Biliary excretion of dolichols and beta-hexosaminidase--effect of ethanol and glucagon

Alcohol has been reported to increase the urinary excretion of dolichols, and urinary dolichols are suggested to be derived from the lysosomes of the renal cells. In the present study we examined the effects of alcohol and glucagon on the biliary excretion of dolichols in rats. Chronic ethanol treatment decreased both biliary dolichol and beta-hexosaminidase excretion. The absolute amount of dolichol excreted into the bile correlated highly significantly with the absolute amount of biliary beta-hexosaminidase. Our results indicate that biliary dolichols are--at least in part--derived from hepatic lysosomes. Decreased biliary dolichol output during chronic alcohol administration suggests that urinary and biliary dolichol excretions are regulated independently of each other.     

Chronic liver diseases for the risk of hepatocellular carcinoma: a case-control study in Japan. Etiologic association of alcohol consumption, cigarette smoking and the development of chronic liver diseases

BACKGROUND/AIMS: A great number of hepatocellular carcinoma (HCC) develop from chronic liver disease. Among a total of 23,000 deaths of HCC in 1988 in Japan, 82% had positive antibodies against HBV and/or HCV. In the present study we investigated the etiological factors involved in this process, employing patients with chronic hepatitis as controls. METHODOLOGY: In this study, alcohol consumption and cigarette smoking were investigated in 104 male patients with HCC which developed from chronic liver disease and 104 male controls with chronic liver disease without HCC (one for each case) matched for age. RESULTS: When compared with non-drinkers and non-smokers, the relative risk (RR) for developing HCC rose to 17.9 among those with both drinking and smoking habits. The risk was greater than for those in whom either habit existed alone. The RR decreased among ex-smokers who were non-drinkers or ex-drinkers, but it was still as high as 9.4. For current smokers, even if they were non- or ex-drinkers, the RR was 15.4. CONCLUSIONS: Drinking and the cigarette smoking were both risk factors, but the existence of synergism between them was also suggested. Therefore, patients with chronic liver disease should be thoroughly counseled to refrain from both drinking and smoking.     

Comparison of serum beta-hexosaminidase isoenzyme B activity with serum carbohydrate-deficient transferrin and other markers of alcohol abuse

We have compared beta-hexosaminidase (beta-Hex) activity, carbohydrate-deficient transferrin (CDT), mean corpuscular volume (MCV), gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values in serum from male alcoholic patients with the corresponding values in moderate and non-drinking subjects. The total beta-Hex activity was 2.5 times higher in the alcoholics than in the moderate drinkers and this increase was mainly due to a 5-fold increase in the activity of the B-isoform of the enzyme. This was expressed as a percentage of the total beta-Hex activity and called 'beta-Hex B%'. Strong correlations were found between alcohol consumption (g/ day) and beta-Hex B% (r = 0.757, P < 0.001, n = 42), alcohol consumption and CDT (r = 0.671, P < 0.001, n = 42), and beta-Hex B% and CDT (r = 0.628, P < 0.001, n = 57). Serum beta-Hex B% had a sensitivity of 94% and a specificity of 91% in detecting alcoholic drinking of > 60 g/day. As a single marker of alcoholic drinking, it was markedly more sensitive than MCV and the liver enzymes GGT, AST and ALT, and slightly more sensitive than serum CDT (94 vs 83%). At the CDT cut-off level of 20 U/l, 17% of the moderate and non-drinkers would have been classified as alcoholic drinkers and 17% of the alcoholics would have been classified as moderate drinkers. Some of these misclassifications were eliminated if the beta-Hex B% results were taken into account. We suggest that serum beta-Hex B% can be a useful and inexpensive laboratory test for alcohol abuse.     

Neonatal urinary uric acid/creatinine [correction of ceratinine] ratio as an additional marker of perinatal asphyxia

The diagnosis and evaluation of perinatal asphyxia can be problematic and objective means of assessing its severity are lacking. To study the validity of urinary uric acid as a marker of the degree of perinatal asphyxia, the ratio of urinary uric acid to creatinine (UA/Cr) in urine specimens obtained after birth was measured in two groups of infants. Eighteen term infants with Apgar scores < or = 5 at 5 min and/or an umbilical cord blood pH < or = 7.2, and a base deficit > or = 12 meq/l were compared to 50 healthy controls. The severity of the perinatal asphyxia was determined by using an ASPHYXIA SCORE. The UA/Cr was higher in the asphyxiated group when compared to controls. (2.06 +/- 1.12, vs. 0.64 +/- 0.48; P < 0.001). Within the perinatal asphyxia group, a significant correlation was found between the UA/Cr ratio and the asphyxia score. (r = 0.86, P < 0.01). CONCLUSION: Infants with perinatal asphyxia have a significantly higher urinary UA/Cr ratio. This may be used as an indicator of the severity of perinatal asphyxia.     

Male mouse (Mus musculus) attraction to airborne urinary odors of conspecifics and to food odors: Effects of food deprivation.

Five experiments demonstrated that 112 male mice were strongly attracted to the urinary odors of females, and that male urinary odors were considerably less attractive. The strong attraction to female urinary odors did not require that the males have postweaning experience with females. Males with continuous access to food and water were much more strongly attracted to female urinary odors than to the airborne food odors. Female urinary odors remained more attractive than food odors after 24-hr food deprivation, and only after 48-hr deprivation did the attractiveness of food odors approximate that of female urine. Although 48-hr food deprivation appeared to equalize the attractiveness of urinary and food odors, this regimen did so not by diminishing the attractiveness of female urine but rather by increasing the attractiveness of food odors. It is argued that the attraction that male mice exhibited to female urinary odors in this odor-testing apparatus reflected, at least in part, a biologically important precopulatory communication system. (29 ref) (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Determinants of suicidal ideation: the role of substance use disorders

BACKGROUND: This study tested the hypothesis that the amount of psychoactive substance consumed (frequency and/or quantity), life problems resulting from this use, and a DSM-IV diagnosis of substance abuse/dependence are independent risk factors associated with increased suicidal ideation in a population of psychiatric inpatients with major depressive disorder. METHOD: 891 hospitalized patients with a primary diagnosis of nonpsychotic major depressive disorder (MDD) received a standardized, psychiatrist-administered assessment battery. To examine the relationship between admission suicidality and demographic, psychiatric history, and admission variables, chi-square analyses were used for categorical data and one-way ANOVAs were used for continuous indices. Stepwise hierarchical multiple regression analyses were performed to determine the set of variables that was independently related to admission suicidality level. RESULTS: There was general agreement between our findings and previous literature in regard to the association between severity of Axis I diagnosis, depressed mood, hopelessness, male gender, unemployment, involuntary treatment, and alcohol/drug problems and higher suicidal ideation. In our sample of hospitalized patients with unipolar major depressive disorder, higher current drug and/or alcohol dependency and high current use of alcohol or other substances of abuse were independently associated with higher levels of suicidal ideation. CONCLUSION: This association with higher suicidal ideation lends support to the importance of treating patients for both alcohol/drug problems and depression in an effort to decrease their risk for future suicide. We hope that our findings will improve the care that patients with dual diagnoses receive.     

Longitudinal trends in total serum cholesterol levels in a Japanese cohort, 1958-1986

This study is a preliminary examination of the reliability of adolescent self-reported pretreatment alcohol and other drug (AOD) use frequency. Assessments of self-reported pretreatment AOD use were conducted at admission and discharge (approximately a 1-month time period) at an adolescent drug misuser treatment program. The sample consisted of 197 male and female adolescents. There were statistically significant increases between admission and discharge assessments of pretreatment AOD use frequency. The greatest discrepancy was found for alcohol use, in which three-fourths (76%) of the sample reported a higher level of pretreatment alcohol use frequency at discharge assessment as compared to their admission assessment. Over one-third (35%) of the sample was found to have a significantly higher level of pretreatment alcohol use frequency at discharge assessment. The cause of this response discrepancy is unknown, but if it represents underreporting at admission, it may cause diagnostic and referral errors, as well as attenuate effect sizes in treatment outcome studies.     

Employment and alcohol: analysis of a clinical casuistic

The relationship between alcohol and work was studied in a group of 537 voluntary patients (393 male and 144 female) admitted to the department of Medicina del Lavoro, Pavia University for alcohol rehabilitation. The highest incidence of alcohol abuse was found in non-working subjects (pensioners, unemployed, housewives) although the start of excessive drinking takes place after beginning a working activity; a cause-effect relationship between these two factors can not be clearly determined, however. It is true that the stress provoked by this new condition (introduction to the work experience) can, in certain subjects, be a contributing factor in alcohol abuse. The increasingly lower age of initiation to alcohol reconfirms the need for prevention and instruction even at scholastic level. We can deduce how no working condition, low age and low education can constitute makers of risk for alcohol abuse.     

Posture, age, menopause, and osteopenia do not influence the circadian variation in the urinary excretion of pyridinium crosslinks

This study was performed to investigate whether the circadian variation in urinary pyridinium crosslinks is related to physical activity, age, the menopause, and asymptomatic osteopenia. We measured urinary pyridinoline/creatinine (Pyr/Cr) and deoxypyridinoline/creatinine (D-Pyr/Cr) in 9 healthy premenopausal women in two 27 h studies, before and at the end of 5 days of total bed rest. Both Pyr/Cr and D-Pyr/Cr showed highly significant circadian variations, with the peak at night and the nadir during the day (p < 0.001). The 5 days of complete bed rest produced no changes in the circadian pattern, but a general increase of 28% was observed in pyridinium crosslinks. A group of 12 healthy, early postmenopausal women (aged 55 +/- 2 years), 12 healthy, elderly postmenopausal women (aged 73 +/- 1 years), and 12 elderly osteopenic but otherwise healthy women (aged 73 +/- 1 years) were also studied for 27 h. All three groups showed highly significant (p < or = 0.001) circadian variations in the urinary excretion of pyridinium crosslinks. As expected, both Pyr/Cr (p < 0.05) and D-Pyr/Cr (p < 0.001) increased at the time of menopause, but the circadian variations in Pyr/Cr and D-Pyr/Cr were similar in all groups studied. We conclude that the circadian variation in the urinary excretion of pyridinium crosslinks is independent of physical factors. Furthermore, the circadian variation in pyridinium crosslinks was not related to age, menopausal status, or asymptomatic osteopenia.     

Incidence of alcohol abuse among patients with emergency admissions to a psychiatric department. Evaluation based on clinical and biochemical markers

Alcoholism and drug abuse were investigated in psychiatric patients, who were acutely admitted to a general psychiatric ward at Silkeborg Hospital in Denmark during a six month period. Several standardized diagnostic systems and assessment instruments were applied: ICD-8 and DSM-III diagnoses and the WHO Alcohol Use Disorder Identification Test (AUDIT) and Short Michigan Alcoholism Screening Test (SMAST). Furthermore, several biochemical markers were studied, including carbohydrate-deficient-transferrin (CDT), gamma-glutamyltransferase (GGT), and S-ethanol. Finally, thin layer chromatography of the urine was used to detect drugs abuse. A diagnosis of Alcoholism (code 303) was obtained in 39% of the included patients, while 13% were considered drug abusers (main and subsidiary diagnosis). These findings are in accordance with several previously published Danish studies and illustrate that alcohol abuse is a common diagnosis among acutely admitted patients to a psychiatric department situated outside the metropolitan areas in Denmark. When comparing alcohol abuse as assessed by clinical information and by biochemical markers, only CDT and GGT gave estimates similar to clinical evaluations. CDT was positive in 41% of the patients. Taking ICD-8 diagnoses of alcoholism as "golden standards" the sensitivity and specificity of the marker was 0.67 and 0.74, respectively. Although this is not as high as previously found values, these figures suggest CDT to be a useful biological marker in the delineation of alcohol related problems in psychiatric patients.     

Alcohol dependence and domestic violence as sequelae of abuse and conduct disorder in childhood

OBJECTIVES: To examine in the Navajo population: (1) the importance of childhood abuse as a risk factor for conduct disorder; (2) the importance of each form of abuse and conduct disorder as risk factors for alcohol dependence; and (3) the relative importance of each form of abuse, conduct disorder, and alcohol dependence as risk factors for being a perpetrator and/or victim of domestic violence. METHOD: The study is based on a case-control design. Cases (204 men and 148 women) between the ages of 21 and 65 were interviewed in alcohol treatment program and matched to community controls. There were two groups of controls: alcohol dependent (374 men, 60 women) and nonalcohol dependent (157 men, 143 women). When adjusted for stratification by age, community of residence, and sex, the combined control groups comprise a representative sample of the Navajo male and female population 21-65 years of age. RESULTS: The prevalence of physical and sexual abuse before age 15 is within limits observed in other populations. Each form of abuse is a risk factor for conduct disorder. Along with conduct disorder, physical abuse is a risk factor for alcohol dependence. Physical abuse and alcohol dependence are independent risk factors for being involved in domestic violence as both perpetrator and victim. There appears to have been no secular trend in the incidence of childhood abuse over the past several generations, but there is suggestive evidence that domestic violence has become more common. CONCLUSIONS: Physical abuse is a significant risk factor for alcohol dependence as well as for domestic violence independent of the effects of alcohol abuse. The effects of sexual abuse with regard to both domestic violence and alcohol dependence do not appear to be significant.     

Prevalence of alcohol dependence and abuse in general practice

The aim of this study is to deliver representative epidemiological data about the prevalence of alcohol abuse and dependence in general practices in an urban area. In 12 general practices at Luebeck, a Northern German city with 220,000 inhabitants, a total of 929 patients (aged between 14 and 75 years) were screened using the CAGE and the Short Michigan Alcoholism Screening Test. If one of these screening questionnaires or the General Practitioners' assessment of the patient indicated an alcohol problem, the patient underwent a standardized diagnostic interview using the alcohol section of the Schedules for Clinical Assessment in Neuropsychiatry. The prevalence rates according to ICD-10 or DSM-III-R were 3.5% for alcohol abuse and 7.2% for alcohol dependence, the sex ratio was 1:2.8 (female:male). These results are compared with previous findings, and general epidemiological implications of this study are discussed.     

Ethnic differences in the biological consequences of alcohol abuse: a comparison between south Asian and European males

Twenty-two South Asian men and 32 European men who had abused alcohol for at least 1.5 years were studied at the time of admission for detoxification to an Alcohol and Drug Dependency unit. The self-confessed average alcohol consumption during the preceding 3 months was similar in the South Asians (mean 383 g/day) and Europeans (mean 435 g/day) but the total duration of alcohol abuse was significantly shorter in South Asians (geometric mean 7.4 years) than Europeans (geometric mean 13.1 years). The geometric mean values for the concentration of carbohydrate-deficient transferrin in the serum were similar in the two ethnic groups. However, the red cell distribution width, the percentages of HbA1a+b, HbA1c and total HbA1 in red cell lysates and the activities of gamma-glutamyl transpeptidase, aspartate aminotransferase and alanine aminotransferase in the serum were all significantly higher in the South Asians than Europeans. The data suggest that South Asian men who abuse alcohol may be more susceptible to alcohol-related liver damage and acetaldehyde-mediated haemoglobin modification than European men who abuse alcohol to a similar extent for a considerably longer period.     

Effect of vomeronasal organ removal from male mice on their preference for and neural Fos responses to female urinary odors.

Four experiments were conducted to determine whether vomeronasal organ (VNO) inputs in male mice mediate the rewarding properties of estrous female urinary odors. Sexually naive male mice with either an intact (VNOi) or lesioned (VNOx) VNO preferred to investigate female urine over water in Y-maze tests. Subsequently, VNOi males ran significantly more quickly and remained in nasal contact longer with estrous female urine than with male urine, whereas VNOx males investigated these odors equally. In home-cage habituation-dishabituation tests, VNOi males also investigated female urine significantly longer than did VNOx males, although both groups investigated female urine longer than other non-body odors. Finally, female urinary odors induced Fos in the nucleus accumbens core of VNOi males but not of VNOx males. Our results suggest that female urinary odors retain some incentive value in VNOx males. However, once direct nasal contact is made with female urine, VNO inputs further activate forebrain mechanisms that amplify the reward salience of this stimulus for the male mouse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Carbohydrate deficient transferrin and other markers of alcohol consumption in the general hospital

BACKGROUND: The ascertainment of patients who consume important amounts of alcohol admitted to a hospital is essential to prevent medical and psychological complications. Carbohydrate deficient transferrin (CDT) is a new marker of alcohol consumption which requires validation in the hospital setting. METHODS: The values of carbohydrate deficient transferrin (CDT), glutamic oxalacetic transaminase (GOT), gamma glutamil transpeptidase (GGT) and mean corpuscular volume (MCV) were measured in 101 consecutive patients admitted to the Internal Medicine and Surgery Departments. Considering amounts higher than 60 g/day of ethanol for male patients and higher than 40 g/day for female patients as risk consumption, the values for sensitivity, specificity and area under the curve were calculated for the different biological tests. RESULTS: Twenty-six percent of patients reported a consumption of risk. The sensitivity of the tests were lower than 50% and specificities higher than 77%. CDT had the lowest sensitivity (15%) but it was very specific (98%). CDT had a better sensitivity among women than among men. None of the tests had an area under the curve with adequate efficiency levels. CONCLUSIONS: CDT among the hospitalized patients and other biological markers of alcohol consumption have a low efficiency.     

Mechanisms of elevation of serum and urinary concentrations of soluble thrombomodulin in diabetic patients: possible application as a marker for vascular endothelial injury

Serum and urinary levels of soluble thrombomodulin (TM) were measured in 71 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 132 age-matched control subjects to elucidate the mechanisms involved in increased TM levels. We compared the TM level with urinary albumin excretion (UAE), creatinine (Cr) clearance, and indices of renal tubular damage such as urinary beta2-microglobulin. Serum TM was significantly higher in diabetic patients versus control subjects (P < .001) regardless of whether the patients had diabetic nephropathy. Urinary TM levels were also higher in diabetic patients than in control subjects (P < .001). Serum TM in diabetic patients was correlated positively with serum Cr and UAE and inversely with the Cr clearance rate (P < .001, respectively). The urinary level of TM in diabetic patients was significantly correlated with 24-hour glucose excretion and the serum level of 1,5-anhydroglucitol (1,5-AG) (P < .001). However, no correlations were found between urinary TM levels and renal function in diabetic patients. There was also no correlation between serum and urinary levels of TM in the patients. These results suggest that although the serum TM level is influenced by an impairment of the renal clearance of TM, this parameter may be a useful marker for vascular endothelial injury in diabetic patients. On the other hand, since the elevated urinary level of TM in the patients paralleled their urinary excretion of glucose, urinary TM levels do not correlate with vascular endothelial injury in diabetic patients.     

Protection against preterm delivery in mice by urinary trypsin inhibitor

OBJECTIVE: To investigate the precise mechanism by which urinary trypsin inhibitor suppresses cytokine production in the prevention of preterm delivery. METHODS: In vivo and in vitro studies were performed using ascites and peritoneal macrophages obtained on day 15 of pregnancy from female C3H/HeN mice that had been impregnated by B6D2F1 male mice. Lipopolysaccharide receptor, the intracellular signal transduction system, and nuclear factor-kappaB level were examined. RESULTS: In the in vivo study, we found that urinary trypsin inhibitor ameliorated the deterioration of intraperitoneal conditions induced by lipopolysaccharide (ie, increases in ascitic volume, peritoneal cell count, and tumor necrosis factor-alpha level) and caused a decrease in the binding of lipopolysaccharide to mouse macrophages. In the in vitro studies, urinary trypsin inhibitor decreased the binding capacity of lipopolysaccharide for its receptor, blocked the intracellular signal transduction induced by lipopolysaccharide, and decreased the nuclear factor-kappaB level. Increases were induced in the binding capacity of the macrophages for urinary trypsin inhibitor and its incorporation into them in the presence of lipopolysaccharide. CONCLUSION: We postulate that urinary trypsin inhibitor may suppress the production of inflammatory cytokines induced by lipopolysaccharide in mouse peritoneal macrophages through suppression of the lipopolysaccharide receptor, inhibition of the intracellular signal transduction system, and decrease in the nuclear factor-kappaB level.     

What is the latent structure of alcohol use disorders? A taxometric analysis of the Personality Assessment Inventory Alcohol Problems Scale in male and female prison inmates.

Three indicators derived from the Personality Assessment Inventory (PAI) Alcohol Problems scale (ALC)—tolerance/high consumption, loss of control, and negative social and psychological consequences—were subjected to taxometric analysis—mean above minus below a cut (MAMBAC), maximum covariance (MAXCOV), and latent mode factor analysis (L-Mode)—in 1,374 federal prison inmates (905 males, 469 females). Whereas the total sample yielded ambiguous results, the male subsample produced dimensional results, and the female subsample produced taxonic results. Interpreting these findings in light of previous taxometric research on alcohol abuse and dependence it is speculated that while alcohol use disorders may be taxonic in female offenders, they are probably both taxonic and dimensional in male offenders. Two models of male alcohol use disorder in males are considered, one in which the diagnostic features are categorical and the severity of symptomatology is dimensional, and one in which some diagnostic features (e.g., withdrawal) are taxonic and other features (e.g., social problems) are dimensional. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Association of smoking with lower urinary tract symptoms

PURPOSE: We studied the association of smoking with lower urinary tract symptoms. MATERIALS AND METHODS: In 1994 we performed a population based study by mailing a questionnaire to all 3,143 men born in 1924, 1934 or 1944 who resided in Tampere, or in 11 rural or semirural municipalities in the same county. Of this population 68% were ultimately included in the study. A modified Danish Prostate Symptom Score-1 was used to assess urinary symptoms and associated bothersomeness. A symptom index was created by multiplying the symptom and bothersomeness scores of hesitancy, incomplete emptying, urge, urge incontinence, nocturia and daytime frequency, and totaling the products. The index for lower urinary tract symptoms was defined as positive when it reached 7 points. Subjects were also asked whether they had smoked for at least a year, and they were defined as smoking currently, formerly and never according to the response. RESULTS: Compared with respondents who never smoked age adjusted odds ratios were 1.47 (95% confidence interval 1.09 to 1.98) and 1.38 (1.08 to 1.78), respectively, for those who currently and formerly smoked. After further adjusting for alcohol consumption, body mass index, previous prostate surgery, pelvic area surgery, prostate cancer and bladder cancer, the odds ratios for current and former smokers were 1.39 (95% confidence interval 1.02 to 1.93) and 1.34 (1.03 to 1.75), respectively. CONCLUSIONS: Smoking increases the prevalence of lower urinary tract symptoms. The similarity in the odds ratios of these symptoms between current and former smokers suggests that changes caused by smoking occur long term or the pathological process resulting in symptoms starts early in smokers. The decreased risk of lower urinary tract symptoms after the cessation of smoking suggests that the process is reversible but recovery is a long-term process.     

The developmental interface between nature and nurture: A mutual influence model of child antisocial behavior and parent behaviors.

Using an adoption design to collect data on biological and adoptive parents of children adopted at birth, this study explored a possible mechanism through which heritable characteristics of adopted children evoke adoptive parent responses and lead to reciprocal influences between adoptive parent and adopted child behavior. Participants were 25 male and 20 female adoptees, 12-18 years of age, having either a biological parent with substance abuse/dependency or antisocial personality or a biological parent with no such history. The study found that psychiatric disorders of biological parents were significantly related to children's antisocial/hostile behaviors and that biological parents' psychiatric disorders were associated with adoptive parents' behaviors. This genotype-environment association was largely mediated by adoptees' antisocial/hostile behaviors. Results also suggest that the adoptee's antisocial/hostile behavior and adoptive mother's parenting practices affect each other. (PsycINFO Database Record (c) 2010 APA, all rights reserved)