Serotonergic neurotransmission in the dorsal raphe nucleus recruits in situ 5-HT2A/2C receptors to modulate the post-ictal antinociception

The post-ictal immobility syndrome is followed by a significant increase in the nociceptive thresholds in animals and humans. The aim of this study was to assess the involvement of the dorsal raphe nucleus (DRN) in the post-ictal antinociception. The second aim was to study the role of serotonergic intrinsic mechanisms of the DRN in this hypo-algesic phenomenon. Pentylenetetrazole (PTZ), an ionophore GABA-mediated Cl- influx antagonist, was peripherally used to induce tonic-clonic seizures in Wistar rats. The nociceptive threshold was measured by the tail-flick test. Neurochemical lesions of the DRN, performed with microinjection of ibotenic acid (1.0 mu g/0.2 mu L), caused a significant decrease of tonic-clonic seizure-induced antinociception, suggesting the involvement of this nucleus in this antinociceptive Process. Microinjections of methysergide (1.0 and 5.0 mu g/0.2 mu L), a non-selective serotonergic receptor antagonist, into DRN caused a significant decrease in the post-ictal antinociception in seizing animals, compared to controls, in all post-ictal periods Presently studied. These findings were corroborated by microinjections of ketanserin (at 1.0 and 5.0 mu g/0.2 mu L) into DRN. Ketanserin is an antagonist with large affinity for 5-HT2A/2C serotonergic receptors, which, in this Case, Caused a significant decrease in the tail-flick latencies in seizing animals, compared to controls after the first 20 min following tonic-clonic convulsive reactions. These results indicate that serotonergic neurotransmission of the DRN neuronal clusters is involved in the organization of the post-ictal hypo-algesia. The 5-HT2A/2C receptors of DRN neurons seem to be critically involved in the increase of nociceptive thresholds following tonic-clonic seizures. (c) 2008 Elsevier Inc, All rights reserved.

Activation of cannabinoid CB, receptors in the dorsolateral periaqueductal gray induces anxiolytic effects in rats submitted to the Vogel conflict test

There are contradictory results concerning the effects of systemic injections of cannabinoid agonists in anxiety-induced behavioral changes. Direct drug administration into brain structures related to defensive responses could help to clarify the role of cannabinoids in these changes. Activation of cannabinoid CB, receptors in the dorsolateral periaqueductal gray induces anxiolytic-like effects in the elevated plus maze. The aim of this work was to verify if facilitation of endocannabinoid-mediated neurotransmission in this region would also produce anxiolytic-like effects in another model of anxiety, the Vogel conflict test. Male Wistar rats (n = 5-9/group) with cannulae aimed at the dorsolateral periaqueductal gray were water deprived for 24 h and pre-exposed to the apparatus where they were allowed to drink for 3 min. After another 24 h-period of water deprivation, they received the microinjections and, 10 min later, were placed into the experimental box. in this box an electrical shock (0.5 nnA, 2 s) was delivered in the spout of a drinking bottle at every twenty licks. The animals received a first microinjection of vehicle (0.2 mu l) or AM251 (a cannabinoid CB1 receptor antagonist; 100 pmol) followed, 5 min later, by a second microinjection of vehicle, anandamide (an endocannabinoid, 5 pmol), AM404 (an inhibitor of anandamide uptake, 50 pmol) or URB597 (an inhibitor of Fatty Acid Amide Hydrolase, 0.01 or 0.1 nmol). Anandamide, AM404 and URB597 (0.01 nmol) increased the total number of punished licks. These effects were prevented by AM251. The results give further support to the proposal that facilitation of CB1 receptor-mediated endocannabinoid neurotransmission in the dorsolateral periaqueductal gray modulates defensive responses. (C) 2008 Elsevier B.V. All rights reserved.

A reassessment of the in vitro RBC haemolysis assay with defibrinated sheep blood for the determination of the ocular irritation potential of cosmetic products: Comparison with the in vivo Draize rabbit test

We examined the correlation between results obtained from the in vivo Draize test for ocular irritation and in vitro results obtained from the sheep red blood cell (RBC) haemolytic assay, which assesses haemolysis and protein denaturation in erythrocytes, induced by cosmetic products. We sought to validate the haemolytic assay as a preliminary test for identifying highly-irritative products, and also to evaluate the in vitro test as alternative assay for replacement of the in vivo test. In vitro and in vivo analyses were carried out on 19 cosmetic products, in order to correlate the lesions in the ocular structures with three in vitro parameters: (i) the extent of haemolysis (H50); (ii) the protein denaturation index (131); and (iii) the H50/DI ratio, which reflects the irritation potential (IP). There was significant correlation between maximum average scores (MAS) and the parameters determined in vitro (r = 0.752-0.764). These results indicate that the RBC assay is a useful and rapid test for use as a screening method to assess the IP of cosmetic products, and for predicting the IP value with a high level of concordance (94.7%). The assay showed high sensitivity and specificity rates of 91.6% and 100%, respectively.

High levels of anxiety and depression have a negative effect on quality of life of women with chronic pelvic pain

Chronic pelvic pain (CPP) is a common and complex disease whose cause is often clinically inexplicable, with consequent difficulty in diagnosis and treatment. Patients with CPP have high levels of anxiety and depression, with a consequent impairment of their quality of life. The objective of this study was to determine the prevalence of anxiety and depression and their impact on the quality of life of women with CPP. A cross-sectional controlled study was conducted on 52 patients with CPP and 54 women without pain. Depression and anxiety were evaluated by the Hospital Anxiety and Depression Scale, and quality of life was evaluated by the World Health Organization Quality of life Whoqol-bref questionnaire. Data were analysed statistically by the Mann-Whitney U-test, the Fisher exact test, chi-square test and Spearman correlation test. The prevalence of anxiety was 73% and 37% in the CPP and control groups, respectively, and the prevalence of depression was 40% and 30% respectively. Significant differences between groups were observed in the physical, psychological and social domains. Patients with higher anxiety and depression scores present lower quality of life scores. The fact that DPC is a syndromic complex, many patients enter a chronic cycle of search for improvement of medical symptoms. The constant presence of pain may be responsible for affective changes in dynamics, family, social and sexual. Initially the person is facing the loss of a healthy body and active, to a state of dependence and limitations. In this study, patients with higher scores of anxiety and depression scores had lower quality of life and patients with lower scores of anxiety and depression had scores of quality of life. These results show that perhaps the depression and anxiety may be related to the negative impact on quality of life of these patients. In view of this association, we emphasise the importance of a specific approach to the treatment of anxiety and depression together with clinical treatment to improve the quality of life of these patients.

Two-step tuberculin skin test and booster phenomenon prevalence among Brazilian medical students

SETTING: Five medical schools in three cities in Rio de Janeiro State, Brazil, with different tuberculosis (TB) incidence rates. OBJECTIVE: To evaluate the prevalence of the booster phenomenon and its associated factors in a voting universally BCG-vaccinated TB-exposed population. DESIGN: A two-step tuberculin skin test (TST) was performed among undergraduate medical students. Boosting was defined as an induration >= 10 mm in the second TST (TST2), with an increase of at least 6 mm over the first TST (TST1). The association of boosting with independent variables was evaluated using multivariate analysis. RESULTS: Of the 764 participants (mean age 21.9 +/- 2.7 years), 672 (87.9%) had a BCG scar. The overall booster SUMMARY phenomenon prevalence was 8.4% (95%CI 6.5-10.6). Boosting was associated with TST1 reactions of 1-9 mm (aOR 2.5, 95%CI 1.04-5.9) and with BCG vaccination, mostly after infancy, i.e., after age two years (aOR 9.1, 95%,CI 1.2-70.7). CONCLUSION: The prevalence of the booster phenomenon was high. A two-step TST in young BCG-vaccinated populations, especially in those with TST1 reactions of 1-9 mm, can avoid misdiagnosis as a false conversion and potentially reduce unnecessary treatment for latent TB infection.

The prednisolone suppression test in depression: Dose-response and changes with antidepressant treatment

Depressed patients have reduced glucocorticoid receptor (GR) function, as demonstrated by resistance to the suppressive effects of the synthetic glucocorticoid hormone, and GR agonist, dexamethasone. We have developed a suppressive test with prednisolone, a synthetic glucocorticoid that is similar to cortisol in its pharmacodynamics and pharmacokinetics, and binds to both the GR and the mineralocorticoid receptor (MR). We have found that depressed patients suppress normally to prednisolone, unless they are particularly non-responsive to treatment. In the present study, we evaluated 28 inpatients with treatment-resistant depression (TRD), and compared salivary cortisol secretion (at 0900 h, 1200 h and 1700 h) after placebo or after prednisolone (5 mg), before and after an inpatient treatment admission. Half of the patients (n = 14) reached treatment response. When comparing the assessment between admission and discharge, cortisol output after placebo fell (-26% of area under the curve; p = 0.024) while the output after prednisolone did not change. Moreover, there was no change in the response to prednisolone (percentage suppression) between admission at discharge, and this was not influenced by treatment response. Finally, we could confirm and extend our previously published data with prednisolone (5 mg), showing that depressed patients (n = 12) and controls (n = 12) suppressed equally to both 5 and 10 mg doses of prednisolone. This study suggests that the response to prednisolone is similar in depressed patients and controls at different doses of prednisolone, and does not change with symptomatic improvement. This is in contrast with findings, from us and others, using other measures of hypothalamic-pituitary-adrenal axis function, such as basal cortisol levels or the response to dexamethasone. Thus, we propose that the prednisolone suppression test may offer specific biological and clinical information, related to its action at both the GR and the MR. (C) 2010 Elsevier Ltd. All rights reserved.

Administration of cannabidiol and imipramine induces antidepressant-like effects in the forced swimming test and increases brain-derived neurotrophic factor levels in the rat amygdala

Objective: Cannabidiol is a chemical constituent from Cannabis sativa and it has multiple mechanisms of action, including antidepressant effects. The main objective of the present study was to evaluate behavioural and molecular effects induced by administration of cannabidiol and imipramine in rats. Methods: In the present study, rats were acutely or chronically treated for 14 days once a day with saline, cannabidiol (15, 30 and 60 mg/kg) or imipramine (30 mg/kg) and the animals behaviour was assessed in forced swimming and open-field tests. Afterwards, the prefrontal cortex, hippocampus and amygdala brain-derived neurotrophic factor (BDNF) levels were assessed by enzyme-linked immunosorbent sandwich assay. Results: We observed that both acute and chronic treatments with imipramine at the dose of 30 mg/kg and cannabidiol at the dose of 30 mg/kg reduced immobility time and increased swimming time; climbing time was increased only with imipramine at the dose of 30 mg/kg, without affecting locomotor activity. In addition, chronic treatment with cannabidiol at the dose of 15 mg/kg and imipramine at the dose of 30 mg/kg increased BDNF levels in the rat amygdala. Conclusion: In conclusion, our results indicate that cannabidiol has an antidepressant-like profile and could be a new pharmacological target for the treatment of major depression.

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.

Psychometric qualities of the Brazilian versions of the Fagerstrom Test for Nicotine Dependence and the Heaviness of Smoking Index

This study examined the psychometric properties of the Brazilian versions of the Fagerstrom Test for Nicotine Dependence (FTND) and the Heaviness of Smoking Index (HSI). The test-retest reliability of the FTND was assessed in a sample of 61 smoking university students, with a 15-day interval between assessments. The interrater reliability was examined in 30 smoking patients of a psychosocial care center for alcohol and drug users (PCC-AD). The reliability coefficient was estimated by the kappa and intraclass correlation coefficients. The predictive validity, internal consistency, and factor structure of the FTND and the HSI were evaluated by factor analysis in 271 smokers treated at an emergency unit and at the PCC-AD. The gold standard was the nicotine dependence criteria of DSM-IV, as assessed by the Structured Clinical Interview for DSM-IV. The FTND showed high reliability, with correlation coefficients of .92 for test-retest reliability and .99 for interrater reliability. Both the FTND and the HSI presented high levels of sensitivity and specificity. The internal consistency evaluation yielded a Cronbach`s alpha coefficient of .83 for the FTND and of .56 for the HSI. An exploratory factor analysis found 2 factors in the FTND, which were validated by a confirmatory factor analysis. The results obtained in this study confirm the validity and reliability of the Brazilian versions of the FTND and the HSI.

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.