pituitrin and Alcoholism

Arginine vasopressin (VP) has been implicated in a number of neuropsychiatric disorders with an emphasis on situations where stress increased the severity of the disorder. Based on this hypothesized role for VP in neuropsychiatric disorders, much research is currently being undertaken in humans and animals to test VP as a target for treatment of a number of these disorders including alcohol abuse.. To provide a summary of the literature regarding the role of VP in alcohol- and stress-related behaviors including the use of drugs that target VP in clinical trials.. Changes in various components of the VP system occur with alcohol and stress. Manipulating VP or its receptors can alter alcohol- and stress-related behaviors including tolerance to alcohol, alcohol drinking, and anxiety-like behavior. Finally, the hypothalamic-pituitary-adrenal axis response to alcohol is also altered by manipulating the VP system. However, clinical trials of VP antagonists have had mixed results.. A review of VP's involvement in alcohol's actions demonstrates that there is much to be learned about brain regions involved in VP-mediated effects on behavior. Thus, future work should focus on elucidating relevant brain regions. By using previous knowledge of the actions of VP and determining the brain regions and/or systems involved in its different behavioral effects, it may be possible to identify a specific receptor subtype target, drug treatment combination, or specific clinical contexts that may point toward a more successful treatment.

Topics: Alcohol Drinking; Alcoholism; Animals; Antidiuretic Hormone Receptor Antagonists; Anxiety; Arginine Vasopressin; Ethanol; Humans; Hypothalamo-Hypophyseal System; Neurophysins; Pituitary-Adrenal System; Protein Precursors; Stress, Psychological; Vasopressins

Traumatic injury ranks as the number one cause of death for the younger than 44 years age group and fifth leading cause of death overall (www.nationaltraumainstitute.org/home/trauma_statistics.html). Although improved resuscitation of trauma patients has dramatically reduced immediate mortality from hemorrhagic shock, long-term morbidity and mortality continue to be unacceptably high during the postresuscitation period particularly as a result of impaired host immune responses to subsequent challenges such as surgery or infection. Acute alcohol intoxication (AAI) is a significant risk factor for traumatic injury, with intoxicating blood alcohol levels present in more than 40% of injured patients. Severity of trauma, hemorrhagic shock, and injury is higher in intoxicated individuals than that of sober victims, resulting in higher mortality rates in this patient population. Necessary invasive procedures (surgery, anesthesia) and subsequent challenges (infection) that intoxicated trauma victims are frequently subjected to are additional stresses to an already compromised inflammatory and neuroendocrine milieu and further contribute to their morbidity and mortality. Thus, dissecting the dynamic imbalance produced by AAI during trauma is of critical relevance for a significant proportion of injured victims. This review outlines how AAI at the time of hemorrhagic shock not only prevents adequate responses to fluid resuscitation but also impairs the ability of the host to overcome a secondary infection. Moreover, it discusses the neuroendocrine mechanisms underlying alcohol-induced hemodynamic dysregulation and its relevance to host defense restoration of homeostasis after injury.

Topics: Alcoholism; Autonomic Nervous System; Ethanol; Hemodynamics; Humans; Neurophysins; Neurosecretory Systems; Protein Precursors; Resuscitation; Shock, Hemorrhagic; Vasopressins; Wounds and Injuries

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

The primary enzymes involved in alcohol metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Both enzymes occur in several forms that are encoded by different genes; moreover, there are variants (i.e., alleles) of some of these genes that encode enzymes with different characteristics and which have different ethnic distributions. Which ADH or ALDH alleles a person carries influence his or her level of alcohol consumption and risk of alcoholism. Researchers to date primarily have studied coding variants in the ADH1 B, ADH1C, and ALDH2 genes that are associated with altered kinetic properties of the resulting enzymes. For example, certain ADH1B and ADH1C alleles encode particularly active ADH enzymes, resulting in more rapid conversion of alcohol (i.e., ethanol) to acetaldehyde; these alleles have a protective effect on the risk of alcoholism. A variant of the ALDH2 gene encodes an essentially inactive ALDH enzyme, resulting in acetaldehyde accumulation and a protective effect. It is becoming clear that noncoding variants in both ADH and ALDH genes also may influence alcohol metabolism and, consequently, alcoholism risk; the specific nature and effects of these variants still need further study.

Topics: Alcohol Dehydrogenase; Alcoholism; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase 1 Family; Alleles; Ethanol; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Genotype; Humans; Linkage Disequilibrium; Neurophysins; Protein Precursors; Retinal Dehydrogenase; Vasopressins

Native Americans as a group have the highest rates of alcohol-related deaths of all ethnicities in the United States; however, it remains unclear how and why a greater proportion of individuals in some Native American communities develop alcohol-related problems and alcohol use disorders (AUDs). One potential factor that can influence responses to alcohol are variations in alcohol-metabolizing enzymes. Researchers have analyzed the frequencies of variants in the alcohol-metabolizing enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in some Native American populations. So far the studies have yielded no evidence that an ALDH2 variant, which has shown protective effects in other populations, is found in either American Indians or Alaska Natives. A variant of the ALDH1 enzyme that is encoded by the ALDH1A1*2 allele, however, was found in a small proportion of a group of Southwest California Indians and had a protective effect against alcoholism in that population. Furthermore, a variant of the ADH1B enzyme that is encoded by the ADH1B*3 allele was found in a similar proportion of Southwest California Indians and also was associated with a protective effect. However, these findings do not explain the high prevalence of alcoholism in the tribes investigated.

Topics: Alcohol Dehydrogenase; Alcoholism; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial; Asian People; California; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Humans; Indians, North American; Inuit; Neurophysins; Polymorphism, Genetic; Protein Precursors; Vasopressins

This review discusses some of the mechanisms through which alcohol (EtOH) alters the activity of the hypothalamic-pituitary-adrenal (HPA) axis. In adult rats, acute EtOH treatment increases plasma ACTH and corticosteroids levels primarily by stimulating the release of corticotropin-releasing factor (CRF) and possibly vasopressin (VP) from nerve terminals in the median eminence. Increased CRF gene transcription in the hypothalamus may also be important. The HPA axis remains activated during chronic EtOH exposure, although habituation may take place. Changes in the responsiveness of hypothalamic neurons, a phenomenon itself dependent in part on a number of intermediate secretagogues, as well as decreased pituitary responsiveness to VP, all play a role. Finally, the activity of the HPA axis is influenced by exposure to EtOH during embryonic development, with mature offspring showing hyporesponsiveness to many stimuli. These altered responses appear to be caused in part by changes in the synthesis/release CRF, possibly under the influence of nitric oxide. CRF, VP, ACTH, and corticosteroids are important regulators of the immune system, behavior, metabolic pathways, and reproductive parameters. Alcohol therefore may influence such functions through the pathological secretion of these hormones. A better understanding of the mechanisms through which the drug alters their release thus may permit the development of therapies designed to alleviate some of the consequences of alcoholism.

Topics: Adrenocorticotropic Hormone; Alcohol Drinking; Alcoholism; Animals; Corticotropin-Releasing Hormone; Ethanol; Female; Fetal Alcohol Spectrum Disorders; Humans; Hypothalamo-Hypophyseal System; Male; Median Eminence; Pituitary-Adrenal System; Pregnancy; Rats; Species Specificity; Stimulation, Chemical; Vasopressins

The acute effect of ethyl alcohol ingestion is to induce diuresis with excretion of free water and preservation of electrolytes. This occurs as the blood alcohol concentration is increasing and is due to the suppression by alcohol of the endogenous release of ADH. During a steady blood alcohol concentration, alcohol acts as an antidiuretic, causing retention of water and electrolytes. While at steady state, additional doses of alcohol will produce progressively smaller and eventually absent diuretic responses. The chronic effect of alcohol is to promote isosmotic retention of water and electrolytes due to increased ADH levels. Excess water and electrolytes are acutely excreted in response to additional alcohol ingestion. With the cessation of alcohol intake, this excess will be excreted over several days. Routine parenteral fluid administration to chronic and withdrawing alcoholics should be avoided. The role of potassium and magnesium in the genesis of specific manifestations of the alcohol withdrawal syndrome is not clear. Alcoholic patients may have electrolyte abnormalities due to alcohol-induced diseases, poor nutrition, or vomiting and diarrhea. Each case must be individually evaluated.

Topics: Alcoholism; Electrolytes; Emergency Medicine; Ethanol; Hemodynamics; Humans; Magnesium; Substance Withdrawal Syndrome; Vasopressins; Water-Electrolyte Imbalance

Topics: Adrenal Cortex; Adrenal Medulla; Alcoholism; Bone and Bones; Endocrine Glands; Female; Gastrointestinal Hormones; Humans; Hypothalamus; Male; Ovary; Pituitary Gland; Prolactin; Renin-Angiotensin System; Testis; Thyroid Gland; Vasopressins

Topics: Adrenocorticotropic Hormone; Alcoholism; Animals; Drug Tolerance; Ethanol; Female; Follicle Stimulating Hormone; Growth Hormone; Humans; Luteinizing Hormone; Male; Mice; Oxytocin; Pituitary Hormones; Pregnancy; Rats; Substance-Related Disorders; Vasopressins

Topics: Alcoholism; Animals; Barbiturates; Drug Tolerance; Ethanol; Humans; Morphine; Morphine Dependence; Narcotics; Neurophysins; Oxytocin; Peptides; Pituitary Hormones, Posterior; Psychotropic Drugs; Substance-Related Disorders; Vasopressins

Topics: Acetylcholine; Alcoholism; Animals; Biogenic Amines; Dopamine; Endorphins; Female; Fetal Alcohol Spectrum Disorders; gamma-Aminobutyric Acid; Growth Hormone; Histamine; Humans; Hypothalamo-Hypophyseal System; Insulin; Male; Norepinephrine; Ovary; Oxytocin; Pituitary-Adrenal System; Pregnancy; Serotonin; Somatostatin; Testis; Thyroid Gland; Vasopressins

Topics: Acute Kidney Injury; Alcoholism; Animals; Dogs; Ethanol; Glomerular Filtration Rate; Glomerulonephritis; Humans; Kidney; Kidney Diseases; Kidney Glomerulus; Pyelonephritis; Rats; Urinary Bladder; Vasopressins

Topics: Acute Kidney Injury; Alcoholism; Animals; Dogs; Ethanol; Glomerular Filtration Rate; Glomerulonephritis; Humans; Kidney; Kidney Diseases; Kidney Glomerulus; Pyelonephritis; Rats; Urinary Bladder; Vasopressins

Topics: Alcoholism; Animals; Diuretics; Female; Humans; Infant, Newborn; Kidney Diseases; Lactation Disorders; Magnesium; Magnesium Deficiency; Porphyrias; Pregnancy; Vasopressins

Topics: Alcoholism; Aldosterone; Animals; Diuretics; Dogs; Humans; Kidney; Kidney Failure, Chronic; Magnesium; Magnesium Deficiency; Parathyroid Hormone; Rats; Uremia; Vasopressins

1. Plasma oxytocin (OX), vasopressin (VP), estrone (ES) and beta-endorphin (beta-end) levels were measured in 13 male non-chirrotic alcoholics, at 1, 4, 7, 15 and 28 days after alcohol withdrawal and only once in 9 sex- and age-matched normal controls. 2. At all examined time points, plasma OX and ES, but not VP, levels were significantly higher in alcoholics than in controls. Alcoholics showed plasma beta-end levels lower than normal. 3. A positive relationship was found between ES and OX levels suggesting that elevated estrogens levels in chronic alcoholics might exert a stimulatory effect on OX. 4. In light of the well-known effect of OX on learning and memory, an involvement of OX in alcohol-induced neuropsychological deficits may be supposed.

Topics: Adult; Alcoholism; beta-Endorphin; Estrone; Female; Humans; Male; Middle Aged; Oxytocin; Psychiatric Status Rating Scales; Substance Withdrawal Syndrome; Time Factors; Vasopressins

The intranasal administration of the hypothalamic peptide hormones vasopressin and corticotropin was used in the therapy of alcohol abstinence syndrome, acute and chronic alcoholic psychoses and in the conditioned reflex therapy of alcoholism. The proposed methods of therapy were fairly effective and free of complications and marked side effects.

Topics: Administration, Intranasal; Adrenocorticotropic Hormone; Adult; Alcohol Amnestic Disorder; Alcoholism; Anti-Anxiety Agents; Clinical Trials as Topic; Conditioning, Classical; Ethanol; Humans; Middle Aged; Piracetam; Substance Withdrawal Syndrome; Vasopressins; Vitamin B Complex

Activation of V

Topics: Alcoholism; Central Amygdaloid Nucleus; Humans; Neurons; Phosphatidylinositol 4,5-Diphosphate; Phospholipase C beta; TRPC Cation Channels; Vasopressins

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

Signatures of recent positive selection often overlap across human populations, but the question of how often these overlaps represent a single ancestral event remains unresolved. If a single selective event spread across many populations, the same sweeping haplotype should appear in each population and the selective pressure could be common across populations and environments. Identifying such shared selective events could identify genomic loci and human traits important in recent history across the globe. In addition, genomic annotations that recently became available could help attach these signatures to a potential gene and molecular phenotype selected across populations. Here, we present a catalogue of selective sweeps in humans, and identify those that overlap and share a sweeping haplotype. We connect these sweep overlaps with potential biological mechanisms at several loci, including potential new sites of adaptive introgression, the glycophorin locus associated with malarial resistance and the alcohol dehydrogenase cluster associated with alcohol dependency.

Topics: Alcoholism; Glycophorins; Haplotypes; Humans; Malaria; Neurophysins; Protein Precursors; Selection, Genetic; Vasopressins

Topics: Acidosis, Lactic; Acute Disease; Administration, Intravenous; Adult; Aged; Alcoholism; Anti-Bacterial Agents; Bicarbonates; Comorbidity; Confusion; Glasgow Coma Scale; Humans; Hyperlactatemia; Hypotension; Intubation, Intratracheal; Male; Norepinephrine; Respiration, Artificial; Respiratory Insufficiency; Tachycardia; Thiamine; Vasoconstrictor Agents; Vasopressins; Vitamin B Complex

Chronic alcohol consumption causes a spectrum of liver diseases, but the pathogenic mechanisms driving the onset and progression of disease are not clearly defined. We show that chronic alcohol feeding sensitizes rat hepatocytes to Ca

Topics: Alcohol Drinking; Alcoholism; Animals; Calcium; Calcium Signaling; Hepatocytes; Inositol 1,4,5-Trisphosphate; Liver; Male; Rats, Sprague-Dawley; Type C Phospholipases; 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

Topics: Adult; Alcoholism; Beer; Emergency Nursing; Emergency Service, Hospital; Humans; Hyponatremia; Male; Myelinolysis, Central Pontine; Nursing Assessment; Vasopressins

Hemodynamic instability may occur during liver transplantation especially following unclamping the portal vein. A period of hypotension (postreperfusion syndrome) is usually responsive to treatment with fluids, calcium, sodium bicarbonate, and vasoactive drugs, but if hypotension persists, other causes must be sought out. In this report, we present a case in which anaphylaxis, most likely due to a component of the University of Wisconsin preservation solution, occurred coincident with liver reperfusion and severely exacerbated reperfusion hemodynamic instability. To our knowledge, this is the first report of anaphylaxis at the time of reperfusion and may provide an explanation for cases of vasoplegic syndrome associated with graft reperfusion.

Topics: Alcoholism; Anaphylaxis; Bile; Blood Pressure; Dopamine; Hepatitis C, Chronic; Humans; Liver Transplantation; Male; Middle Aged; Phenylephrine; Reperfusion Injury; Respiration, Artificial; Treatment Outcome; Vasopressins

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

In males, long-term alcohol consumption provokes neurochemical changes in the medial parvocellular division of the PVN (PVNmp) that are partially reversed by withdrawal. Because gonadal steroids modulate the activity of the hypothalamo-pituitary-adrenal axis, we analyzed the possibility that the repercussions of chronic alcohol consumption and withdrawal on the anatomy and neurochemistry of the PVNmp might differ between the sexes. Male and female Wistar rats were examined after ingesting a 20% alcohol solution for 6 months or after 2 months of withdrawal from 6 months of alcohol consumption. The levels of gonadal steroids and the basal concentrations of corticosterone were also evaluated. Chronic alcohol consumption and withdrawal did not alter the global cytoarchitectonic features of the PVNmp in rats of both sexes. However, alcohol consumption was associated with a decrease in the number of vasopressin (VP) neurons only in females and of corticotropin releasing hormone (CRH) neurons in males and females. Further, the response to withdrawal was sexually dimorphic because in males there was a partial recovery of the number of CRH neurons whereas in females there was a further loss of VP and CRH neurons. Corticosterone levels were unchanged by alcohol consumption, but they were decreased by withdrawal in females. Alcohol consumption and withdrawal did not alter estrogen and progesterone concentrations in females, but decreased testosterone levels in males. These findings show that the response of CRH and VP neurons to excess alcohol is gender-specific, with females being more vulnerable during alcohol consumption and, most notably, after withdrawal.

Topics: Alcohol-Induced Disorders, Nervous System; Alcoholism; Animals; Cell Death; Chronic Disease; Corticosterone; Corticotropin-Releasing Hormone; Disease Models, Animal; Down-Regulation; Female; Gonadal Steroid Hormones; Gonads; Hypothalamo-Hypophyseal System; Male; Nerve Degeneration; Paraventricular Hypothalamic Nucleus; Pituitary-Adrenal System; Rats; Rats, Wistar; Sex Characteristics; Substance Withdrawal Syndrome; Vasopressins

Although numerous data showing severe morphological impairment of magnocellular and parvocellular hypothalamic neurons due to chronic alcoholic consumption have been gathered from animal experiments, only one study (Harding et al., 1996) was performed on POST MORTEM human brain. This study showed a reduction in the number of vasopressin (VP)-immunoreactive neurons in the supraoptic (SON) and paraventricular (PVN) nuclei, but did not provide any data regarding the effect of chronic alcohol intake on human parvocellular neurons. In order to assess whether the changes observed in the animal model also occur in humans and provide a structural basis for the results of clinical tests, we performed immunohistochemical and morphometric analysis of magnocellular (VP and oxytocin, OT) and parvocellular (corticotropin-releasing hormone, CRH) neurons in post-mortem brains of patients afflicted with chronic alcoholic disease. We analyzed 26-male alcoholics and 22 age-matched controls divided into two age groups--"young" (< 40 yr) and "old" (> 40 yr). Hypothalamic sections were stained for OT, VP, and CRH. The analysis revealed: 1) decrease in VP-immunoreactivity in the SON and PVN as well as OT-immunoreactivity in the SON in alcoholic patients; 2) increase in OT-immunoreactivity in the PVN; 3) increase in CRH-immunoreactivity in parvocellular neurons in the PVN. Furthermore, the proportion of cells containing CRH and VP was increased in alcoholics. These findings indicate that chronic alcohol consumption does indeed impair the morphology of magnocellular neurons. The enhancement of CRH-immunoreactivity and increased co-production of CRH and VP in parvocellular neurons may be due to a decline in glucocorticoid production, implied by the hypoplasic impairment of adrenal cortex we observed in alcoholics during the course of this study.

Topics: Adrenal Glands; Adult; Alcoholism; Corticotropin-Releasing Hormone; Humans; Hypothalamus, Anterior; Male; Middle Aged; Neurons; Oxytocin; Paraventricular Hypothalamic Nucleus; Pituitary Gland, Posterior; Retrospective Studies; Vasopressins

Basal arginine vasopressin (AVP) plasma levels in alcoholic patients are persistently decreased over months of controlled alcohol abstinence. As a potential explanation of this phenomenon, a reduction of AVP immunoreactive neurons was described in the hypothalamus of alcohol-dependent humans and rodents. This study was therefore designed to examine whether long-term abstinent alcoholics have a compromised response of AVP to osmostimulation.. Fifteen male alcoholics, aged 42 +/- 2 years, were examined (1) over 12 months of strictly controlled abstinence (longitudinal study) and (2) during an osmostimulation test (5% NaCl infusion at 0.06 ml/kg/min over 2 hr) and were compared with 15 healthy male subjects, aged 41 +/- 2 years. AVP and routine laboratory parameters, including electrolytes and osmolality, were measured.. Starting from lower basal concentrations, alcoholics showed increases similar to those of controls in AVP and plasma osmolality after osmostimulation. The first sensation of thirst was announced significantly later by alcoholics than by controls. Twenty-hour-posttest urine volume and sodium excretion were reduced in alcoholics compared with controls.. Despite their persistently decreased basal AVP plasma levels, long-term abstinent alcoholics have a well preserved AVP response to osmostimulation. This finding indicates a peripheral suppression of AVP levels that is most likely due to a regulatory set-point shift toward hypotonic hyperhydration, rather than to a reduced central capacity of AVP secretion.

Topics: Adult; Alcoholism; Humans; Infusions, Intravenous; Longitudinal Studies; Male; Middle Aged; Osmolar Concentration; Sodium Chloride; Statistics, Nonparametric; Temperance; Vasopressins

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

The ability of alcohol to activate the hypothalamic-pituitary-adrenal (HPA) axis is well documented in investigations based in acute and short-term experimental paradigms. Herein, we have addressed the possibility that the prolonged exposure to ethanol concentrations that are initially effective in stimulating corticosteroid secretion might induce alterations in the response of the HPA axis that cannot be evinced by shorter exposures. Using conventional histological techniques, immunohistochemistry and in situ hybridization, we have examined the medial parvocellular division of the paraventricular nucleus (PVNmp), and the synthesis and expression of corticotropin-releasing hormone (CRH) and vasopressin (VP) by its constituent neurons, in rats submitted to 6 months of ethanol treatment and to withdrawal (2 months after 6 months of alcohol intake). Ethanol treatment and withdrawal did not produce neuronal loss in the PVNmp. However, the total number of CRH- and VP-immunoreactive neurons and the CRH mRNA levels were significantly decreased by ethanol treatment. In withdrawn rats, the number of CRH- and VP-immunostained neurons and the gene expression of CRH were increased relative to ethanol-treated rats and did not differ from those of controls. No significant variations were detected in VP mRNA levels as a result of ethanol treatment or withdrawal. These results show that prolonged alcohol intake blunts the expression of CRH and VP in the parvocellular neurons of the PVN, and that this effect is, partially at least, reversible by withdrawal. They also suggest that the development of tolerance to the effects of ethanol involve changes that take place at the hypothalamic level.

Topics: Alcohol Drinking; Alcoholism; Animals; Central Nervous System Depressants; Corticotropin-Releasing Hormone; Ethanol; Gene Expression; Hypothalamo-Hypophyseal System; Immunohistochemistry; In Situ Hybridization; Male; Nerve Degeneration; Neurons; Paraventricular Hypothalamic Nucleus; Pituitary-Adrenal System; Rats; Rats, Wistar; RNA, Messenger; Substance Withdrawal Syndrome; Time Factors; Vasopressins

Previous data revealed that numerous neurons in the supraoptic nucleus degenerate after prolonged ethanol exposure, and that the surviving neurons increase their activity in order to prevent dramatic changes in water metabolism. Conversely, excess alcohol does not induce cell death in the suprachiasmatic nucleus, but leads to depression of neuropeptide synthesis that is further aggravated by withdrawal. The aim of the present study is to characterize the effects of prolonged ethanol exposure on the magnocellular neurons of the paraventricular nucleus (PVN) in order to establish whether or not magnocellular neurons display a common pattern of reaction to excess alcohol, irrespective of the hypothalamic cell group they belong. Using conventional histological techniques, immunohistochemistry and in situ hybridization, the structural organization and the synthesis and expression of vasopressin (VP) and oxytocin (OXT) in the magnocellular component of the PVN were studied under normal conditions and following chronic ethanol treatment (6 or 10 months) and withdrawal (4 months after 6 months of alcohol intake). After ethanol treatment, there was a marked decrease in the number of VP- and OXT-immunoreactive magnocellular neurons that was attributable to cell death. The surviving neurons were hypertrophied and the VP and OXT mRNA levels in the PVN unchanged. Withdrawal did not alter the number of VP- and OXT-producing neurons or the gene expression of these peptides. These results substantiate the view that after prolonged ethanol exposure numerous neurons of the hypothalamic magnocellular system degenerate, but the mRNA levels of VP and OXT are not decreased due to compensatory changes undergone by the surviving neurons.

Topics: Alcohol Drinking; Alcoholism; Animals; Central Nervous System Depressants; Ethanol; Gene Expression; Immunohistochemistry; In Situ Hybridization; Male; Nerve Degeneration; Neurons; Organ Size; Oxytocin; Paraventricular Hypothalamic Nucleus; Rats; Rats, Wistar; RNA, Messenger; Substance Withdrawal Syndrome; Vasopressins

We tested the hypothesis that ethanol impairs liver regeneration by abrogating receptor-mediated elevation of cytosolic free calcium ([Ca2+]i). In rats fed for 16 weeks with ethanol, hepatocellular proliferation induced by partial hepatectomy was greatly impaired. Similarly, EGF-induced DNA synthesis was reduced in cultured hepatocytes from ethanol-fed rats. There was no change in the number or affinity of EGF receptors on hepatocytes from ethanol-fed rats. Despite this, EGF-mediated production of inositol 1,4,5-trisphosphate (Ins[1,4,5]P3) was lower in hepatocytes from ethanol-fed rats, and the EGF-induced [Ca2+]i transient appeared to be abrogated. When vasopressin or phenylephrine were used as cell surface receptor ligands, hepatocytes cultured from ethanol-fed rats exhibited major reductions in Ins(1,4,5)P3 synthesis. This was associated with greatly truncated [Ca2+]i transients. These changes were not due to an effect on the Ins(1,4,5)P3 receptor on the endoplasmic reticulum or to a decrease in the size of the Ins(1,4,5)P3-mobilizable intracellular Ca+2 store. Further, mobilization of the same Ca2+ store by 2,5-di-tert-butylhydroquinone or thapsigargin restored the ability of hepatocytes from ethanol-fed rats to proliferate when exposed to EGF. It is concluded that chronic ethanol consumption inhibits liver regeneration by a mechanism that is, at least partly, the result of impaired receptor-operated [Ca2+]i signaling due to reduced generation of Ins(1,4,5)P3.

Topics: Alcoholism; Animals; Calcium; Cell Membrane; Cell Membrane Permeability; Cells, Cultured; Epidermal Growth Factor; Hepatectomy; Inositol 1,4,5-Trisphosphate; Liver; Liver Regeneration; Male; Phenylephrine; Protein Binding; Rats; Rats, Wistar; Receptors, Cell Surface; Vasopressins

The chronic consumption of alcohol significantly reduces the number of vasopressin-producing neurons in the rat supraoptic nucleus [Maderia et al. (1993) Neourscience 56, 657-672] suggesting this region is particularly vulnerable to alcohol neurotoxicity. As hypothalamic vasopressin producing neurons are necessary for fluid homeostasis, it is important to assess if similar changes occur in humans. We analysed arginine vasopressin-immunoreactive neurons in the magnocellular hypothalamic nuclei of ten chronic alcoholic men (consuming > 80 g of ethanol per day) and four age- and sex-matched controls (consuming < 10g of ethanol per day). Brains were collected at autopsy and fixed in formalin. Serial 50 mu m-thick-sections of the hypothalamus were stained and assessed. The volume of the paraventricular and supraoptic nuclei and number of neurons were estimated using Cavalieri's principle and the optical dissector technique. The volume of these nuclei significantly correlated with the number of neurons and the number of vasopressin-immunoreactive neurons, and these measures significantly correlated with the maximum daily intake of alcohol. There was a loss of neurons at consumption levels greater than 100 g of ethanol per day, principally affecting the supraoptic nucleus although neuron loss also occurred in the paraventricular nucleus in cases with long histories of alcohol consumption. These results indicate that chronic alcohol consumption is toxic to hypothalamic vasopressin-producing neurons in a concentration- and time-dependent manner. As these magnocellular neurons are osmo-receptive, neuronal loss may result in fluid imbalances.

Topics: Adult; Aged; Alcoholism; Dose-Response Relationship, Drug; Ethanol; Female; Humans; Male; Middle Aged; Neurons; Time Factors; Vasopressins

We have previously shown that female rats exposed to an alcohol (ethanol, E) diet exhibited a blunted ACTH response to systemically administered interleukin-1 beta (IL-1 beta). Because of the presence of gender differences in the activity of the hypothalamic-pituitary-adrenal (HPA) axis, and of the possible role played by sex steroids in modulating the inhibitory influence of E in females, we studied the ability of a 10-day E diet to alter ACTH and corticosterone secretion of intact or castrated male rats injected with IL-1 beta or endotoxin, a releaser of endogenous cytokines. Pituitary responsiveness to secretagogues that mediate the endocrine effects of IL-1 beta, namely corticotropin-releasing factor (CRF) and vasopressin (VP), was also investigated. The ACTH responses of animals fed ad libitum (C group) or pair-fed (PF group) to the intravenous administration of IL-1 beta or endotoxin were not statistically different (p > 0.05); therefore, results from these two groups were combined in the initial experiments. Subsequent experiments only used E and C animals. When compared with this latter group, intact E males showed a significant (p < 0.01) decrease in ACTH levels measured 30 and 60 min after the intravenous injection of IL-1 beta or endotoxin. In contrast, E rats released as much corticosterone as C rats in response to IL-1 beta, but significantly (p < 0.05) more following administration of endotoxin (lipopolysaccharide). The stimulatory effect of VP on ACTH release was also measurably blunted by alcohol, whereas that of CRF was not. In none of these experiments were any significant differences observed between C and PF rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenocorticotropic Hormone; Alcoholism; Animals; Corticosterone; Corticotropin-Releasing Hormone; Hypothalamo-Hypophyseal System; Interleukin-1; Male; Pituitary-Adrenal System; Rats; Rats, Sprague-Dawley; Testosterone; Vasopressins

Controversial results of fluid and electrolyte derangements in patients with moderate alcohol intoxication have been described. However, no information is available about severe alcohol intoxication. We investigated differences of hormonal disorders between alcohol-habituated and alcohol-naive subjects with severe ethanol intoxication. The hormonal derangements and recommendations on therapy of these patients are discussed. Thirty-three patients [10 alcohol-naive (group A) and 23 alcohol-habituated (group B) subjects] with severe alcohol intoxication (blood ethanol > 200 mg/dl) were selected for the study. Electrolytes and osmolarity of serum and urine, blood ethanol, vasopressin, renin, and aldosterone were determined on admission 2, 4, and 6 hr later. Fluid balance was calculated for each hour. All patients received isotonic saline solution according to urine production. Group A: On admission, serum osmolarity was increased (308 mOsmol/kg). Concomitantly, vasopressin level was elevated on admission (9.12 pg/ml). Increased serum osmolarity was correlated with elevated vasopressin levels (r = 0.8211; p < 0.005). Serum electrolytes, renin, and aldosterone values were within normal ranges. Group B: On admission, vasopressin level was significantly decreased (0.9 pg/ml), despite an elevated serum osmolarity (309 mOsmol/kg). Serum osmolarity remained high despite a sufficient fluid substitution. In addition, vasopressin level remained suppressed over the observation period. Aldosterone level was significantly increased on admission (319 ng/ml). Accordingly, serum sodium was increased from 142 to 148 mM/liter, and serum potassium was decreased from 3.9 to 3.4 mM/liter. Response to hyperosmolarity due to severe alcohol intoxication is different in alcohol-naive and alcohol-habituated subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Alcoholic Intoxication; Alcoholism; Aldosterone; Ethanol; Female; Humans; Kidney Function Tests; Male; Middle Aged; Potassium; Renin; Sodium; Vasopressins; Water-Electrolyte Balance; Water-Electrolyte Imbalance

We have previously shown that prolonged alcohol ingestion leads to neuronal loss in the supraoptic nucleus of the rat and that the surviving neurons, mainly the vasopressinergic ones, display marked increase in volume. In an attempt to establish correlates for the volumetric alterations we have studied the organelles of supraoptic nucleus neurons in three groups of rats--ethanol-fed, pair-fed, and dehydrated, in all cases treated from 2 to 12 months of age. The volume and surface area of the rough endoplasmic reticulum and Golgi apparatus, and the volume of nucleoli and neurosecretory granules were estimated on the basis of the respective volume and surface densities. The volumes and surface areas of all quantified organelles were increased in both alcohol-fed and dehydrated animals, although the increases were greater in the former group. Changes in the organelles studied are commonly regarded as reliable indicators of the neurosecretory activity of magnocellular neurons. Thus, our results suggest that under conditions of chronic alcohol exposure, the synthesizing activity of the surviving supra-optic neurons is augmented to compensate for the alcohol-induced neuronal loss and/or as a consequence of the alcohol-induced hyperosmolality. Changes in the transport and release of the neurosecretory material cannot, however, be ruled out as an additional cause of neuronal enlargement.

Topics: Adaptation, Physiological; Alcoholism; Animals; Cell Size; Dehydration; Ethanol; Male; Neurons; Organelles; Osmolar Concentration; Rats; Rats, Wistar; Stereotaxic Techniques; Supraoptic Nucleus; Vasopressins; Water-Electrolyte Balance

Opioid peptides derived from the precursor, prodynorphin, are co-localized with vasopressin in the hypothalamus and posterior pituitary, and vasopressin and prodynorphin synthesis are coordinately regulated during salt-loading. We had previously found that chronic ethanol ingestion resulted in decreased levels of hypothalamic and extrahypothalamic vasopressin mRNA, and the current study investigated the effect of ethanol ingestion on prodynorphin mRNA levels. A cRNA probe was constructed from a PCR product amplified from mouse genomic DNA. Cloning and sequencing of the PCR product revealed that the sequence of the mouse prodynorphin gene used to synthesize the probe is highly conserved, with high sequence similarity to corresponding regions of the gene in other mammalian species. In situ hybridization using the cRNA probe showed a widespread distribution of prodynorphin mRNA in mouse brain. In dehydrated mice, prodynorphin mRNA was significantly increased in the hypothalamus and nearly all other brain areas examined. In ethanol-fed mice, prodynorphin mRNA was also significantly increased in hypothalamus (50-60%) and in most brain areas. In the same mice, measurement of hypothalamic vasopressin mRNA confirmed a significant (approximately 60%) decrease. These results indicate that hypothalamic vasopressin and prodynorphin mRNA can be differentially regulated in certain situations.

Topics: Alcoholism; Amino Acid Sequence; Animals; Base Sequence; Brain; Enkephalins; Ethanol; Gene Expression Regulation; Hypothalamus; In Situ Hybridization; Male; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Polymerase Chain Reaction; Protein Precursors; RNA, Messenger; Vasopressins

Vasopressin mRNA content was studied by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in the hypothalami of rats chronically treated with ethanol (EtOH). Quantitative RT-PCR allows for the accurate measurement of peptide mRNA levels in discrete regions of the brain of individual animals. EtOH markedly reduced the level of vasopressin mRNA. Furthermore, salt loading was ineffective in inducing a significant increase in vasopressin mRNA level in EtOH-treated rats, unlike in controls. The present results suggest that EtOH not only decreases vasopressin mRNA content in the rat hypothalamus, but also impairs its capacity to respond to salt loading.

Topics: Alcoholism; Animals; Base Sequence; Hypothalamus; Male; Molecular Sequence Data; Polymerase Chain Reaction; Rats; Rats, Wistar; RNA, Messenger; Vasopressins

To observe the mechanism of alcoholic testicular damage, in a previous experiment we used weanling male SD rats aged 45 days, weighing about 200 g, and fed a liquid diet (Lieber's) containing 5% ethanol. The latter accounted for 36% of total caloric intake for 7 weeks, but did not result in testicular atrophy. In a later experiment, we used a liquid diet in which ethanol accounted for 46% of the total calorie count. It provided a high-fat, low-protein content which simulated the nutritional background of patients with alcoholic liver diseases. This diet resulted in testicular atrophy. Histological and biochemical changes accompanying this experimental testicular atrophy included the following: 1) The testes of alcohol-fed animals contained smaller seminiferous tubules with reduced numbers of total cells, but no degeneration was seen in the spermatids. 2) In the peritubular wall of the seminiferous tubules, we observed curvature, irregularities, infolding of the basement membrane, and lamellation of the lamina densa, as well as hyperplasia of collagen fibers in the tunica propria. 3) In the cytoplasm of the Sertoli cells, deposits of gigantic fat droplets and stratification of the mitochondria were observed. The permeability of the Sertoli cell tight junction was confirmed using the Lanthanum method. 4) Testosterone levels in both the serum and testes declined. 5) Lactate dehydrogenase-X (LDH-X) activity in the testes declined. 6) Low Km alcohol dehydrogenase (ADH) activity localized in the testicular interstitial tissue was increased. These results indicate that the composition of three major nutritional elements as well as alcohol concentration are important in the mechanism of alcoholic testicular damage, and this damage affects both the testicular interstitial cell and the seminiferous tubules, particularly the Sertoli cells and peritubular wall of the latter. In addition, the findings suggest that ADH is involved in alcohol metabolism in the interstitial cells of the testes.

Topics: Alcoholism; Animals; Body Weight; Ethanol; Male; Rats; Rats, Inbred Strains; Seminiferous Tubules; Spermatogenesis; Testicular Diseases; Testis; Vasopressins

Forty-one male alcoholics suffering from alcohol withdrawal syndrome were investigated to assess the relationship between vasopressin (ADH), water homeostasis and alcohol withdrawal. During 10 d, we found a significant decrease in serum vasopressin, from 3.08 +/- 0.61 to 1.71 +/- 0.22 pg/nl. There were no concomitant changes in osmolality, so that a general dysregulatory state of vasopressin secretion during alcohol withdrawal cannot be assumed. Only patients with delirium tremens (8/41) had higher vasopressin levels despite lowered serum osmolalities. These findings support the hypothesis of an inappropriate rebound secretion of vasopressin in severe alcohol withdrawal. Furthermore, they may contribute to the pathogenesis of focal alcoholic brain damage, because rapid and/or profound changes in osmolality are suspected to cause circumscribed cerebral demyelinization.

Topics: Adult; Alcohol Withdrawal Delirium; Alcoholism; Hospitalization; Humans; Inappropriate ADH Syndrome; Male; Middle Aged; Vasopressins; Water-Electrolyte Balance

The activation of phosphoinositide-specific phospholipase C by ethanol was compared in hepatocytes isolated from ethanol-fed rats and from pair-fed control animals. Ethanol (100-300 mM) caused a dose-dependent transient increase in cytosolic free Ca2+ levels in indo-1-loaded hepatocytes from both groups of animals. The rate of Ca2+ increase was similar in hepatocytes from control and ethanol-fed rats, but the decay of the Ca2+ increase was somewhat slower in the latter preparation. The ethanol-induced Ca2+ increase caused activation of glycogen phosphorylase, with 50% response at 50 mM-ethanol and a maximal response at 150-200 mM-ethanol, not significantly different in hepatocytes from control and ethanol-fed animals. Ins(1,4,5)P3 formation in response to ethanol (300 mM) or vasopressin (2 nM or 40 nM) was also similar in the two preparations. It is concluded that long-term ethanol feeding does not lead to an adaptive response with respect to the ethanol-induced phospholipase C activation in rat hepatocytes. The ability of ethanol in vitro to decrease membrane molecular order in liver plasma membranes from ethanol-fed and control rats was measured by e.s.r. Membranes from ethanol-fed animals had a significantly lower baseline order parameter compared with control preparations (0.313 and 0.327 respectively), indicative of decreased membrane molecular order. Addition of 100 mM-ethanol significantly decreased the order parameter in control preparations by 2.1%, but had no effect on the order parameter of plasma membranes from ethanol-fed rats, indicating that the plasma membranes had developed tolerance to ethanol, similar to other membranes in the liver. Thus the membrane structural changes associated with this membrane tolerance do not modify the ethanol-induced activation of phospholipase C. The transient activation of phospholipase C by ethanol in hepatocytes may play a role in maintaining an adaptive phenotype in rat liver.

Topics: Alcoholism; Animals; Calcium; Cell Membrane; Cells, Cultured; Electron Spin Resonance Spectroscopy; Enzyme Activation; Inositol Phosphates; Kinetics; Liver; Male; Membrane Lipids; Phospholipids; Rats; Rats, Inbred Strains; Reference Values; Type C Phospholipases; Vasopressins

On the basis of their properties of noradrenergic and/or thromboxane inhibition, or on their activation of the dopaminergic reward system and/or beta-endorphin, the following substances or treatments are predicted to be effective in treating alcohol or drug addiction: ginger; carbon dioxide; dietary sulfur; methionine; calcium; LHRH; high intensity light; interferon; negative ions; serotonin antagonists such as methysergide and cyproheptadine; guanabenz and guenfacine; antihistamines; head-out water immersion; X-irradiation; and forced unilateral left nostril breathing.

Topics: Alcoholism; Dopamine Agents; Endorphins; Humans; Thromboxane-A Synthase; Thromboxanes; Vasopressins

Nineteen patients were studied during the first 4 days after withdrawal from alcohol. Plasma vasopressin was raised (P less than 0.05) and fluid retention occurred (P less than 0.05), with falls in haematocrit (P less than 0.01) and calculated plasma osmolality (P less than 0.02), which were consistent with expansion of plasma volume. Despite these changes mean total body water was within normal limits although there were substantial inter-individual variations. There was no correlation between any measure of fluid balance and the severity of withdrawal symptoms.

Topics: Adult; Aged; Alcoholism; Female; Humans; Male; Middle Aged; Osmolar Concentration; Plasma Volume; Substance Withdrawal Syndrome; Vasopressins; Water-Electrolyte Balance

Male reproductive failure and infertility are quite common in alcoholics. There are very high correlations between elevated vasopressin levels and male infertility on the one hand, and probable deficiencies of prostaglandin E1 which may raise levels of PGE2 and endorphins which, in turn, release vasopressin on the other. Since head-out water immersion rapidly decreases vasopressin levels, a suggested joint protocol of head-out water immersion and a prostaglandin E-1 precursor is proposed for male reproductive failure in alcoholics.

Topics: 8,11,14-Eicosatrienoic Acid; Alcoholism; Alprostadil; Humans; Immersion; Infertility, Male; Male; Vasopressins; Water

Topics: Adult; Alcoholism; Embolization, Therapeutic; Humans; Injections, Intra-Arterial; Male; Mallory-Weiss Syndrome; Vasopressins

Topics: Adult; Alcoholism; Body Water; Brain; Female; Humans; Magnetic Resonance Spectroscopy; Male; Vasopressins

Topics: Adult; Alcohol Drinking; Alcoholism; Aldosterone; Blood Pressure; Double-Blind Method; Ethanol; Humans; Hydrocortisone; Hypertension; Renin; Time Factors; Vasopressins

Topics: Alcoholism; Body Water; Brain; Humans; Osmolar Concentration; Substance Withdrawal Syndrome; Vasopressins

Topics: Acute Disease; Adult; Alcoholism; Brain; Brain Diseases; Female; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Substance Withdrawal Syndrome; Vasopressins; Water Intoxication

Topics: Adrenocorticotropic Hormone; Alcoholism; Animals; Endorphins; Enkephalins; Humans; Memory; Mice; Rats; Substance-Related Disorders; Vasopressins

Pontine myelinolysis can be suspected clinically on the basis of the following criteria: (1) Electrolyte disturbance manifested mainly by hyponatremia; (2) progressive neurologic deficits resulting in a "locked-in" syndrome; (3) usually, but not necessarily, alcohol abuse; and (4) frequent iatrogenic precipitation of the syndrome by inappropriate rehydration of patients at risk. A major pathophysiologic mechanism for this disorder seems to be the anatomic grid structure of the base of the pons, which is more vulnerable to edema than the cerebral hemispheres. Treatment should be focused on rapid reversal of electrolyte imbalance and judicious use of dehydrating agents. Early diagnosis and treatment might reverse an otherwise malignant syndrome.

Topics: Adolescent; Adult; Aged; Alcoholism; Brain Edema; Brain Stem; Child; Child, Preschool; Demyelinating Diseases; Female; Humans; Hyponatremia; Male; Middle Aged; Pons; Vasopressins; Water-Electrolyte Imbalance

Autopsy in a patient with severe hyponatremia showed central pontine myelinolysis. Review of our patients with central pontine myelinolysis and those described in the English literature to data disclosed that 61 percent had documented hyponatremia. While the exact mechanism involving hyponatremia and central pontine myelinolysis cannot be defined, a circumstantial relationship is apparent. The purpose of this paper is to emphasize this relationship and to suggest that the possibility of central pontine myelinolysis be considered in any patient with hyponatremia and neurologic dysfunction.

Topics: Alcoholism; Demyelinating Diseases; Diuretics; Fatty Liver; Female; Humans; Hypertension; Hyponatremia; Liver Function Tests; Middle Aged; Pons; Sodium; Vasopressins

One of the may vital functions of the liver is the biodegradation of foreign substances. The enzyme systems responsible for this liver function are frequently the site of drug interactions, both therapeutic and detrimental. Various substances can alter these enzymes by inducing, inhibiting, or competing with them, thus affecting drug response. In most instances, the liver detoxifies and deactivates chemicals, protecting the body from their harmful effects. In some biotransformation processes, however, toxic metabolites are produced that may be injurious to liver tissue as well as other body organs and systems. The effect of alcohol on the liver is a prime example. Although significant strides have been made in recent years, much is yet to be learned concerning the effect of the liver on drugs, the effect of drugs on the liver, and the pharmacologic management of various liver diseases.

Topics: Acetaldehyde; Alcoholism; Chemical and Drug Induced Liver Injury; Diuretics; Drug-Related Side Effects and Adverse Reactions; Ethanol; Hepatic Encephalopathy; Humans; Inactivation, Metabolic; Lactulose; Levodopa; Liver; Liver Cirrhosis; Liver Diseases; Microsomes, Liver; Neomycin; Oxidation-Reduction; Pharmaceutical Preparations; Spironolactone; Vasopressins

Topics: Acid-Base Imbalance; Adult; Alcoholism; Beer; Heart Diseases; Humans; Hyponatremia; Liver Diseases; Male; Nutrition Disorders; Vasopressins

Topics: Alcohol Oxidoreductases; Alcoholism; Animals; Diuresis; Ethanol; Humans; Nicotine; Osmolar Concentration; Pituitary Gland, Posterior; Rats; Tissue Extracts; Vasopressins; Water

Four patients with chronic illnesses and stable hyponatremia and plasma hypotonicity had normal urinary diluting capacity, with excretion of greater than 80% of a standard water load (20 ml/kg) within 4 hours and maintenance of a urine osmolality less than 100 mosmol/kg, during sustained water diuresis. Administration of a chronic salt load did not correct the hyponatremia. However, it was stabilized after treatment of the underlying medical condition. These subjects may represent a true resetting of the osmostat or a variant of the syndrome of inappropriate antidiuretic hormone secretion.

Topics: Aged; Alcoholism; Diagnosis, Differential; Female; Humans; Hyponatremia; Kidney; Kidney Concentrating Ability; Male; Middle Aged; Osmolar Concentration; Tuberculosis, Pulmonary; Vasopressins; Water-Electrolyte Balance

The histochemical, immunohistological and histoenzymatic study of the hypothalamo-neurohypophysial system of the rat shows that chronic ethanol administration induces: a temporary blockage of vasopressin synthesis, a vasoconstriction of the neurohypophysial capillaries, a dendritic storage of immunoreactive vasopressin. In our experimental conditions, a long ethanol treatment disturbs the balance between vasopressin synthesis and release.

Topics: Alcoholism; Animals; Dendrites; Ethanol; Humans; Hypothalamo-Hypophyseal System; Male; Pituitary Gland, Posterior; Rats; Vasopressins

The administration of ehtanol by gavage immediately produced a maintened hyperdiuresis, a transient decrease of urinary osmolality and antidiuretic hormone secretion, followed by increased plasmatic and urinary antidiuretic hormone concentrations. Chronic intoxication enhanced these effects probably due to central disturbance.

Topics: Alcoholism; Animals; Creatinine; Diuresis; Ethanol; Humans; Hydrogen-Ion Concentration; Kidney; Male; Osmolar Concentration; Potassium; Rats; Sodium; Urine; Vasopressins

Over a four-year period, 585 patients were hospitalized for massive upper gastrointestinal bleeding. Endoscopy diagnosed the cause of bleeding in 80% of 200 patients so studied. Selective angiography localized the bleeding site in 12 of 20 patients, and infusion of vasopressor stopped hemorrhage in six. Barium studies was 90% accurate in diagnosing ulcer disease but failed to detect gastritis. One hundred thirty (22%) patients were operated upon for medically uncontrolled bleeding. The proportion of patients requiring surgery fell from 33% in year one to 13% in year four. Benign ulcer disease caused bleeding in 51% of surgical patients, while gastritis was found in 20%, esophageal varices in 15% and stress ulcer in 8%. Overall operative mortality was 29%. Among 38 duodenal ulcer patients, mortality was 18%. Vagotomy and pyloroplasty were more effective than resection in this group. Resection for distal gastric ulcers in 22 patients resulted in a mortality of 14% and no rebleeding. While V&P controlled bleeding in 12 alcoholics with gastritis, five (42%) died postoperatively. Mortality among 20 patients with esophageal varices was 35%, although all five survived who had porto-caval shunts. Eight of 10 patients operated upon for stress ulcer bleeding died. Postoperative rebleeding occurred in 14 patients, eight of whom were again operated upon. In all but one a new lesion was found to be responsible for hemorrhage. Increasing use of gastroscopy and selective angiography can be expected to improve diagnostic capabilities in patients with upper gastrointestinal bleeding. Infusing vasopressor into selected arteries should reduce the need for surgical control of gastritis, variceal and stress ulcer bleeding, conditions poorly managed by current operative techniques.

Topics: Alcoholism; Angiography; Barium Sulfate; Esophageal and Gastric Varices; Gastritis; Gastrointestinal Hemorrhage; Gastroscopy; Humans; Injections, Intra-Arterial; Peptic Ulcer Hemorrhage; Recurrence; Retrospective Studies; Risk; Vasopressins

Topics: Acidosis; Alcoholism; Blood; Depression, Chemical; Diuresis; Ethanol; Gout; Humans; Lactates; Magnesium; Magnesium Deficiency; Osmolar Concentration; Uric Acid; Vasopressins

Topics: Alcoholism; Esophageal and Gastric Varices; Hemorrhage; Humans; Hypothermia, Induced; Ligation; Liver Cirrhosis; Pituitary Hormones, Posterior; Portacaval Shunt, Surgical; Pressure; Stomach; Vasopressins

Topics: Alcoholism; Angiography; Autopsy; Esophageal and Gastric Varices; Fatty Liver; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Infarction; Injections, Intra-Arterial; Intestine, Small; Liver Cirrhosis; Male; Mesenteric Arteries; Mesenteric Vascular Occlusion; Mesenteric Veins; Thrombosis; Vasopressins

Topics: Adult; Aged; Alcoholism; Blood Transfusion; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Male; Middle Aged; Portacaval Shunt, Surgical; Postoperative Complications; Tampons, Surgical; Therapeutic Irrigation; Time Factors; Vasopressins

The vasopressin test gave pathological results in 12 cases of optic atrophy and normal results in three cases. One of the patients with a pathological response had Leber's disease and three had tobacco-alcholic amblyopia, while in the rest the optic atrophy was of uncertain origin. In the cases with normal results the aetiology was also unclear. The Metopirone test was normal in 13 cases and pathological in only one case of optic atrophy. In three out of five patients with optic neuritis the vasopressin test gave pathological responses. The high frequency of pathological vasopressin tests in patients with optic lesions indicates a simultaneous disturbance of the hypothalamo-hypophyseal function. The background to this might be a disturbed vascular supply. The vasopressin test was of no help in diagnosing tumours as a cause of optic atrophy.

Topics: Adolescent; Adult; Aged; Alcoholism; Amblyopia; Circadian Rhythm; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Metyrapone; Middle Aged; Nicotiana; Optic Atrophy; Optic Neuritis; Plants, Toxic; Scotoma; Smoking; Vasopressins

Topics: Acute Disease; Adult; Aged; Alcoholism; Animals; Colitis; Colitis, Ulcerative; Diverticulum, Colon; Dogs; Epinephrine; Female; Gastrointestinal Hemorrhage; Humans; Ileitis; Injections, Intra-Arterial; Male; Mesenteric Arteries; Middle Aged; Peptic Ulcer Hemorrhage; Propranolol; Regional Blood Flow; Stomach Ulcer; Vasoconstrictor Agents; Vasopressins

Topics: Adult; Alcoholism; Cortisone; Creatinine; Deficiency Diseases; Ethanol; Humans; Hyponatremia; Male; Middle Aged; Potassium; Sodium; Tuberculosis, Pulmonary; Vasopressins; Water

Topics: Adolescent; Adult; Aged; Alcoholism; Child; Emergencies; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Liver Cirrhosis; Liver Function Tests; Male; Middle Aged; Portacaval Shunt, Surgical; Postoperative Complications; Vasopressins

Topics: Alcoholism; Animals; Ethanol; Histocytochemistry; Humans; Hypothalamo-Hypophyseal System; Neurosecretion; Oxytocin; Rats; Vasopressins

Topics: Acid-Base Equilibrium; Adult; Aged; Alcoholism; Blood; Blood Volume; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Potassium; Sodium; Substance Withdrawal Syndrome; Urine; Vasopressins; Water-Electrolyte Balance

Topics: Alcoholism; Ethanol; Humans; Thirst; Vasopressins

Topics: Alcoholism; Blood Pressure Determination; Blood Volume Determination; Heart Function Tests; Hepatic Veins; Humans; Hypertension; Hypertension, Portal; Iodine Isotopes; Liver Circulation; Liver Cirrhosis; Liver Function Tests; Oxytocin; Pharmacology; Pituitary Hormones, Posterior; Rose Bengal; Serum Albumin; Serum Albumin, Radio-Iodinated; Vasopressins

Topics: Alcoholism; Arginine Vasopressin; Body Fluids; Diuresis; Metabolism; Rats; Research; Urine; Vasopressins; Water