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 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of 'agonist therapy' for cocaine and methamphetamine addiction involves administration of stimulant-like medications (e.g. monoamine releasers) to reduce withdrawal symptoms and prevent relapse. A significant problem with this strategy is that many candidate medications possess abuse liability due to activation of mesolimbic dopamine (DA) neurons in the brain. One way to reduce DA-mediated abuse liability of candidate drugs might be to add in serotonin (5-HT)-releasing properties, since substantial evidence shows that 5-HT neurons provide an inhibitory influence over mesolimbic DA neurons. This chapter addresses several key issues related to the development of dual DA/5-HT releasers for the treatment of substance use disorders. First, we briefly summarize the evidence supporting a dual deficit in DA and 5-HT function during withdrawal from chronic cocaine or alcohol abuse. Second, we discuss data demonstrating that 5-HT release can dampen DA-mediated stimulant effects, and the 'anti-stimulant' role of 5-HT(2C) receptors is considered. Next, the mechanisms underlying potential adverse effects of 5-HT releasers are described. Finally, we discuss recently published data with PAL-287, a novel non-amphetamine DA/5-HT-releasing agent that suppresses cocaine self-administration but lacks positive reinforcing properties. It is concluded that DA/5-HT releasers could be useful therapeutic adjuncts for the treatment of cocaine and alcohol addictions as well as for obesity, attention deficit disorder and depression.
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PMID:Dopamine/serotonin releasers as medications for stimulant addictions. 1877 43

Narcotic analgesics are commonly prescribed drugs in patients with chronic hepatitis C (CHC) infection. In vitro data have shown that morphine enhances hepatitis C virus replication in human hepatic cells, however the effect of narcotics on hepatitis C virus disease progression remains uncertain. The aim of this study was to evaluate the potential effects of narcotic analgesic use on the progression of hepatic fibrosis in patients with CHC infection. We identified CHC patients who had been seen at our institution and had undergone a liver biopsy between 1990 and 2005. Their charts were reviewed for the presence of narcotic analgesic and known risk factors for progression of hepatic fibrosis including male sex, age > or =40, obesity, diabetes, and alcohol abuse. All biopsy were reviewed and fibrosis scores were standardized using the Batts and Ludwig scoring system (stage 0 to 4). A total of 1147 evaluable patients were identified and 171 of these had narcotic analgesic use. In univariate analysis, narcotic analgesic use was associated with the presence of alcohol abuse (P<0.001), obesity (P=0.02), and advanced fibrosis defined as stage 3 to 4 fibrosis (P=0.02), but not with male sex or diabetes. In multivariate logistic regression analysis, obesity [odds ratio (OR) 1.68 (confidence interval (CI), 1.21-2.33)], alcohol abuse [OR 1.45 (CI, 1.04-2.02)], age > or =40 [OR 1.85 (CI, 1.22-2.89)], and diabetes [OR 2.43 (CI, 1.41-4.14)] all independently predicted advanced liver fibrosis but narcotic analgesic use did not [OR 1.71 (CI, 0.99-2.89)]. As the amount of narcotic analgesic use increased from no use, to <3 months use, to > or =3 months use, the frequency of obesity, alcohol abuse, and advanced fibrosis increased accordingly (P=0.005), suggesting that it is difficult to separate these known risk factors from narcotic use as the cause for advanced fibrosis in this population.
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PMID:Narcotic analgesics and progression of fibrosis in patients with chronic hepatitis C. 1903 42

School nursing is ripe for development and could well be an interesting specialist area to work in for the innovative nurse, given some of the problems nowadays. For example, child abuse, the increasing problem of children with obesity and poor diet, alcohol abuse, smoking and sexual health issues. Although the nature of some of the health problems has changed there are some commonalities with what was happening 100 years ago in Britain at the time.
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PMID:Role of the school nurse 100 years ago. 1906 Aug 17

"Agonist therapy" for cocaine and methamphetamine addiction involves administration of stimulant-like medications (e.g., monoamine releasers) to reduce withdrawal symptoms and prevent relapse. A significant problem with this strategy is that many candidate medications possess abuse liability because of activation of mesolimbic dopamine (DA) neurons in the brain. One way to reduce DA-mediated abuse liability of candidate drugs is to add in serotonin (5-HT) releasing properties, since substantial evidence shows that 5-HT neurons provide an inhibitory influence over mesolimbic DA neurons. This article addresses several key issues related to the development of dual DA/5-HT releasers for the treatment of substance use disorders. First, the authors briefly summarize the evidence supporting a dual deficit in DA and 5-HT function during withdrawal from chronic cocaine or alcohol abuse. Second, the authors discuss data demonstrating that 5HT release can dampen DA-mediated stimulant effects, and the "antistimulant" role of 5-HT-sub(2C) receptors is considered. Next, the mechanisms underlying potential adverse effects of 5-HT releasers are described. Finally, the authors discuss recently published data with PAL-287, a novel nonamphetamine DA/5-HT releasing agent that suppresses cocaine self-administration but lacks positive reinforcing properties. It is concluded that DA/5-HT releasers could be useful therapeutic adjuncts for the treatment of cocaine and alcohol addictions, as well as for obesity, attention-deficit disorder, and depression.
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PMID:Dual dopamine/serotonin releasers: potential treatment agents for stimulant addiction. 1908 67

Highly-active antiretroviral therapy (HAART) has proven remarkably effective for prolonging the life of patients with human immunodeficiency virus (HIV). However, while most HAART agents are safe, many have the potential to cause liver toxicity. Physicians must therefore consider the possibility of drug-induced liver injury in the management of HIV-infected patients, especially those with certain risk factors such as coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV), female gender, alcohol abuse, older age, or obesity. Understanding how, when, and why drug-related liver damage occurs is key to managing these patients safely and effectively. Knowledge of HAART-related liver effects will help ensure that patients receive the most benefit with the least toxicity from any given drug regimen. As more information about the mechanisms of drug related liver injury is known, clinicians will be better able to tailor therapies to suit individual situations, resulting in greater patient safety and outcomes.
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PMID:HIV-related liver disease: ARV drugs, coinfection, and other risk factors. 1921 29

Endogenous cannabinoids (ECs) are ubiquitous lipid signaling molecules provided by a number of central and peripheral effects, which are mediated mainly by the specific receptors CB1 and CB2. In the last decade a considerable number of studies has shown that ECs and their receptors play an important role in the pathophysiology of liver diseases. The EC system is strongly up-regulated during chronic liver diseases. Until now it has been implicated in the pathogenesis of fatty liver disease associated with obesity, alcohol abuse, and hepatitis C, in the progression of fibrosis to cirrhosis, and in the development of portal hypertension, hyperdynamic circulatory syndrome and its complications, and cirrhotic cardiomyopathy. Furthermore, the EC system can participate in the pathogenesis of acute liver injury by modulating the mechanisms responsible for cell injury and inflammatory response. Thus, targeting the CB1 and CB2 receptors represents a potential therapeutic goal for the treatment of liver diseases.
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PMID:The role of the endocannabinoid system in liver diseases. 1928 61

This article presents an overview of biases in studies among the aged as a consequence of under-coverage and non-response. The question studied is whether participants and non-participants in research differed in their socioeconomic status (education; income; SES of neighbourhood), social integration (marital status; living arrangements; social participation; ethnicity) and health (general health situation; mortality in the period after study; lifestyle and risk factors, namely obesity and alcohol abuse; contact with physicians). In all, 65 studies were reviewed. The results showed that research participants had a higher socioeconomic status, were more integrated socially and in better health than research non-participants. The differences (effect sizes) were small to moderate. On the basis of these results, we can conclude that univariate distributions and prevalence estimates as well as relationships between variables in published research will frequently be biased.
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PMID:[Selective loss of participants as a consequence of under-coverage and non-response in research among the aged: an overview]. 1932 97

Uric acid seems to be causally involved in a variety of medical disorders involving oxidative stress. Although alcohol abuse and obesity are known to increase serum uric acid, the interactions between moderate drinking, adiposity, and uric acid metabolism have remained poorly understood. We examined serum uric acid concentrations from 2062 apparently healthy volunteers (970 men, 1092 women) reporting either no alcohol (abstainers) or <40 g of ethanol consumption per day (moderate drinkers). The study population was further classified according to BMI as follows: <19 (underweight), 19-25 (normal weight), 25-30 (overweight), and >30 (obese). Serum uric acid concentrations in male moderate drinkers were significantly higher, and in females they were lower, than in the corresponding groups of abstainers. In the BMI-based subgroups, the highest concentrations were found in those who were overweight or obese. Significant two-factor interactions occurred between gender and drinking status (p<0.001) and between gender and BMI (p<0.02). Serum uric acid also correlated with indices of hepatocellular health (GGT, ALT, AST). The data indicate distinct gender-dependent impacts of alcohol consumption and BMI on serum uric acid. These findings should be applicable to the assessment of oxidative stress status and associated morbidity in alcohol consumers and individuals with excess body weight.
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PMID:Gender-dependent impacts of body mass index and moderate alcohol consumption on serum uric acid--an index of oxidant stress status? 1943 11

We aimed to examine baseline predictors of treatment response in bulimic patients. 241 seeking-treatment females with bulimia nervosa completed an exhaustive assessment and were referred to a six-session psychoeducational group. Regression analyses of treatment response were performed. Childhood obesity, lower frequency of eating symptomatology, lower body mass index, older age, and lower family's and patient's concern about the disorder were predictors of poor abstinence. Suicidal ideation, alcohol abuse, higher maximum BMI, higher novelty seeking and lower baseline purging frequency predicted dropouts. Predictors of early symptom changes and dropouts were similar to those identified in longer CBT interventions.
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PMID:Predictors of early change in bulimia nervosa after a brief psychoeducational therapy. 1950 87

Acute pancreatitis (AP) is an inflammatory disease characterized by steady, acute abdominal pain of varying severity, often radiating from the epigastrium to the back. Its presentation ranges from a self-limiting mild disorder to a more severe and fulminant disease. Severe acute pancreatitis accounts for 30% of all deaths related to pancreatitis. The incidence of AP is increasing progressively with a corresponding increase in the incidence of its risk factors. Alcohol abuse and gallstone migration are the established risk factors for development of AP. In recent years, genetic factors and obesity have also been identified as risk factors responsible for the development of AP. The pathophysiology of AP involves acute inflammation of the acinar cells. Excessive acinar cell injury leads to a condition called systemic inflammatory response syndrome (SIRS). Protracted SIRS is responsible for most of the life-threatening complications associated with AP. Most common AP-related complications include pulmonary, renal, cardiovascular, and central nervous system dysfunction. Thus prompt and accurate diagnosis of AP is of paramount importance. The medical management of AP includes controlling pain, providing adequate nutritional support, and monitoring complications. Endoscopic retrograde cholangiopancreatography and surgery have also shown to reduce the mortality and morbidity associated with AP. Drugs such as resveratrol and rosiglitazone are being investigated as potential candidates for the treatment of AP.
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PMID:Acute pancreatitis: a literature review. 1956 40


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