Lack of effects of clomipramine on Fos and NADPH-diaphorase double-staining in the periaqueductal gray after exposure to an innate fear stimulus

Lack of effects of clomipramine on Fos and NADPH-diaphorase double-staining in the periaqueductal gray after exposure to an innate fear stimulus - nitric oxide (NO) acts as a neurotransmitter in the rat dorsolateral periaqueductal gray (dIPAG), a midbrain structure that modulates fear and defensive behavior. Since defensive reactions can be alleviated by anxiolytic/anti-panic drugs, the present study tested the effect of clomipramine, a serotonin re-uptake inhibitor, on the activation of NO-producing neurons in the dlPAG of rats exposed to a live predator. Double staining was performed using Fos immunohistochemistry and NADPH-diaphorase as techniques to mark neural activation and to detect NO-producing neurons, respectively. Male Wistar rats received acute or chronic (21 days) injections of saline or clomipramine (10 or 20 mg/kg/day) and were exposed to a live cat. The animals exhibited a robust defensive reaction accompanied by an increase in the number of Fos- and doublestained neurons in the dlPAG, suggesting that cat exposure activates NO-producing neurons. Such effects were not significantly attenuated by clomipramine treatments. The intensity of fear reaction correlated with the intensity of neural staining in the dlPAG, regardless the drug treatment. Thus, the present results reinforce the hypothesis that NO may coordinate defensive responses in the dIPAG and indicate that this mechanism may not be modulated by a serotonin re-uptake inhibitor. (C) 2008 Elsevier Inc. All rights reserved.

Basal levels of DNA damage detected by micronuclei and comet assays in untreated breast cancer patients and healthy women

Breast cancer is the second most frequent type of cancer worldwide and is the most common malignant disease among women. Risk factors for breast cancer include early menarche, late menopause, hormonal therapies, exposure to environmental pollutants, smoking and alcohol use. However, increased or prolonged exposure to estrogen is the most important risk factor. It has been suggested that accumulation of DNA damage may contribute to breast carcinogenesis. Epidemiological studies suggest that cytogenetic biomarkers such as micronuclei in peripheral blood lymphocytes may predict cancer risk because they indicate genomic instability in target tissues. The objective of the present study was to evaluate the frequencies of micronuclei and the extent of DNA damage detected by comet assay in peripheral blood lymphocytes of untreated breast cancer patients and healthy women. The study was conducted using peripheral blood lymphocytes from 45 women diagnosed for Ductal ""in situ"" or invasive breast carcinoma and 85 healthy control women. Micronuclei and comet assays were performed to detect spontaneous DNA damage. The results showed that micronuclei frequencies and tail intensity, detected by comet assay, were significantly higher in the breast cancer group than in controls. The levels of DNA damage were similar in smokers and non-smokers, and aging did not influence the frequencies of micronuclei or tail intensity values observed in either group. In conclusion, the present work demonstrates higher levels of DNA damage in untreated breast cancer patients than in healthy women.

Relation between alcohol consumption and traffic violations and accidents in the region of Ribeirao Preto, Sao Paulo State

In recent years, alcohol consumption has been considered an important public health problem. Ethanol, the alcohol used in beverages, is a drug that affects the central nervous system (CNS) and impairs driving skills and co-ordination, increasing risk of deaths and injuries derived from crashes and road accidents. Consumption of alcoholic beverages is implicated with premature deaths, injuries and damages caused by motor vehicle crashes, which result in high costs to government and society. Considering that alcohol consumption is the main responsible factor for deaths and disabilities in young people, the aim of this work was to evaluate the prevalence of blood alcohol in offenders and/or fatal and non-fatal victims of traffic occurrences in the region of Ribeirao Preto, Sao Paulo State, from 2005 to 2007. The results revealed that in 2134 cases investigated, blood alcohol positivity was generally found in young adults, 25-45 years old and male. The study showed the high risk of drinking and driving and the importance in establishing actions of prevention and intervention to promote the reduction in the number of traffic occurrences related to consumption of alcoholic beverages. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

The Fast Alcohol Screening Test (FAST) is as Good as the AUDIT to Screen Alcohol Use Disorders

This study was aimed at assessing the psychometric qualities of the fast alcohol screening test (FAST), and at comparing these qualities to those of the alcohol use disorders identification test (AUDIT) in three samples of Brazilian adults: (i) subjects attended at an emergency department (530); (ii) patients from a psychosocial care center (40); and (iii) university students (429). The structured clinical interview for diagnosis (SCID)-IV was used as gold standard. The FAST demonstrated high test-retest and interrater reliability coefficients, as well as high predictive and concurrent validity values. The results attest the validity and reliability of the Brazilian version of the FAST for the screening of indicators of alcohol abuse and dependence.

Stigmatization of alcohol and other drug users by primary care providers in Southeast Brazil

This study reports on the views of Primary Health Care (PHC) providers in Southeast Brazil on the use of alcohol and other drugs which reflect stigma, moralization, or negative judgment. Six hundred nine PHC professionals from the Brazilian states of Sao Paulo and Minas Gerais took part in the study. The majority (86.5%) of these professionals were female. Attitudes toward the use of alcohol and other drugs were evaluated in comparison to Hansen`s disease, obesity, depression, schizophrenia. HIV/AIDS, and tobacco use. The use of tobacco, marijuana/cocaine, and alcohol were the most negatively judged behaviors (p < 0.05). Nursing assistants and community health care workers demonstrated the severest judgment of alcohol use. In addition, marijuana/cocaine addicts and alcoholics suffered the highest rate of rejection by professionals. The hypothesis that the use of alcohol and other drugs is a behavior stigmatized by health professionals being confirmed, it is important to develop strategies for changing provider attitudes in order to provide a higher quality of service to these patients. This study is important as a first study among PHC professionals about social stigma of alcohol and other drugs users. (C) 2009 Elsevier Ltd. All rights reserved.

Cigarette smoke exposure impairs respiratory epithelial ciliogenesis

Background: Cigarette smoke exposure is considered an important negative prognostic factor for chronic rhinosinusitis (CRS) patients. However, there is no clear mechanistic evidence implicating cigarette smoke exposure in the poor clinical evolution of the disease or in the maintenance of the inflammatory state characterizing CRS. This study aimed to evaluate the effects of cigarette smoke exposure on respiratory cilia differentiation. Methods: Monse nasal septal epithelium cultures grown at an air-liquid interface were used as a model of respiratory epithelium. After 5 days of cell growth, cultures were exposed to air on the apical surface. Additionally, cigarette smoke condensate (CSC; the particulate phase of tobacco smoke) or cigarette smoke extract (CSE; the volatile phase) Were diluted in the basolateral compartment in different concentrations. After 15 days of continuous exposure, scanning electron microscopy and immunofluorescence for type IV tubulin were used to determine presence and maturation of cilia. Transepithelial resistance was also recorded to evaluate confluence and physiological barrier integrity. Results: CSC and CSE impair ciliogenesis in a dose-dependent manner with notable effects in concentrations higher than 30 mu g/mL, yielding >70% nonciliation and shorter cilia compared With control. No statistical difference on transepithelial resistance was evident. Conclusion: CSC and CSE exposure negatively impacts ciliogenesis of respiratory cells at concentrations not effecting transepithelial resistance. The impairment on ciliogenesis reduce the mucociliary clearance apparatuts after injury and/or infection and may explain the poor response to therapy for CRS patients exposed to tobacco smoke.

Exposure to maternal smoking during fetal life affects food preferences in adulthood independent of the effects of intrauterine growth restriction

Experimental animal studies have shown that nicotine exposure during gestation alters the expression of fetal hypothalamic neuropeptides involved in the control of appetite. We aimed to determine whether the exposure to maternal smoking during gestation in humans is associated with an altered feeding behavior of the adult offspring. A longitudinal prospective cohort study was conducted including all births from Ribeirao Preto (Sao Paulo, Brazil) between 1978 and 1979. At 24 years of age, a representative random sample was re-evaluated and divided into groups exposed (n = 424) or not (n = 1586) to maternal smoking during gestation. Feeding behavior was analyzed using a food frequency questionnaire. Covariance analysis was used for continuous data and the chi(2) test for categorical data. Results were adjusted for birth weight ratio, body mass index, gender, physical activity and smoking, as well as maternal and subjects` schooling. Individuals exposed to maternal smoking during gestation ate more carbohydrates than proteins (as per the carbohydrate-to-protein ratio) than non-exposed individuals. There were no differences in the consumption of the macronutrients themselves. We propose that this adverse fetal life event programs the individual`s physiology and metabolism persistently, leading to an altered feeding behavior that could contribute to the development of chronic diseases in the long term.

Violence between intimate partners and alcohol use: prevalence and associated factors

Objective. To estimate physical violence between intimate partners and to examine the association between violence and sociodemographic variables, use of alcohol, and other related factors. Method. This epidemiologic survey included a stratified probabilistic sample representative of the population from the city of Sao Paulo in economic and educational terms. The Gender, Alcohol and Culture: An International Study (GENACIS) questionnaire was employed. The sampling unit was the home, where all individuals older than 18 years were candidates for interview. The final sample included 1 631 people. Statistical analysis employed the Rao Scott test and logistic regression. Results. The response rate was 74.5%. Most participants were female (58.8%), younger than 40 years of age (52%), or had 5 to 12 years of schooling. Of the overall group, 5.4% reported having been victims of physical violence by an intimate partner and 5.4% declared having been aggressors of intimate partners in the past 2 years. Most men declared that none of those involved had ingested alcohol at the moment of aggression. Most women reported that nobody or only the man had drunk. Being a victim or an aggressor was associated with younger age and having a heavy-drinking partner. Women suffered more serious aggression, requiring medical care, and expressed more anger and disgust at aggression than men. Conclusions. The results underscore the importance of the association between alcohol use and risk of aggression between intimate partners, and may contribute to the design of public policies aimed to control this situation.

Pediatric glioblastoma cell line shows different patterns of expression of transmembrane ABC transporters after in vitro exposure to vinblastine

Resistance to drug is a major cause of treatment failure in pediatric brain cancer. The multidrug resistance (MDR) phenotype can be mediated by the superfamily of adenosine triphosphate-binding cassette (ABC) transporters. The dynamics of expression of the MDR genes after exposure to chemotherapy, especially the comparison between pediatric brain tumors of different histology, is poorly described. To compare the expression profiles of the multidrug resistance genes ABCB1, ABCC1, and ABCG2 in different neuroepithelial pediatric brain tumor cell lines prior and following short-term culture with vinblastine. Immortalized lineages from pilocytic astrocytoma (R286), anaplasic astrocytoma (UW467), glioblastoma (SF188), and medulloblastoma (UW3) were exposed to vinblastine sulphate at different schedules (10 and 60 nM for 24 and 72 h). Relative amounts of mRNA expression were analyzed by real-time quantitative polymerase chain reaction. Protein expression was assessed by immunohistochemistry for ABCB1, ABCC1, and ABCG2. mRNA expression of ABCB1 increased together with augmenting concentration and time of exposure to vinblastine for R286, UW467, and UW3 cell lines. Interestingly, ABCB1 levels of expression diminished in SF188. Following chemotherapy, mRNA expression of ABCC1 decreased in all cell lines other than glioblastoma. ABCG2 expression was influenced by vinblastine only for UW3. The mRNA levels showed consistent association to protein expression in the selected sets of cell lines analyzed. The pediatric glioblastoma cell line SF188 shows different pattern of expression of multidrug resistance genes when exposed to vinblastine. These preliminary findings may be useful in determining novel strategies of treatment for neuroepithelial pediatric brain tumors.

Effects of Nicotine Exposure on Renal Function of Normal and Hypercholesterolemic Rats

Background/Aims: Renal risks of nicotine exposure associated with hypercholesterolemia are still unknown. Methods: Thus, hypercholesterolemic rats (HC) and their control (C) were evaluated by inulin clearance (InCl) measured at baseline and during nicotine infusion (100 mu g/kg b.w.). Five groups were studied: (i) C; (ii) DEN (C submitted to a renal denervation); (iii) C + L-arginine (0.25% in drinking water); (iv) HC, and (v) HC + L-arginine (0.25% in drinking water). Furthermore, C and HC had their renal blood flow (RBF) measured and they have also been chronically treated with nicotine (12.5 mu g/ml in drinking water) to assess InCl on the 8th day. Results: Nicotine increased blood pressure in C, DEN and HC and reduced InCl only in C. L-Arginine treatment blunted nicotine effects on blood pressure and increased InCl only in C. Moreover, nicotine did not change RBF in C but elicited in HC, whereas renal vascular resistance was increased in C and unchanged in HC. Indeed, chronic nicotine exposure has also reduced InCl in C. Conclusion: Nicotine acted on the adrenergic system and nitric oxide counteracted this action in C, but the same may not be applied to HC. An impairment in renal autoregulation may explain why InCl was unchanged in HC. Copyright (C) 2009 S. Karger AG, Basel

Histometric Study of Alveolar Bone in Rats Submitted to Ethanol During Lactation

The present work studied the adverse effects of maternal exposure of rats to alcohol during lactation, on the development of their offspring. Histometric evaluation by karyometry and of the alveolar bone at the level of the first upper molar of the sucking was perfomed. Two groups of animals, one coming from mothers exposed to drinking water containing 20% ethanol during the total lactation period and the other of controls coming from mothers receiving only alcohol-free drinking water during this period. On the 21 first day of lactation the young of each group were aleatorily selected and following anesthesia, their heads severed; after histological treatment, serial 6 mu m sections on the frontal plane at the molar level, stained with hematoxilin and eosin, were obtained. The experimental results produced, suggest that sucking from ethanol-treated mothers, show retarded post-natal growth, their alveolar bones presenting scarce, little calcified trabeculae, and a more abundant bone marrow compared to controls.

Haematological and immunological effects of repeated dose exposure of rats to integerrimine N-oxide from Senecio brasiliensis

This study is the first in the literature to focus attention on the possible immunotoxic effect of integerrimine N-oxide content in the butanolic residue (BR) of Senecio brasiliensis, a poisonous hepatotoxic plant that contains pyrrolizidine alkaloids (PAs). PAs have been reported as a pasture and food contaminant and as herbal medicine used worldwide and are responsible for poisoning events in livestock and human beings. After the plant extraction, BR extracted from Senecio brasiliensis was found to contain approximately 70% integerrimine N-oxide by elemental and spectral analyses ((1)H and (13)C NMR), which was administered to adult male Wistar Hannover rats at doses of 3, 6 and 9 mg/kg for 28 days. Body weight gain, food consumption, lymphoid organs, neutrophil analysis, humoural immune response, cellular immune response and lymphocyte analysis were evaluated. Our study showed that integerrimine N-oxide could promote an impairment in the body weight gain, interference with blood cell counts and a reducing T cell proliferative activity in rats; however, no differences in the neutrophil activities, lymphocytes phenotyping and humoural and cellular immune responses were observed. It is concluded that doses of integerrimine N-oxide here employed did not produce marked immunotoxic effects. (C) 2011 Elsevier Ltd. All rights reserved.

Prenatal Lipopolysaccharide Exposure Affects Maternal Behavior and Male Offspring Sexual Behavior in Adulthood

Objective: This study investigates the effects of prenatal lipopolysaccharide (LPS) exposure on the maternal behavior of pregnant rats and the physical development and sexual behavior of their male offspring in adulthood. Methods: For two experiments, pregnant rats were injected with LPS (250 mu g/kg, i.p.) on gestation day (GD) 21. In the first experiment, the maternal behavior (postnatal day, PND, 6) and the dam`s open-field general activity (PND7) were evaluated. In the second experiment, the maternal pre- and postnatal parameters, the pup`s development, the offspring`s sexual behavior in adulthood, and the pup`s organ weights were assessed. Results: Compared to the control group, the LPS-treated dams presented reduced maternal behavior, decreased general activity, a smaller body weight difference between GD21 and PND1, a greater number of perinatal deaths, and smaller litters. For the male pups, LPS treatment resulted in a decreased body weight on PND2, whereas the anogenital distance and the day of testis descent were not modified. The male sexual behavior was impaired by prenatal LPS. Particularly the number of ejaculating animals was reduced. The testis weight was also lower in the prenatally LPS-treated rats than in the control rats. Conclusion: We propose that prenatal LPS exposure on GD21 acts as an imprinting factor that interferes with the programming of brain sexual determination in offspring. Copyright (C) 2009 S. Karger AG, Basel

Prenatal LPS exposure reduces olfactory perception in neonatal and adult rats

Prenatal lipopolysaccharide (LPS) exposure causes reproductive, behavioral and neurochemical defects in both dams and pups. The present study evaluated male rats prenatally treated with LPS for behavioral and neurological effects related to the olfactory system, which is the main sensorial path in rodents. Pregnant Wistar rats received 100 mu g/kg of LPS intraperitoneally (i.p.) on gestational day (GD) 9.5, and maternal behavior was evaluated. Pups were evaluated for (1) maternal odor preference, (2) aversion to cat odor, (3) monoamine levels and turnover in the olfactory bulb (OB) and (4) protein expression (via immunoblotting) within the OB dopaminergic system and glial cells. Results showed that prenatal LPS exposure impaired maternal preference and cat odor aversion and decreased dopamine (DA) levels in the OB. This dopaminergic impairment may have been due to defects in another brain area given that protein expression of the first enzyme in the DA biosynthetic pathway was unchanged in the OB. Moreover, there was no change in the protein expression of the DA receptors. The fact that the number of astrocytes and microglia was not increased suggests that prenatal LPS did not induce neuroinflammation in the OB. Furthermore, given that maternal care was not impaired, abnormalities in the offspring were not the result of reduced maternal care. (C) 2011 Elsevier Inc. All rights reserved.

Single early prenatal lipopolysaccharide exposure prevents subsequent airway inflammation response in an experimental model of asthma

Aims: There has been emerging interest in the prenatal determinants of respiratory disease. In utero factors have been reported to play a role in airway development, inflammation, and remodeling. Specifically, prenatal exposure to endotoxins might regulate tolerance to allergens later in life. The present study investigated whether prenatal lipopolysaccharide (LPS) administration alters subsequent offspring allergen-induced inflammatory response in adult rats. Main methods: Pregnant Wistar rats were treated with LPS (100 mu g/kg, i.p.) on gestation day 9.5 and their ovariectomized female offspring were sensitized and challenged with OVA later in adulthood. The bronchoalveolar lavage (BAL) fluid, peripheral blood, bone marrow leukocytes and passive cutaneous anaphylaxis were evaluated in these 75-day-old pups. Key findings: OVA sensitized pups of NaCl treated rats showed an increase of leucocytes in BAL after OVA challenge. This increase was attenuated, when mothers were exposed to a single LPS injection early in pregnancy. Thus, LPS prenatal treatment resulted in (1) lower increased total and differential (macrophages, neutrophils, eosinophils and lymphocytes) BAL cellularity count; (2) increased number of total, mononuclear and polymorphonuclear cells in the peripheral blood; and (3) no differences in bone marrow cellularity or passive cutaneous anaphylaxis. Significance: In conclusion, female pups treated prenatally with LPS presented an attenuated response to experimentally-induced asthma. We observed reduced immune cell migration from peripheral blood to the lungs, with no effect on the production of bone marrow cells or antibodies. It was suggested that inflammatory events such as exposure to LPS in early fetal life can attenuate allergic inflammation in the lung, which is a common symptom in asthma. (C) 2011 Elsevier Inc. All rights reserved.