Cellular Abnormalities and Emerging Biomarkers in Alcohol-Associated Liver Disease.

Alcohol-associated liver disease (AALD) is the third most common preventable cause for disease burden and mortality in the US. AALD, including alcoholic hepatitis (AH), contributes to half of admissions from decompensated liver disease and 20% of all liver transplants in the US. Peripheral blood cells contribute to systemic inflammation, oxidative stress, mitochondrial dysfunction, and fibrosis in AALD and AH. Alcohol dysregulates function of lymphocytes, neutrophils, monocytes, and tissue macrophages of the innate immune system. These alterations in turn can modulate adaptive immune responses. In this review, we describe these disruptive effects of alcohol on cells of the innate and adaptive immune system and focus on cellular-based emerging biomarkers on diagnosis and prognosis of patients with AALD and AH.

Occurrence, Predictors, and Prognosis of Alcohol Withdrawal Syndrome and Delirium Tremens Following Traumatic Injury.

OBJECTIVES: We sought to determine occurrence, predictors, and prognosis of alcohol withdrawal syndrome and delirium tremens in patients with traumatic injury. DESIGN: Retrospective multicenter cohort study. SETTING: Three U.S. trauma centers. PATIENTS: Twenty-eight thousand one hundred one trauma patients admitted from 2010-2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measures included occurrence of alcohol withdrawal syndrome and delirium tremens, injury characteristics, risk factors for alcohol withdrawal syndrome, clinical outcomes, pharmacologic treatment for alcohol withdrawal syndrome, and Clinical Institute Withdrawal Assessment for Alcohol, Revised (CIWA-Ar) scores. Alcohol withdrawal syndrome severity was defined by CIWA-Ar score as minimal (< 10), moderate (10-20), and severe (> 20). Alcohol withdrawal syndrome developed in 0.88% (n = 246), including 12% minimal, 36% moderate, and 53% severe. Alcohol withdrawal syndrome progressed to delirium tremens in 11%. Before adjustment, alcohol withdrawal syndrome severity was associated with injury severity, hypokalemia, baseline CIWA-Ar score, and established alcohol withdrawal syndrome risk factors. Logistic regression identified the following predictors of delirium tremens: baseline CIWA-Ar score greater than or equal to 10 (odds ratio, 6.05; p = 0.02) and age greater than or equal to 55 (odds ratio, 3.24; p = 0.03). In patients with severe alcohol withdrawal syndrome, severe head injury also predicted progression to delirium tremens (odds ratio, 6.08; p = 0.01), and hypokalemia was borderline significant (odds ratio, 3.23; p = 0.07). Clinical outcomes of hospital length of stay, ICU length of stay, and alcohol withdrawal syndrome complications differed significantly by alcohol withdrawal syndrome severity and were worse with more severe manifestations of alcohol withdrawal syndrome. Mortality also significantly differed by alcohol withdrawal syndrome severity but was only greater in patients who progressed to delirium tremens (11.1%; p = 0.02); otherwise, there were no differences in mortality by severity (4%, 4%, and 0% by minimal, moderate, and severe alcohol withdrawal syndrome). CONCLUSIONS: Trauma patients with alcohol withdrawal syndrome experience a high occurrence of delirium tremens that is associated with significant mortality. These data demonstrate the predictive ability of baseline CIWA-Ar score, age, and severe head injury for developing delirium tremens.

Cross-sectional study on N,N-dimethylformamide (DMF); effects on liver and alcohol intolerance.

PURPOSE: There are still concerns regarding occupational exposure to hepatotoxic DMF. This study was designed to evaluate possible liver damaging effects of DMF under current workplace conditions in synthetic fibres industries. METHODS: Among other laboratory parameters, liver function parameters (alkaline phosphatase (ALP), aspartate aminotransferase, alanine aminotransferase and gamma-glutamyltransferase), the mean corpuscular erythrocyte volume (MCV) and carbohydrate-deficient transferrin (CDT) of the workforce of two companies present at the days of study were investigated. Internal exposure to DMF was assessed via three different biomarkers [sum of N-methylformamide and N-hydroxymethyl-N-methylformamide, N-acetyl-S-(N-carbamoyl)cysteine (AMCC) and 3-methyl-5-isopropylhydantoin (MIH)]. Alcohol consumption was assessed by means of direct ethanol metabolites (ethylglucuronide and ethylsulfate). RESULTS: None of the tested liver enzyme activities showed a positive association with any of the three exposure markers, nor did CDT and MCV. CDT was negatively associated with AMCC and the ALP activity negatively with all three exposure markers. Changes in liver function are seen mainly in conjunction with ethanol consumption but also with increasing body weight and age. MCV was associated with smoking. Almost half of the workers stated to experience alcohol flush reaction. CONCLUSION: The present study indicates that long-term exposure to DMF, which was specified by median urinary AMCC levels of 4.84 mg/g creatinine and DMF haemoglobin adduct levels of 60.5 nmol/MIH/g globin, respectively, does not result in any adverse liver effects. In contrast, these DMF exposure levels still elicit certain alcohol intolerance reactions.

Alcohol and bone.

Alcohol is widely consumed across the world in different cultural and social settings. Types of alcohol consumption differ between (a) light, only occasional consumption, (b) heavy chronic alcohol consumption, and (c) binge drinking as seen as a new pattern of alcohol consumption among teenagers and young adults. Heavy alcohol consumption is detrimental to many organs and tissues, including bones. Osteoporosis is regularly mentioned as a secondary consequence of alcoholism, and chronic alcohol abuse is established as an independent risk factor for osteoporosis. The review will present the different mechanisms and effects of alcohol intake on bone mass, bone metabolism, and bone strength, including alcoholism-related "life-style factors" such as malnutrition, lack of exercise, and hormonal changes as additional causative factors, which also contribute to the development of osteoporosis due to alcohol abuse.

An imbalance between VEGF and endostatin underlies impaired angiogenesis in gastric mucosa of aging rats.

Gastric mucosa of aging individuals exhibits increased susceptibility to injury and delayed healing. Our previous studies in young rats showed that healing of mucosal injury depends on and is critically dependent on VEGF and angiogenesis. Since angiogenesis in aging gastric mucosa has not been examined before, in this study we examined the extent to which angiogenesis is impaired in gastric mucosa of aging vs. young rats and determined the underlying mechanisms with a focus on mucosal expression of VEGF (proangiogenic factor) and endostatin (antiangiogenic factor). Aging rats had significantly impaired gastric angiogenesis by ~12-fold, 5-fold, 4-fold, and 3-fold, respectively (vs. young rats; all P < 0.001) at 24, 48, 72, and 120 h following ethanol-induced gastric injury and reduced and delayed healing of mucosal erosions. In gastric mucosa of aging (vs. young) rats at baseline, VEGF expression was significantly reduced, whereas endostatin levels were significantly increased (P < 0.05 and P < 0.01, respectively). In contrast to young rats, gastric mucosal VEGF levels did not increase following ethanol-induced injury in aging rats. MMP-9 enzyme activity was significantly higher in gastric mucosa of aging vs. young rats both at baseline (2.7-fold) and 24 h (3.8-fold) after ethanol injury (both P < 0.001). Since endostatin is generated from collagen XVIII by MMP-9, this finding can explain the mechanism of increased endostatin expression in aging gastric mucosa. The above findings demonstrate that reduced VEGF and increased endostatin result in the impaired angiogenesis and delayed injury healing in gastric mucosa of aging rats.

Analysis of QT Dispersion, Corrected QT Dispersion, and P-Wave Dispersion Values in Alcohol Use Disorder Patients With Excessive Alcohol Use.

OBJECTIVE: To identify the changes in QT dispersion (QTd), corrected QTd (QTcd), and P-wave dispersion (Pd) values with long-term alcohol abuse that could lead to severe ventricular arrhythmia, atrial fibrillation, and sudden death in alcohol use disorder (AUD) patients with excessive alcohol use. METHODS: This cross-sectional study included 48 individuals diagnosed with AUD based on DSM-5 criteria. Patients with a history of psychiatric diseases were not included. The control group comprised 48 individuals with no psychiatric diagnosis who did not abuse alcohol or other substances. Participants with body mass index > 24.9 kg/m² were excluded. Twelve-derivation electrocardiograms (ECG) were obtained from all participants. RESULTS: The mean ± SD age was 44.35 ± 10.24 years in the AUD group and 40.90 ± 13.45 years in the control group. There was no significant difference between the groups based on age (P = .108). There was a significant difference between the groups based on smoking status (P = .000). The mean ± SD period of alcohol use was 20.71 ± 12.04 years, and the alcohol intake was 5.88 ± 1.65 units/d. The AUD group demonstrated elevations in all ECG measures (QTd: 46.56 vs 26.67 ms, QTcd: 54.25 vs 30.88 ms, Pd: 44.69 vs 28.54 ms, all P = .000). CONCLUSIONS: AUD patients with excessive alcohol use had a higher risk of arrhythmia and sudden death compared to the control group. Consideration of ECG and referral to cardiologic examinations would contribute to the follow-up and health of patients with AUD.

Gender Equality, Drinking Cultures and Second-Hand Harms from Alcohol in the 50 US States.

BACKGROUND: Gender inequality and cultures of binge drinking may increase the risk of second-hand harms from alcohol. METHODS: Using the 2014-2015 National Alcohol Survey and 2015 National Alcohol's Harm to Others Survey (N = 7792), we examine associations of state-level gender equality measures (contraceptive access, abortion rights, women's economic equality) and binge drinking cultures (rates of men's and women's binge drinking) with individual-level indicators of second-hand harms by drinking strangers and partners/spouses. RESULTS: In main effects models, only male binge drinking was associated with greater odds of harms from drinking strangers. There were significant interactions of gender equality with male binge drinking: High male binge drinking rates were more strongly associated with stranger-perpetrated harms in states low on contraceptive access or abortion rights compared to states high on these measures. Conversely, male binge drinking was more strongly associated with spouse/partner-perpetrated second-hand harms in states with more economic equality, compared to states lower on this measure. CONCLUSIONS: Detrimental effects of high male binge drinking rates may be modified by gender equality. Targeted interventions may reduce alcohol-related harms experienced by women in states with high rates of male binge drinking. Restrictions in access to contraception and abortion may exacerbate harms due to men's drinking.

Effects of Clavulanic Acid Treatment on Reinstatement to Methamphetamine, Glial Glutamate Transporters, and mGluR 2/3 Expression in P Rats Exposed to Ethanol.

Evidence demonstrated that the glutamatergic system is implicated in mediating relapse to several drugs of abuse, including methamphetamine (METH). Glutamate homeostasis is maintained by a number of glutamate transporters, such as glutamate transporter type 1 (GLT-1), cystine/glutamate transporter (xCT), and glutamate aspartate transporter (GLAST). In addition, group II metabotropic glutamate receptors (mGluR2/3) were found to be implicated in relapse-seeking behavior. Ample evidence showed that ß-lactam antibiotics are effective in upregulating GLT-1 and xCT expression, thus improving glutamate homeostasis and attenuating relapse to drugs of abuse. In this study, we investigated the reinstatement of METH using conditioned place preference (CPP) in male alcohol-preferring (P) rats exposed to home-cage free choice ethanol drinking. Here, we tested the effect of clavulanic acid (CA), a ß-lactam, on the reinstatement of METH-seeking and ethanol drinking. In addition, we examined the expression of GLT-1, xCT, and GLAST as well as metabotropic glutamate receptor (mGluR2/3) in the nucleus accumbens (NAc) shell, NAc core, and dorsomedial prefrontal cortex (dmPFC). A priming i.p. injection of METH reinstated preference in METH-paired chamber following extinction. Chronic exposure to ethanol decreased the expression of GLT-1 and xCT in the NAc shell, but not in the NAc core or dmPFC. CA treatment blocked the reinstatement of METH-seeking, decreased ethanol intake, and restored the expression of GLT-1 and xCT in the NAc shell. In addition, the expression of mGluR2/3 was increased by CA treatment in the NAc shell and dmPFC. These findings suggest that these glutamate transporters and mGluR2/3 might be potential therapeutic targets for the attenuation of reinstatement to METH-seeking.

Hypothalamic-pituitary-adrenal axis activity, dehydroepiandrosterone sulphate and their relationships with aggression in early and late alcohol withdrawal.

The study aims at investigating the relationship between hypothalamic-pituitary-adrenal (HPA) axis alterations and aggression level in alcoholic patients during early and late alcohol withdrawal. Serum levels of basal cortisol and dehydroepiandrosterone sulphate (DHEAS) were measured three times, and cortisol and DHEAS response to dexamethasone twice during the early and late withdrawal periods in alcohol dependent males (n=30) and once in healthy control males (n=20). Abnormal cortisol non-suppression response to dexamethasone in dexamethasone suppression test (DST) was observed in some proportion of the patients in early withdrawal, which normalized in late withdrawal. The study revealed reduced basal DHEAS levels and reduced DHEAS response to dexamethasone in late withdrawal. When the patients were assessed in two separate groups as high- and low-aggressives, in the high-aggression group abnormality in DST was observed during both early and late withdrawal periods, in the low-aggression group it was observed only in early withdrawal. While basal DHEAS levels were low in the high-aggression group only in early withdrawal, it was reduced in the low-aggression group during late withdrawal period. Some alterations of the HPA axis during alcohol withdrawal might be associated not only with alcohol use per se but also with aggressivity tendency of alcoholic patients.

Binge Drinking's Effects on the Body.

Studies have focused on the effects of chronic alcohol consumption and the mechanisms of tissue injury underlying alcoholic hepatitis and cirrhosis, with less focus on the pathophysiological consequences of binge alcohol consumption. Alcohol binge drinking prevalence continues to rise, particularly among individuals ages 18 to 24. However, it is also frequent in individuals ages 65 and older. High blood alcohol levels achieved with this pattern of alcohol consumption are of particular concern, as alcohol can permeate to virtually all tissues in the body, resulting in significant alterations in organ function, which leads to multisystemic pathophysiological consequences. In addition to the pattern, amount, and frequency of alcohol consumption, additional factors, including the type of alcoholic beverage, may contribute differentially to the risk for alcohol-induced tissue injury. Preclinical and translational research strategies are needed to enhance our understanding of the effects of binge alcohol drinking, particularly for individuals with a history of chronic alcohol consumption. Identification of underlying pathophysiological processes responsible for tissue and organ injury can lead to development of preventive or therapeutic interventions to reduce the health care burden associated with binge alcohol drinking.

Etomidate and propofol-hyposensitive GABAA receptor beta3(N265M) mice show little changes in acute alcohol sensitivity but enhanced tolerance and withdrawal.

Gamma-aminobutyric acid-A (GABAA) receptors are ligand-gated ion channels comprised of subunits from several classes (alpha, beta, gamma, delta). Recent studies have clearly demonstrated that the functional properties of GABAA receptors are altered following chronic ethanol administration that could provide the molecular basis for the previously proposed role of these receptors in ethanol tolerance and dependence. Because the subunit composition of GABAA receptors determines receptor pharmacology, the present study was devoted to assess if the behavioral sensitivity after acute and chronic ethanol exposure depends on beta3-containing GABAA receptors. In the present study, we used knock-in mice harboring a point mutation (N265M) in the second transmembrane region of the beta3 subunit of the GABAA receptor in order to study acute and chronic behavioral effects of ethanol. More specifically, we tested tolerance to loss of righting reflex (LORR) and the development of withdrawal signs after chronic ethanol exposure using ethanol vapor chambers. Our results show that the beta3(N265M) mutation does not play a major modulatory role of acute ethanol-induced LORR. However, following repeated LORR testing, enhanced tolerance to the intoxicating effects of ethanol was observed--a finding which was unrelated to the pharmacokinetics of ethanol as both genotypes had the same blood alcohol concentrations following repeated LORR testing. In addition, following chronic alcohol vapor exposure, mouse mutants displayed increased handling-induced convulsions during withdrawal. The results of the present study suggest that the alcohol effects abolished by the beta3(N265M) mutation do not play a dominant role in acute alcohol intoxication but influence ethanol tolerance and withdrawal.

Molecular and cellular events in alcohol-induced muscle disease.

Alcohol consumption induces a dose-dependent noxious effect on skeletal muscle, leading to progressive functional and structural damage of myocytes, with concomitant reductions in lean body mass. Nearly half of high-dose chronic alcohol consumers develop alcoholic skeletal myopathy. The pathogenic mechanisms that lie between alcohol intake and loss of muscle tissue involve multiple pathways, making the elucidation of the disease somewhat difficult. This review discusses the recent advances in basic and clinical research on the molecular and cellular events involved in the development of alcohol-induced muscle disease. The main areas of recent research interest on this field are as follows: (i) molecular mechanisms in alcohol exposed muscle in the rat model; (ii) gene expression changes in alcohol exposed muscle; (iii) the role of trace elements and oxidative stress in alcoholic myopathy; and (iv) the role of apoptosis and preapoptotic pathways in alcoholic myopathy. These aforementioned areas are crucial in understanding the pathogenesis of this disease. For example, there is overwhelming evidence that both chronic alcohol ingestion and acute alcohol intoxication impair the rate of protein synthesis of myofibrillar proteins, in particular, under both postabsorptive and postprandial conditions. Perturbations in gene expression are contributory factors to the development of alcoholic myopathy, as ethanol-induced alterations are detected in over 400 genes and the protein profile (i.e., the proteome) of muscle is also affected. There is supportive evidence that oxidative damage is involved in the pathogenesis of alcoholic myopathy. Increased lipid peroxidation is related to muscle fibre atrophy, and reduced serum levels of some antioxidants may be related to loss of muscle mass and muscle strength. Finally, ethanol induces skeletal muscle apoptosis and increases both pro- and antiapoptotic regulatory mechanisms.

Ethanol affects the generation, cosignaling molecule expression, and function of plasmacytoid and myeloid dendritic cell subsets in vitro and in vivo.

The influence of ethanol (EtOH) on multiple dendritic cell (DC) subsets, in the steady state or following their mobilization in vivo, has not been characterized. Herein, generation of mouse bone marrow-derived DC (BMDC) in response to fms-like tyrosine kinase 3 ligand was inhibited by physiologically relevant concentrations of EtOH with selective suppression of plasmacytoid (p)DC. EtOH reduced surface expression of costimulatory molecules (CD40, CD80, CD86) but not that of coinhibitory CD274 (B7-H1) on resting or CpG-stimulated DC subsets. Interleukin (IL)-12p70 production by activated DC was impaired. Consistent with these findings, EtOH-exposed BMDC exhibited a reduced capacity to induce naïve, allogeneic T cell proliferation and impaired ability to prime T cells in vivo. DC subsets freshly isolated from EtOH-fed mice were also examined. Liver DC, inherently immature and resistant to maturation, exhibited little change in their low surface cosignaling molecule expression, whereas splenic DC showed reduced expression of surface costimulatory molecules in response to CpG stimulation in vivo. These splenic DC elicited reduced naïve, allogeneic T cell proliferation in vitro, and the stimulatory capacity of resting but not CpG-activated liver DC was reduced by chronic EtOH administration. T cells from animals primed with EtOH-exposed DC produced elevated levels of IL-10 following ex vivo challenge with donor alloantigen. Thus, EtOH impairs cytokine-driven differentiation and function of myeloid DC and pDC in vitro. Hepatic DC from chronic EtOH-fed mice are less affected than splenic DC, which exhibit impaired functional maturation following CpG stimulation. These results indicate a potential mechanism by which alcohol consumption is associated with immunosuppression.

Complex partial status epilepticus is an unrecognised feature in SESA syndrome: new insights into its pathophysiology.

We report a patient diagnosed as having subacute encephalopathy with frequent seizures in alcoholics (SESA syndrome), in which recurrent, non-convulsive seizures of frontal origin contributed significantly to the alteration of the mental state. Our case suggests that the occurrence of episodes of complex partial status epilepticus (CPSE) may contribute greatly to the origin and pathophysiology of the confusional state in this rare, epileptic entity.

Focus on aggressive behaviour in mental illness.

Background: Aggression is a behaviour with evolutionary origins, but in today's society it is often both destructive and maladaptive. Increase of aggressive behaviour has been observed in a number of serious mental illnesses, and it represents a clinical challenge for mental healthcare provider. These phenomena can lead to harmful behaviours, including violence, thus representing a serious public health concern. Aggression is often a reason for psychiatric hospitalization, and it often leads to prolonged hospital stays, suffering by patients and their victims, and increased stigmatization. Moreover, it has an effect on healthcare use and costs in terms of longer length of stay, more readmissions and higher drug use. Materials and methods: In this review, based on a selective search of 2010-2016 pertinent literature on PubMed, we analyze and summarize information from original articles, reviews, and book chapters about aggression and psychiatric disorders, discussing neurobiological basis and therapy of aggressive behaviour. Results: A great challenge has been revealed regarding the neurobiology of aggression, and an integration of this body of knowledge will ultimately improve clinical diagnostics and therapeutic interventions. The great heterogeneity of aggressive behaviour still hampers our understanding of its causal mechanisms. Still, over the past years, the identification of specific subtypes of aggression has released possibilities for new and individualized treatment approaches. Conclusions: Neuroimaging studies may help to further elucidate the interrelationship between neurocognitive functioning, personality traits, and antisocial and violent behaviour. Recent studies point toward manipulable neurobehavioral targets and suggest that cognitive, pharmacological, neuromodulatory, and neurofeedback treatment approaches can be developed to ameliorate urgency and aggression in schizophrenia. These combined approaches could improve treatment efficacy. As current pharmacological and therapeutic interventions are effective but imperfect, new insights into the neurobiology of aggression will reveal novel avenues for treatment of this destructive and costly behaviour.

Chronic Pancreatitis.

Chronic pancreatitis is a debilitating condition often associated with severe abdominal pain and exocrine and endocrine dysfunction. The underlying cause is multifactorial and involves complex interaction of environmental, genetic, and/or other risk factors. The pathology is dependent on the underlying pathogenesis of the disease. This review describes the clinical, gross, and microscopic findings of the main subtypes of chronic pancreatitis: alcoholic chronic pancreatitis, obstructive chronic pancreatitis, paraduodenal ("groove") pancreatitis, pancreatic divisum, autoimmune pancreatitis, and genetic factors associated with chronic pancreatitis. As pancreatic ductal adenocarcinoma may be confused with chronic pancreatitis, the main distinguishing features between these 2 diseases are discussed.

Nest building is a novel method for indexing severity of alcohol withdrawal in mice.

Withdrawal after chronic ethanol (EtOH) affects body temperature, goal-directed behavior and motor function in mice and increases general central nervous system excitability. Nest-building tests have been used to assay these states but to this point have not been employed as measures of EtOH withdrawal severity. We first refined nest-scoring methods using a genetically heterogeneous stock of mice (HS/Npt). Mice were then made physically dependent following three days of chronic EtOH vapor inhalation to produce average blood EtOH concentrations (BECs) of 1.89 mg/mL. EtOH withdrawal affected the progression of nest building over time when mice were tested 2-4 days after removal from three days of chronic exposure to EtOH. In a separate group of mice, chronic EtOH vapor inhalation (BECs 1.84 mg/mL) suppressed nest building over days 1-2 but not days 2-3 of withdrawal. In a following experiment, EtOH withdrawal dose-dependently slowed recovery of nest building for up to 32 h. Finally, we determined that long-lasting nest-building deficits extend to mice undergoing withdrawal from a high dose (4 g/kg) of acute EtOH. Sex differences for nest building were absent following EtOH exposure. In mice naïve to EtOH treatments, male mice had lower pre-test body temperatures and increased nest scores across a two-day testing period compared to females. These results suggest that nest building can be used to assess chronic and acute EtOH withdrawal severity in mice.

Alcohol withdrawal severity in inbred mouse (Mus musculus) strains.

Male mice (Mus musculus) from 15 standard inbred strains were exposed to a nearly constant concentration of ethanol (EtOH) vapor for 72 hr, averaging 1.59 +/- 0.03 mg EtOH/mL blood at withdrawal. EtOH- and air-exposed groups were tested hourly for handling-induced convulsions for 10 hr and at Hours 24 and 25. Strains differed markedly in the severity of withdrawal (after subtraction of control values), and by design these differences were independent of strain differences in EtOH metabolism. Correlation of strain mean withdrawal severity with other responses to EtOH supported previously reported genetic relationships of high EtOH withdrawal with low drinking, high conditioned taste aversion, low tolerance to EtOH-induced hypothermia, and high stimulated activity after low-dose EtOH. Also supported were the positive genetic correlations among EtOH, barbiturate, and benzodiazepine withdrawal. Sensitivity of naive mice to several chemical convulsant-induced seizures was also correlated with EtOH withdrawal.

Mechanisms of cardiovascular dysregulation during alcohol withdrawal.

Alcohol withdrawal (AW) is often accompanied by functional cardiovascular abnormalities which return to normal in few days. However, in some patients, they can predict future alterations in the cardiovascular system, even if they remain in abstinence. These changes are mediated by several central and peripheral mechanisms closely related to AW. The level of activation in the sympathetic nervous system is an important factor regulating the functioning of the cardiovascular system in AW directly and/or indirectly with L-type calcium channels and nitric oxide (NO). Other factors may contribute to cardiovascular alterations in AW including the renin-angiotensin-aldosterone system, vasopressin, cortisol and sodium sensitivity. Monitoring of the cardiovascular system is needed in patients undergoing treatment for AW. The patients with elevated systolic blood pressure (SBP) and diastolic blood pressure (DBP) after resolution of AW may require a fuller work-up of their cardiovascular system.

Using a symptom-triggered approach to manage patients in acute alcohol withdrawal.

Nurses working in the medical-surgical setting routinely care for patients experiencing acute alcohol withdrawal. Symptom-triggered therapy using the revised Clinical Institute Withdrawal Assessment (CIWA-Ar) (Sullivan, Sykora, Schneiderman, Naranjo, & Sellers, 1989) is currently recommended. Scoring patient symptoms using the CIWA-Ar and educating staff nurses are keys to providing consistent management of a patient in acute alcohol withdrawal.