Abstract Citrus species are widely related to antihyperalgesic and anti-inflammatory effects. The aim of this study was to investigate if treatment with ethanolic extract from peels of mature Citrus reticulata Blanco causes antihyperalgesic effects on the referred mechanical hyperalgesia in a model of dextran sulphate of sodium (DSS)-induced colitis in mice, as well as the possible oxidative damage in different regions of the brain induced by its inflammatory reaction. Antihyperalgesia (30 to 300 mg/kg) was investigated by behavioral response (frequency of response to von Frey filament stimulation) in Swiss mice, while damage to central nervous system was investigated through techniques that evaluated oxidative stress using male black C57 BL6 mice (n=8). Treatment of the animals with the extract (100 mg/kg) from days 3 to 5 after colitis induction reduced referred the mechanical hyperalgesia (32.6 ± 5.1) in relation to the control group (57.4 ± 2.0). Levels of lipid peroxidation or carbonyl proteins were augmented in colitis-induced animals in relation to the disease group. These results indicated an antihyperalgesic effect of the studied extract and a potential impairment of the central nervous system functioning caused by inflammation during colitis, which could be related to mental disorders observed in patients suffering of this pathology.

Abstract Silicone breast implant is associated with complications inherent to the surgical procedure. Prosthesis coating with polyurethane, however, commonly reduces the incidence of such complications. In this paper, the authors evaluated the inflammatory histomorphometric profile and oxidative damage associated to the implant of polyester urethane sheets. Forty-eight Wistar rats were divided into Sham or polyester urethane groups (n = 8/group) and underwent a polyester urethane implant in the dorsal skinfold. Tissue samples were collected on days seven, 30, and 90 after surgery and subjected to histomorphometric analysis and biochemical tests. Results were analyzed by one-way ANOVA (p ≤ 0.05). Peri-implant tissue samples exhibited characteristic inflammatory response associated with the biomaterial, with increased vascularization on day seven and augmented levels of IL1-b and TNF-a after 30 days. Peri-implant fibrocystic population was small on day seven, but increased considerably after 90 days. A rise in the carbonyl group levels of skin samples in the polyester urethane group was observed on day seven. Findings suggest that polyester urethane sheets undergo biodegradation at an early stage after implantation, followed by increased vascularity and microencapsulation of biomaterial fragments, without persistent oxidative damage. Fiber arrangement inside the collagen matrix results in a fibrotic scar because of polyester urethane degradation.

Nós investigamos os níveis do Fator Neurotrófico Derivado do Cérebro (BDNF), citosinas e parâmetros oxidativos em soro e correlacionamos com a idade e funcionalidade dos pacientes com Distrofias Musculares Progressivas (PMD). Os pacientes foram separados em seis grupos (casos e controles pareados por idade e sexo), como segue: Distrofia Muscular de Duchenne (DMD); Distrofia Miotônica de Steinert (SMD); e Distrofia Muscular de Cinturas do tipo 2A (LGMD2A). Pacientes com DMD (±17,9 anos de idade) tiveram uma diminuição da funcionalidade, aumento nos níveis de IL-1β e TNF-α e uma diminuição dos níveis de IL-10 e da atividade da superóxido dismutase no soro. Pacientes com SMD (±25,8 anos de idade) tiveram uma diminuição dos níveis de BDNF e IL-10 e da atividade da superóxido dismutase e um aumento dos níveis de IL-1β no soro. Pacientes com LGMD2A (±27,7 anos de idade) tiveram uma diminuição somente nos níveis de IL-10 no soro. Esta pesquisa mostrou a primeira evidência do envolvimento dos níveis de BDNF em pacientes com SMD e um possível desequilíbrio entre fatores pró e antiinflamatórios de citosinas e uma diminuição da atividade da superóxido dismutase em soro de pacientes com DMD e SMD.

We investigated the levels of brain derived-neurotrophic factor (BDNF), cytokines and oxidative parameters in serum and tried to correlate them with the age and functionality of patients with Progressive Muscle Dystrophies (PMD). The patients were separated into six groups (case and controls pared by age and gender), as follows: Duchenne Muscular Dystrophy (DMD); Steinert Myotonic Dystrophy (SMD); and Limb-girdle Muscular Dystrophy type-2A (LGMD2A). DMD patients (±17.9 years old) had a decrease of functionality, an increase in the IL-1β and TNF-α levels and a decrease of IL-10 levels and superoxide dismutase activity in serum. SMD patients (±25.8 years old) had a decrease of BDNF and IL-10 levels and superoxide dismutase activity and an increase of IL-1β levels in serum. LGMD2A patients (±27.7 years old) had an decrease only in serum levels of IL-10. This research showed the first evidence of BDNF involvement in the SMD patients and a possible unbalance between pro-inflammatory and anti-inflammatory cytokine levels, along with decreased superoxide dismutase activity in serum of DMD and SMD patients.

Objective: To evaluate the influence of environmental enrichment (EE) on memory, cytokines, and brain-derived neurotrophic factor (BDNF) in the brain of adult rats subjected to experimental pneumococcal meningitis during infancy. Methods: On postnatal day 11, the animals received either artificial cerebrospinal fluid (CSF) or Streptococcus pneumoniae suspension intracisternally at 1 × 106 CFU/mL and remained with their mothers until age 21 days. Animals were divided into the following groups: control, control + EE, meningitis, and meningitis + EE. EE began at 21 days and continued until 60 days of age (adulthood). EE consisted of a large cage with three floors, ramps, running wheels, and objects of different shapes and textures. At 60 days, animals were randomized and subjected to habituation to the open-field task and the step-down inhibitory avoidance task. After the tasks, the hippocampus and CSF were isolated for analysis. Results: The meningitis group showed no difference in performance between training and test sessions of the open-field task, suggesting habituation memory impairment; in the meningitis + EE group, performance was significantly different, showing preservation of habituation memory. In the step-down inhibitory avoidance task, there were no differences in behavior between training and test sessions in the meningitis group, showing aversive memory impairment; conversely, differences were observed in the meningitis + EE group, demonstrating aversive memory preservation. In the two meningitis groups, IL-4, IL-10, and BDNF levels were increased in the hippocampus, and BDNF levels in the CSF. Conclusions: The data presented suggest that EE, a non-invasive therapy, enables recovery from memory deficits caused by neonatal meningitis.

OBJETIVO: Hidrocloridrato de metilfenidato é a medicação preferida para o tratamento e manutenção do transtorno de atenção e hiperatividade. No entanto, os efeitos do tratamento crônico com hidrocloridrato de metilfenidato em diferentes idades e ciclos sobre o comportamento relacionado à ansiedade e à depressão ainda não está claro. Neste contexto, o presente estudo teve como objetivo avaliar os efeitos do tratamento com hidrocloridrato de metilfenidato sobre o comportamento relacionado à ansiedade e à depressão em diferentes idades e no ciclo claro e escuro. MÉTODO: Foram utilizados ratos Wistar machos jovens e adultos que receberam uma vez ao dia (ciclo claro e escuro) hidrocloridrato de metilfenidato (2mg/kg) ou salina com injeção intraperitoneal, durante 28 dias. Após duas horas da última injeção, os animais foram submetidos ao testes de labirinto em cruz elevada e natação forçada. RESULTADOS: A fase do ciclo claro e escuro foi um fator significativo para o comportamento relacionado à ansiedade. Além disso, não houve interação significativa entre os ciclos claro e escuro, idade e metilfenidato no comportamento relacionado à ansiedade e à depressão, mas foi observada uma interação significativa entre ciclo claro e escuro e idade no teste de natação forçada. CONCLUSÃO: Nossos resultados mostraram que a idade e o ciclo claro e escuro são moduladores significativos de ambos os comportamentos quanto do tratamento com hidrocloridrato de metilfenidato.

OBJECTIVE: Methylphenidate hydrochloride is the most widely used medication for treatment and management of attention-deficit hyperactivity disorder. However, the chronic effects of methylphenidate hydrochloride on anxiety- and depressive-like rat behaviors remain poorly investigated. In this context, the present study evaluated the effects of treatment with methylphenidate hydrochloride on anxiety- and depressive-like behaviors using young and adult rats during the light and the dark cycle. METHOD: Male Wistar rats (25 or 60 days old) received a once-daily (in either the light or dark cycle) methylphenidate hydrochloride (2mg/kg) or saline intraperitoneal injection for 28 days. We performed elevated plus maze and forced swimming test two hours after the last injection. RESULTS: The light/dark cycle was a significant factor in the anxiety-like behaviors; however, no significant interaction between all three factors (cycle, age and methylphenidate hydrochloride) was found. Nevertheless, we observed a nominally significant interaction between the light/ dark cycle and age in the forced swimming test. CONCLUSION: Our results have shown that age and the light/dark cycle are more significant modulators of anxiety- and depressive-like behaviors than methylphenidate hydrochloride treatment.

OBJETIVO: Vários achados clínicos sugerem que a cetamina apresenta efeito antidepressivo. O presente estudo tem como objetivo comparar efeitos comportamentais e a atividade da creatina quinase em regiões específicas do encéfalo após a administração de cetamina e imipramina em ratos. MÉTODO: Ratos Wistar receberam uma administração aguda de cetamina ou imipramina e a atividade antidepressiva foi avaliada pelo teste de nado forçado; a atividade da creatina quinase foi medida em diferentes regiões encefálicas. RESULTADOS: Os resultados mostraram que a cetamina (10 e 15mg/kg) e a imipramina (20 e 30mg/kg) diminuíram o tempo de imobilidade quando comparados ao grupo salina. Também foi observado que a cetamina (10 e 15mg/kg) e a imipramina (20 e 30mg/kg) aumentaram a atividade da creatina quinase no estriado e córtex cerebral. A dose mais alta de cetamina (15mg/kg) e a imipramina (20 e 30mg/kg) aumentaram a atividade da creatina quinase no cerebelo e córtex pré-frontal. Por outro lado, o hipocampo não foi alterado. CONCLUSÃO: Considerando que a diminuição no metabolismo provavelmente está envolvida na fisiopatologia da depressão, a modulação do metabolismo energético (como um aumento na atividade da creatina quinase) por antidepressivos pode ser um importante mecanismo de ação destes fármacos.

OBJECTIVE: Clinical findings suggest that ketamine may be used for the treatment of major depression. The present study aimed to compare behavioral effects and brain Creatine kinase activity in specific brain regions after administration of ketamine and imipramine in rats. METHOD: Rats were acutely given ketamine or imipramine and antidepressant-like activity was assessed by the forced swimming test; Creatine kinase activity was measured in different regions of the brain. RESULTS: The results showed that ketamine (10 and 15mg/kg) and imipramine (20 and 30mg/kg) reduced immobility time when compared to saline group. We also observed that ketamine (10 and 15mg/kg) and imipramine (20 and 30mg/kg) increased Creatine kinase activity in striatum and cerebral cortex. Ketamine at the highest dose (15mg/kg) and imipramine (20 and 30mg/kg) increased Creatine kinase activity in cerebellum and prefrontal cortex. On the other hand, hippocampus was not affected. CONCLUSION: Considering that metabolism impairment is probably involved in the pathophysiology of depressive disorders, the modulation of energy metabolism (like increase in Creatine kinase activity) by antidepressants could be an important mechanism of action of these drugs.