Antioxidant Therapy Alters Brain MAPK-JNK and BDNF Signaling Path-ways in Experimental Diabetes Mellitus.

This study was designed to investigate the effects of treatment with the antioxidants N-acetylcysteine (NAC) and deferoxamine (DFX) in intracellular pathways in the brain of diabetic rats. To conduct this study we induced diabetes in Wistar rats with a single injection of alloxan, and afterwards rats were treated with NAC or DFX for 14 days. Following treatment completion, the immunocontent of c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase-38 (MAPK38), brain-derived neurotrophic factor (BDNF), and protein kinases A and C (PKA and PKC) were determined in the prefrontal cortex (PFC), hippocampus, amygdala and nucleus accumbens (NAc). DFX treatment increased JNK content in the PFC and NAc of diabetic rats. In the amygdala, JNK was increased in diabetics treated with saline or NAC. MAPK38 was decreased in the PFC of control and in diabetic rats treated with NAC or DFX; and in the NAc in all groups. PKA was decreased in the PFC with DFX treatment. In the amygdala, PKA content was increased in diabetic rats treated with either saline or NAC, compared to controls; and it was decreased in either NAC or DFX-treated groups, compared to saline-treated diabetic animals. In the NAc, PKA was increased in NAC-treated diabetic rats. PKC was increased in the amygdala of NAC-treated diabetic rats. In the PFC, the BDNF levels were decreased following treatment with DFX in diabetic rats. In the hippocampus of diabetic rats the BDNF levels were decreased. However, treatment with DFX reversed this effect. In the amygdala the BDNF increased with DFX in non-diabetic rats. In the NAc DFX treatment increased the BDNF levels in diabetic rats. In conclusion, both diabetes and treatment with antioxidants were able to alter intracellular pathways involved in the regulation of cell survival in a brain area and treatment-dependent fashion.

Social support for people living with acquired immunodeficiency syndrome / Apoyo social de las personas que viven con síndrome de inmunodeficiencia adquirida / Suporte social de pessoas que vivem com a síndrome da imunodeficiência adquirida

ABSTRACT The aim of this study was to evaluate the social support for people with AIDS. It was a cross-sectional study, with 215 outpatients at a University Hospital in Northeastern Brazil. Data were collected from August to December 2012, through interviews, using a Socio-demographic and Clinical Form and a Social Support Scale for People Living with HIV/AIDS. Statistical Package for the Social Science was used for data analysis. Results showed that average scores of social emotional and instrumental support were satisfactory and not influenced by sex (p=0.954; p=0.508), education (p=0.756; p=0.194), marital status (p=0.076; p=0.446) and length of antiretroviral therapy (p=0.480; p=0.120). People diagnosed for less than three years had more instrumental support (p=0.048) than those diagnosed over three years (p=0.370). Neighbors, employers and health professionals provided less support. The conclusion was that people with AIDS have satisfactory social support, especially from friends and family not living in the same household.

RESUMEN Este estudio objetivó evaluar el apoyo social a personas con SIDA. Estudio transversal con muestra de 215 pacientes ambulatorios de un hospital universitario del nordeste de Brasil. Los datos recolectados entre agosto y diciembre de 2012, a través de entrevistas utilizando el formulario sociodemográfico y clínico y la Escala de Apoyo Social para las Personas que Viven con VIH/SIDA. El Statistical Package for the Social Science fue utilizado para análisis de datos. Los resultados evidenciaron que las puntuaciones medias de apoyo social emocionales e instrumentales fueron satisfactorios, y no influenciados por el sexo (p=0,954; p=0,508), educación (p=0,756; p=0,194), estado civil (p=0,076; p=0,446) y tiempo de terapia antirretroviral (p=0,480; p=0,120). Las personas diagnosticadas en menos de tres años tenían más apoyo instrumental (p=0,048) que los diagnosticados hace más de tres años (p=0,370). Los vecinos, jefe y profesionales de salud proporcionaban menos apoyo. Se concluyó que personas con SIDA tienen un apoyo social satisfactorio, principalmente por parte de amigos y familiares que no viven en el mismo hogar.

RESUMO Teve-se como objetivo avaliar o suporte social de pessoas com aids. Estudo transversal, com amostra de 215 pacientes ambulatoriais de um hospital universitário do Nordeste brasileiro. Dados coletados de agosto a dezembro de 2012, por meio de entrevista, utilizando formulário sociodemográfico e clínico e Escala de Suporte Social para Pessoas Vivendo com HIV/aids. O Statistical Package for the Social Science foi utilizado para análise de dados. Resultados mostraram que médias de escores de suporte social emocional e instrumental foram satisfatórias e não influenciadas pelo sexo (p=0,954; p=0,508), escolaridade (p=0,756; p=0,194), situação conjugal (p=0,076; p=0,446) e tempo de terapia antirretroviral (p=0,480; p=0,120). Pessoas diagnosticadas há menos de três anos tiveram mais suporte instrumental (p=0,048) que os diagnosticados há mais de três anos (p=0,370). Vizinhos, chefe e profissionais da saúde forneceram menos apoio. Concluiu-se que pessoas com aids possuem suporte social satisfatório, principalmente, de amigos e familiares que não moram no mesmo domicílio.

Preclinical Evidences for an Antimanic Effect of Carvedilol.

Oxidative imbalance, alterations in brain-derived neurotrophic factor (BDNF), and mitochondrial dysfunction are implicated in bipolar disorder (BD) pathophysiology and comorbidities, for example, cardiovascular conditions. Carvedilol (CVD), a nonselective beta-blocker widely used for the treatment of hypertension, presents antioxidant and mitochondrial stabilizing properties. Thus, we hypothesized that CVD would prevent and/or reverse mania-like behavioral and neurochemical alterations induced by lisdexamfetamine dimesylate (LDX). To do this, male Wistar rats were submitted to two different protocols, namely, prevention and reversal. In the prevention treatment the rats received daily oral administration (mg/kg) of CVD (2.5, 5 or 7.5), saline, valproate (VAL200), or the combination of CVD5 + VAL100 for 7 days. From the 8th to 14th day LDX was added. In the reversal protocol LDX was administered for 7 days with the drugs being added from the 8th to 14th day of treatment. Two hours after the last administration the behavioral (open field and social interaction) and neurochemical (reduced glutathione, lipid peroxidation, and BDNF) determinations were performed. The results showed that CVD prevented and reversed the behavioral and neurochemical alterations induced by LDX. The administration of CVD5 + VAL100 potentiated the effect of VAL200 alone. Taken together these results demonstrate a possible antimanic effect of CVD in this preclinical model.

Cancer patients under maintenance hemodialysis: relationship between quality of life, depression, sleep quality and malnutrition-inflammation score.

BACKGROUND: The kidney is one major organ affected by cancer and its associated therapies. The aim of this study was to compare the levels of depression, quality of life and sleep quality in hemodialysis patients with or without cancer, and to analyze the associations with the malnutrition-inflammation score (MIS). PATIENTS AND METHODS: In this cross-sectional study, 40 cancer patients under hemodialysis and 44 patients under hemodialysis without cancer who served as the control group were included. Participants underwent structured interviews to investigate depression, quality of life, sleep quality and restless legs syndrome. RESULTS: Hemodialysis patients with cancer had a greater depression score (16.5 ± 4.8 vs. 10.8 ± 5.2, p < 0.001). Patients had similar physical and mental composite quality of life scores. Patients under hemodialysis with cancer had poor quality of sleep (mean score 8.8 ± 3.5 vs. 6.4 ± 4.1, p = 0.011) and a higher prevalence of restless leg syndrome (55.9 vs. 25.7%, p = 0.011). These features were associated with MIS in patients without cancer but not in patients with cancer. CONCLUSION: Cancer patients undergoing hemodialysis present a higher prevalence of depression, poor quality of life, sleep disorders; however, associations of these features with MIS are different in hemodialysis patients with or without cancer. These findings can change the clinical approach to these patients.

Prevention and reversal of ketamine-induced schizophrenia related behavior by minocycline in mice: Possible involvement of antioxidant and nitrergic pathways.

It has been hypothesized that oxidative imbalance and alterations in nitrergic signaling play a role in the neurobiology of schizophrenia. Preliminary evidence suggests that adjunctive minocycline treatment is efficacious for cognitive and negative symptoms of schizophrenia. This study investigated the effects of minocycline in the prevention and reversal of ketamine-induced schizophrenia-like behaviors in mice. In the reversal protocol, animals received ketamine (20 mg/kg per day intraperitoneally or saline for 14 days, and minocycline (25 or 50 mg/kg daily), risperidone or vehicle treatment from days 8 to 14. In the prevention protocol, mice were pretreated with minocycline, risperidone or vehicle prior to ketamine. Behaviors related to positive (locomotor activity and prepulse inhibition of startle), negative (social interaction) and cognitive (Y maze) symptoms of schizophrenia were also assessed. Glutathione (GSH), thiobarbituric acid-reactive substances (TBARS) and nitrite levels were measured in the prefrontal cortex, hippocampus and striatum. Minocycline and risperidone prevented and reversed ketamine-induced alterations in behavioral paradigms, oxidative markers (i.e. ketamine-induced decrease and increase in GSH levels and TBARS content, respectively) as well as nitrite levels in the striatum. These data provide a rationale for evaluating minocycline as a novel psychotropic agent and suggest that its mechanism of action includes antioxidant and nitrergic systems.

Effects of doxycycline on depressive-like behavior in mice after lipopolysaccharide (LPS) administration.

Current evidences support inflammation, oxidative and nitrogen stress, as well as brain-derived neurotrophic factor (BDNF) signaling mechanisms as important in depression pathophysiology. Tetracycline antibiotics have anti-inflammatory and antioxidant properties. Preliminary evidence indicates that minocycline has antidepressant properties. Doxycycline (DOXY) has favorable pharmacokinetic and safety profiles when compared to other tetracycline congeners. The antidepressant activity of DOXY has not been adequately investigated. This study evaluated the effects of DOXY (25 and 50 mg/kg, i.p.) on LPS-induced (0.5 mg/kg, i.p.) depressive-like behavior. Doxycycline was administered 30 min before LPS (pre-LPS) or 1.5 and 23.5 h following LPS (post-LPS) administration in mice. LPS-treated animals presented an increase in immobility time in the forced swimming test (FST) when compared to controls 24 h after endotoxin administration. Similarly to imipramine (IMI-10 mg/kg, i.p.), DOXY at both doses prevented and reversed LPS-induced alterations in the FST. IL-1ß content was increased 24 h after LPS administration in striatum, hippocampus and prefrontal cortex. IMI and DOXY prevented and reversed LPS-induced increase in IL-1ß. IMI and DOXY also prevented and reversed LPS-induced alterations in nitrite content and oxidative stress parameters (lipid peroxidation and reduced glutathione levels). Both DOXY and IMI prevented LPS-induced decrease in hippocampal BDNF levels. Taken together, our results demonstrate that DOXY is comparable to IMI in effectively ameliorate LPS-induced depressive-like behavior, providing a rationale for testing DOXY's antidepressant efficacy in humans.

Validação da versão brasileira da escala de religiosidade de Duke (DUREL) / Validity of the Brazilian version of the Duke Religious Index (DUREL)

CONTEXTO: Há escassez de instrumentos validados para o estudo da religiosidade em amostras brasileiras. Um recente estudo realizado em uma amostra comunitária sugeriu adequada validade para a versão em português brasileiro do índice de Religiosidade de Duke (P-DUREL). Entretanto, as propriedades psicométricas do P-DUREL não foram estudadas em amostras psiquiátricas e/ou de estudantes universitários. OBJETIVO: Determinar a consistência interna, a confiabilidade teste-reteste e a validade convergente-discriminante do P-DUREL em duas amostras distintas. MÉTODOS: Amostra 1: estudantes universitários (n = 323). Amostra 2: pacientes psiquiátricos (n = 102). Foram aplicados o P-DUREL e o Instrumento de Qualidade de Vida da Organização Mundial da Saúde - Módulo Espiritualidade, Religiosidade e Crenças Pessoais (WHOQOL-SRPB) em ambas as amostras; os sintomas psicológicos foram medidos por meio do Inventário Beck de Depressão (IDB) e do Inventário Beck de Ansiedade (IAB) na amostra 1 e da Escala Hospitalar de Ansiedade e Depressão (HADS) na amostra 2. RESULTADOS: O P-DUREL teve adequada consistência interna (α de Cronbach > 0,80) e confiabilidade teste-reteste (Coeficiente de Correlação Intraclasse > 0,90) em ambas as amostras. Correlações moderadas entre as subescalas da P-DUREL (0,58 < r < 0,71) foram observadas. Além disso, correlações significantes entre os escores do P-DUREL com o escore geral do WHOQOL-SRPB, bem como com medidas de sintomas psicológicos, foram observadas em ambas as amostras. CONCLUSÃO: O presente estudo abre perspectivas para o uso do P-DUREL para a investigação das dimensões da religiosidade em amostras brasileiras com características sociodemográficas diversas.

BACKGROUND: There is a shortage of validated instruments for the study of religiousness in Brazilian samples. A recent study in a community sample pointed to an adequate validity for the Brazilian Portuguese version of the Duke Religiosity Index (P-DUREL). Nevertheless, no study to date has investigated the psychometric properties of the P-DUREL in psychiatric and/or university student samples. OBJECTIVE: To determine the internal consistency, the test-retest reliability and the convergent-discriminant validity of the P-DUREL in two distinct samples. METHODS: Sample 1: university students (n = 323). Sample 2: psychiatric patients (n = 102). The P-DUREL and the World Health Organization's Quality of Life Instrument-Spirituality, Religion and Personal Beliefs module (WHOQOL-SRPB); psychological distress symptoms were measured by means the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI) in sample 1, and the Hospital Anxiety and Depression Scale (HADS) in sample 2. RESULTS: The P-DUREL had adequate internal consistency (Cronbach's α > 0.80) and test-retest reliability (Intraclass Correlation Coefficient > 0.90) in both samples. Moderate correlations (0.58 < r < 0.71) between the P-DUREL subscales were observed. Furthermore, significant correlations between the P-DUREL scores with the general WHOQOL-SRPB scores as well as with psychological distress symptoms measures were observed in both samples. DISCUSSION: The present study opens perspective for the use of P-DUREL for the investigation of religiousness dimensions in Brazilian samples with diverse socio-demographic backgrounds.

B vitamins attenuate haloperidol-induced orofacial dyskinesia in rats: possible involvement of antioxidant mechanisms.

Tardive dyskinesia (TD) is a serious motor disorder related to antipsychotic therapy, whose pathophysiology is associated to oxidative stress. Treatments that maintain antipsychotic efficacy while reducing TD risk are awaited. Haloperidol (HAL), a typical antipsychotic, is used as a putative murine model of TD. Here, we evaluated the protective role of vitamins B1, B6, and B12 alone or in combination (vitamin B cocktail) in preventing the HAL-induced orofacial dyskinesia (OD), based on their antioxidant properties. HAL (1 mg/kg) administered intraperitoneally to Wistar rats for 21 days caused OD and increased catalepsy time. The daily administration of B vitamins (B1 : B6 : B12 at 60 : 60 : 0.6 mg/kg) alone or the vitamin B cocktail, along with HAL, prevented the development of OD. Catalepsy time reduced in all groups treated with B vitamins, but to a lesser extent than OD. The participation of oxidative stress was assessed by the determination of reduced glutathione (GSH) levels and lipid peroxide formation in the striatum. HAL significantly decreased GSH levels and enhanced lipid peroxidation, whereas B1, B12, and vitamin B cocktail prevented the decrease in GSH levels. All groups treated with B vitamins presented a decrease in lipid peroxide formation. The data suggest a promising role for B vitamins in the prevention of OD.

Inhibition of ketamine-induced hyperlocomotion in mice by the essential oil of Alpinia zerumbet: possible involvement of an antioxidant effect.

OBJECTIVES: The antipsychotic, hypnotic, myorelaxant and antioxidant effects of the essential oil of Alpinia zerumbet (EOAZ) were studied. METHODS: EOAZ (50, 100 and 200 mg/kg i.p.) was administered once to mice for the determination of antipsychotic activity (evaluated by ketamine-induced hyperlocomotion), hypnotic activity (induced by sodium pentobarbital, 40 mg/kg i.p.), motor coordination (rotarod test), antioxidant effects (determination of lipid peroxidation and GSH levels), as well as alterations in nitric oxide levels (determination of nitrite content). KEY FINDINGS: EOAZ at doses of 100 and 200 mg/kg prevented ketamine hyperlocomotion, as did haloperidol (0.2 mg/kg i.p). EOAZ at a dose of 200 mg/kg decreased sleep latency, while all doses increased sleeping time. There was no effect on motor coordination. The in-vitro antioxidant capacity of the oil caused a decrease in lipid peroxidation and increase in GSH levels. EOAZ also prevented the decrease in nitrite content caused by oxidative stress. CONCLUSIONS: The results suggest antipsychotic and antioxidant effects for the EOAZ that may have promising efficacy for the treatment of schizophrenia.

Myasthenia gravis in Ceará, Brazil: clinical and epidemiological aspects / Miastenia gravis no Ceará, Brasil: aspectos clínicos e epidemiológicos

A retrospective chart review was performed on patients diagnosed as having myasthenia gravis in Ceará State, Brazil and who were followed from October 1981 to June 2009. Clinical and epidemiologic aspects were evaluated. In this work, 122 patients were studied, of whom 85 (69.7 percent) were females and 37 (30.3 percent) were males. The disease duration ranged from five months to 50 years (8.9±8.1 years). Age at the first symptoms varied from 0 to 74 years (31.9±14.4 years). The first main symptoms and signs were ptosis, diplopia and limb weakness. Generalized myasthenia was the most common clinical presentation, but 5.1 percent (n=6) persisted as ocular myasthenia. Thymectomy was performed in 42.6 percent (n=52) of myasthenic patients. A thymoma was present in 10 patients. Serum acetylcholine receptor (AChR) antibodies were present in 80 percent (n=20) of specimens tested. The data presented are similar to those of studies performed in other countries.

Foram analisados, retrospectivamente, os prontuários de pacientes miastênicos, diagnosticados e seguidos entre outubro de 1981 e junho de 2009 no Estado do Ceará, Brasil. Foram coletados dados clínicos e epidemiológicos. Na casuística foram estudados 122 pacientes: 85 (69,7 por cento) do sexo feminino e 37 (30,3 por cento) do sexo masculino. O tempo de doença variou de 5 meses a 50 anos (8,9±8,1 anos). A idade de inicio da doença variou de 0 a 74 anos (31,9±14,4 anos). Na amostra estudada, os primeiros sintomas foram principalmente ptose, diplopia e fraqueza dos membros. A maioria dos pacientes apresentou a forma generalizada, enquanto 5,1 por cento (n= 6) persistiram com miastenia ocular. Timectomia foi realizada em 42,6 por cento (n=52) dos pacientes. Timoma estava presente em 10 pacientes. Anticorpo anti-receptor de acetilcolina foi positivo em 80 por cento (n=20) das amostras testadas. Os aspectos clínicos e epidemiológicos da amostra estudada têm semelhança com aqueles estudados em outros países.

Myasthenia gravis in Ceará, Brazil: clinical and epidemiological aspects.

A retrospective chart review was performed on patients diagnosed as having myasthenia gravis in Ceará State, Brazil and who were followed from October 1981 to June 2009. Clinical and epidemiologic aspects were evaluated. In this work, 122 patients were studied, of whom 85 (69.7%) were females and 37 (30.3%) were males. The disease duration ranged from five months to 50 years (8.9±8.1 years). Age at the first symptoms varied from 0 to 74 years (31.9±14.4 years). The first main symptoms and signs were ptosis, diplopia and limb weakness. Generalized myasthenia was the most common clinical presentation, but 5.1% (n=6) persisted as ocular myasthenia. Thymectomy was performed in 42.6% (n=52) of myasthenic patients. A thymoma was present in 10 patients. Serum acetylcholine receptor (AChR) antibodies were present in 80% (n=20) of specimens tested. The data presented are similar to those of studies performed in other countries.

Instrumentos de avaliação de qualidade de vida relacionada à saúde no diabetes melito: [revisão] / Assessment instruments for a Health-Related Quality of Life in diabetes mellitus: [review]

A avaliação da qualidade de vida (QV) vem se tornando cada vez mais utilizada para medir o impacto geral de doenças na vida dos indivíduos. O diabetes melito (DM) é uma doença crônica associada com morbimortalidade elevada e prejuízo na QV. Em estudos longitudinais, o impacto psicossocial da DM prediz a mortalidade nessa doença. Esta revisão busca descrever e analisar os principais instrumentos de avaliação da QV em pacientes com DM. Foram analisados instrumentos genéricos, como Quality of Well-Being Scale (QWB), The Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) e EuroQol (EQ-5D), e instrumentos específicos, como Diabetes Care Profile (DCP), Diabetes Quality of Life Measure (DQOL), Diabetes Impact Measurement Scales (DIMS), Appraisal of Diabetes Scale (ADS), Audit of Diabetes-Dependent Quality of Life (ADDQoL), Diabetes Health Profile (DHP-1 e DHP-18), Questionnaire on Stress in Patients with Diabetes-Revised (QSD-R), Well-Being Enquiry for Diabetics (WED), Diabetes-Specific Quality-of-life Scale (DSQOLS), Diabetes 39 (D-39) e Problems Areas in Diabetes (PAID). O PAID é o único instrumento traduzido e validado para uso no Brasil. Tanto os instrumentos genéricos quanto os específicos têm vantagens e desvantagens na aferição da QV de pacientes com DM. O uso combinado de instrumentos genéricos (como o SF-36) e específicos (como o PAID) parece ser uma forma consistente de avaliação da QV em pacientes diabéticos no Brasil. O presente artigo revisa os vários instrumentos e enfatiza a necessidade urgente de estudos para validação desses instrumentos em pacientes diabéticos brasileiros.

The assessment of Health-Related Quality of Life (HRQoL) has been increasingly used to measure the overall impact of diseases in people's life. Diabetes mellitus (DM) is a chronic disease associated with high morbidity, mortality, and HRQoL impairment in patients. In longitudinal studies, the psychosocial impact of DM predicts mortality. The objective of this review is to describe and to analyze the main instruments used for the HRQoL evaluation in patients with DM. Generic instruments such, as the Quality of Well-Being Scale (QWB), Medical Outcomes Study 36-item Short-Form Health Survey (SF-36), EuroQol (EQ-5D) and specific instruments as the Diabetes Care Profile (DCP), Diabetes Quality of Life Measure (DQOL), Diabetes Impact Measurement Scales (DIMS), Appraisal of Diabetes Scale (ADS), Audit of Diabetes-Dependent Quality of Life (ADDQoL), Diabetes Health Profile (DHP-1 and DHP-18), Questionnaire on Stress in Patients with Diabetes-Revised (QSD-R), Well-Being Enquiry goes Diabetics (WED), Diabetes-Specific Quality-of-life Scale (DSQOLS), Diabetes 39 (D-39) Problems Areas in Diabetes (PAID) were analyzed. PAID is the only translated and validated instrument available in Brazil. The generic and specific instruments have their stregths and shortcomings for evaluation of HRQL in patients with DM. The combined use of both generic (such as the SF-36) and specific (such as the PAID) appears to be a consistent way to evaluate HRQoL as a construct in Brazilian patients with DM. The present article reviews a variety of instruments and emphasizes the urgent need for validation studies of such instruments to be used in Brazilian subjects with DM.

Associaçäo rara entre tetralogia de Fallot e miocardiopatia hipertrófica / Tetralogy of Fallot and hypertrophic cardiomyopathy. A rare association

Tetralogy of Fallot is known as the most common cyanotic congenital heart disease and has a prevalence of 10 percent of all congenital heart diseases. Although many other heart anomalies may coexist, the association of tetralogy of Fallot and hypertrophic cardiomyopathy is extremely rare. We report this association in a 15-month-old female, cyanotic since birth, in her first hospital admission for diagnosis and treatment of recurring cyanotic crises. In addition, a review of the literature and of the problems related to the treatment is provided