Efeito antidepressivo do óleo de peixe

Resumo: A fisiopatologia da depressão ainda não é completamente conhecida, mas estudos apontam para uma disfunção no sistema serotoninérgico como possível causa. Estudos mostram que a suplementação, em ratos, com Óleo de Peixe (OP) rico em Ácido Docosahexaenóico (DHA) e Ácido Eicosapentaenóico (EPA), durante períodos críticos do desenvolvimento, produz efeito antidepressivo através de um aumento da neurotransmissão serotoninérgica, particularmente no hipocampo. Considerando este efeito, que também é mediado pela ativação dos receptores 5-HT1A hipocampais, o presente estudo dedicou-se em investigar o impacto da suplementação com OP (na gestação e lactação) sobre os receptores 5-HT1A pós-sinápticos, bloqueando estes receptores com um antagonista seletivo, o WAY100635, administrado diretamente no hipocampo de ratos de 90 dias de idade. As fêmeas foram suplementadas com OP durante a habituação, acasalamento, gestação e lactação. A prole, mantida sem suplementação até a vida adulta, foi submetida à testes comportamentais e análises neuroquímicas foram feitas para quantificar os níveis hipocampais de serotonina (5-HT) e seu metabólito, o Ácido 5-Hidroxiindolacético (5-HIAA). Além disso, a expressão dos receptores 5-HT1A hipocampais foi mensurada através da técnica de Western Blot. No Teste da Natação Forçada Modificado (TNFM) os resultados mostram que os animais suplementados com OP apresentaram menor comportamento depressivo, refletido por frequência diminuída de imobilidade e aumentada de natação, mais ainda, este efeito antidepressivo foi revertido pela administração do antagonista 5-HT1A no hipocampo, o que ressalta o envolvimento destes receptores no efeito antidepressivo da suplementação, apesar de não ter sido observada nenhuma alteração na expressão destes receptores no hipocampo, através da análise por Western Blot. Em relação à análise de neurotransmissores, foi encontrado um aumento dos níveis de 5-HT no hipocampo de ratos suplementados. Os presentes achados sugerem envolvimento dos receptores 5HT1A hipocampais no efeito antidepressivo da suplementação com óleo de peixe. Os presentes achados sugerem envolvimento dos receptores 5HT1A hipocampais no efeito antidepressivo da suplementação com óleo de peixe

A survey of clinical features of allergic rhinitis in adults

Background: Allergic rhinitis (AR) has high prevalence and substantial socio-economic burden. Material/Methods: The study included 35 Italian Centers recruiting an overall number of 3383 adult patients with rhinitis (48% males, 52% females, mean age 29.1, range 18\u201345 years). For each patient, the attending physician had to fill in a standardized questionnaire, covering, in particular, some issues such as the ARIA classification of allergic rhinitis (AR), the results of skin prick test (SPT), the kind of treatment, the response to treatment, and the satisfaction with treatment. Results: Out of the 3383 patients with rhinitis, 2788 (82.4%) had AR: 311 (11.5%) had a mild intermittent, 229 (8.8%) a mild persistent, 636 (23.5%) a moderate-severe intermittent, and 1518 (56.1%) a moderate-severe persistent form. The most frequently used drugs were oral antihistamines (77.1%) and topical corticosteroids (60.8%). The response to treatment was judged as excellent in 12.2%, good in 41.3%, fair in 31.2%, poor in 14.5%, and very bad in 0.8% of subjects. The rate of treatment dissatisfaction was significantly higher in patients with moderate-to-severe AR than in patients with mild AR (p<0.0001). Indication to allergen immunotherapy (AIT) was significantly more frequent (p<0.01) in patients with severe AR than with mild AR. . Conclusions: These fndings confirm the appropriateness of ARIA guidelines in classifying the AR patients and the association of severe symptoms with unsuccessful drug treatment. The optimal targeting of patients to be treated with AIT needs to be reassessed

Papel da enzima indoleamina-2,3-dioxigenase no efeito antidepressivo da suplementação com óleo de peixe

Orientadora : Profª. Drª. Anete Curte FerrazCoorientadora : Profª. Drª. Janaína M. ZanoveliTese (doutorado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Fisiologia. Defesa: Curitiba, 11/12/2017Inclui referências : f. 57-66Resumo: A depressão é uma doença psiquiátrica grave, com uma grande prevalência durante a vida. De acordo com a Organização Mundial da Saúde aproximadamente 320 milhões de pessoas sofrem de depressão em todo o mundo. O tratamento atual é baseado na Teoria Monoaminérgica, porém muitas evidências apontam para o envolvimento da inflamação na patogênese da depressão. Alguns autores mostram que a ligação entre a inflamação e a depressão é feita pela enzima Indoleamina-2,3- dioxygenase (IDO), que é responsável por catabolizar o triptofano dando origem às kinureninas, o que leva à diminuição da síntese de serotonina e promove sintomas depressivos. Estudos já mostraram que compostos com atividade anti-inflamatória, como os Ácidos Graxos Poli-insaturados Ômega-3, apresentam atividade antidepressiva, e são capazes de aumentar os níveis de serotonina no hipocampo de ratos. Devido a essas evidências, nós hipotetizamos que o efeito antidepressivo do ômega- 3 está relacionado com suas propriedades anti-inflamatórias, levando à inibição da enzima IDO e consequentemente aumentando os níveis de serotonina. Para testar essa hipótese, realizamos dois experimentos independentes, nos quais os animais foram suplementados com óleo de peixe (rico em ômega-3) por 50 dias. Após a suplementação, foi realizada uma única injeção sistêmica com o Lipopolissacarídeo bacteriano (LPS), capaz de induzir uma resposta inflamatória, e 24 horas após os animais foram submetidos aos testes do campo aberto e natação forçada modificado. No primeiro experimento, os animais receberam um pré-tratamento com com o inibidor competitivo da IDO 1-metil-DL-Triptofano (1-MT) e no experimento 2 os animais foram tratados com minociclina, um inibidor indireto dessa enzima. O pré-tratamento com esses inibidores foi feito 23h, 5h e 1h antes dos testes comportamentais. Após os testes, os animais foram ortotanasiados e os hipocampos obtidos para a quantificação de serotonina e seu metabólito ácido 5-hidroxiindolacético (5-HIAA) através da técnica de HPLC e para a expressão da IDO através do western blot. A injeção com LPS foi capaz de induzir um comportamento tipo-depressivo, que foi bloqueado pelo 1-MT, pela minociclina e pela suplementação. Os animais suplementados apresentaram maior fequência de natação comparados aos animais tratados com 1-MT e minociclina. A suplementação e a minociclina foram capazes de diminuir a expressão da IDO, sem efeitos adicionais sobre esta enzima quando os tratamentos foram combinados. Como esperado, o 1-MT não foi capaz de diminuir a expressão da IDO, uma vez que esta droga inibe diretamente esta enzima, impedindo apenas sua atividade. Os dados neuroquímicos mostram que o LPS foi capaz de diminuir a concentração de serotonina e aumentar seu turnover, e esses efeitos foram bloqueados pelos compostos anti-inflamatórios minociclina e óleo de peixe, mas não pelo 1-MT. Ainda, a suplementação com óleo de peixe teve efeito antidepressivo relacionado com o aumento de serotonina no hipocampo. É importante destacar que os animais suplementados que receberam apenas injeções de salina apresentaram níveis de serotonina, expressão da IDO e frequência de natação semelhantes aos animais que foram suplementados e receberam os outros tratamentos combinados. Esse fato indica que a inibição da IDO, embora importante, não é a única explicação para o efeito antidepressivo do ômega-3, e que este composto aumenta os níveis de serotonina através de outros mecanismos. Palavras-chave: depressão, ômega-3, óleo de peixe, inflamação, LPS, Indoleamina- 2,3-Dioxigenase, IDO, serotoninaAbstract:Depression is a severe psychiatric disease, with a high prevalence during life. Is twice common in women and according to World Health Organization approximately 320 million people suffer from depression worldwide. The Monoaminergic Theory is the basis of current treatment, but there are many evidence pointing out to the role of inflammation on pathogenesis of depression. Depressed patients have an increased rate of autoimmune disorders, and patients with inflammatory diseases, like cancer, HIV and rheumatoid arthritis have higher rates of depression. In animal models, systemic injection of bacterial endotoxin lipopolysaccharide evokes an acute inflammatory response and 24h after the injection rodents exhibit a depressive-like behavior, seen by higher immobility in the forced swim test. The link between inflammation and depression is made by the enzyme Indoleamine-2,3-dioxygenase (IDO), which is activated by pro-inflammatory cytokines. This enzyme catabolizes tryptophan into kynurenines, decreasing the levels of serotonin and promoting depressive symptoms. Anti-inflammatory compounds, such as Omega-3 Polyunsaturated Fatty Acids, have antidepressant activity, increasing serotonin levels in hippocampus of rats. Here we hypothesized that this antidepressant effect of omega-3 is due to its antiinflammatory properties, and the mechanism is through IDO inhibition. In order to test this hypothesis, we performed two independent experiments, using the LPS model in fish-oil supplemented animals. In the first experiment, animals received a pretreatment with 1-MT and in the experiment 2 they were treated with minocycline. The use of these two inhibitors of IDO was made to test a possible potentiation of omega- 3 antidepressant activity. The supplementation was made for 50 days and LPS was injected 24h before the open field test and the modified forced swimming test. The pretreatment with the inhibitors was made 23h, 5h and 1h before these behavioral tests. After the tests, the hippocampi were obtained for quantification of serotonin and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA) by HPLC and IDO expression by western blot. We found a depressive-like state induced by LPS, which was blocked by 1-MT, Minocycline and fish-oil supplementation. Also, the supplemented animals presented higher swimming behavior compared to 1-MT and Minocycline. Minocycline and fish oil suppressed IDO expression, with no additional effects when these treatments were combined. LPS induced a decrease in serotonin levels and an increase in 5-HIAA/5-HT ratio, both blocked by the anti-inflammatory compounds minocycline and fish oil. The antidepressant-like behavior induced by omega-3 was related to an increase in serotonin levels in hippocampus, compared to all nonsupplemented groups. The fact that IDO expression in non-stressed animals is not significant, and the supplemented animals who received only saline presented higher levels of serotonin, support the idea that IDO inhibition is not the only explanation for antidepressant effect of fish-oil supplementation, and this compound increases serotonin through diffrent mechanisms. Key-words: depression, omega-3, fish oil, inflammation, LPS, Indoleamine-2,3- Dioxygenase, IDO, serotonin

Persistent exercise fatigue and associative learning deficits in combination with transient glucose dyshomeostasis in a mouse model of Gulf War Illness.

AimsTo characterize exercise fatigue, metabolic phenotype and cognitive and mood deficits correlated with brain neuroinflammatory and gut microbiome changes in a chronic Gulf War Illness (GWI) mouse model. The latter have been described in an accompanying paper [1].Main methodsAdult male C57Bl/6N mice were exposed for 28&nbsp;days (5&nbsp;days/week) to pyridostigmine bromide: 6.5&nbsp;mg/kg, b.i.d., P.O. (GW1) or 8.7&nbsp;mg/kg, q.d., P.O. (GW2); topical permethrin (1.3&nbsp;mg/kg in 100% DMSO) and N,N-diethyl-meta-toluamide (DEET 33% in 70% EtOH) and restraint stress (5&nbsp;min). Exercise, metabolic and behavioral endpoints were compared to sham stress control (CON/S).Key findingsRelative to CON/S, GW2 presented persistent exercise intolerance (through post-treatment (PT) day 161), deficient associative learning/memory, and transient insulin insensitivity. In contrast to GW2, GW1 showed deficient long-term object recognition memory, milder associative learning/memory deficit, and behavioral despair.SignificanceOur findings demonstrate that GW chemicals dose-dependently determine the presentation of exercise fatigue and severity/type of cognitive/mood-deficient phenotypes that show persistence. Our comprehensive mouse model of GWI recapitulates the major multiple symptom domains characterizing GWI, including fatigue and cognitive impairment that can be used to more efficiently develop diagnostic tests and curative treatments for ill Gulf War veterans

Institutional Registry of Elderly Patients With Hip Fracture in a Community-Based Tertiary Care Hospital in Argentina (RIAFC)

Background: A clinical registry encompasses a selective set of rigorously collected and stored clinical data focused on a specific condition. Hip fracture is a common complication of osteoporosis in elderly patients. Hip fracture substantially increases the risk of death and major morbidity in the elderly patients. Limited data regarding hip fracture are available from Latin America and Argentina. The purpose of this project is to create an institutional registry of elderly patients with hip fracture in order to obtain data that reveal the impact of this disease in our environment, allowing us to evaluate different strategies of patient’s care and clinical outcomes. Objective: To describe the implementation of an institutional registry of elderly patients with hip fracture in Argentina. Methods: In this article, we described the creation, implementation, and data management of a prospective registry of elderly patients with hip fracture. The registry contains information on baseline demographics, comorbidities, laboratory, and radiological data. Follow-up at 3 and 12 months postfracture is done by phone interview to assess physical function, readmissions, and morbi-mortality. Clinical Trials registry number NCT02279550. Conclusion: In this project, we have created a hip fracture registry. We hope that this registry will provide valuable data that can lead us to new lines of research, addressed to answer questions raised in clinical practice

Induction of distinct neuroinflammatory markers and gut dysbiosis by differential pyridostigmine bromide dosing in a chronic mouse model of GWI showing persistent exercise fatigue and cognitive impairment

AimsTo characterize neuroinflammatory and gut dysbiosis signatures that accompany exaggerated exercise fatigue and cognitive/mood deficits in a mouse model of Gulf War Illness (GWI).MethodsAdult male C57Bl/6N mice were exposed for 28 d (5&nbsp;d/wk) to pyridostigmine bromide (P.O.) at 6.5&nbsp;mg/kg/d, b.i.d. (GW1) or 8.7&nbsp;mg/kg/d, q.d. (GW2); topical permethrin (1.3&nbsp;mg/kg), topical N,N-diethyl-meta-toluamide (33%) and restraint stress (5&nbsp;min). Animals were phenotypically evaluated as described in an accompanying article [124] and sacrificed at 6.6&nbsp;months post-treatment (PT) to allow measurement of brain neuroinflammation/neuropathic pain gene expression, hippocampal glial fibrillary acidic protein, brain Interleukin-6, gut dysbiosis and serum endotoxin.Key findingsCompared to GW1, GW2 showed a more intense neuroinflammatory transcriptional signature relative to sham stress controls. Interleukin-6 was elevated in GW2 and astrogliosis in hippocampal CA1 was seen in both GW groups. Beta-diversity PCoA using weighted Unifrac revealed that gut microbial communities changed after exposure to GW2 at PT188. Both GW1 and GW2 displayed systemic endotoxemia, suggesting a gut-brain mechanism underlies the neuropathological signatures. Using germ-free mice, probiotic supplementation with Lactobacillus reuteri produced less gut permeability than microbiota transplantation using GW2 feces.SignificanceOur findings demonstrate that GW agents dose-dependently induce differential neuropathology and gut dysbiosis associated with cognitive, exercise fatigue and mood GWI phenotypes. Establishment of a comprehensive animal model that recapitulates multiple GWI symptom domains and neuroinflammation has significant implications for uncovering pathophysiology, improving diagnosis and treatment for GWI

Maternal Omega-3 Supplement Improves Dopaminergic System in Pre- and Postnatal Inflammation-Induced Neurotoxicity in Parkinson's Disease Model

Evidence suggests that idiopathic Parkinson's disease (PD) is the consequence of a neurodevelopmental disruption, rather than strictly a consequence of aging. Thus, we hypothesized that maternal supplement of omega-3 polyunsaturated fatty acids (omega-3 PUFA) may be associated with neuroprotection mechanisms in a self-sustaining cycle of neuroinflammation and neurodegeneration in lipopolysaccharide (LPS)-model of PD. To test this hypothesis, behavioral and neurochemical assay were performed in prenatally LPS-exposed offspring at postnatal day 21. To further determine whether prenatal LPS exposure and maternal omega-3 PUFAs supplementation had persisting effects, brain injury was induced on PN 90 rats, following bilateral intranigral LPS injection. Pre- and postnatal inflammation damage not only affected dopaminergic neurons directly, but it also modified critical features, such as activated microglia and astrocyte cells, disrupting the support provided by the microenvironment. Unexpectedly, our results failed to show any involvement of caspase-dependent and independent apoptosis pathway in neuronal death mechanisms. On the other hand, learning and memory deficits detected with a second toxic exposure were significantly attenuated in maternal omega-3 PUFAs supplementation group. In addition, omega-3 PUFAs promote beneficial effect on synaptic function, maintaining the neurochemical integrity in remaining neurons, without necessarily protect them from neuronal death. Thus, our results suggest that omega-3 PUFAs affect the functional ability of the central nervous system in a complex way in a multiple inflammation-induced neurotoxicity animal model of PD and they disclose new ways of understanding how these fatty acids control responses of the brain to different challenges.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Fundacao Araucaria - Governo do Estado do Parana fellowshipCNPq fellowshipUniv Fed Parana, Dept Fisiol, Lab Neurofisiol, Setor Ciencias Biol, Ave Francisco H dos Santos S-N, BR-81531990 Curitiba, PR, BrazilUniv Fed Parana, Dept Patol Basica, Lab Neurobiol, Curitiba, PR, BrazilUniv Fed Sao Paulo, Dept Psicobiol, Sao Paulo, SP, BrazilUniv Fed Pernambuco, Dept Fisiol & Farmacol, Ctr Ciencias Biol, Lab Neurofisiol, Recife, PE, BrazilUniv Fed Sao Paulo, Dept Psicobiol, Sao Paulo, SP, BrazilWeb of Scienc