Changes in expression of BDNF and its receptors TrkB and p75NTR in the hippocampus of a dog model of chronic alcoholism and abstinence

Chronic ethanol consumption can produce learning and memory deficits. Brain-derived neurotrophic factor (BDNF) and its receptors affect the pathogenesis of alcoholism. In this study, we examined the expression of BDNF, tropomyosin receptor kinase B (TrkB) and p75 neurotrophin receptor (p75NTR) in the hippocampus of a dog model of chronic alcoholism and abstinence. Twenty domestic dogs (9-10 months old, 15-20 kg; 10 males and 10 females) were obtained from Harbin Medical University. A stable alcoholism model was established through ad libitum feeding, and anti-alcohol drug treatment (Zhong Yao Jie Jiu Ling, the main ingredient was the stems of watermelon; developed in our laboratory), at low- and high-doses, was carried out. The Zhong Yao Jie Jiu Ling was effective for the alcoholism in dogs. The morphology of hippocampal neurons was evaluated using hematoxylin-eosin staining. The number and morphological features of BDNF, TrkB and p75NTR-positive neurons in the dentate gyrus (DG), and the CA1, CA3 and CA4 regions of the hippocampus were observed using immunohistochemistry. One-way ANOVA was used to determine differences in BDNF, TrkB and p75NTR expression. BDNF, TrkB and p75NTR-positive cells were mainly localized in the granular cell layer of the DG and in the pyramidal cell layer of the CA1, CA3 and CA4 regions (DG>CA1>CA3>CA4). Expression levels of both BDNF and TrkB were decreased in chronic alcoholism, and increased after abstinence. The CA4 region appeared to show the greatest differences. Changes in p75NTR expression were the opposite of those of BDNF and TrkB, with the greatest differences observed in the DG and CA4 regions.

Noninvasive classification of liver disease in asymptomatic and oligosymptomatic male alcoholics

The predominant type of liver alteration in asymptomatic or oligosymptomatic chronic male alcoholics (N = 169) admitted to a psychiatric hospital for detoxification was classified by two independent methods: liver palpation and multiple quadratic discriminant analysis (QDA), the latter applied to two parameters reported by the patient (duration of alcoholism and daily amount ingested) and to the data obtained from eight biochemical blood determinations (total bilirubin, alkaline phosphatase, glycemia, potassium, aspartate aminotransferase, albumin, globulin, and sodium). All 11 soft and sensitive, and 13 firm and sensitive livers formed fully concordant groups as determined by QDA. Among the 22 soft and not sensitive livers, 95% were concordant by QDA grouping. Concordance rates were low (55%) in the 73 firm and not sensitive livers, and intermediate (76%) in the 50 not palpable livers. Prediction of the liver palpation characteristics by QDA was 95% correct for the firm and not sensitive livers and moderate for the other groups. On a preliminary basis, the variables considered to be most informative by QDA were the two anamnestic data and bilirubin levels, followed by alkaline phosphatase, glycemia and potassium, and then by aspartate aminotransferase and albumin. We conclude that, when biopsies would be too costly or potentially injurious to the patients to varying extents, clinical data could be considered valid to guide patient care, at least in the three groups (soft, not sensitive; soft, sensitive; firm, sensitive livers) in which the two noninvasive procedures were highly concordant in the present study.

Aspectos clínicos e sorológicos de 47 pacientes com paracoccidioidomicose tratados pela anfotericina B

In the present study, clinic and serologic aspects of 47 paracoccidioidomycosis patients were reviewed. The clinic-radiologie-laboratorial data of each patient were obtained from the medical chart before, during and after therapy with Amphotericin B. The age of the patients ranged between 13 to 50 years; the ratio male: female was 10:1. The most frequently associated diseases were alcoholism and tabagism; tuberculosis was present in 14.2% of the cases. Most patients came from Botucatu of adjacent towns (central area of the State of São Paulo). Cough with sputum production, dyspnea and anorexia were the most frequent clinic manifestations. All 47 patients, but 5 presented pulmonary involvement which showed the radiologic pattern of interstitial exudate nodular type and fibrocicatritial lesions in 85.7%. There was associated emphysema in 37.7% of the patients. Blood urea, creatinin and kaliemia increased during therapy with Amphotericin B. Clinic-laboratorial follow-up showed electrocardiographic changes in 13, hypertension in 9 and hyperreactivity in Thorn test in 1 patient. Complement fixation was the best serologic test for monitoring patients with paracoccidioidomycosis. Incomplete dosage of Amphotericin B led to therapeutic ineffectivenes.

FATAL DISSEMINATED CRYPTOCOCCOSIS WITH RENAL INVOLVEMENT IN AN HIV-INFECTED PATIENT

SUMMARY Introduction: We present a fatal case of disseminated cryptococcosis in a young man whose diagnosis of HIV infection was made at the time of admission to the emergency room. Case report: The patient was a twenty-three-year-old man, with a history of daily fever during one month associated with diarrhea, weight loss, headache, vomiting and generalized seizures. He also had a history of diabetes mellitus, alcoholism and drug addiction. Upon physical examination the patient was pale, disoriented and had periods of agitation. White blood cells count was 3,440/mm3 (5% lymphocytes), hemoglobin was 10g/dL, platelets were 83,000/ mm3. Creatinine was 0.7 mg/dL; urea 19 mg/dL; Na, K, and liver enzymes were within normal limits. Lactic dehydrogenase was 494 IU/L. Cerebrospinal fluid (CSF) analysis revealed 10 white blood cells/mm3 (58% neutrophils, 31% lymphocytes, 11% monocytes) and 2 red blood cells/mm3. India ink test revealed six Cryptococcus yeasts/mm3. CSF glucose was 122 mg/dL and protein was 36 mg/ dL. VDRL test was negative and anti-HIV test was positive. Intravenous hydration, insulin, phenytoin, fluconazole, pyrimethamine, sulfadiazine, folinic acid, and amphotericin B were started. The patient did not improve and became obtunded and hypotensive. He was intubated and put on mechanical respiration. He received vasoactive drugs and died less than 24 hours after admission. A postmortem examination was performed and revealed disseminated cryptococcosis, with severe involvement of the kidneys. Conclusion: Cryptococcosis, as a rule, is a systemic disease that affects mostly immunocompromised individuals, especially patients with AIDS. When diagnosed late in its course it has a very high mortality.

Histoplasmosis in immunocompetent individuals living in an endemic area in the Brazilian Southeast

Introduction The distribution of infection by Histoplasma capsulatum in Brazil is heterogeneous, and the number of cases affecting immunocompetent individuals is relatively small. This study reports the epidemiological and clinical data regarding histoplasmosis in non-immunosuppressed individuals. Methods The study included only the immunocompetent patients with histoplasmosis who were diagnosed between 1970 and 2012 at a university hospital located in Ribeirão Preto, State of São Paulo, Brazil. Clinical and epidemiological data were collected retrospectively from the patient records. Results Of the 123 patients analyzed, 95 had an active disease that manifested in the different clinical forms of histoplasmosis. Men were the predominant gender, and most patients resided in the Northeast of the State of São Paulo and in the nearby municipalities of the State of Minas Gerais. The risk factors for acquiring histoplasmosis and prolonged contact in a rural environment were recorded in 43.9% and 82.9% of cases, respectively. Smoking, alcoholism, and comorbidity rates were high among the patients with the chronic pulmonary and subacute/chronic disseminated forms of histoplasmosis. Many patients achieved clinical cure spontaneously, but 58.9% required antifungals; the disease lethality rate was 5.3%. Conclusions Immunocompetent individuals manifested the diverse clinical forms of histoplasmosis over a period of 4 decades, revealing an additional endemic area of this fungal disease in the Brazilian Southeast.

Case-control study of factors associated with chronic Chagas heart disease in patients over 50 years of age

A case-control study on chronic Chagas heart disease (CCHD) was carried out between 1997 and 2005. Ninety patients over 50 years of age were examined for factors related to (CCHD). Fourty-six patients (51.1%) with Chagas heart disease (anomalous ECG) were assigned to the case group and 44 (48.9%) were included in the control group as carriers of undetermined forms of chronic disease. Social, demographic (age, gender, skin color, area of origin), epidemiological (permanence within an endemic zone, family history of Chagas heart disease or sudden death, physical strain, alcoholism, and smoking), and clinical (systemic hypertension) variables were analyzed. The data set was assessed through single-variable and multivariate analysis. The two factors independently associated with heart disease were age - presence of heart disease being three times higher in patients over 60 years of age (odds ratio, OR: 2.89; confidence interval of 95%: 1.09-7.61) - and family history of Chagas heart disease (OR: 2.833, CI 95%: 1.11-7.23). Systemic hypertension and gender did not prove to hold any association with heart disease, as neither did skin color, but this variable showed low statistical power due to reduced sample size.

A case-control study on the association of hepatitis B virus infection and hepatocellular carcinoma in Northeast Brazil

Hepatitis B virus (HBV) serological markers were investigated in 40 incident cases of hepatocellular carcinoma (HCC) and in two age and sex matched control groups, comprising 40 patients with other cancers and 80 healthy individuals, resident in Bahia, Brazil. Serologic tests were done by radioimmunoassay. The study observed high proportion of seropositivity to HBsAg (42.5%) and of those presenting HBsAg or antiHBc (65.0%) among HCC cases, higher in men than women and in those aged 17 to 30 years old. HBsAg seropositivity among HCC patients was greater than in the control group with other cancers (7.5%) and in healthy controls (2.5%), corresponding to odds ratio estimates of 15.0 (95% CI 3.29, 68.30) and 33.0 (95% CI 9.13, 119.28), both statistically significant. HBeAg was not observed and antiHBe was present in 41.2% of cases, suggesting the absence of viral replication, possibly with viral DNA intergration into the hepatocyte genome. The presence of cirrhosis was associated with HBsAg seropositivity among HCC cases. A history of chronic alcoholism is shown to be more frequently related to those cases with cirrhosis. This study highlights the relevant association between HCC and HBV in Northeast Brazil, particularly for young individuals, and the high risk of development of HCC for HBsAg carriers.

Smoking, consumption of alcohol and sedentary life style in population grouping and their relationships with lipemic disorders

The study, part of the project "Atherosclerotic cardiovascular diseases, lipemic disorders, hypertension, obesity and diabetis mellitus in a population of the metropolitan area of the southeastern region of Brazil", had the following objectives: a) the characterization and distribution among typical human socio-economic groupings, of the prevalence of some particular habits which constitute aspects of life-style-the use of tobacco, the use of alcohol and sedentary activity; b) the establishment of the interrelation between the above-mentioned habits and some lipemic disorders. The prevalence of the habits cited behaved in the following manner: the use of tobacco predominated among men, distributed uniformly throughout the social strata; among the women the average percentage of smokers was 18,9%, a significant difference occurring among the highest socio-economic class, where the average was of 40.2%. The sedentary style of life presented high prevalence, among both men and women with exception of the women of the highest socio-economic level and of the skilled working class. The use of alcohol, as one would expect, is a habit basically practised by the men, without any statistically significant differences between classes. For the purpose of establishing associations between these risk fictors and lipemic conditions four situations were chosen, of the following characteristics: 1- total cholesterol > or = 220 mg/dl and triglycerides > or = 150 mg/dl; 2- HDL cholesterol <35 mg/dl for men and <45 mg/dl for women and triglycerides levels > or = 150 mg/dl; 3- HDL cholesterol <35 mg/dl for men and <45 mg/dl for women and triglycerides levels <150 mg/dl; 4- total cholesterol 220 mg/dl with triglycerides levels <150 mg/dl. Six models of multiple (backward) regression were established, with seven independent variables- age, sex, use of tobacco, consumption of alcohol, light physical activity, hypertension and obesity. Significant associations (P<0,05) were revealed with hypercholesterolemia, accompanied by triglyceride levels > or = 150 mg/dl, and the following independent variables: age, use of tobacco and the interactions between obesity and smoking, age and sedentary lifestyle, sex and obesity (R2=22%); the standardized B coefficient showed that the variables with the greatest weight in the forecasting of the variation in the levels of cholesterol were smoking and the interaction between obesity and smoking. The hypercholesterolemia accompanied by triglycerides levels <150 mg/dl showed a positive association between total cholesterol and sex and the interactions obesity/smoking and sex/obesity. As regards HDL cholesterol accompanied by triglyceride/ levels > or = 150 mg/dl was inversely associated with obesity and the interaction smoking/ age and directly with age (R=31%). The standardized B coeffients, indicated that the variables obesity and the interactions smoking/age possessed a weight three times greater than age alone in accounting for the variation in the serum levels of HDL cholesterol. When accompanied by triglycerides <150 mg/dl there was no association between and the independent variables and the set of them presented R equal to 22%. The sum of top, in the population stutied in this project, the component habits of life-style (smoking, alcohol consumption and sedentary activity) which constitute risk factors which determine morbidity from atherosclerotic cardiovascular diseases are be found distributed through all the typical social groupings of this particular form of social organization. On the other hand, the seven independent variables used in the multiple regression models for the explanation of the lipemic conditions considered presented multiple determination coefficients which varied, approximately, between 20% and 30%. Thus it is important that in the genetic epidemiology the study of the morbidities in question be emphasized.

Evaluation of alcohol outlet density and its relation with violence

OBJECTIVES: The current study set out to investigate alcohol availability in a densely populated, residential area of suburban São Paulo associated with high levels of social deprivation and violence. Gun-related deaths and a heavy concentration of alcohol outlets are notable features of the area surveyed. Given the strong evidence for a link between alcohol availability and a number of alcohol-related problems, including violent crime, measures designed to reduce accessibility have become a favored choice for alcohol prevention programs in recent years. METHODS: The interviewers were 24 residents of the area who were trained for the study. It was selected an area of nineteen streets, covering a total distance of 3.7 km. A profile of each alcohol outlet available on the area was recorded. RESULTS: One hundred and seven alcohol outlets were recorded. The number of other properties in the same area was counted at 1,202. Two measures of outlet density may thus be calculated: the number of outlets per kilometer of roadway (29 outlets/km); and the proportion of all properties that sold alcohol (1 in 12). CONCLUSIONS: The results of this study is compared with others which are mainly from developed countries and shown that the area studied have the highest density of alcohol outlet density ever recorded in the medical literature. The implication of this data related to the violence of the region is discussed. By generating a profile of alcohol sales and selling points, it was hoped to gain a better understanding of alcohol access issues within the sample area. Future alcohol prevention policy would be well served by such knowledge.

Alcohol drinking patterns by gender, ethnicity, and social class in Bahia, Brazil

OBJECTIVE: To study patterns of alcohol consumption and prevalence of high-risk drinking. METHODS: A household survey was carried out in a sample of 2,302 adults in Salvador, Brazil. Cases of High-Risk Drinking (HRD) were defined as those subjects who referred daily or weekly binge drinking plus episodes of drunkenness and those who reported any use of alcoholic beverages but with frequent drunkenness (at least once a week). RESULTS: Fifty-six per cent of the sample acknowledged drinking alcoholic beverages. Overall consumption was significantly related with gender (male), marital status (single), migration (non-migrant), better educated (college level), and social class (upper). No significant differences were found regarding ethnicity, except for cachaça (Brazilian sugarcane liquor) and other distilled beverages. Overall 12-month prevalence of high-risk drinking was 7%, six times more prevalent among males than females (almost 13% compared to 2.4%). A positive association of HRD prevalence with education and social class was found. No overall relationship was found between ethnicity and HRD. Male gender and higher socioeconomic status were associated with increased odds of HRD. Two-way stratified analyses yielded consistent gender effects throughout all strata of independent variables. CONCLUSIONS: The findings suggest that social and cultural elements determine local patterns of alcohol-drinking behavior. Additional research on long-term and differential effects of gender, ethnicity, and social class on alcohol use and misuse is needed in order to explain their role as sources of social health inequities.

Prevalence of alcohol abuse and associated factors in a population-based study

OBJECTIVE: To estimate the prevalence of alcohol abuse/dependence and identify associated factors among demographic, family, socioeconomic and mental health variables. METHODS: A household survey was carried out in the urban area of Campinas, southeastern Brazil, in 2003. A total of 515 subjects, aged 14 years or more were randomly selected using a stratified cluster sample. The Self-Report Questionnaire and the Alcohol Use Disorder Identification Test were used in the interview. Prevalences were calculated, and univariate and multivariate logistic analyses performed by estimating odds ratios and 95% confidence intervals. RESULTS: The estimated prevalence of alcohol abuse/dependence was 13.1% (95% CI: 8.4;19.9) in men and 4.1% (95% CI: 1.9;8.6) in women. In the final multiple logistic regression model, alcohol abuse/dependence was significantly associated with age, income, schooling, religion and illicit drug use. The adjusted odds ratios were significantly higher in following variables: income between 2,501 and 10,000 dollars (OR=10.29); income above 10,000 dollars (OR=10.20); less than 12 years of schooling (OR=13.42); no religion (OR=9.16) or religion other than Evangelical (OR=4.77); and illicit drug use during lifetime (OR=4.47). Alcohol abuse and dependence patterns were different according to age group. CONCLUSIONS: There is a significantly high prevalence of alcohol abuse/dependence in this population. The knowledge of factors associated with alcohol abuse, and differences in consumption patterns should be taken into account in the development of harm reduction strategies.

India's homosexual discrimination and health consequences

A large number of countries worldwide have legalized homosexual rights. But for 147 years, since when India was a British colony, Section 377 of the Indian Penal Code defines homosexuality as a crime, punishable by imprisonment. This outdated law violates the fundamental rights of homosexuals in India. Despite the fact that literature drawn from Hindu, Buddhist, Muslim, and modern fiction testify to the presence of same-sex love in various forms, homosexuality is still considered a taboo subject in India, by both the society and the government. In the present article, the continuation of the outdated colonial-era homosexuality law and its impact on the underprivileged homosexual society in India is discussed, as well as consequences to this group's health in relation to HIV infection.

ELEVATED ALANINE AMINOTRANSFERASE (ALT) IN BLOOD DONORS: AN ASSESSMENT OF THE MAIN ASSOCIATED CONDITIONS AND ITS RELATIONSHIP TO THE DEVELOPMENT OF HEPATITIS C

The determination of aminotranferases levels is very useful in the diagnosis of hepatopathies. In recent years, an elevated serum ALT level in blood donors has been associated with an increased risk of post-transfusion hepatitis (PTH). The purpose of the study was to research the factors associated with elevated ALT levels in a cohort of voluntary blood donors and to evaluate the relationship between increased ALT levels and the development of hepatitis C (HCV) infection. 166 volunteer blood donors with elevated ALT at the time of their first donation were studied. All of the donors were questioned about previous hepatopathies, exposure to hepatitis, exposure to chemicals, use of medication or drugs, sexual behaviour, contact with blood or secretions and their intake of alcohol. Every three months, the serum levels of AST, ALT, alkaline phosphatase, gamma glutamyl transpeptidase, cholesterol, triglyceride and glycemia are assessed over a two year follow-up. The serum thyroid hormone levels as well as the presence of auto-antibodies were also measured. Abdominal ultrasound was performed in all patients with persistently elevated ALT or AST levels. A needle biopsy of liver was performed in 9 donors without definite diagnostic after medical investigation. The presence of anti-HCV antibodies in 116 donors were assayed again the first clinical evaluation. At the end of follow-up period (2 years later) 71 donors were tested again for the presence of anti-HCV antibodies. None of donors resulted positive for hepatitis B or hepatitis C markers during the follow-up. Of the 116 donors, 101 (87%) had persistently elevated ALT serum levels during the follow-up. Obesity and alcoholism were the principal conditions related to elevated ALT serum levels in 91/101 (90.1%) donors. Hypertriglyceridemia, hypercholesterolemia, hypothyroidism and diabetes mellitus also were associated with increased ALT levels. Only 1/101 (0.9%) had mild chronic active non A-G viral hepatitis and 3/101 (2.9%) had liver biopsy with non-specific reactive hepatitis. The determination of ALT levels was not useful to detect donors infected with HCV at donation in Brazil, including the initial seronegative anti-HCV phase.

PREVALENCE OF HEPATITIS B AND HEPATITIS C MARKERS IN ALCOHOLICS WITH AND WITHOUT CLINICALLY EVIDENT HEPATIC CIRRHOSIS

We assessed the frequency of serological markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in 365 alcoholics by determining, by ELISA, the presence of HBsAg, anti-HBc, anti-HBs and anti-HCV. Fifty patients were cirrhotics and 315 had no evidence of hepatic cirrhosis; of the latter HBsAg was assessed in all, anti-HBc and anti-HBs in 130, and anti-HCV in 210. Among the alcoholics the frequencies of HBsAg (1.9%), anti-HBc (28.3%) and anti-HCV (3.8%) were higher (p<0.001) than among the controls (N=17,059), 0.4%, 4.0% and 0.4% respectively. The frequency of positive HBsAg was higher (p<0.001) in the cirrhotic patients (8.0%) than in alcoholics without cirrhosis (0.95%) and in controls (0.4%), and similar between the latter; of anti-HBc in alcoholics without cirrhosis (28.5%) was similar in cirrhotics patients (28.0%) and higher (p<0.001) than in the controls (4.0%); of anti-HBs in alcoholics without cirrhosis (20.8%) was similar to that of the cirrhotic patients (10.0%), and the anti-HCV was similar between alcoholics with (6.0%) and without cirrhosis (3.3%) and higher (p<0.001) than in controls (0.4%). We concluded that: a) alcoholics with or without cirrhosis have similar frequencies of infection with HBV and HCV between them, and higher than in nonalcoholics; b) alcoholics without cirrhosis had a frequency of HBV active infection (HBsAg+) which was similar to the controls, whereas among those who progressed to cirrhosis this frequency was significantly higher, what suggests that HBV may be implicated in the pathogenesis of cirrhosis in a few alcoholic individuals.

Hepatitis virus and hepatocellular carcinoma in Brazil: a report from the State of Espírito Santo

IntroductionFew studies have examined hepatocellular carcinoma (HCC) in Brazil, and the incidence and risk factors for this type of malignancy vary greatly geographically. In this paper, we report several risk factors associated with HCC diagnosed at the University Hospital in Vitória, ES, Brazil.MethodsWe reviewed 274 cases of HCC (January 1993 to December 2011) in which hepatitis B (HBV) and C (HCV) virus infection and chronic alcoholism were investigated. A diagnosis of hepatocellular carcinoma was confirmed by histology or by the presence of a characteristic pattern on imaging.ResultsHCC with associated liver cirrhosis was noted in 85.4% of cases. The mean ages of men and women were 56.6 years and 57.5 years, respectively. The male-to-female ratio was 5.8:1. Associated risk factors included the following: HBV, 37.6% (alone, 23.4%; associated with chronic alcoholism, 14.2%); HCV, 22.6% (alone, 13.5%; associated with chronic alcoholism, 9.1%), chronic alcoholism, 17.1%, non-alcoholic steatohepatitis, 2.6% and cryptogenic, 19.3%. The male-to-female ratio was higher in cases associated with HBV or chronic alcoholism compared with HCV-associated or cryptogenic cases. In 40 cases without associated cirrhosis, the male-to-female ratio and mean age were lower than those in cirrhosis-associated cases.ConclusionsThese results demonstrate that the main risk factor associated with HCC in the State of Espírito Santo is HBV. Chronic alcoholism is an important etiological factor, alone or in association with HBV or HCV infection.