Linoleic Acid-Derived Oxylipins Differentiate Early Stage Alcoholic Hepatitis From Mild Alcohol-Associated Liver Injury.

Alcohol-associated liver disease (ALD) is a spectrum of liver disorders ranging from steatosis to steatohepatitis, fibrosis, and cirrhosis. Alcohol-associated hepatitis (AH) is an acute and often severe form of ALD with substantial morbidity and mortality. The mechanisms and mediators of ALD progression and severity are not well understood, and effective therapeutic options are limited.

PPARγ activation by pioglitazone does not suppress cravings for alcohol, and is associated with a risk of myopathy in treatment seeking alcohol dependent patients: a randomized controlled proof of principle study.

Rationale: Proinflammatory processes have been implicated in alcohol addiction, craving, and relapse, while studies in experimental animals have suggested that activation of peroxisome proliferator-activated receptor gamma (PPARγ) inhibits proinflammatory signaling. Accordingly, it is hypothesized that medications with PPARγ activity may have therapeutic potential in alcohol dependence.

Objectives: We conducted a double-blind, placebo-controlled mechanistic proof of principle study in alcohol-dependent inpatients to investigate the effect of pioglitazone on alcohol craving.

Conquering the Craving: Treatment to Curb Alcohol Use Disorder.

Largely underutilized in North America, the use of medications to treat alcohol dependence is frequently a successful method of reducing alcohol craving and promoting abstinence. Recovery from alcohol addiction can be a complicated process, requiring nutritional, social, psychological, spiritual, and physical aspects of healing and self-directed behavioral change. Nurses can intervene in alcohol use disorder via screening, referrals, support of medical and behavioral treatments, and spiritual care that emphasizes hope, forgiveness, and relief from shame and guilt.

DHA brain uptake and APOE4 status: a PET study with [1-C]-DHA.

Background: The apolipoprotein E ɛ4 (APOE4) allele is the strongest genetic risk factor identified for developing Alzheimer's disease (AD). Among brain lipids, alteration in the ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) homeostasis is implicated in AD pathogenesis. APOE4 may influence both brain DHA metabolism and cognitive outcomes.

Liver Injury and Endotoxemia in Male and Female Alcohol-Dependent Individuals Admitted to an Alcohol Treatment Program.

Background: Interactions between the liver, the gut, and the immune system are critical components of alcoholic liver disease (ALD). The aim of this study was to explore the associations between alcohol-induced liver injury, endotoxemia, and inflammation at admission and over time during abstinence, as well as to examine the sex-related differences in these parameters in alcohol-dependent individuals admitted to an alcohol treatment program.

Methods: A cohort of 48 otherwise healthy participants with alcohol use disorder, but no clinical signs of alcoholic liver injury (34 males [M]/14 females [F]) admitted to an alcohol detoxification program, was stratified into 2 groups based on baseline plasma alanine aminotransferase (ALT) levels (as a marker of liver injury).

Cerebrospinal fluid monocyte chemoattractant protein-1 in alcoholics: support for a neuroinflammatory model of chronic alcoholism.

Background: Liver inflammation in alcoholism has been hypothesized to influence the development of a neuroinflammatory process in the brain characterized by neurodegeneration and altered cognitive function. Monocyte chemoattractant protein-1/chemokine (C-C motif) ligand 2 (MCP-1/CCL2) elevations have been noted in the alcoholic brain at autopsy and may have a role in this process.

Methods: We studied cerebrospinal fluid (CSF) levels of MCP-1 as well as interleukin-1β and tumor necrosis factor-α in 13 healthy volunteers and 28 alcoholics during weeks 1 and 4 following detoxification.

Brain docosahexaenoic acid [DHA] incorporation and blood flow are increased in chronic alcoholics: a positron emission tomography study corrected for cerebral atrophy.

Objective: Chronic alcohol dependence has been associated with disturbed behavior, cerebral atrophy and a low plasma concentration of docosahexaenoic acid (DHA, 22∶6n-3), particularly if liver disease is present. In animal models, excessive alcohol consumption is reported to reduce brain DHA concentration, suggesting disturbed brain DHA metabolism. We hypothesized that brain DHA metabolism also is abnormal in chronic alcoholics.

The physician's unique role in preventing violence: a neglected opportunity?

Background: Episodes of explosive rage and violence comprise a symptom complex which can have a devastating effect on a person's life. In the community this behavior is seen as workplace violence, domestic abuse and road rage, while in the clinical setting, this behavior is rarely mentioned by patients, despite evidence that it can signify an important biological disorder that may afflict more than three percent of the population.

Discussion: Patients are often reluctant to seek help for episodic attacks of rage, especially attacks which are accompanied by physical violence.

Dietary supplements and their future in health care: commentary on draft guidelines proposed by the Food and Drug Administration.

The Dietary Supplement and Health and Education Act of 1994 gives the U.S. Food and Drug Administration (FDA) responsibility for oversight of the dietary supplement industry.

The utility of (11)C-arachidonate PET to study in vivo dopaminergic neurotransmission in humans.

We developed a novel method to study dopaminergic neurotransmission using positron emission tomography (PET) with [1-(11)C]arachidonic acid ([1-(11)C]AA). Previous preclinical studies have shown the utility of [1-(11)C]AA as a marker of signal transduction coupled to cytosolic phospholipase A(2) (cPLA(2)). Using [1-(11)C]AA and [(15)O]water PET, we measured regional incorporation coefficients K(*) for AA and regional cerebral blood flow (rCBF), respectively, in healthy male volunteers given the D(1)/D(2) agonist (10 or 20 μg/kg subcutaneous) apomorphine.

Pharmacologically induced alcohol craving in treatment seeking alcoholics correlates with alcoholism severity, but is insensitive to acamprosate.

Modulation of alcohol craving induced by challenge stimuli may predict the efficacy of new pharmacotherapies for alcoholism. We evaluated two pharmacological challenges, the α(2)-adrenergic antagonist yohimbine, which reinstates alcohol seeking in rats, and the serotonergic compound meta-chlorophenylpiperazine (mCPP), previously reported to increase alcohol craving in alcoholics. To assess the predictive validity of this approach, the approved alcoholism medication acamprosate was evaluated for its ability to modulate challenge-induced cravings.

Effect of acamprosate on magnetic resonance spectroscopy measures of central glutamate in detoxified alcohol-dependent individuals: a randomized controlled experimental medicine study.

Context: Acamprosate is approved for the treatment of alcoholism, but its mechanism of action remains unclear. Results of animal studies suggest that a persistent hyperglutamatergic state contributes to the pathogenesis of alcoholism and that acamprosate may exert its actions by intervening in this process. Human translation of these findings is lacking.

Fluoxetine treatment of alcoholic perpetrators of domestic violence: a 12-week, double-blind, randomized, placebo-controlled intervention study.

Objective: Behaviorally based therapies for the treatment of perpetrators who initiate intimate partner violence (IPV) have generally shown minimal therapeutic efficacy. To explore a new treatment approach for IPV, we examined the effects of a selective serotonin reuptake inhibitor on the irritability subscale score of the Modified Overt Aggression Scale. This score served as a surrogate marker for the anger and physical aggression that characterize perpetrators of IPV.

Biological Correlates of Intimate Partner Violence Perpetration.

An extensive literature documents biological correlates of general aggression, but there has been less focus on biological correlates of intimate partner violence (IPV). The purpose of this review is to summarize the research literature to date that has reported on biological factors in IPV perpetration. We review the existing literature on four domains of biological processes that have been examined with respect to IPV perpetration, including: head injury and neuropsychology; psychophysiology; neurochemistry, metabolism and endocrinology; and genetics.

Imaging incorporation of circulating docosahexaenoic acid into the human brain using positron emission tomography.

Docosahexaenoic acid (DHA; 22:6n-3) is a critical constituent of the brain, but its metabolism has not been measured in the human brain in vivo. In monkeys, using positron emission tomography (PET), we first showed that intravenously injected [1-(11)C]DHA mostly entered nonbrain organs, with approximately 0.5% entering the brain.