Role of 5-HT in stress, anxiety, and depression

There are conflicting results on the function of 5-HT in anxiety and depression. To reconcile this evidence, Deakin and Graeff have suggested that the ascending 5-HT pathway that originates in the dorsal raphe nucleus (DRN) and innervates the amygdala and frontal cortex facilitates conditioned fear, while the DRN-periventricular pathway innervating the periventricular and periaqueductal gray matter inhibits inborn fight/flight reactions to impending danger, pain, or asphyxia. To study the role of the DRN 5-HT system in anxiety, we microinjected 8-OH-DPAT into the DRN to inhibit 5 HT release. This treatment impaired inhibitory avoidance (conditioned fear) without affecting one-way escape (unconditioned fear) in the elevated T-maze, a new animal model of anxiety. We also applied three drug treatments that increase 5-HT release from DRN terminals: 1) intra-DRN microinjection of the benzodiazepine inverse agonist FG 4172, 2) intra-DRN microinjection of the excitatory amino acid kainic acid, and 3) intraperitoneal injection of the 5-HT releaser and uptake blocker D-fenfluramine. All treatments enhanced inhibitory avoidance in the T-maze. D-Fenfluramine and intra-DRN kainate also decreased one-way escape. In healthy volunteers, D-fenfluramine and the 5-HT agonist mCPP (mainly 5-HT2C) increased, while the antagonists ritanserin (5-HT2A/(2C)) and SR 46349B (5-HT2A) decreased skin conductance responses to an aversively conditioned stimulus (tone). In addition, D-fenfluramine decreased, whereas ritanserin increased subjective anxiety induced by simulated public speaking, thought to represent unconditioned anxiety. Overall, these results are compatible with the above hypothesis. Deakin and Graeff have suggested that the pathway connecting the median raphe nucleus (MRN) to the dorsal hippocampus promotes resistance to chronic, unavoidable stress. In the present study, we found that 24 h after electrolytic lesion of the rat MRN glandular gastric ulcers occurred, and the immune response to the mitogen concanavalin A was depressed. Seven days after the same lesion, the ulcerogenic effect of restraint was enhanced. Microinjection of 8-OH-DPAT, the nonselective agonist 5-MeO-DMT, or the 5-HT uptake inhibitor zimelidine into the dorsal hippocampus immediately after 2 h of restraint reversed the deficits of open arm exploration in the elevated plus-maze, measured 24 h after restraint. The effect of the two last drugs was antagonized by WAY-100135, a selective 5-HT1A receptor antagonist. These results are compatible with the hypothesis that the MRN-dorsal hippocampus 5-HT system attenuates stress by facilitation of hippocampal 5-HT1A-mediated neurotransmission. Clinical implications of these results are discussed, especially with regard to panic disorder and depression.

Influence of fluid concentration on freezing point depression and thermal conductivity of frozen orange juice

The freezing point depression (FPD) of orange juice at different concentrations was measured by using a simple apparatus. Results showed that the initial freezing point decreased approximately 90% with the increase of juice concentration between 46degrees and 66degrees Brix (water content respectively between 52.8 and 32.8% w/w). The thermal conductivity of orange juice as a function of fluid concentration was also investigated by using a coaxial dual-cylinder apparatus. Below the freezing point, the thermal conductivity was strongly affected by both the orange juice concentration and temperature. Simple equations in terms of water content and temperature could be adjusted to experimental data of FPD and thermal conductivity.

Perinatal estrogen exposure: Later repercussion on the fertility of rats

The aim of the present study was to investigate the effects of perinatal estrogen exposure in the fertility of rats. Thus, rats were treated with estrogen on the 21st or 22nd day of intra-uterine life or treated with estrogen immediately after birth. It was observed that the testicular descent of males and beginning of puberty of females were advanced in all estrogen-treated groups. The females from estrogen-treated groups showed reduced frequency of estrous in 15 consecutive days of study, and there was an increase in estrous duration. Their fertility also were impaired and a reduction in the number of alive fetuses, as well as enhancement of pre- and postimplantation loss, mainly in the group treated with estrogen on the 21st day of intra-uterine life. However, the alterations observed in the fertility of estrogen-treated male rats were slighter and only females mated with male rats from the group treated with estrogen immediately after birth showed enhanced preimplantation loss. We suggest that the reproductive function is impaired by exposure to estrogen in the perinatal life of rats, and that the mechanisms involved in this effect are distinct for males and females. (C) 1997 Elsevier B.V.

An animal model for the study of Chamomilla in stress and depression: pilot study

The behavioral and hematological effects of treatment with Chamomilla 6cH in mice subjected to experimental stress are described. Swiss mice were randomly divided into pairs, one animal was inoculated with Ehrlich's tumor, the other was treated daily with Chamomilla 6cH or control or received no treatment. After 7 days, the animals were observed in an open-field arena and blood samples taken. Mice who cohabitated with a sick cage-mate showed a decrease in their general activity, but those treated with Chamomilla 6cH were less severely affected (p = 0.0426). No hematologicall changes were observed.In a second experiment, the forced swimming test was applied to mice pre-treated with Chamomilla 6cH, controls were: water, 10% ethanol or amitriptyline. Only the amitriptyline and ethanol treated groups showed significant excitatory behavior (p = 0.0020), Chamomilla 6cH treated animals' scores intermediate between water control and ethanol or amitriptyline. A decrease in the leukocyte count was observed in the amitriptyline and Chamomilla 6cH treated groups (p = 0.039). These data suggest that treatment with Chamomilla 6cH is related to the recovery of basal behavioral conditions in mice subjected to stressful conditions.

Double-blind comparison of venlafaxine and amitriptyline in outpatients with major depression with or without melancholia

The purpose of this study was to compare the efficacy and tolerability of venlafaxine and amitriptyline in outpatients with major depression with or without melancholia. This was an 8-week, multicentre, randomized, double-blind, parallel-group comparison of venlafaxine and amitriptyline. Outpatients with DSM-IV major depression, a minimum score of 20 on the 21-item Hamilton Depression Rating Scale (HAM-D), and depressive symptoms for at least 1 month were eligible. Patients were randomly assigned to venlafaxine or amitriptyline, both drugs titrated to a maximum of 150 mg/day until study day 15. The primary efficacy variables were the final on-therapy scores on the HAM-D, Montgomery-Asberg Depression Rating Scale and Clinical Global Impression severity scales. Data were evaluated on an intent-to-treat basis using the LOCF method. One hundred and 16 patients were randomized, and 115 were evaluated for efficacy. Both drugs showed efficacy in the treatment of depression with or without melancholia. No significant differences were noted between treatments for any efficacy parameter. However, significantly (p < 0.05) more patients in the amitriptyline group had at least one adverse event. These results should support the efficacy and tolerability of venlafaxine in comparison with amitriptyline for treating major depression with or without melancholia.

Efficacy of hormone therapy with and without methyltestosterone augmentation of venlafaxine in the treatment of postmenopausal depression: A double-blind controlled pilot study

Objective: This study evaluated the augmentation of venlafaxine with hormone therapy in the treatment of postmenopausal depression. The hormones evaluated were estrogen (0.625 mg) in combination with medroxyprogesterone acetate (2.5 mg) and methyltestosterone (2.5 mg). Design: Seventy-two menopausal women (mean age: 53.6 ± 4.27 years) diagnosed with depression (Montgomery-Åsberg Depression Rating Scale [MADRS] scores ≥ 20) were treated with venlafaxine and one of the following hormone therapy combinations, in a double-blind regimen: estrogen + medroxyprogesterone + methyltestosterone (group 1, n = 20); estrogen + medroxyprogesterone acetate (group 2, n = 20); methyltestosterone only (group 3, n = 16); and no hormone therapy (group 4, n = 16). Study duration was 24 weeks. Primary efficacy outcome was remission according to the MADRS, whereas secondary efficacy measures included the Clinical Global Impression (CGI), Blatt-Kupperman Index, and Women's Health Questionnaire (WHQ). Results: Forty-eight patients completed the study. All groups showed significant improvement from baseline. Group 3 demonstrated significant improvement on the MADRS compared with placebo (group 4) at weeks 20 (P = 0.048) and 24 (P = 0.030); effect size 8.04 (0.83; 15.26) (P = 0.029), but also had the highest dropout rate. Groups 1 and 3 had significant CGI improvement rates compared with placebo: 42.23% (P = 0.012) and 44.45% (P = 0.08), respectively. There were no differences in the WHQ or BKI scores among the groups. Conclusions: Methyltestosterone 2.5 mg had the highest effect size compared with placebo, but the high dropout rate prevented its efficacy from being determined. Estrogen plus medroxyprogesterone, combined with methyltestosterone or otherwise, demonstrated a trend toward increased efficacy of venlafaxine. Further larger-scale clinical trials are needed to elucidate the findings of this pilot study. © 2006 by The North American Menopause Society.

Depression severity levels and cognitive functions in institutionalized elderly patients

Depression is a highly prevalent illness among institutionalized aged and assumes peculiar characteristics such as the risk for progressing to dementia. The aims of this study was to assess the cognitive functions of institutionalized elderly with clinical diagnosis of depression and compare the severity of depressive symptoms with cognitive performance. From 120 residents at a nursing home in Rio Claro, Brazil, we study 23 individuals (mean age: 74.3 years; mean schooling: 4.0 years) with diagnosis of depression. At first, a clinical diagnosis of depression and measurement of its symptoms using the Geriatric Depression Scale were performed. The patient then underwent a neuropsychological assessment based on the following tests: Mini-Mental Examination, Verbal Fluency, Visual Perception, Immediate Memory, Recent Memory, Recognition, Clock Drawing Test. The patients were divided into two groups: those with less severe depression symptoms (Group 1: N=9) and more severe symptoms (Group 2: N=14). The significant difference between symptom severity of the two groups was p=0.0001. Patients with more severe symptoms revealed a slightly inferior cognitive performance in most of the tests when compared to those with less severe symptoms (p>0.05). In relation to Verbal Fluency, patients with more severe depression symptoms presented a significantly inferior cognitive performance when compared to those with less severe symptoms (p=0.0082). Verbal Fluency revealed to be a more sensitive test for measuring early cognitive alterations in institutionalized aged with depression, and appears to be a useful resource in monitoring the cognitive functions of patients faced with the risk of dementia. © Copyright Moreira Jr. Editora.

Insulinoterapia, controle glicêmico materno e prognóstico perinatal - Diferença entre o diabetes gestacional e o clínico

PURPOSE: to evaluate the insulin therapy protocol and its maternal and perinatal outcome in patients with clinical or gestational diabetes in a high risk reference service. METHODS: descriptive and prospective study including 103 pregnant women with gestational or clinical diabetes treated with insulin and attended by the reference service from October 2003 to December 2005. Gemellarity, miscarriages, unfinished prenatal care and deliveries not attended by the service were excluded. The gestational age at the beginning of the treatment, dosage, doses/day, increment of insulin (UI/kg), glycemic index (GI) and perinatal outcomes were compared. ANOVA, Fisher's exact test and Goodman's test considering p<0.05 were used. RESULTS: multiparity (92 versus 67.9%), pre-gestational body mass index (BMI) >25 kg/m 2 (88 versus 58.5%), weight gain (WG) <8 kg (36 versus 17%) and a high increment of insulin characterized the gestational diabetes. For the patients with clinical diabetes, despite the highest GI (120 mg/dL (39.2 versus 24%)) at the end of the gestational period, insulin therapy started earlier (47.2 versus 4%), lasted longer (56.6 versus 6%) and higher doses of insulin (92 versus 43 UI/day) were administered up to three times a day (54.7 versus 16%). Macrosomia was higher among newborns from the cohort of patients with gestational diabetes (16 versus 3.8%), being the only significant neonatal outcome. There were no neonatal deaths, except for one fetal death in the cohort of patients with clinical diabetes. There were no differences in the other neonatal complications in both cohorts, and most of the newborns were discharged from hospital up to seven days after delivery (46% versus 55.8%). CONCLUSIONS: the analysis of these two cohorts has shown differences in the insulin therapy protocol in quantity (UI/day), dosage (UI/kg weight) and number of doses/day, higher for the clinical diabetes cohort, and in the increment of insulin, higher for the gestational diabetes cohort. Indirectly, the quality of maternal glycemic control and the satisfactory perinatal outcome have proven that the treatment protocol was adequate and did not depend on the type of diabetes.

Childhood trauma in substance use disorder and depression: An analysis by gender among a Brazilian clinical sample

Objective: In this study, we compared the frequency and intensity of childhood traumas in alcohol- or other drug-dependent patients, in patients with depression, and in a control group without psychiatric diagnoses. Methods: The study had a retrospective design of a clinical sample of men and women from the groups listed above. They were evaluated by the same standardized instrument: the Childhood Trauma Questionnaire.. Results: A higher frequency and intensity of emotional, physical, and sexual abuse were found in alcohol- and other drug-dependent patients than in patients with depression, who, in turn, presented significantly higher proportions than the control group. In all of the cases, the frequency was higher among women than men. Conclusion: Because of the high frequency and intensity of childhood traumas among alcohol- or other drug-dependent patients and depressed patients, the assessment of problems due to childhood traumas among these patients is essential to a better understanding of the etiology of those disorders and to their treatment. © 2010 Elsevier Ltd. All rights reserved.

Perinatal exposure to parasiticide ivermectin: Long-term effects on reproductive parameters of adult male rats

Ivermectin is one of the most widely used antiparasitic drugs globally. The aim of this study was to evaluate the chronic effects of perinatal exposure to ivermectin on male reproductive parameters in rats. Pregnant rats were treated daily by oral gavage with 0.4 or 1.6 mg kg -1 of ivermectin or vehicle, from gestational day 6 until post-natal day 10. In the adulthood stage, there were significant reductions in the relative testicular weight of rats exposed to the low dose and in relative prostate weight of male rats exposed to the high dose of ivermectin. Furthermore, the animals exposed to the low dose also presented an increased seminal vesicle weight compared to controls. However, neither of the ivermectin doses interfered in daily sperm production, sperm number in testis, or sexual behavior of exposed males. In conclusion, perinatal exposure to ivermectin neither altered the male reproductive system development markedly, nor produced any adverse effects on the parameters evaluated. © 2011 Taylor & Francis.

Comorbid major depression in obsessive-compulsive disorder patients

Although major depressive disorder (MDD) has been consistently considered the most frequent complication of obsessive-compulsive disorder (OCD), little is known about the clinical characteristics of patients with both disorders. This study assessed 815 Brazilian OCD patients using a comprehensive psychiatric evaluation. Clinical and demographic variables, including OCD symptom dimensions, were compared among OCD patients with and without MDD. Our findings showed that prevalence rates of current MDD (32%) and lifetime MDD (67.5%) were similar for both sexes in this study. In addition, patients with comorbid MDD had higher severity scores of OCD symptoms. There was no preferential association of MDD with any particular OCD symptom dimension. This study supports the notion that depressed OCD patients present more severe general psychopathology. © 2011 Elsevier Inc. All rights reserved.

Niveles, tendencias y diferenciales de la mortalidad infantil y perinatal en el mundo, con especial referencia a la situacion en la America Latina

Incluye Bibliografía

Estimación de la mortalidad infantil a partir de la historia clínica perinatal

Incluye Bibliografía

Inbreeding depression on production and reproduction traits of buffaloes from Brazil

The objective of this study was to evaluate the influence of inbreeding depression on traits of buffaloes from Brazil. Specifically, the traits studied were body weight at 205 and 365 days of age, average daily gain from birth to 205 days (ADG_205), average daily gain between 205 and 365 days (ADG205_365) in Mediterranean buffaloes, and milk yield, lactation length, age of first calving and calving intervals in Murrah buffaloes. Inbreeding effects on the traits were determined by fitting four regression models (linear, quadratic, exponential and Michaelis-Menten) about the errors generated by the animal model. The linear model was only significant (P<0.05) for growth traits (exception of ADG205_365). The exponential and Michaelis-Menten models were significant (P<0.01) for all the studied traits while the quadratic model was not significant (P>0.05) for any of the traits. Weight at 205 and 365 days of age decreased 0.25kg and 0.39kg per 1% of increase in inbreeding, respectively. The inbred animals (F=0.25) produced less milk than non-inbred individuals: 50.4kg of milk. Moreover, calving interval increased 0.164 days per 1% of increase in inbreeding. Interestingly, inbreeding had a positive effect on age at first calving and lactation length, decreasing age of first calving and increasing lactation length. © 2012 Japanese Society of Animal Science.