atrial-natriuretic-factor and Alcoholism

As a continuation of "Postmortem Chemistry Update Part I," Part II deals with molecules linked to liver and cardiac functions, alcohol intake and alcohol misuse, myocardial ischemia, inflammation, sepsis, anaphylaxis, and hormonal disturbances. A very important array of new material concerning these situations had appeared in the forensic literature over the last two decades. Some molecules, such as procalcitonin and C-reactive protein, are currently researched in cases of suspected sepsis and inflammation, whereas many other analytes are not integrated into routine casework. As in part I, a literature review concerning a large panel of molecules of forensic interest is presented, as well as the results of our own observations, where possible.

Topics: Alcohol Drinking; Alcoholism; Anaphylaxis; Atrial Natriuretic Factor; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Forensic Pathology; Glucuronates; Heart Diseases; Heart Function Tests; Hormones; Humans; Inflammation; Liver; Liver Function Tests; Postmortem Changes; Protein Precursors; Sepsis; Sulfuric Acid Esters; Transferrin

There is growing evidence for a role of appetite-related peptides and volume-regulating hormones in alcoholism. In particular, recent evidence has suggested that hormones, such as ghrelin, insulin and leptin and volume-regulating hormones, could play a role in alcohol-seeking behaviour. The goal of this review is to discuss the results of recent preclinical and clinical investigations on this topic. The findings indicate that neuroendocrinological mechanisms are potentially involved in the neurobiology of alcohol craving. Accordingly, research on this topic could lead to possible development of new therapeutic approaches in the treatment of patients with alcohol problems.

Topics: Alcohol Drinking; Alcoholism; Animals; Appetite Regulation; Atrial Natriuretic Factor; Ghrelin; Humans; Insulin; Leptin; Motivation; Peptide Hormones; Societies, Medical; Vasopressins

Monoamine oxidase (MAO) catalyzes the biological degradation of the neurotransmitters monoamines. The altered substrate specificity of MAO may be of pathogenic importance in some cases and MAO inhibitors showed a therapeutical effect in the experimental setting. Analyzing the efficacy of various compounds in inhibiting MAO A and B revealed new approaches to designing new-generation MAO inhibitors. Tribulin is a fraction of endogenous MAO inhibitors that are present in human and animal tissues and biological fluids. Isatin is an endogenous indole which was initially derived from a tribulin fraction. An investigation of the biological properties of tribulin revealed its heterogeneity and some chemical components were identified. It was shown that deficiency of tribulin components that selectively inhibited MAO A long with a larger number of molecules of this enzyme might be of great importance for the development of alcoholism. In addition to MAO inhibition, the physiological concentrations of isatin inhibited the receptor-binding of atrial natriuretic peptides and ANP-stimulated guanylate cyclase (GC). The sensitivity of ANP-GC to isatin might be allosterically regulated. Selective antagonists of natriuretic peptide receptors were found among isatin analogues which may be an effective pharmacological tool for further studies of the role of natriuretic peptides in the body.

Topics: Adrenal Cortex; Alcoholism; Animals; Atrial Natriuretic Factor; Brain; Humans; Isatin; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Neurotransmitter Agents; Receptors, Atrial Natriuretic Factor

Topics: Adrenocorticotropic Hormone; Adult; Alcohol Drinking; Alcoholism; Atrial Natriuretic Factor; Ethanol; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Leptin; Male; Middle Aged; Outpatients; Self Administration; Self Disclosure; Substance Withdrawal Syndrome; Time Factors

Both atrial natriuretic peptide (ANP) and vasopressin (VP) influence alcohol intake and withdrawal as well as craving and are also regulated by epigenetic factors. Disturbances in expression and promoter methylation status have been described in patients suffering from alcohol use disorder and alcohol withdrawal therapy.. In this study, we wanted to map the progression of cytosine-phosphatidyl-guanine (CpG) methylation of the respective gene promoter of ANP and VP immediately after starting alcohol withdrawal therapy when compared with healthy controls METHODS: We recruited 34 males suffering from alcohol addiction or harmful use alongside 43 healthy male controls. Blood samples for methylation analyses were drawn on days 1, 2, 3, 4, and 7-10.. There was no difference in mean methylation for both VP and ANP during withdrawal. There was no difference at the ANP CpG-sites after correction for multiple testing. Regarding VP, methylation was significantly higher at CpG 033, CpG 064, CpG 103, CpG 118, and CpG 194 and significantly lower at CpG 053, CpG 060, and CpG 214 when compared to healthy controls. Via in silico analysis, we identified transcription factor binding sites that could potentially influence methylation-dependent gene transcription.. While there was no change in methylation status during withdrawal, significant differences in average methylation of specific CpG sites were observed for VP. We also identified the role of transcription factors in the context of promoter methylation as one potential mechanism that could explain the differences in VP levels between alcohol-dependent patients and healthy controls.

Topics: Alcoholism; Atrial Natriuretic Factor; Case-Control Studies; DNA Methylation; Humans; Male; Substance Withdrawal Syndrome; Vasopressins

Disturbances of volume-regulating peptides like vasopressin (AVP) and atrial natriuretic peptide (ANP) have been described in early abstinent alcohol-dependent patients. In a longitudinal approach, we investigated whether changes in AVP and ANP serum levels correlated to cytosine-phosphatidyl-guanine (CpG) methylation of the respective gene promoters on days 1, 7 and 14 of alcohol withdrawal. We analyzed the blood samples of 99 patients suffering from alcohol dependence alongside age- and BMI-matched controls. Concerning AVP promoter methylation, we observed an interaction between time of measurement and CpG loci with CpG 2 showing a significant increase in methylation from day 1 to 14. Serum levels of AVP were significantly decreased in the patient group. Compared to healthy controls, promoter-related DNA methylation of the ANP promoter was significantly reduced on days 7 and 14. Moreover, we detected a significant interaction between CpG position and group. In both cases the difference was mainly observed at CpG 1. The present study shows significant changes in the methylation status of individual CpG sites of AVP and ANP. Observing respective alterations of AVP serum protein levels in alcohol-dependent patients during detoxification treatment, we consider methylation as a possible mode of regulation for these proteins during alcohol detoxification.

Topics: Adult; Alcoholism; Atrial Natriuretic Factor; Case-Control Studies; CpG Islands; DNA Methylation; Humans; Male; Promoter Regions, Genetic; Substance Withdrawal Syndrome; Vasopressins; Young Adult

In alcoholism, both relapse to alcohol drinking and treatment response are suggested to be genetically modulated. This study set out to determine whether the top 15 single nucleotide polymorphisms (SNPs) of a recent genome-wide association (GWA) and follow-up study of alcohol dependence are associated with relapse behavior and pharmacological treatment response in 374 alcohol-dependent subjects who underwent a randomized, double-blind, placebo-controlled trial with acamprosate, naltrexone or placebo. The single nucleotide polymorphism, rs13273672, an intronic SNP in the gene for GATA-binding protein 4 (GATA4), was associated with relapse within the 90-day medical treatment period (P<0.01). Subsequent pharmacogenetic analyses showed that this association was mainly based on patients treated with acamprosate (P<0.01). In line with the observation that natriuretic peptide promoters are modulated by GATA4, a significant gene dose effect on the variance of atrial natriuretic peptide (ANP) plasma concentration in the different GATA4 genotypes (P<0.01) was found. Hence, genetic variations in GATA4 might influence relapse and treatment response to acamprosate in alcohol-dependent patients via modulation of ANP plasma levels. These results could help to identify those alcohol-dependent patients who may be at an increased risk of relapse and who may better respond to treatment with acamprosate.

Topics: Acamprosate; Adult; Alcohol Deterrents; Alcoholism; Alcohols; Atrial Natriuretic Factor; Female; GATA4 Transcription Factor; Gene Dosage; Genetic Association Studies; Genetic Variation; Humans; Linkage Disequilibrium; Male; Middle Aged; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Randomized Controlled Trials as Topic; Recurrence; Risk; Taurine

Disturbances of volume regulating peptides like vasopressin and atrial natriuretic peptide (ANP) have been described in early abstinent patients. Aim of the present study was to evaluate possible alterations of the promoter-related DNA methylation of the ANP and vasopressin precursor genes and the related mRNA-expression of these genes in early alcohol withdrawal. We analyzed blood samples of 57 healthy controls and of 111 patients suffering from alcohol dependence that were admitted for detoxification treatment. Promoter-related DNA methylation and mRNA-expression of vasopressin and ANP genes were assessed using real-time PCR. Vasopressin mRNA-expression was not statistically different between patients and controls. However, we found a significantly elevated promoter-related DNA methylation of the vasopressin gene in patients with alcohol dependence (Mann-Whitney U-test: Z=-2.178, p=0.029). ANP mRNA-expression was significantly elevated in alcoholic patients (Z=-6.240, p<0.001) while promoter-related DNA methylation of ANP was significantly decreased (Z=-2.282, p=0.023). Furthermore, promoter-related DNA methylation of ANP was significantly correlated to the extent of craving measured with the OCDS (r=-0.197, p=0.040). The findings of the present study show significant alterations of the mRNA-expression and promoter-related DNA methylation of vasopressin and especially ANP precursor genes in patients with alcohol dependence. Further studies focusing on longitudinal changes of epigenetic regulation and gene expression of both peptides are needed to clarify the pathophysiological role of these findings.

Topics: Adult; Alcoholism; Atrial Natriuretic Factor; Case-Control Studies; DNA Methylation; Epigenesis, Genetic; Female; Humans; Male; Middle Aged; Promoter Regions, Genetic; Reference Values; RNA, Messenger; Substance Withdrawal Syndrome; Vasopressins; Water-Electrolyte Balance; Young Adult

During alcohol withdrawal and early abstinence, severe alterations of electrolyte and water homeostasis and their regulating hormones are well recognized. Almost nothing is known about regeneration of these functions with long-term abstinence. This cohort study was designed to monitor determinants of electrolyte and water balance over 280 days of abstinence in alcohol-dependent men compared with healthy controls.. Vasopressin (AVP), N-terminal proatrial natriuretic peptide, aldosterone, angiotensin II, and electrolytes, together with major parameters of kidney and liver function, were monitored in 35 male alcoholics aged 44 +/- 8 years. Of these, 21 could be followed up to 280 days of strictly controlled abstinence due to their participation in the Outpatient Long-Term Intensive Therapy for Alcoholics. The control group comprised 20 healthy male volunteers aged 39 +/- 7 years.. Basal AVP levels were found to be suppressed over the whole study period. In contrast, N-terminal proatrial natriuretic peptide remained increased over all 280 days. No persistent alterations were found for aldosterone or angiotensin II. Sodium and potassium in plasma and urine returned to normal within a few weeks. Creatinine clearance, urea nitrogen in plasma and urine, urinary osmolality, hematocrit, and hemoglobin remained low as compared with controls over the entire study.. Chronic alcohol abuse causes severe and persistent alterations in the hormonal regulatory systems of electrolyte and water balance. The suppressed basal secretion of AVP may reflect a dysregulation in the brain that influences the hypothalamic-pituitary-adrenal axis function, mood, memory, addiction behavior, and craving during alcohol abstinence. These findings may provide a ground for future therapeutic approaches to stable abstinence.

Topics: Adult; Alanine Transaminase; Alcoholism; Aldosterone; Angiotensin II; Aspartate Aminotransferases; Atrial Natriuretic Factor; Blood; Blood Urea Nitrogen; Drinking; gamma-Glutamyltransferase; Humans; Kidney; Liver; Male; Middle Aged; Osmolar Concentration; Protein Precursors; Substance Withdrawal Syndrome; Time Factors; Urea; Urine; Vasopressins; Water-Electrolyte Balance

Transthoracic echocardiography was used in a rodent animal model to determine whether long-term alcohol consumption (8 and 12 months) was associated with the development of a dilated cardiomyopathy. We also investigated whether alcohol-induced changes in cardiac structure corresponded to activation of the renin-angiotensin system and the natriuretic peptide (NP) system.. Male rats received either the Lieber-DeCarli liquid alcohol diet (EtOH) (9%v/v) (n = 8) or control diet (CON) (n = 8). Echocardiography (echo) was used to determine left-ventricular (LV) dimensions, and isolated heart studies (Langendorff and atrium) were used to assess ex vivo contractility. Plasma and tissue angiotensin-I converting enzyme (ACE) activity was measured. Gene expression, plasma, and tissue levels of the NPs were determined by northern blot analysis and radioimmunoassay, respectively.. After 8 months of alcohol consumption, there was a trend for the end diastolic dimension, end systolic dimension, and LV mass to be greater in the 8 month EtOH group compared with the CON group. However, after 12 months of alcohol consumption, significant increases were found between the groups in several echo parameters. Tissue ACE activity (nmoles/min/mg protein) was greater in the 12 month EtOH group compared with the 12 month CON and 8 month EtOH group (p < 0.05). We found no differences between groups in gene expression (messenger RNA), plasma, and tissue levels of the NPs.. Echocardiography revealed that 8 to 12 months of alcohol consumption was associated with the development of a dilated cardiomyopathy. However, this was not preceded by an increase in tissue ACE activity, and these changes occurred in the absence of increased plasma and LV tissue levels of the NPs.

Topics: Alcoholism; Animals; Atrial Natriuretic Factor; Cardiomyopathy, Alcoholic; Disease Models, Animal; Echocardiography; Male; Myocardium; Natriuretic Peptide, Brain; Peptidyl-Dipeptidase A; Rats; Rats, Sprague-Dawley; Stroke Volume

Using an animal model, we have investigated the effects of chronic ethanol ingestion on the regulation of atrial natriuretic peptide (ANP) synthesis and release. Male Sprague-Dawley rats were maintained for 6 weeks on a liquid diet of ethanol (up to 20% v/v) as part of a 2% solution of calf milk replacer. Weight-matched controls received an equal volume of ethanol-free solution, and normal animals drank ad libitum. All animals received rat chow throughout the experiment. This model produced physiologically relevant levels of blood ethanol, as concentrations at the time of sacrifice were 171.98 +/- 39.26 mg/dl. Plasma renin activity was significantly elevated in response to ethanol treatment, whereas circulating aldosterone concentration was reduced. No alterations in the plasma or atrial tissue levels of ANP were evident, although we did observe a significant increase in the ventricular tissue levels of ANP from 45.1 to 71.8 ng/g as a consequence of ethanol treatment. Levels of both atrial and ventricular ANP mRNA were not different between alcohol-treated and liquid-restricted control animals, although both groups showed significant increases in the amount of transcript in comparison with rats drinking ad libitum. No significant increases in either arterial blood pressure or heart/body weight ratio were observed for ethanol-treated rats. These results suggest that modifications in the renin-aldosterone axis can occur independently of alterations in the regulation of ANP under the influence of chronic ethanol ingestion.

Topics: Alcoholism; Animals; Atrial Natriuretic Factor; Blood Pressure; Ethanol; Male; Rats; Rats, Sprague-Dawley; Renin-Angiotensin System; Water-Electrolyte Balance

Topics: Adult; Alcohol Withdrawal Delirium; Alcoholism; Aldosterone; Atrial Natriuretic Factor; Central Nervous System; Humans; Male; Radioimmunoassay; Renin; Sodium; Water-Electrolyte Imbalance