Differential effects of moderate alcohol consumption on motion and contrast processing

Although a moderate blood alcohol concentration already affects attention, an effect on early visual processing is still questionable. Using psychophysical measures and visually evoked potentials (VEP), we examined the effects of alcohol on the processing of contrast and motion features. In our tasks, two lateralized stimuli were briefly presented, and participants had to identify either the stimulus of higher contrast or motion coherence. In the contrast task, alcohol was found to decrease the discrimination ability and induced a global attenuation of VEP amplitudes. In the motion task, discrimination was not impaired. VEP amplitudes were reduced contralateral to the target position, indicating an effect of alcohol on the deployment of visuospatial attention. In sum, our data suggest that specialized areas for motion and contrast processing within the visual cortex are differently sensitive to moderate alcohol exposure.     

Genetic variation at the chemokine receptors CCR5/CCR2 in myocardial infarction

Our objective was to examine the association between myocardial infarction (MI) and two DNA-polymorphisms at the proinflammatory chemokine receptors CCR2 (I64V) and CCR5 (32 bp deletion, (Delta)ccr5), defining if these polymorphisms influence the age for the onset of MI. A total of 214 patients with an age at the first MI episode <55 years, 96 patients that suffered the first MI episode when older than 60 years, and 360 population controls were polymerase chain reaction genotyped for the CCR2-V64I and CCR5-Delta32/wt polymorphisms. Patients and controls were male from the same Caucasian population (Asturias, northern Spain). The frequency of the Deltaccr5 allele was significantly higher in controls compared to patients <55 years (P = 0.004), or in patients >60 years compared to patients <55 years (P = 0.002). Taking the patients >60 years as the reference group, non-carriers of the (Delta)ccr5-allele would have a three-fold higher risk of suffering an episode of MI at <55 years of age (OR = 3.06; 95% CI = 1.46-6.42). Gene and genotype frequencies for the CCR2 polymorphism did not differ between patients <55 years and controls or patients >60 years. Our data suggest that the variation at the CCR5 gene could modulate the age at the onset of MI. Patients carrying the (Delta)ccr5-allele would be protected against an early episode of MI. CCR5 and the CCR5-ligands are expressed by cells in the arteriosclerotic plaque. Thus, the protective role of (Delta)ccr5 could be a consequence of an attenuated inflammatory response, that would determine a slower progression of the arteriosclerotic lesion among (Delta)ccr5-carriers. Our work suggests that the pharmacological blockade of CCR5 could be a valuable therapy in the treatment of MI.     

Association of the gastric alcohol dehydrogenase gene ADH7 with variation in alcohol metabolism

Seven alcohol-metabolizing enzymes are encoded by the human alcohol dehydrogenase (ADH) gene cluster on chromosome 4q22-23. One of these genes, ADH7, is uniquely expressed in the stomach mucosa and can influence metabolism of alcohol before its absorption into the blood. However, the contribution of ADH7 to the overall genetic variation in alcohol oxidation in vivo is unknown. Data on in vivo alcohol metabolism were obtained for 206 Australian twin pairs of Caucasian ancestry, following ingestion of a standard dose (0.75 g kg(-1) body weight) of alcohol. Twenty-five single nucleotide polymorphisms that cover the ADH7 encoding region were genotyped. The patterns of linkage disequilibrium among these SNPs identified a recombinational hotspot within intron 7 of the ADH7 gene. A model for the absorption and elimination of alcohol from the body led to the identification of haplotypes associated with inter-individual variation in the early stages of alcohol metabolism. These are within a 35 kb DNA tract contained in the region 5' of intron 7 in the ADH7 gene. The region accounts for 18% of the linkage for alcohol concentration associated with the ADH region, or approximately 11% of the genetic variance.     

Age-related effects of moderate alcohol consumption on GAP-43 levels in rat hippocampus

The effects of moderate intake of ethanol and ageing were investigated on the levels of the growth-associated protein GAP-43, whose expression has been used as an indicator of axonal growth during development, regeneration and remodelling of synaptic connections. Groups of female Wistar rats (12 and 24 months of age), were alcohol-fed for one month while age-matched control groups received an isocaloric diet. A quantitative evaluation of GAP-43 was performed in hippocampus and in hippocampal selected areas in view of the vulnerability of this complex to alcohol aggression by means of two different methods, namely Western blot analysis and immunohistochemistry. While the former measures total extractable GAP-43, the latter allows visualisation of in situ changes in topographical distribution of GAP-43. Western blot analysis revealed an age-dependent reduction (-47%) and an ethanol-associated increase (81%) of GAP-43 demonstrated only in the old group. Conversely, quantitative immunohistochemistry of GAP-43 in the entire hippocampus showed a non-significant ethanol-related decrement in 24-month-old rats (-30%), although the age-dependent reduction was confirmed. Ageing was associated with a decrement of GAP-43 immunostaining in CA3 stratum radiatum (CA3) and in inner molecular layer of dentate gyrus (IML). Treatment determined a decrease of GAP-43 immunostaining in adult rat CA3 and IML and no change in CA1 stratum radiatum (CA1). Our results suggest that immunohistochemistry evaluation underestimates GAP-43 levels in ethanol-treated animals possibly as a consequence of conformational changes induced by alcohol, resulting in non-targeting of the specific antibody. Western blot analysis demonstrate that although there is a reduction of GAP-43 levels in hippocampus of aged rats, this structure retain a remarkable potential to compensate for ethanol toxicity during ageing.     

Acute effects of moderate alcohol consumption on fibrinolytic factors in healthy middle-aged men

Acute effects of moderate alcohol consumption on fibrinolytic factors were investigated in 8 healthy middle-aged men (between 45 and 55 years) in a carefully controlled study. Alcohol consumption comprised two glasses of red wine during dinner and two glasses of Dutch gin in combination with a snack during the evening (40g of alcohol in total). During the control treatment corresponding volumes of mineral water were consumed. Blood samples were drawn before dinner (around 15:00), 1 h after dinner (around 19:00), 1 h after the snack (around 23:00) and the next morning (around 08:00). PAI activity was increased by 230% (p<0.001) after alcohol consumption at the late evening measurement. PAI-1 antigen levels, however, were not significantly affected. The specific activity of PAI (activity/antigen quotient) was significantly increased by alcohol consumption at all three times of measurement after dinner. As a consequence tissue-type plasminogen activator (t-PA) activity was reduced by up to 95% (p<0.001), around 23:00. Levels of t-PA antigen, on the other hand, were increased after alcohol consumption (up to +42%, p<0.01). No effects of alcohol consumption on the urokinase plasminogen activator (u-PA) system were observed. We conclude that shortly after moderate alcohol consumption both t-PA antigen and PAI activity levels are increased, resulting, however, in a decreased activity of t-PA. Increased PAI activity persists after an overnight fast.     

The insulin-sensitizing activity of moderate alcohol consumption may promote leanness in women

Cross-sectional epidemiology reveals that women who drink alcohol regularly and moderately, on average, tend to have a decidedly lower body-mass index (BMI) than non-drinking women, despite slightly higher caloric intakes. In men, moderate drinkers are no heavier than non-drinkers, yet they consume considerably more calories. The thermogenic effect which this implies is not explained by the modest acute thermic effect of ethanol ingestion. However, there is indirect evidence that regular alcohol consumption has an insulin-sensitizing effect on skeletal muscle that down-regulates insulin secretion. Decreased insulin activity on adipocytes and the liver may discourage fat storage and promote hepatic mechanisms of ketogenesis, gluconeogenesis, and associated thermogenesis, thus possibly accounting for the relative leanness of female drinkers. The possibility that prescribing moderate alcohol intake could aid weight control in non-drinking overweight females should receive clinical evaluation. The impact of moderate drinking on risk for diabetes in women appears to be quite dramatic.     

Geographic variation in the incidence of myocardial calcification associated with acute myocardial infarction

There is reason to believe that calcium influx into heart muscle during acute myocardial infarction (AMI) can aggravate myocyte injury. Furthermore, the degree of such influx might correlate with the occurrence of microscopic myocyte calcification observed at autopsy. We have searched for evidence of myocyte calcification in hearts of patients found to have AMI at autopsy at the Veterans Administration Medical Center in Salt Lake City (SLCVA), a region with a low myocardial infection death rate, and at the George Washington University Medical Center in Washington, DC (GWUMC), a region with a high myocardial infection death rate. Of 23 consecutive cases examined under "blind" conditions at the GWUMC in which AMI was found, there were 15 instances of cardiac myocyte calcification observed in von Kossa-stained sections. Not a single example of myocyte calcification was found in 23 comparable cases at the SLCVA. The basis of this difference in myocyte calcification is unknown, but may be related to the fact that the Salt Lake City drinking water contains a higher level of magnesium, which is known to protect against soft tissue calcification, than does that of Washington, DC. This may be the basis for the apparent protection that dietary magnesium exerts against myocardial infarction death.     

The beneficial effects of deferred delivery on the efficiency of hydrogel therapy post myocardial infarction

Biomaterials are increasingly being investigated as a means of reducing stress within the ventricular wall of infarcted hearts and thus attenuating pathological remodelling and loss of function. In this context, we have examined the influence of timing of delivery on the efficacy of a polyethylene glycol hydrogel polymerised with an enzymatically degradable peptide sequence. Delivery of the hydrogel immediately after infarct induction resulted in no observable improvements, but a delay of one week in delivery resulted in significant increases in scar thickness and fractional shortening, as well as reduction in end-systolic diameter against saline controls and immediately injected hydrogel at both 2 and 4 weeks post-infarction (p < 0.05). Hydrogels injected at one week were degraded significantly slower than those injected immediately and this may have played a role in the differing outcomes. The hydrogel assumed markedly different morphologies at the two time points having either a fibrillar or bulky appearance after injection immediately or one week post-infarction respectively. We argue that the different morphologies result from infarction induced changes in the cardiac structure and influence the degradability of the injectates. The results indicate that timing of delivery is important and that very early time points may not be beneficial.     

Genetic polymorphisms of inflammatory cytokines and myocardial infarction in the elderly

Cardiovascular diseases (CVD), such as myocardial infarction (MI), are major causes of disability and mortality in the elderly. The increasing burden of CVD in ageing industrialized populations requires intensive research in order to improve preventive and therapeutic strategies especially in old people and if possible slow the processes of cardiovascular disease generation and progression. Ageing is accompanied by an age-dependent up-regulation of the inflammatory response, due to chronic antigenic stress stimulation, which potentially triggers the onset of inflammatory diseases, especially CVD. However, the exact mechanisms are still poorly understood. Since CVD are caused by interactions between genetic and environmental factors, a possible approach to their prevention is to identify the potential genetic component of inflammatory cardiovascular risk factors, providing the basis for personalized lifestyle modification and improved pharmacological therapy. Some common gene polymorphisms associated with high production of inflammatory molecules have been associated with atherosclerosis. Therefore, controlling inflammation might play a protective role against CVD, especially in ageing. Although a large number of studies of pro- and anti-inflammatory gene variants in association with CVD and MI exists, the emerging data are quite conflicting and do not provide definitive evidence for a role of these polymorphisms in the pathogenesis of MI. In this paper we review the evidence for a possible role of genetic polymorphisms of the most important inflammatory cytokines (IL-6, TNF-alpha, IL-10) and immune receptors (CD14 receptor and TLR-4) in modulating the incidence or the prognosis of MI, with a special focus in ageing population.     

Prenatal loss in the rat following moderate consumption of alcohol incorporated in a liquid diet

The teratogenic potential of alcohol in humans has now been confirmed, and a characteristic pattern of anomalies (Fetal Alcohol Syndrome) is found in infants born to mothers who are chronic alcoholics. The pathogenesis of the fetal alcohol syndrome is unclear: very little is known about the way alcohol acts during pregnancy and alters fetal growth and morphogenesis. The objective of this investigation was to determine the effects of a widely used ethanol liquid diet in the pregnant rat. The ethanol liquid test diet is based on the Lieber-De Carli formula. 20 Sprague-Dawley rats were matched closely by weights and assigned in pairs to either an alcohol treated or a pair-fed control group. Control animals received the same amount of the liquid diet with maltose-dextrins substituted isocalorically for the ethanol. Graduated tubes were used for the oral delivery of the diets. Ethanol was gradually introduced into the diet as follows: 100 Kcal/l, days 1-2; 200 Kcal/l, days 3-5; 350 Kcal/l, days 6-12. Following this initial treatment period, all animals were then given rodent pellets and tap water ad libitum. The mothers showed no overt signs of gross toxicity. The mean maternal weight gain of the ethanol treated animals did not differ significantly from the controls. The incidence of fetal resorptions was increased, intrauterine growth was not affected and the offspring at term appeared normal. The results indicate that moderate alcohol consumption during early gestation in the rat led to significant prenatal loss but proved to be non-teratogenic.     

A prospective study of moderate alcohol consumption and the risk of coronary disease and stroke in women

In 1980, 87,526 female nurses 34 to 59 years of age completed a dietary questionnaire that assessed their consumption of beer, wine, and liquor. By 1984, during 334,382 person-years of follow-up, we had documented 200 incident cases of severe coronary heart disease (164 nonfatal myocardial infarctions and 36 deaths due to coronary disease), 66 ischemic strokes, and 28 subarachnoid hemorrhages. Follow-up was 98 percent complete. As compared with nondrinkers, women who consumed 5 to 14 g of alcohol per day (three to nine drinks per week) had a relative risk of coronary disease of 0.6 (95 percent confidence interval, 0.4 to 0.9); for 15 to 24 g per day the relative risk was 0.6 (0.3 to 1.1), and for 25 g or more per day it was 0.4 (0.2 to 0.8), after adjustment for risk factors for coronary disease. Alcohol intake was also associated with a decreased risk of ischemic stroke. For 5 to 14 g of alcohol per day the relative risk was 0.3 (0.1 to 0.7), and for 15 g per day or more it was 0.5 (0.2 to 1.1). In contrast, although the number of cases of subarachnoid hemorrhage was small, alcohol intake tended to be associated with an increased risk of this disorder; for 5 to 14 g per day the relative risk was 3.7 (1.0 to 13.8). These prospective data suggest that among middle-aged women, moderate alcohol consumption decreases the risks of coronary heart disease and ischemic stroke but may increase the risk of subarachnoid hemorrhage.     

Circadian variation in the frequency of onset of acute myocardial infarction

To determine whether the onset of myocardial infarction occurs randomly throughout the day, we analyzed the time of onset of pain in 2999 patients admitted with myocardial infarction. A marked circadian rhythm in the frequency of onset was detected, with a peak from 6 a.m. to noon (P less than 0.01). In 703 of the patients, the time of the first elevation in the plasma creatine kinase MB (CK-MB) level could be used to time the onset of myocardial infarction objectively. CK-MB-estimated timing confirmed the existence of a circadian rhythm, with a three-fold increase in the frequency of onset of myocardial infarction at peak (9 a.m.) as compared with trough (11 p.m.) periods. The circadian rhythm was not detected in patients receiving beta-adrenergic blocking agents before myocardial infarction but was present in those not receiving such therapy. If coronary arteries become vulnerable to occlusion when the intima covering an atherosclerotic plaque is disrupted, the circadian timing of myocardial infarction may result from a variation in the tendency to thrombosis. If the rhythmic processes that drive the circadian rhythm of myocardial-infarction onset can be identified, their modification may delay or prevent the occurrence of infarction.     

Effect of low to moderate levels of smoking and alcohol consumption on serum immunoglobulin concentrations.

AIM: To determine the effect of low to moderate levels of smoking and alcohol consumption on immunoglobulin concentrations. METHODS: Serum samples from 1787 subjects with approximately equal numbers in each five year group from 15 to 64 years were obtained from a large random population survey in Northern Ireland. Details were available on each subject concerning the number of units of alcohol consumed per week and the number of cigarettes smoked per day. IgG, IgM, and IgA concentrations were measured by laser nephelometry on all serum samples. RESULTS: Low to moderate consumption of alcohol was associated with a decrease in IgG and IgM median concentrations in contrast to an increase in IgA median concentrations. The decrease in IgM and especially IgG median concentrations appeared to be related to the smoking habits of the subjects. Alcohol consumption alone was associated with increased IgA median concentrations whereas cigarette smoking alone was associated with reduced IgG median concentrations. CONCLUSION: Low levels of alcohol consumption and cigarette smoking influence IgG, IgM, and IgA serum concentrations. This should be borne in mind when selecting subjects for use in research and clinical settings.     

Macroscopic identification of early myocardial infarction by dehydrogenase alterations

A method utilizing a general dehydrogenase reaction has been used to demonstrate early gross myocardial infarctions. The procedure takes advantage of substrate and enzyme loss from the damaged myocardium. In the viable muscle, where endogenous substrates, coenzymes, and dehydrogenases are present, reduction of Nitro-BT yields a dark blue formazan. Necrotic muscle fibres remain unstained by this technique.A survey of 31 human hearts obtained at necropsy disclosed that there is no alteration in the Nitro-BT reaction following acute coronary insufficiency with sudden death or severe congestive heart failure. The earliest myocardial infarct to show loss of dehydrogenase activity was of eight hours' duration. Post-infarction scars and patchy interstitial fibrosis provided very precise information concerning topographic relationships when this method was applied to heart slices.     

Genetic and physiological analysis of the lethal effect of L-(+)-lactate dehydrogenase deficiency in Streptococcus mutans: complementation by alcohol dehydrogenase from Zymomonas mobilis.

CH4ts is a previously isolated recombinant mutant of Streptococcus mutans NG8 which produces a thermolabile L-(+)-lactate dehydrogenase (LDH) activity. It does not grow at 42 degrees C under a variety of cultivation conditions. In this study, we show that a batch culture of CH4ts shifted from 30 to 42 degrees C underwent rapid cessation of growth and accelerated cell death. The mutant grew at 42 degrees C in continuous culture under glucose-limiting conditions. Under these conditions, lactate production was replaced by production of ethanol and, to a smaller extent, acetoin. The cloned Zymomonas mobilis gene for alcohol dehydrogenase II, placed under the control of the S. mutans spaP regulatory signals, complemented LDH deficiency. The alcohol dehydrogenase-complemented mutant grew as well or better than NG8 on a variety of carbon sources at 42 degrees C and produced significant amounts of ethanol in place of lactic acid. These results are in accord with other approaches indicating that S. mutans has other enzymatic activities, including pyruvate formate-lyase and pyruvate dehydrogenase, for pyruvate metabolism. However, at high glucose concentrations, the levels of activity of these enzymes are apparently insufficient to compensate for the absence of LDH.