Biological pathways associated with neuroprogression in bipolar disorder

There is evidence suggesting clinical progression in a subset of patients with bipolar disorder (BD). This progression is associated with worse clinical outcomes and biological changes. Molecular pathways and biological markers of clinical progression have been identified and may explain the progressive changes associated with this disorder. The biological basis for clinical progression in BD is called neuroprogression. We propose that the following intertwined pathways provide the biological basis of neuroprogression: inflammation, oxidative stress, impaired calcium signaling, endoplasmic reticulum and mitochondrial dysfunction, and impaired neuroplasticity and cellular resilience. The nonlinear interaction of these pathways may worsen clinical outcomes, cognition, and functioning. Understanding neuroprogression in BD is crucial for identifying novel therapeutic targets, preventing illness progression, and ultimately promoting better outcomes

Effects of lithium on inflammatory and neurotrophic factors after an immune challenge in a lisdexamfetamine animal model of mania

Objective: To evaluate whether an animal model of mania induced by lisdexamfetamine dimesylate (LDX) has an inflammatory profile and whether immune activation by lipopolysaccharides (LPS) has a cumulative effect on subsequent stimuli in this model. We also evaluated the action of lithium (Li) on inflammatory and neurotrophic factors. Methods: Adult male Wistar rats were subjected to an animal model of mania. After the open-field test, they were given LPS to induce systemic immune activation. Subsequently, the animals’ blood was collected, and their serum levels of brain-derived neurotrophic factor and inflammatory markers (tumor necrosis factor [TNF]-a, interleukin [IL]-6, IL-1b, IL-10, and inducible nitric oxide synthase [iNOS]) were measured. Results: LDX induced hyperactivity in the animals, but no inflammatory marker levels increased except brain-derived neurotrophic factor (BDNF). Li had no effect on serum BDNF levels but prevented iNOS levels from increasing in animals subjected to immune activation. Conclusion: Although Li prevented an LPS-induced increase in serum iNOS levels, its potential antiinflammatory effects in this animal model of mania were conflicting

Effects of childhood trauma on BDNF and TBARS during crack-cocaine withdrawal

Objective: To evaluate the association between childhood trauma (CT) and serum levels of brainderived neurotrophic factor (BDNF) and thiobarbituric acid-reactive substances (TBARS) during crackcocaine withdrawal. Method: Thirty-three male crack-cocaine users were recruited at admission to a public addiction treatment unit. Serum BDNF and TBARS levels were evaluated at intake and discharge. Information about drug use was assessed by the Addiction Severity Index-6th Version (ASI-6); CT was reported throughout the Childhood Trauma Questionnaire (CTQ). CTQ scores were calculated based on a latent analysis model that divided the sample into low-, medium-, and high-level trauma groups. Results: There was a significant increase in BDNF levels from admission to discharge, which did not differ across CT subgroups. For TBARS levels, we found a significant time vs. trauma interaction (F2,28 = 6.357, p = 0.005,Zp 2 = 0.312). In participants with low trauma level, TBARS decreased, while in those with a high trauma level, TBARS increased during early withdrawal. Conclusion: TBARS levels showed opposite patterns of change in crack-cocaine withdrawal according to baseline CT. These results suggest that CT could be associated with more severe neurological impairment during withdrawal

Perfil sociodemográfico, comportamental e nutricional de adultos atendidos em uma Clínica-escola de Nutrição em Salvador, Bahia

Introduction: the gathering of the characteristics of the population who attends the school clinics of Nutrition is crucial for the organizationof the service, as well as for the planning and implementation of strategies for prevention and control of nutritional disorders. Objective:to identify the socioeconomic, demographic, behavioral and nutritional profile of adult patients treated at a School Clinic of Nutrition inSalvador, Bahia. Methodology: this is a descriptive, cross-sectional study, performed with secondary data obtained from medical records of adults treated at the School Clinic of Nutrition of a Public Institution of Higher Education, from July 2012 to June 2013. Results: the population of the study consisted of 424 individuals, predominantly female (83.7%); age group varying from 20 to 29 years (34.4%); selfdeclaredblack (54.2%); single (53.8%); with complete high school level (34.6%); with family income between 1 and 3 minimum wages (54.9%), non-alcoholic (58%) and non-smokers (96.2%). The prevalence observed for overweight and obesity was 37.3% and 35.6%,respectively. Conclusion: the sociodemographic and behavioral characteristics and nutritional status, according to the Body Mass Index, of patients treated at the school clinic were similar to those described in studies performed in other outpatient clinics. The knowledge of the profile of users can contribute to the improvement of services provided and planning of effective nutrition education actionsIntrodução: o levantamento das características da população que frequenta as clínicas-escola de Nutrição é indispensável para a organização do serviço, bem como para o planejamento e a implementação de estratégias de prevenção e controle de agravos nutricionais. Objetivo: identificar o perfil socioeconômico, demográfico, comportamental e nutricional de pacientes adultos atendidos em uma clínica-escola de Nutrição em Salvador, Bahia. Metodologia: trata-se de um estudo descritivo, transversal, realizado com dados secundários obtidos de prontuários de pacientes adultos atendidos na clínica-escola de Nutrição de uma Instituição Pública de Ensino Superior, no período de julho de 2012 a junho de 2013. Resultados: a população do estudo foi constituída por 424 indivíduos, com predominância de: sexo feminino (83,7%); faixa etária de 20 a 29 anos (34,4%); autodeclarados pretos (54,2%); solteiros (53,8%); ensino médio completo (34,6%); renda familiar entre 1 e 3 salários mínimos (54,9%), não etilistas (58%) e não tabagistas (96,2%). A prevalência de sobrepeso e obesidade foi de 37,3% e 35,6%, respectivamente. Conclusão: as características sociodemográficas e comportamentais e o estado nutricional, segundo o Índice de Massa Corporal, dos pacientes atendidos na clínica-escola foram semelhantes às descritas em estudos realizados em outros ambulatórios. O conhecimento do perfil dos usuários pode contribuir para a melhoria dos serviços prestados e planejamento de ações de educação nutricional efetivas

Dexamethasone and azathioprine promote cytoskeletal changes and affect mesenchymal stem cell migratory behavior

Glucocorticoids and immunosuppressive drugs are commonly used to treat inflammatory disorders, such as inflammatory bowel disease (IBD), and despite a few improvements, the remission of IBD is still difficult to maintain. Due to their immunomodulatory properties, mesenchymal stem cells (MSCs) have emerged as regulators of the immune response, and their viability and activation of their migratory properties are essential for successful cell therapy. However, little is known about the effects of immunosuppressant drugs used in IBD treatment on MSC behavior. The aim of this study was to evaluate MSC viability, nuclear morphometry, cell polarity, F-actin and focal adhesion kinase (FAK) distribution, and cell migratory properties in the presence of the immunosuppressive drugs azathioprine (AZA) and dexamethasone (DEX). After an initial characterization, MSCs were treated with DEX (10 μM) or AZA (1 μM) for 24 hrs or 7 days. Neither drug had an effect on cell viability or nuclear morphometry. However, AZA treatment induced a more elongated cell shape, while DEX was associated with a more rounded cell shape (P < 0.05) with a higher presence of ventral actin stress fibers (P < 0.05) and a decrease in protrusion stability. After 7 days of treatment, AZA improved the cell spatial trajectory (ST) and increased the migration speed (24.35%, P < 0.05, n = 4), while DEX impaired ST and migration speed after 24 hrs and 7 days of treatment (-28.69% and -25.37%, respectively; P < 0.05, n = 4). In conclusion, our data suggest that these immunosuppressive drugs each affect MSC morphology and migratory capacity differently, possibly impacting the success of cell therapy