Alcohol and thermally oxidized pufa induced oxidative stress: role of N-acetyl cysteine

Alcohol related disabilities are one of the world's major public health concerns. The effects of alcohol intake include alteration of redox state, acetaldehyde and free radical production, which lead to membrane damage. The damage caused by alcohol is enhanced by polyunsaturated fatty acid ingestion. When alcohol is taken along with thermally oxidized sunflower oil, the toxicity is still more pronounced due to toxic metabolites produced during heating. In our study, we have analysed the effects of a thiol supplier N-acetyl cysteine on alcohol, thermally oxidized sunflower oil and alcohol + thermally oxidized sunflower oil induced toxic effects in male Wistar rats. The activities of liver marker enzymes (alkaline phosphatase and gamma-glutamyl transferase), triglycerides in plasma and lipid peroxidative indices (thiobarbituric acid reactive substances and hydroperoxides) were increased in these groups when compared to normal, which were brought down in N-acetyl cysteine treated groups. The antioxidant status (Superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase) was decreased in tissues of these groups, which were found to be improved in N-acetyl cysteine treated groups. Thus our results show that N-acetyl cysteine regresses the oxidative damage induced by Alcohol, thermally oxidized sunflower oil and alcohol + thermally oxidized sunflower oil.     

The quadratic cumulative odds regression model for scored ordinal outcomes: application to alcohol dependence

In this paper, we develop new regression models for the analysis of scored ordinal data (i.e. ordinal outcomes where the categories are assigned numeric values). The novel feature of these models is that they enable one to capture and identify nonlinear aspects of the relationship between an ordinal clinical measurement (used for disease diagnosis) and risk factors. These nonlinearities may be useful in generating hypotheses about the risk factor's role in the etiologic process as well as suggesting how to design future studies of the risk factor. We apply our model to study the effects of race, gender, and family history on alcohol dependence among a cohort of lifetime drinkers from the 1992 National Longitudinal Alcohol Epidemiologic Survey.     

Alcohol and Acute Pancreatitis

Alcohol abuse is associated with the development of both acute and chronic pancreatitis. The majority of patients who abuse alcohol will not develop pancreatitis; the reasons for different susceptibilities to alcohol are unknown. Most patients who present with acute alcoholic pancreatitits will have underlying chronic disease, but up to a third will have no evidence of chronic pancreatitis. Alcohol has a number of acute effects on the pancreas that are potentially toxic. These include increasing pancreatic duct pressure, decreasing pancreatic blood flow, generating free radicals, and stimulating pathologic zymogen activation within the pancreatic acinar cell.     

Polytomous disease mapping to detect uncommon risk factors for related diseases

A statistical model for jointly analysing the spatial variation of incidences of three (or more) diseases, with common and uncommon risk factors, is introduced. Deaths for different diseases are described by a logit model for multinomial responses (multinomial logit or polytomous logit model). For each area and confounding strata population (i.e. age-class, sex, race) the probabilities of death for each cause (the response probabilities) are estimated. A specic disease, the one having a common risk factor only, acts as the baseline category. The log odds are decomposed additively into shared (common to diseases different by the reference disease) and specic structured spatial variability terms, unstructured unshared spatial terms and confounders terms (such as age, race and sex) to adjust the crude observed data for their effects. Disease specic spatially structured effects are estimated; these are considered as latent variables denoting disease-specic risk factors. The model is presented with reference to a specic application. We considered the mortality data (from 1990 to 1994) relative to oral cavity, larynx and lung cancers in 13 age groups of males, in the 287 municipalities of Region of Tuscany (Italy). All these pathologies share smoking as a common risk factor; furthermore, two of them (oral cavity and larynx cancer) share alcohol consumption as a risk factor. All studies suggest that smoking and alcohol consumption are the major known risk factors for oral cavity and larynx cancers; nevertheless, in this paper, we investigate the possibility of other different risk factors for these diseases, or even the presence of an interaction effect (between smoking and alcohol risk factors) but with different spatial patterns for oral and larynx cancer. For each municipality and age-class the probabilities of death for each cause (the response probabilities) are estimated. Lung cancer acts as the baseline category. The log odds are decomposed additively into shared (common to oral cavity and larynx diseases) and specic structured spatial variability terms, unstructured unshared spatial terms and an age-group term. It turns out that oral cavity and larynx cancer have different spatial patterns for residual risk factors which are not the typical ones such as smoking habits and alcohol consumption. But, possibly, these patterns are due to different spatial interactions between smoking habits and alcohol consumption for the first and the second disease.     

Alcohol induces Golgi fragmentation in differentiated PC12 cells by deregulating Rab1-dependent ER-to-Golgi transport

In the present study, we analyze the effects of ethanol on the Golgi structure and membrane transport in differentiated PC12 cells, which are used as a model of neurons. Chronic exposure to moderate doses of ethanol induces Golgi fragmentation, a common characteristic of many neurodegenerative diseases. Alcohol impaired the lateral linking of stacks without causing microtubule damage. Extensive immunocytochemical and western blot analyses of representative Golgi proteins showed that few, but important, proteins are significantly affected. Thus, alcohol exposure induced a significant ER-to-Golgi transport delay, the retention of the GTPase Rab1 in the Golgi membranes and the accumulation of tethering factor p115 in the cytosol. These modifications would explain the observed fragmentation. The amount of p115 and the stacking protein GRASP65 increased in alcohol-treated cells, which might be a mechanism to reverse Golgi damage. Importantly, the overexpression of GTP-tagged Rab1 but not of a dominant-negative Rab1 mutant, restored the Golgi morphology, suggesting that this protein is the main target of alcohol. Taken together, our results support the view that alcohol and neurodegenerative diseases such as Parkinson have similar effects on intracellular trafficking and provide new clues on the neuropathology of alcoholism.     

Drinking and driving pancreatitis: links between endoplasmic reticulum stress and autophagy

Alcohol abuse is the leading etiologic factor of pancreatitis, although many heavy drinkers do not develop pancreatic damage. Alcohol promotes pancreatitis through a combination of remote (e.g., increased gut permeability to bacterial products such as lipopolysaccharide) and more proximal effects (e.g., altered pancreatic cholinergic inputs), including oxidative damage at the level of the pancreatic acinar cell. Recent evidence indicates that alcohol exposure to rodents disturbs proteostasis in the exocrine pancreas, an effect counterbalanced by homeostatic processes that include both the unfolded protein response (UPR) and autophagy. A corollary to this notion is that pancreatitis results when adaptive responses are insufficiently robust to alleviate the cellular stress caused by alcohol.     

Drinking and driving pancreatitis

Alcohol abuse is the leading etiologic factor of pancreatitis, although many heavy drinkers do not develop pancreatic damage. Alcohol promotes pancreatitis through a combination of remote (e.g., increased gut permeability to bacterial products such as lipopolysaccharide) and more proximal effects (e.g., altered pancreatic cholinergic inputs), including oxidative damage at the level of the pancreatic acinar cell. Recent evidence indicates that alcohol exposure to rodents disturbs proteostasis in the exocrine pancreas, an effect counterbalanced by homeostatic processes that include both the unfolded protein response (UPR) and autophagy. A corollary to this notion is that pancreatitis results when adaptive responses are insufficiently robust to alleviate the cellular stress caused by alcohol.     

Vascular effects of maternal alcohol consumption

Maternal alcohol consumption during pregnancy is a significant field of scientific exploration primarily because of its negative effects on the developing fetus, which is specifically defined as fetal alcohol spectrum disorders. Though the effects on the mother are less explored compared with those on the fetus, alcohol produces multiple effects on the maternal vascular system. Alcohol has major effects on systemic hemodynamic variables, endocrine axes, and paracrine factors regulating vascular resistance, as well as vascular reactivity. Alcohol is also reported to have significant effects on the reproductive vasculature including alterations in blood flow, vessel remodeling, and angiogenesis. Data presented in this review will illustrate the importance of the maternal vasculature in the pathogenesis of fetal alcohol spectrum disorders and that more studies are warranted in this field.     

International Commission for Protection Against Environmental Mutagens and Carcinogens. ICPEMC Working Paper 7/1/2. Shared risk factors for cancer and atherosclerosis--a review of the epidemiological evidence

This paper reviews the epidemiological literature of relevance for the hypothesis that somatic mutation is involved in the formation of the atherosclerotic plaque. Assuming that somatic mutations are involved in atherogenesis, one would expect at least some of the risk factors for cancer and for atherosclerosis to be identical. Therefore, the review covers the correlated occurrence of cancer and atherosclerotic disease. Special interest is given to populations at high risk of cancer, including subpopulations with certain genetic diseases, and populations exposed to certain carcinogenic environmental agents including ionizing radiation, vinyl chloride monomer (VCM), arsenic, tobacco, and various industrial combustion effluents containing polycyclic aromatic hydrocarbons (PAHs). Exposure to combustion effluents from burning of tobacco or fuel is associated with an increased risk of cancer and atherosclerotic disease. Combustion effluents constitute a complex mixture of potentially hazardous agents, however, and the observed correlation of cancer and atherosclerosis among exposed persons cannot be unambiguously interpreted as evidence of a common etiology of the two groups of diseases. For ionizing radiation, arsenic, and VCM there is suggestive evidence that these agents possess an atherogenic effect beside their well-known carcinogenic properties. Both arsenic and VCM seem to have a specific affinity to the vascular bed causing various lesions including angiosarcomas and atherosclerotic plaques. Regarding ionizing radiation, the atherogenic effects seem to be localized to heavily irradiated fields. Beside the carcinogenic and atherogenic effects, exposure to arsenic, VCM, and ionizing radiation brings about an increase in the incidence of mutations and chromosomal aberrations. A theory involving somatic mutation in the pathogenesis of the atherosclerotic plaque could be consistent with the observed biological effects of ionizing radiation, arsenic, and VCM. The scant data from families with certain inherited diseases may also be consistent with an involvement of the genome in the pathogenesis of atherosclerosis. In conclusion, there is strong epidemiological evidence that several factors associated with an increased risk of cancer are also associated with an increased risk of atherosclerosis.     

Arsenic Uptake by Lemna minor in Hydroponic System

Arsenic is hazardous and causes several ill effects on human beings. Phytoremediation is the use of aquatic plants for the removal of toxic pollutants from external media. In the present research work, the removal efficiency as well as the arsenic uptake capacity of duckweed Lemna minor has been studied. Arsenic concentration in water samples and plant biomass were determined by AAS. The relative growth factor of Lemna minor was determined. The duckweed had potential to remove as well as uptake arsenic from the aqueous medium. Maximum removal of more than 70% arsenic was achieved at initial concentration of 0.5 mg/l arsenic on 15th day of experimental period of 22 days. Removal percentage was found to decrease with the increase in initial concentration. From BCF value, Lemna minor was found to be a hyperaccumulator of arsenic at initial concentration of 0.5 mg/L, such that accumulation decreased with increase in initial arsenic concentration.     

Alcohol reverses the proconflict effect of corticotropin-releasing factor

Alcohol has tension reducing properties in man that are reflected in a release of punished responding in a rat operant conflict test. In contrast, corticotropin releasing factor (CRF), injected centrally produces a suppression of punished and non-punished responding in the conflict test consistent with its hypothesized role in mediating behavioral responses to stress. Alcohol in a dose of 0.75 g/kg reversed the suppressive effects of 0.5 microgram CRF injected intracerebroventricularly on punished responding but augmented the suppression of unpunished responding by CRF. Results suggest that one mechanism for the tension reducing properties of acute alcohol intoxication may involve a suppression of brain CRF systems.     

Moderation in Australia-policy and achievements

Alcohol has been consumed in Australia since European settlement in 1788. In 1998, approximately 60% of Australians consumed an alcoholic beverage at least once per week. The effects of alcohol on the human body are dose dependent, where the harmful effects of alcohol are generally observed only when alcohol consumption exceeds moderate consumption levels of 30 to 40 g of alcohol per day. The discovery that a J-shaped curve described the relationship between level of alcohol consumption and risk of cardiovascular disease was, however, only made in 1990-cardiovascular disease is the leading cause of death in the western world. Thus prior to 1990, Australian public health policy focused primarily on the harmful effects of alcohol consumption and the health benefits of a moderate level of alcohol consumption have only recently been recognized in public policy. This paper chronicles changes in Australian Federal government policy on alcohol since the initial draft National health policy on alcohol in Australia was presented to the Ministerial Council on Drug Strategy in 1987 to the National Drug Strategic plan for action 2001 to 2003-2004 which was launched in July last year.     

The Epidemiology of Alcohol Use and Alcohol Use Disorders among Young People in Northern Tanzania

IntroductionAlcohol use is a global public health problem, including as a risk factor for HIV infection, but few data are available on the epidemiology of alcohol use and alcohol use disorders (AUD) among young people in sub-Saharan Africa.MethodsWe conducted a cross-sectional survey among 4 groups of young people aged 15–24 years old (secondary school students, college/university students, employees of local industries and casual labourers) in two regions (Kilimanjaro and Mwanza) of northern Tanzania. Using a multistage stratified random sampling strategy, we collected information on demographics, alcohol use, and behavioural factors. We screened severity of alcohol use using the Alcohol Use Disorder Identification Test (AUDIT) and estimated the quantity and frequency of alcohol consumption using the timeline-follow-back-calendar (TLFB) method.ResultsA total of 1954 young people were surveyed. The prevalence of reported alcohol use was higher among males (47–70% ever users and 20–45% current users) than females (24–54% ever users and 12–47% current users). Prevalence of use was substantially higher in Kilimanjaro than Mwanza region. In both regions, participants reported high exposure to alcohol advertisements, and wide alcohol availability. College students reported the highest prevalence of current alcohol use (45% among males; 26% among females) and of heavy episodic drinking (71% among males; 27% among females) followed by casual labourers. Males were more likely to have AUD (an AUDIT score ≥8) than females, with 11–28% of males screening positive for AUD. Alcohol use was associated with male gender, being in a relationship, greater disposable income, non-Muslim religion and a higher number of sexual partners.ConclusionsAlcohol use is a significant problem among young people in northern Tanzania. There is an urgent need to develop, pilot and deliver interventions to help young people delay initiation and reduce levels of harmful drinking, particularly among college students and casual labourers.     

Selenium interactions and toxicity: a review

Selenium is an essential trace element for mammals. Through selenoproteins, this mineral participates in various biological processes such as antioxidant defence, thyroid hormone production, and immune responses. Some reports indicate that a human organism deficient in selenium may be prone to certain diseases. Adverse health effects following selenium overexposure, although very rare, have been found in animals and people. Contrary to selenium, arsenic and cadmium are regarded as toxic elements. Both are environmental and industrial pollutants, and exposure to excessive amounts of arsenic or cadmium can pose a threat to many people’s health, especially those living in polluted regions. Two other elements, vanadium and chromium(III) in trace amounts are believed to play essential physiological functions in mammals. This review summarizes recent studies on selenium interactions with arsenic and cadmium and selenium interactions with vanadium and chromium in mammals. Human studies have demonstrated that selenium may reduce arsenic accumulation in the organism and protect against arsenic-related skin lesions. Selenium was found to antagonise the prooxidant and genotoxic effects of arsenic in rodents and cell cultures. Also, studies on selenium effects against oxidative stress induced by cadmium in various animal tissues produced promising results. Reports suggest that selenium protection against toxicity of arsenic and cadmium is mediated via sequestration of these elements into biologically inert conjugates. Selenium-dependent antioxidant enzymes probably play a secondary role in arsenic and cadmium detoxification. So far, few studies have evaluated selenium effects on chromium(III) and vanadium actions in mammals. Still, they show that selenium may interact with these minerals. Taken together, the recent findings regarding selenium interaction with other elements extend our understanding of selenium biological functions and highlight selenium as a potential countermeasure against toxicity induced by arsenic and cadmium.     

Reduced LINE-1 methylation is associated with arsenic-induced genotoxic stress in children

Early life exposure to arsenic has profound effect towards development of arsenic induced toxic outcomes. Some districts in the state of West Bengal, India are highly affected by arsenic, mainly through ground water. In children, not much of the toxic outcomes like dermatological lesions are observed but it is thought that the exposure leads to transient alteration in their biological processes that leads to various deleterious health effects later on. We evaluated the global methylation status by analyzing the LINE-1 methylation profile in children from arsenic exposed region between the age group 5–15 years along with the cytogenetic stress induced by arsenic as measured by lymphocyte micronucleus (MN) frequency. A total of 52 arsenic exposed and 32 unexposed children were analyzed. Whole blood DNA was used to measure the LINE-1 methylation by qRT-MSP. We found a significant association of MN-frequency in exposed individuals with highly depleted LINE-1 methylation compared to the exposed individuals with near baseline (which was comparable to unexposed control) methylation index as well as with those with the hypermethylated LINE-1 promoters. From our results, we interpret that LINE-1 methylation index may serve as a potent global epigenetic mark to detect the degree of arsenic genotoxicity at a very early age. We propose that this may be utilized to determine the extent of toxic influence exerted by arsenic, from a very early age.     

Alcohol Use and Transactional Sex among Women in South Africa: Results from a Nationally Representative Survey

Background

Transactional sex is a risk factor for HIV infection. Alcohol use may increase the risk of transactional sex. No nationally-representative studies have examined the relationship between multiple dimensions of alcohol use and transactional sex in women in South Africa. The aim of the study was to examine the relationship between alcohol dependence, binge drinking and frequency of drinking in the past month and transactional sex in adult women in South Africa.

Methods

A cross-sectional study using multi-stage, cluster sampling collected data from a nationally representative sample of 5,969 women aged 16–55 years in 2012. The analysis conducted for this paper was restricted to women reporting sexual activity in the past 12 months (n = 3,594). Transactional sex was defined as having received money/gifts in exchange for sex with any sex partner in the past year. Alcohol use measures included: alcohol dependence (≥2 positive responses to the CAGE questionnaire); binge drinking (≥4 drinks for women on one occasion); and drinking frequency in the previous month. Logistic regression models were built to test the hypotheses that each dimension of alcohol use was associated with transactional sex.

Results

About 6.3% (n = 225) of sexually active women reported transactional sex. Almost a third (30.6%) of sexually active women had ever drunk alcohol, and 19.2% were current (past month) drinkers. Among lifetime drinkers, 28.0% were alcohol dependent and 56.6% were binge drinkers. Alcohol dependent women were twice as likely to report transactional sex (AOR 2.0, 95% CI 1.1–4.3, p<0.05) than those not alcohol dependent. Binge drinkers were 3.1 times more likely to have had transactional sex (95% CI 1.5–6.6, p<0.01) than non-binge drinkers. There was no significant relationship between frequency of drinking in the past month and transactional sex.

Conclusion

Alcohol dependency and binge drinking are significantly associated with transactional sex in South African women. HIV prevention programmes need to target these women, and address both their alcohol use, as well as the HIV risks associated with transactional sex.     

Role of the Met(287)Thr polymorphism in the AS3MT gene on the metabolic arsenic profile

Chronic exposure to arsenic involves a biotransformation process leading to the excretion of methylated metabolites, such as monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), as well as the parental inorganic species (As(III) and As(V)). Inter-individual variations in arsenic biotransformation have been reported and polymorphisms affecting the genes involved in arsenic biotransformation have been considered as one of the plausible explanations for this variation. Coding and flanking regions of the human arsenic methyltransferase (AS3MT) gene have been analysed in 50 Chilean men exposed to arsenic. Nine polymorphisms were found, including one non-synonymous SNP at exon 9 (Met(287)Thr) with an allele frequency of 0.14. Other four changes occurred at potentially regulatory regions: a variable number of tandem repeats (VNTR) at the 5'-untranslated region (UTR5'), a G/C substitution at the promoter region, a GC/AT substitution inside the VNTR, and a G/A substitution at the 3'-untranslated region (UTR3'). The rest of polymorphisms were located in non-coding regions: a T/G substitution in intron 1, a CTC deletion in intron 2 and a TTT and ATT insertions in intron 5. In addition, the individual urinary arsenic profiles were analysed. Our results indicate that genetic polymorphisms in AS3MT contribute to inter-individual variation in arsenic biotransformation and, therefore, may contribute to inter-individual variations in risk of arsenic toxicity and arsenic carcinogenesis. Individuals with the Met(287)Thr polymorphism displayed increased arsenic methylation and might be at increased risk for toxic and genotoxic effects of arsenic exposure if, as the classical arsenic metabolic pathway indicates, methylation enhances toxicity.