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Chronic Consumption (chronic + consumption)
Selected AbstractsModulatory potential of ellagic acid, a natural plant polyphenol on altered lipid profile and lipid peroxidation status during alcohol-induced toxicity: A pathohistological studyJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 2 2008Nagarajan Devipriya Abstract Polyphenol-rich dietary foodstuffs, consumed as an integral part of vegetables, fruits, and beverages have attracted attention due to their antioxidant and anticancer properties. Ellagic acid (EA), a polyphenolic compound widely distributed in fruits and nuts, has been reported to scavenge free radicals and inhibit lipid peroxidation. Chronic consumption of alcohol potentially results in serious illness including hepatitis, fatty liver, hypertriglyceridemia, and cirrhosis. A little is known about the influence of EA on alcohol toxicity in vivo. Accordingly, in the present study, we have evaluated the protective effects of EA on lipid peroxidation and lipid levels during alcohol-induced toxicity in experimental rats. Forty female albino Wistar rats, which were weighing between 150,170 g were used for the study. The toxicity was induced by administration of 20% alcohol orally (7.9 g/kg body wt.) for 45 days. Rats were treated with EA at three different doses (30, 60, and 90 mg/kg body wt.) via intragastric intubations together with alcohol. At the end of experimental duration, liver marker enzymes (i.e., aspartate transaminase, alanine transaminase), lipid peroxidative indices (i.e., thiobarbituriacid reactive substances and hydroperoxides) in plasma, and lipid levels (i.e., cholesterol, free fatty acids, triglycerides and phospholipids) in tissues were analyzed to evaluate the antiperoxidative and antilipidemic effects of EA. Liver marker enzymes, lipid peroxidative indices, and lipid levels, i.e., cholesterol, triglycerides and free fatty acids, were significantly increased whereas phospholipid levels were significantly decreased in the alcohol-administered group. EA treatment resulted in positive modulation of marker enzymes, peroxidative indices, and lipid levels. EA at the dose of 60 mg/kg body wt. was found to be more effective when compared to the other two doses. Histological changes observed were also inconsistent with the biochemical parameters. Our study suggests that EA exerts beneficial effects at the dosage of 60 mg/kg body wt. against alcohol-induced damage, and it can be used as a potential drug for the treatment of alcohol-abuse ailments in the near future. © 2008 Wiley Periodicals, Inc. J Biochem Mol Toxicol 22:101,112, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20226 [source] Oseltamivir Treatment Prevents the Increased Influenza Virus Disease Severity and Lethality Occurring in Chronic Ethanol Consuming MiceALCOHOLISM, Issue 8 2010Ryan A. Langlois Background:, Chronic consumption of ethanol (EtOH) is well recognized to lead to defective innate and adaptive immune responses and increase the severity of pulmonary infections. Our own studies have demonstrated that chronic EtOH consumption decreases CD8 T-cell immunity to influenza virus infections (IAV) leading to severe infections and mortality. Interestingly, antiviral treatment of IAVs has been shown to be compromised in mice and humans that are immuno-deficient. It is known that EtOH can alter the pharmacokinetics of antivirals. Therefore, the effectiveness of influenza antiviral therapy during chronic ethanol consumption remains in question. Methods:, BALB/c mice were placed on 18% (w/v) EtOH in their drinking water for 8 weeks. Chronic EtOH consuming and water controls were then treated with 10 mg/kg oseltamivir orally and infected intranasally with influenza virus 4 hours post-oseltamivir treatment. The mice were then treated with oseltamivir twice daily until day 7 postinfection. Influenza disease severity was measured by morbidity and mortality, pulmonary viral titers, and histology. Results:, Chronic EtOH consuming mice infected with IAV and treated with oseltamivir have decreased morbidity and mortality, pulmonary viral titers, and pulmonary pathology compared to untreated EtOH mice. Conclusions:, Despite the severe immune defect seen in chronic EtOH mice as well as the potential for EtOH to inhibit the conversion of oseltamivir into an active form, treatment with oseltamivir reduces viral shedding as well as disease severity. These data suggest that the combination of a limited adaptive immune response plus the anti-IAV drug oseltamivir is sufficient to curb high mortality and mediate resolution of IAVs in mice chronically consuming ethanol. [source] Cola-induced hypokalaemia: pathophysiological mechanisms and clinical implicationsINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 6 2009V. Tsimihodimos Summary Background/Aims: The consumption of soft drinks has increased considerably during the last decades. Among them, the cola-based preparations are possibly the refreshments with the largest sales worldwide. In addition to the possible detrimental effects of moderate, chronic cola consumption, it has been proposed that the consumption of large amounts of cola-based soft drinks may result in severe hypokalaemia. Methods: In this review, we discuss the clinical significance of these disturbances and summarise the pathophysiological mechanism that may underlie the development of this rare, but potentially severe, side effect. Results/Conclusion: Several lines of evidence suggest that the chronic consumption of large amounts of cola soft drinks may adversely affect potassium homeostasis and result in potentially severe conditions such as hypokalaemic myopathy. [source] Differential Effects of Acute and Chronic Ethanol Exposure on Orexin Expression in the Perifornical Lateral HypothalamusALCOHOLISM, Issue 5 2010Irene Morganstern Background:, Recent reports support the involvement of hypothalamic orexigenic peptides in stimulating ethanol intake. Our previous studies have examined the effects of ethanol on hypothalamic peptide systems of the paraventricular nucleus (PVN) and identified a positive feedback loop in which PVN peptides, such as enkephalin and galanin, stimulate ethanol intake and ethanol, in turn, stimulates the expression of these peptides. Recently, orexin (OX), a peptide produced mainly by cells in the perifornical lateral hypothalamus (PFLH), has been shown to play an important role in mediating the rewarding aspects of ethanol intake. However, there is little evidence showing the effects that ethanol itself may have on the OX peptide system. In order to understand the feedback relationship between ethanol and the OX system, the current investigation was designed to measure OX gene expression in the PFLH following acute as well as chronic ethanol intake. Methods:, In the first experiment, Sprague,Dawley rats were trained to voluntarily consume a 2 or 9% concentration of ethanol, and the expression of OX mRNA in the PFLH was measured using quantitative real-time polymerase chain reaction (qRT-PCR). The second set of experiments tested the impact of acute oral gavage of 0.75 and 2.5 g/kg ethanol solution on OX expression in the PFLH using qRT-PCR, as well as radiolabeled in situ hybridization. Further tests using digoxigenin-labeled in situ hybridization and immunofluorescence histochemistry allowed us to more clearly distinguish the effects of acute ethanol on OX cells in the lateral hypothalamic (LH) versus perifornical (PF) regions. Results:, The results showed chronic consumption of ethanol versus water to dose-dependently reduce OX mRNA in the PFLH, with a larger effect observed in rats consuming 2.5 g/kg/d (,70%) or 1.0 g/kg/d (,50%) compared to animals consuming 0.75 g/kg/d (,40%). In contrast to chronic intake, acute oral ethanol compared to water significantly enhanced OX expression in the PFLH, and this effect occurred at the lower (0.75 g/kg) but not higher (2.5 g/kg) dose of ethanol. Additional analyses of the OX cells in the LH versus PF regions identified the former as the primary site of ethanol's stimulatory effect on the OX system. In the LH but not the PF, acute ethanol increased the density of OX-expressing and OX-immunoreactive neurons. The increase in gene expression was detected only at the lower dose of ethanol (0.75 g/kg), whereas the increase in OX peptide was seen only at the higher dose of ethanol (2.5 g/kg). Conclusion:, These results lead us to propose that OX neurons, while responsive to negative feedback signals from chronic ethanol consumption, are stimulated by acute ethanol administration, most potently in the LH where OX may trigger central reward mechanisms that promote further ethanol consumption. [source] Upregulation of Serotonin Transporter by Alcohol in Human Dendritic Cells: Possible Implication in Neuroimmune DeregulationALCOHOLISM, Issue 10 2009Dakshayani Kadiyala Babu Background:, Alcohol is the most widely abused substance and its chronic consumption causes neurobehavioral disorders. It has been shown that alcohol affects the function of immune cells. Dendritic cells (DC) serve as the first line of defense against infections and are known to accumulate neurotransmitters such as 5-hydroxytryptamine (5-HT). The enzyme monoamine oxidase-A (MAO-A) degrades 5-HT that is associated with clinical depression and other neurological disorders. 5-HT is selectively transported into neurons through the serotonin transporter (SERT), which is a member of the sodium- and chloride-dependent neurotransmitter transporter (SLC6) family. SERT also serves as a receptor for psychostimulant recreational drugs. It has been demonstrated that several drugs of abuse such as amphetamine and cocaine inhibit the SERT expression; however, the role of alcohol is yet to be elucidated. We hypothesize that alcohol can modulate SERT and MAO-A expression in DC, leading to reciprocal downregulation of 5-HT in extracellular medium. Methods:, Dendritic cells were treated with different concentrations (0.05% to 0.2%v/v) of alcohol for 24,72 hours and processed for SERT and MAO-A expression using Q-PCR and Western blots analysis. In addition, SERT function in DC treated with alcohol both in the presence and absence of imipramine, a SERT inhibitor was measured using 4-[4-(dimethylamino)styryl]-1-methylpyridinium iodide uptake assay. 5-HT levels in culture supernatant and intracellular 5-hydroxy indole acetic acid (5-HIAA) and cyclic AMP were also quantitated using ELISA. Results:, Dendritic cells treated with 0.1% alcohol for 24 hours showed significant upregulation of SERT and MAO-A expression compared with untreated DC. We also observed that 0.1% alcohol enhanced the function of SERT and decreased extracellular 5-HT levels compared with untreated DC cultures, and this was associated with the elevation of intracellular 5-HIAA and cyclic AMP levels. Conclusions:, Our study suggests that alcohol upregulates SERT and MAO-A by elevating cyclic AMP, which may lead to decreased concentration of 5-HT in the extracellular medium. As 5-HT is a major neurotransmitter and an inflammatory mediator, its alcohol-mediated depletion may cause both neurological and immunological deregulation. [source] Environmental neurotoxin-induced progressive model of parkinsonism in ratsANNALS OF NEUROLOGY, Issue 1 2010Wei-Bin Shen PhD Objective Exposure to a number of drugs, chemicals, or environmental factors can cause parkinsonism. Epidemiologic evidence supports a causal link between the consumption of flour made from the washed seeds of the plant Cycas micronesica by the Chamorro population of Guam and the development of amyotrophic lateral sclerosis/parkinsonism dementia complex. Methods We now report that consumption of washed cycad flour pellets by Sprague-Dawley male rats induces progressive parkinsonism. Results Cycad-fed rats displayed motor abnormalities after 2 to 3 months of feeding such as spontaneous unilateral rotation, shuffling gait, and stereotypy. Histological and biochemical examination of brains from cycad-fed rats revealed an initial decrease in the levels of dopamine and its metabolites in the striatum (STR), followed by neurodegeneration of dopaminergic (DAergic) cell bodies in the substantia nigra (SN) pars compacta (SNc). ,-Synuclein (,-syn; proteinase K-resistant) and ubiquitin aggregates were found in the DAergic neurons of the SNc and neurites in the STR. In addition, we identified ,-syn aggregates in neurons of the locus coeruleus and cingulate cortex. No loss of motor neurons in the spinal cord was found after chronic consumption of cycad flour. In an organotypic slice culture of the rat SN and the striatum, an organic extract of cycad causes a selective loss of dopamine neurons and ,-syn aggregates in the SN. Interpretation Cycad-fed rats exhibit progressive behavioral, biochemical, and histological hallmarks of parkinsonism, coupled with a lack of fatality. ANN NEUROL 2010;68:70,80 [source] Symptomatic hypogonadism in male survivors of cancer with chronic exposure to opioidsCANCER, Issue 4 2004Arun Rajagopal M.D. Abstract BACKGROUND Profound hypogonadism has been noted in patients receiving intrathecal opioids. The purpose of the current study was to determine whether chronic consumption of oral opioids by male survivors of cancer also would lead to central hypogonadism and whether this hypogonadism was associated with symptoms of sexual dysfunction, fatigue, anxiety, and depression. METHODS A case,control study was conducted at The University of Texas M. D. Anderson Cancer Center (Houston, TX), in which 20 patients who were chronically consuming opioids were compared with 20 matched controls. Patients completed the Sexual Desire Inventory (SDI), the Hospital Anxiety and Depression Scale (HADS), the Functional Assessment of Chronic Illness Therapy with general and fatigue subscales (FACT-G/FACIT-F), and the Edmonton Symptom Assessment System (ESAS) questionnaires. Serum samples were collected for testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). RESULTS Comparing the opioid group with the control group, 18 of the 20 patients (90%; 95% confidence interval [CI], 65,98%) exhibited hypogonadism, compared with 8 of the 20 control patients (40%; 95% CI, 19,64%). The median testosterone level was 145 ng/dL versus 399.5 ng/dL (5.0 nmol/L vs. 13.9 nmol/L; P < 0.0001), the median FSH level was 2.85 milli,International Units (mIU)/mL versus 5.3 mIU/mL (P = 0.08), the median LH level was 1.8 mIU/mL versus 4.2 mIU/mL (P = 0.0014), the median SDI-dyadic score was 18.5 versus 40 (P = 0.01), the median SDI-solitary score was 0 versus 5 (P = 0.007), the HADS (anxiety) score was 8.5 versus 5.5 (P = 0.053), the HADS (depression) score was 7.5 versus 1.5 (P = 0.0002), the FACT-G score was 64 versus 96.3 (P = 0.0001), and the FACIT-F score was 24 versus 46 (P = 0.0003). CONCLUSIONS Survivors of cancer who chronically consumed opioids experienced symptomatic hypogonadism with significantly higher levels of depression, fatigue, and sexual dysfunction. With the increasing use of opioids among patients with cancer, further research in improving quality-of-life outcomes is warranted. Cancer 2004;100:851,8. © 2004 American Cancer Society. [source] | ||||||||||