deterioration of the kidney function as evidenced by increased inducible nitric oxide synthase (iNOS) protein expression and thus nitroxidative stress and histopathological aberrations leading to aggravation of diabetic nephropathy under alcohol intoxication. Treatment with aqueous green tea extract (300 mg/kg.b.w) to diabetic rats treated with alcohol renders the protection against the decreased body weight, increased hyperglycemia, hyperlipidemia, catecholamines, nitroxidative stress and further tissue damage.

Effect of chronic alcohol intake in a pre-clinical model with cholesterol overload

Effect of chronic alcohol intake in a pre-clinical model with cholesterol overload

Effect of chronic alcohol intake on postoperative analgesia in cancer patients: a large sample, retrospective analysis

Objective To evaluate the effect of chronic alcohol intake on postoperative analgesia in cancer patients. Methods American Society of Anesthesiologists physical status Ⅰ or Ⅱ male patients, aged ≥18 yr, underwent postoperative intelligentized patient-controlled analgesia management from January 1, 2016 to October 22, 2018, searched from wireless analgesia management system database, were selected.The patients were divided into control group and chronic alcoholic intake group according to the history of chronic alcoholic intake.Combined intravenous-inhalational anesthesia was used during surgery.Patient-controlled intravenous or subcutaneous analgesia was performed with sufentanil.When moderate pain occurred (4 points≤numeric rating scale score≤6 points), the parameters of analgesia pump was regulated for rescue analgesia.When severe pain occurred (numeric rating scale score at rest or during activity≥7 points), dezocine 0.5 mg was intravenously injected as rescue analgesic.The effective pressing times, the number of attempts, consumption of sufentanil and occurrence of moderate or severe pain were recorded.The adverse reactions such as nausea and vomiting, pruritus, dizziness and hypotension were also recorded. Results A total of 1 914 patients were enrolled in this study, with 1 508 cases in control group and 406 cases in chronic alcoholic intake group.Compared with control group, the effective pressing times, the number of attempts, consumption of sufentanil and incidence of moderate or severe pain were increased (P<0.05), and no significant change was found in the incidence of nausea and vomiting, pruritus, dizziness or hypotension in chronic alcoholic intake group (P<0.05). Conclusion Chronic alcohol intake can decrease the efficacy of postoperative analgesia in cancer patients. Key words: Alcohol drinking; Pain, postoperative; Analgesia, patient-controlled

Determining the Effect of Diet on Liver and Renal Health in a Mouse Model of Chronic Alcohol Intake

Diet and alcohol consumption are significant contributors to health and disease worldwide. Liver disease is a consequence of poor diet and alcohol consumption; however preclinical animal studies have not adequately considered the combined effect of poor diet and chronic alcohol intake into study design. Given the physiological cross talk between the liver and kidney and the occurrence of hepatorenal syndrome in alcoholics, we set out to determine how poor diet and chronic alcohol intake influence liver and kidney health in mice. All experiments were performed in accordance with protocols approved by the Liberty University IACUC and conform to the FASEB standards for the use of animals in research and education. 3‐week old male C57Bl/6 mice were purchased from The Jackson Laboratory and acclimated to the new environment and chow diet for 1‐week. Mice were then given ad libitum access to chow (18% protein), our novel Americanized diet (AD), or a commercially available “Western” diet (WD) (n=6). After 6 weeks, all mice began a chronic alcohol exposure of 10% ethanol solution given as the only source of water for 3 weeks. Body weight, food, and beverage intake were recorded weekly. Systolic blood pressure was determined using a non‐invasive tail‐cuff method and renal blood flow estimated using contrast‐enhanced ultrasonography. Mice were then euthanized and blood and liver tissues collected. Blood was analyzed for circulating ALT activity and HDL, triglycerides, and glucose concentrations. All statistical analyses were performed using general linear models in SPSS with “Diet” as the independent variable. Diet had a significant effect on ethanol consumption (P&lt;0.001), with mice fed chow having the highest ethanol intake (6 mg ethanol/g body weight) as compared to mice fed the WD (3.4 mg/g). Mice fed the WD had the greatest body weight, dietary intake, adiposity, and circulating HDL concentration as compared to mice fed chow (P&lt;0.001). Mice fed chow had the highest circulating glucose levels (P&lt;0.001). Histological analyses revealed excessive hepatic steatosis as the primary finding and was most severe in mice fed WD. No overt changes were noted in mice fed chow. Circulating ALT activity was elevated in mice fed the WD as compared to mice fed AD or chow, further suggesting increased liver injury in these mice. Mice fed the AD had intermediate values for all measurements with the exception of systolic blood pressure. Mice fed the AD had a 10 mmHg increase in systolic pressure as compared to mice fed chow or the WD (P=0.03). This occurred despite a lack of difference in renal hemodynamics between the different dietary groups (P≥0.3). Our data suggest that diet and alcohol have an additive effect in regards to liver damage and the development of metabolic dysfunction. The physiological mechanism by which consumption of our novel AD caused moderate hypertension in mice when combined with chronic alcohol intake will be pursued in future studies. Taken together, our findings highlight the need to consider the role of diet in preclinical animal models studying the physiological effects of chronic alcohol intake.Support or Funding InformationLUCOM Intramural Grant #2018‐01.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

SREBP1c mediates the effect of acetaldehyde on Cidea expression in Alcoholic fatty liver Mice

Cell death inducing DNA fragmentation factor-alpha-like A (Cidea) is a member of cell death-inducing DFF45-like effector (CIDE) protein. The initial function of CIDE is the promotion of cell death and DNA fragmentation in mammalian cells. Cidea was recently reported to play critical roles in the development of hepatic steatosis. The purpose of present study is to determine the effect of chronic alcohol intake on Cidea expression in the livers of mice with alcoholic fatty liver disease. Cidea expression was significantly increased in the liver of alcohol-induced fatty liver mice. While, knockdown of Cidea caused lipid droplets numbers reduction. Next, we detected the activity of ALDH2 reduction and the concentration of serum acetaldehyde accumulation in our alcohol-induced fatty liver mice. Cidea expression was elevated in AML12 cells exposed to 100uM acetaldehyde. Interestingly, Dual-luciferase reporter gene assay showed that 100 uM acetaldehyde led to the activation of Cidea reporter gene plasmid which containing SRE element. What’s more, the knockdown of SREBP1c suppressed acetaldehyde-induced Cidea expression. Overall, our findings suggest that Cidea is highly associated with alcoholic fatty liver disease and Cidea expression is specifically induced by acetaldehyde, and this up-regulation is most likely mediated by SREBP1c.

Effects of alcohol consumption on blood pressure in hypertensive women

ABSTRACTBackground: Problem drinking carries significant health burdens, including an increased risk of hypertension. The effect of chronic alcohol intake on blood pressure (BP) in women is understudied and poorly understood. Objectives: We sought to examine the relationships between drinking habits and BP in hypertensive women. Methods: We analyzed drinking habits in 113 women followed in the Brigham and Women's Hospital Hypertension Clinic for at least one year. Results: Among these women with well-controlled hypertension, baseline diastolic BP was significantly lower in moderate drinkers compared with women who rarely or never drank. Changes in both systolic and diastolic BP over 12 months showed a significant negative association with changes in percent drinking days. In contrast, there was a trend toward higher baseline systolic BP among those women who consumed more drinks per drinking day. Conclusions: Among these women with controlled hypertension, our data failed to demonstrate an association between drinking beyond recommended limits and higher disease burden. These findings parallel the widely reported difference between drinking frequency, associated with a host of positive health outcomes, and drinking intensity, associated with negative outcomes. Novel to this report is an observed reduction in blood pressure over the one-year follow-up period accompanying an increased drinking frequency in treated hypertensive women. Cautions include the suggestion that a greater number of drinks per drinking day was associated with higher baseline pressure. These data imply that drinking within sensible limits has no negative impact on chronic hypertension. In fact, for women with well-controlled hypertension, such a habit may impart benefit.

Effects of chronic alcohol exposure on ischemia\u2013reperfusion-induced acute kidney injury in mice: the role of \u03b2-arrestin 2 and glycogen synthase kinase 3

Little is known about the effects of chronic alcohol intake on the outcome of acute kidney injury (AKI). Hence, we examined the effects of chronic alcohol intake on the development of renal fibrosis following AKI in an animal model of bilateral renal ischemia–reperfusion (IR) injury. We first found that chronic alcohol exposure exacerbated bilateral IR-induced renal fibrosis and renal function impairment. This phenomenon was associated with increased bilateral IR-induced extracellular matrix deposition and an increased myofibroblast population as well as increased bilateral IR-induced expression of fibrosis-related genes in the kidneys. To explore the mechanisms underlying this phenomenon, we showed that chronic alcohol exposure enhanced β-arrestin 2 (Arrb2) expression and Akt and glycogen synthase kinase-3 (GSK3)β activation in the kidneys. Importantly, pharmacological GSK3 inhibition alleviated bilateral IR-induced renal fibrosis and renal function impairment. Furthermore, we demonstrated that Arrb2−/− mice exhibited resistance to IR-induced renal fibrosis and renal function impairment following chronic alcohol exposure, and these effects were associated with attenuated GSK3β activation in the kidneys. Taken together, our results suggest that chronic alcohol exposure may potentiate AKI via β-arrestin 2/Akt/GSK3β-mediated signaling in the kidney.

Effect of Chronic Alcohol Intake on Auditory System with Changes in Auditory Brainstem Evoked Responses

Effect of Chronic Alcohol Intake on Auditory System with Changes in Auditory Brainstem Evoked Responses

Chronic Alcohol Ingestion and Predisposition to Lung “Cirrhosis”

Although liver is the organ most often associated with the damaging effects of chronic alcohol abuse, other organs may also be affected. In the past decade, data emerged linking chronic alcohol intake to lung dysfunction. However, the mechanisms by which alcohol affects the lung remain incompletely elucidated. In this issue, Sueblinvong and colleagues explore the effect of chronic alcohol intake in the well-known rodent model of bleomycin-induced lung injury. This represents a review of their article and a commentary on its findings in relation to current knowledge in the field. The investigators found that chronic alcohol intake increased lung fibrosis in the bleomycin-model of lung injury. This effect was related to increased production of transforming growth factor β (TGFβ) and expression of α-smooth muscle actin. Diet supplementation with S-adenosylmethionine greatly reduced the effect. These data strengthen published reports linking chronic alcohol intake with TGFβ overproduction and lung disrepair after injury, while implicating oxidant stress as a critical mediator of these effects. A review of Sueblinvong and colleagues' article and the literature strongly suggests that the lung is a target for alcohol, and that chronic alcohol intake may predispose the lung to disrepair after injury. The overexpression of pro-fibrotic growth factors and pro-inflammatory cytokines, and the generation of oxidant stress may lead to lung cellular dysfunction, aberrant tissue remodeling, and loss of lung function. These events may represent targets for intervention, but translational studies evaluating their role in humans are desperately needed.

Chronic Alcohol Consumption Affects Serum Enzymes Levels in the HIV-Infected Patients on Stavudine (d4T)/Lamivudine (3TC)/Nevirapine (NVP) Treatment Regimen

Chronic alcohol use is a common problem globally among the HIV-infected patients on ARV treatment regimens, leading to severe liver damage and increase in serum enzymes. The study determined effect of chronic alcohol intake on serum enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transferase (GGT)) in HIV-infected patients on d4T/3TC/NVP treatment regimen in Uganda using the WHO alcohol use disorders’ identification test (AUDIT) tool and chronic alcohol use biomarkers (ALT, AST, GGT, AST/ALT ≥ 2.0 and mean corpuscular volume (MCV)). A case control study using repeated measure design with serial measurements model was used. Alcohol use biomarkers were used to standardize the gender differences in alcohol use. A total of 41 patients (21 alcohol group and 20 control group) were followed up for 9 months with blood sampling done at 3 month intervals. The serum enzymes’ levels were determined by using the Cobas Intergra 400 Plus analyzer system. The mean GGT levels were higher in chronic alcohol use group as compared to control group in both groups. The levels were above reference ranges during 6 month and three times higher during 9-month follow-up period for both chronic alcohol use self reporting WHO AUDIT tool and biomarkers’ groups. Generally, the mean AST, ALT and AST/ALT levels were slightly higher in alcohol use group as compared to control group and were slightly higher in both groups as compared to reference ranges during the 9 month follow-up period. Chronic alcohol consumption by HIV-infected patients on d4T/3TC/NVP drug regimen increased GGT and AST/ALT serum enzyme levels and hence was used as chronic alcohol use biomarkers.

Overexpression of Hydroxymethylglutaryl CoA Synthase 2 and 2,4-Dienoyl-CoA Reductase in Rat Pancreas Following Chronic Alcohol Consumption

The mechanism of alcohol-induced pancreatic damage is unclear. The aim of this study was to clarify the effects of chronic alcohol intake on the pancreatic proteome. Rats were fed an alcohol-containing Lieber-DeCarli liquid diet, and the pancreatic proteome was compared with that of pair-fed control rats using agarose 2-dimensional gel electrophoresis followed by liquid chromatography-tandem mass spectrometry. The expression of 3 proteins was consistently altered in alcohol-fed rats: 1 protein was down-regulated, and 2 proteins were up-regulated. The 2 up-regulated proteins were identified as 2,4-dienoyl-CoA reductase and hydroxymethylglutaryl-CoA synthase (HMGCS2). The combined concentration of malondialdehyde and 4-hydroxyalkenals was significantly greater in alcohol-fed rats. It is noteworthy that the reactivity of anti-4-hydroxy-2-nonenal antibody was significantly higher toward HMGCS2 isolated from alcohol-fed rats. The activity of HMGCS2 was higher in alcohol-fed rats, but the relative increase in enzyme activity in alcohol-fed rats was less than the relative increase in HMGCS2 expression. Chronic alcohol consumption results in distinct alterations in the expression of 3 pancreatic proteins. The reactivity of 4-hydroxy-2-nonenal toward one of the up-regulated proteins, HMGCS2, increased markedly following chronic alcohol intake, suggesting that up-regulation of HMGCS2 is connected with alterations of lipid peroxidation induced by alcohol.

Effect of chronic alcohol consumption on the red blood cell count and RBC indices in the HIV infected patients on d4T/3TC/NVP drug regimen in Uganda

Alcohol consumption is common problem in Uganda. Among the types of alcohols consumed include beers, spirits, liqueurs, wines and traditional brew. These alcohols are easily accessible and consumed by many people including the HIV infected patients who are on the d4T/3TC/NVP regimen. The aim of this study was to determine the effect of chronic alcohol intake on the red blood cell count (RBC) and the RBC indices in the HIV-infected patients on d4T/3TC/NVP regimen. It was a case control study that used a repeated measures design model where serial measurements of the red blood cell count (RBC) and RBC indices were determined at 3 month interval for 9 months. A total of 41 HIV infected patients were recruited and grouped into two arms; the control group had 21 patients and the chronic alcohol group had 20 patients. The RBC and RBC indices of the whole blood were determined using automated hematological Coulter CBC-5 Hematology Analyzer system using standard procedures. The data was sorted into alcohol-use self reporting by WHO AUDIT tool and alcohol-use biomarkers groups. It was analysed using the SAS 2003 version 9.1 statistical package with the repeated measures fixed model. The means were compared using the student t-test. The mean MCV and MCH values in the chronic alcohol use group were higher than in the control group and there was a significant difference between the 2 groups (p&lt;0.05) for both the WHO AUDIT tool group and chronic alcohol use biomarkers group. The mean RBC count, Hct, HGB and MCHC values in both the control and chronic alcohol use groups were within the normal reference ranges for both groups though the trend was lower in alcohol group. Chronic alcohol use affects the RBC and RBC indices in the HIV infected patients on d4T/3TC/NVP treatment regimen.

HSF1 transcriptional activity mediates alcohol induction of Vamp2 expression and GABA release

Many central synapses are highly sensitive to alcohol, and it is now accepted that short-term alterations in synaptic function may lead to longer-term changes in circuit function. The regulation of postsynaptic receptors by alcohol has been well studied, but the mechanisms underlying the effects of alcohol on the presynaptic terminal are relatively unexplored. To identify a pathway by which alcohol regulates neurotransmitter release, we recently investigated the mechanism by which ethanol induces Vamp2, but not Vamp1, in mouse primary cortical cultures. These two genes encode isoforms of synaptobrevin, a vesicular soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein required for synaptic vesicle fusion. We found that alcohol activates the transcription factor heat shock factor 1 (HSF1) to induce Vamp2 expression, while Vamp1 mRNA levels remain unaffected. As the Vamp2 gene encodes a SNARE protein, we then investigated whether ethanol exposure and HSF1 transcriptional activity alter neurotransmitter release using electrophysiology. We found that alcohol increased the frequency of γ-aminobutyric acid (GABA)-mediated miniature IPSCs via HSF1, but had no effect on mEPSCs. Overall, these data indicate that alcohol induces HSF1 transcriptional activity to trigger a specific coordinated adaptation in GABAergic presynaptic terminals. This mechanism could explain some of the changes in synaptic function that occur soon after alcohol exposure, and may underlie some of the more enduring effects of chronic alcohol intake on local circuit function.

The effects of ethanol upon hydric balance and arterial pressure in rats: Folic acid as a possible hypotensor

AimsChronic alcohol intake is related to hypertension. There are, however, few studies concerning the effect of ethanol upon hydric balance in relation to arterial pressure. Folic acid intake has beneficial effects upon the cardiovascular system decreasing hyperhomocysteinemia, however, more studies imply that it is related with other mechanisms. Therefore, we have studied the effects of chronic alcohol intake (30% v/v) upon hydric-saline balance and hypertension and have found that dietary supplementation with folic acid (8mg/kg) improves the above parameters. Main methodsOur study used four experimental groups of rats: control, alcohol, alcohol with folic acid and control with folic acid. In all cases we measured the clearance of Na+, K+ and aldosterone; osmolarity in urine, liquid and solid ingestion; homocysteine levels in serum; cardiac frequency and arterial blood pressure. Key findingsThe alcohol intake increases serum aldosterone and homocysteine, which is reflected in an increase in arterial blood pressure. In addition, we have found that alcohol intake reduces both liquid and solid ingestion (causing a malnourishment status), the clearance of creatinine, aldosterone, Na+ and K+, and the ratio ClNa+/ClCr; it also increases urine osmolarity. Folic acid supplementation increases the clearance of Na+ and the ratio ClNa+/ClCr. SignificanceFolic acid intake improves the hypertension provoked by alcohol by increasing the aldosterone clearance, drastically reducing the serum levels of this hormone and thus its hypertensor effect.