Browsing by Subject "Ethanol"
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Item Open Access Alcohol abuse and disorder of granulopoiesis.(Pharmacology & therapeutics, 2019-06) Shi, Xin; DeLucia, Angelo L; Bao, Jianxin; Zhang, PingGranulocytes are the major type of phagocytes constituting the front line of innate immune defense against bacterial infection. In adults, granulocytes are derived from hematopoietic stem cells in the bone marrow. Alcohol is the most frequently abused substance in human society. Excessive alcohol consumption injures hematopoietic tissue, impairing bone marrow production of granulocytes through disrupting homeostasis of granulopoiesis and the granulopoietic response. Because of the compromised immune defense function, alcohol abusers are susceptible to infectious diseases, particularly septic infection. Alcoholic patients with septic infection and granulocytopenia have an exceedingly high mortality rate. Treatment of serious infection in alcoholic patients with bone marrow inhibition continues to be a major challenge. Excessive alcohol consumption also causes diseases in other organ systems, particularly severe alcoholic hepatitis which is life threatening. Corticosteroids are the only therapeutic option for improving short-term survival in patients with severe alcoholic hepatitis. The existence of advanced alcoholic liver diseases and administration of corticosteroids make it more difficult to treat serious infection in alcoholic patients with the disorder of granulopoieis. This article reviews the recent development in understanding alcohol-induced disruption of marrow granulopoiesis and the granulopoietic response with the focus on progress in delineating cell signaling mechanisms underlying the alcohol-induced injury to hematopoietic tissue. Efforts in exploring effective therapy to improve patient care in this field will also be discussed.Item Open Access Alcohol and drug dependence symptom items as brief screeners for substance use disorders: results from the Clinical Trials Network.(Journal of psychiatric research, 2012-03) Wu, Li-Tzy; Blazer, Dan G; Woody, George E; Burchett, Bruce; Yang, Chongming; Pan, Jeng-Jong; Ling, WalterAIM:To address an urgent need for screening of substance use problems in medical settings, we examined substance-specific dependence criteria as potential brief screeners for the detection of patients with a substance use disorder (SUD). METHODS:The sample included 920 opioid-dependent adults who were recruited from outpatient treatment settings at 11 programs in 10 U.S. cities and who completed intake assessments of SUDs for a multisite study of the National Drug Abuse Treatment Clinical Trials Network (CTN003). Data were analyzed by factor analysis, item response theory (IRT), sensitivity, and specificity procedures. RESULTS:Across all substances (alcohol, amphetamines, cannabis, cocaine, sedatives), withdrawal was among the least prevalent symptoms, while taking large amounts and inability to cut down were among the most prevalent symptoms. Items closely related to the latent trait of a SUD showed good-to-high values of area under the receiver operating characteristic curve in identifying cases of a SUD; IRT-defined severe and less discriminative items exhibited low sensitivity in identifying cases of a SUD (withdrawal for all substances; time using for alcohol and sedatives; giving up activities for sedatives). CONCLUSIONS:Study results suggest that withdrawal and time using are much less reliable indicators for a SUD than taking larger amounts than intended and inability to cut down and that the latter two items should be studied further for consideration in developing a simplified tool for screening patients for SUDs in medical settings. These findings have implications for the use of common health indicators in electronic health records systems to improve patient care.Item Open Access Characterization of Clostridium ljungdahlii OTA1: a non-autotrophic hyper ethanol-producing strain.(Applied microbiology and biotechnology, 2017-02) Whitham, Jason M; Schulte, Mark J; Bobay, Benjamin G; Bruno-Barcena, Jose M; Chinn, Mari S; Flickinger, Michael C; Pawlak, Joel J; Grunden, Amy MA Clostridium ljungdahlii lab-isolated spontaneous-mutant strain, OTA1, has been shown to produce twice as much ethanol as the C. ljungdahlii ATCC 55383 strain when cultured in a mixotrophic medium containing fructose and syngas. Whole-genome sequencing identified four unique single nucleotide polymorphisms (SNPs) in the C. ljungdahlii OTA1 genome. Among these, two SNPs were found in the gene coding for AcsA and HemL, enzymes involved in acetyl-CoA formation from CO/CO2. Homology models of the respective mutated enzymes revealed alterations in the size and hydrogen bonding of the amino acids in their active sites. Failed attempts to grow OTA1 autotrophically suggested that one or both of these mutated genes prevented acetyl-CoA synthesis from CO/CO2, demonstrating that its activity was required for autotrophic growth by C. ljungdahlii. An inoperable Wood-Ljungdahl pathway resulted in higher CO2 and ethanol yields and lower biomass and acetate yields compared to WT for multiple growth conditions including heterotrophic and mixotrophic conditions. The two other SNPs identified in the C. ljungdahlii OTA1 genome were in genes coding for transcriptional regulators (CLJU_c09320 and CLJU_c18110) and were found to be responsible for deregulated expression of co-localized arginine catabolism and 2-deoxy-D-ribose catabolism genes. Growth medium supplementation experiments suggested that increased arginine metabolism and 2-deoxy-D-ribose were likely to have minor effects on biomass and fermentation product yields. In addition, in silico flux balance analysis simulating mixotrophic and heterotrophic conditions showed no change in flux to ethanol when flux through HemL was changed whereas limited flux through AcsA increased the ethanol flux for both simulations. In characterizing the effects of the SNPs identified in the C. ljungdahlii OTA1 genome, a non-autotrophic hyper ethanol-producing strain of C. ljungdahlii was identified that has utility for further physiology and strain performance studies and as a biocatalyst for industrial applications.Item Open Access Long-term effects of chronic intermittent ethanol exposure in adolescent and adult rats: radial-arm maze performance and operant food reinforced responding.(PloS one, 2013-01) Risher, Mary-Louise; Fleming, Rebekah L; Boutros, Nathalie; Semenova, Svetlana; Wilson, Wilkie A; Levin, Edward D; Markou, Athina; Swartzwelder, H Scott; Acheson, Shawn KBackground
Adolescence is not only a critical period of late-stage neurological development in humans, but is also a period in which ethanol consumption is often at its highest. Given the prevalence of ethanol use during this vulnerable developmental period we assessed the long-term effects of chronic intermittent ethanol (CIE) exposure during adolescence, compared to adulthood, on performance in the radial-arm maze (RAM) and operant food-reinforced responding in male rats.Methodology/principal findings
Male Sprague Dawley rats were exposed to CIE (or saline) and then allowed to recover. Animals were then trained in either the RAM task or an operant task using fixed- and progressive- ratio schedules. After baseline testing was completed all animals received an acute ethanol challenge while blood ethanol levels (BECs) were monitored in a subset of animals. CIE exposure during adolescence, but not adulthood decreased the amount of time that animals spent in the open portions of the RAM arms (reminiscent of deficits in risk-reward integration) and rendered animals more susceptible to the acute effects of an ethanol challenge on working memory tasks. The operant food reinforced task showed that these effects were not due to altered food motivation or to differential sensitivity to the nonspecific performance-disrupting effects of ethanol. However, CIE pre-treated animals had lower BEC levels than controls during the acute ethanol challenges indicating persistent pharmacokinetic tolerance to ethanol after the CIE treatment. There was little evidence of enduring effects of CIE alone on traditional measures of spatial and working memory.Conclusions/significance
These effects indicate that adolescence is a time of selective vulnerability to the long-term effects of repeated ethanol exposure on neurobehavioral function and acute ethanol sensitivity. The positive and negative findings reported here help to further define the nature and extent of the impairments observed after adolescent CIE and provide direction for future research.Item Open Access Patterns of tobacco use and tobacco-related psychiatric morbidity and substance use among middle-aged and older adults in the United States.(Aging & mental health, 2012-01-31) Blazer, Dan G; Wu, Li-TzyTo examine prevalence of tobacco use and identify psychiatric symptoms and substance use correlates of tobacco use comparing adults 50-64 years of age with those 65+ years of age (N = 10,891).Data were from the 2008-2009 US National Surveys on Drug Use and Health.Past-year tobacco use was one-half as frequent among adults aged 65+ years (14.1%) compared to adults aged 50-64 years (30.2%); the latter group surpassed the former in rates of cigarette smoking (24.8% vs. 10.6%), daily cigarette smoking (16.5% vs. 7.1%), cigar smoking (7.4% vs. 2.3%), and smokeless tobacco use (2.5% vs. 1.7%). Increased odds of cigarette smoking were noted among men, whites, African Americans, and those who had less education, had lower income, were not currently married, or were binge drinkers or illicit/non-medical drug users. In controlled analyses, odds ratio in those 65+ years of age who had smoked during the past year was 2.2 for binge drinking and 3.5 for illicit or non-medical drug use. Odds ratio of binge drinking among those 65+ years of age for cigar smokers during the past year was 3.1. Past-year cigarette smoking was not associated with reports of symptoms of depression or anxiety in the 65+ age group.Tobacco use is less prevalent among adults 65+ years of age yet continues to be strongly associated with binge drinking and illicit or non-medical drug use. Preventive efforts to decrease these substance use problems should include programs to decrease tobacco use.Item Open Access Pregnancy, alcohol intake, and intimate partner violence among men and women attending drinking establishments in a Cape Town, South Africa township.(J Community Health, 2012-02) Eaton, Lisa A; Kalichman, Seth C; Sikkema, Kathleen J; Skinner, Donald; Watt, Melissa H; Pieterse, Desiree; Pitpitan, Eileen VThe highest rates of fetal alcohol syndrome worldwide can be found in South Africa. Particularly in impoverished townships in the Western Cape, pregnant women live in environments where alcohol intake during pregnancy has become normalized and interpersonal violence (IPV) is reported at high rates. For the current study we sought to examine how pregnancy, for both men and women, is related to alcohol use behaviors and IPV. We surveyed 2,120 men and women attending drinking establishments in a township located in the Western Cape of South Africa. Among women 13.3% reported being pregnant, and among men 12.0% reported their partner pregnant. For pregnant women, 61% reported attending the bar that evening to drink alcohol and 26% reported both alcohol use and currently experiencing IPV. Daily or almost daily binge drinking was reported twice as often among pregnant women than non-pregnant women (8.4% vs. 4.2%). Men with pregnant partners reported the highest rates of hitting sex partners, forcing a partner to have sex, and being forced to have sex. High rates of alcohol frequency, consumption, binge drinking, consumption and binge drinking were reported across the entire sample. In general, experiencing and perpetrating IPV were associated with alcohol use among all participants except for men with pregnant partners. Alcohol use among pregnant women attending shebeens is alarmingly high. Moreover, alcohol use appears to be an important factor in understanding the relationship between IPV and pregnancy. Intensive, targeted, and effective interventions for both men and women are urgently needed to address high rates of drinking alcohol among pregnant women who attend drinking establishments.