Diminuição dos níveis de BDNF em amígdala e hipocampo após a administração intracerebroventricular de ouabaína

OBJECTIVE: The present study aims to investigate the effects of ouabain intracerebroventricular injection on BDNF levels in the amygdala and hippocampus of Wistar rats. METHODS: Animals received a single intracerebroventricular injection of ouabain (10-3 and 10-2 M) or artificial cerebrospinal fluid and immediately, 1h, 24h, or seven days after injection, BDNF levels were measured in the rat's amygdala and hippocampus by sandwich-ELISA (n = 8 animals per group). RESULTS: When evaluated immediately, 3h, or 24h after injection, ouabain in doses of 10-2 and 10-3 M does not alter BDNF levels in the amygdala and hippocampus. However, when evaluated seven days after injection, ouabain in 10-2 and 10-3 M, showed a significant reduction in BDNF levels in both brain regions evaluated. DISCUSSION: In conclusion, we propose that the ouabain decreased BDNF levels in the hippocampus and amygdala when assessed seven days after administration, supporting the Na/K ATPase hypothesis for bipolar illness.OBJETIVO: O presente estudo tem como objetivo investigar os efeitos da injeção intracerebroventricular de ouabaína sobre os níveis de BDNF na amígdala e no hipocampo de ratos Wistar. MÉTODOS: Os animais receberam uma única injeção intracerebroventricular de ouabaína (10-3 and 10-2 M) ou fluido cerebroespinhal artificial e, imediatamente, 3h, 24h ou sete dias após a injeção, os níveis de BDNF foram mensurados na amígdala e hipocampo dos ratos por ELISA sandwich (n = 8 animais por grupo). RESULTADOS: Quando avaliados imediatamente após a injeção, 3h ou 24h, ouabaína nas doses 10-2 e 10-3 M não alterou os níveis de BDNF em ambas as estruturas avaliadas. Entretanto, quando avaliados sete dias após a injeção, ouabaína nas doses 10-2 e 10-3 M mostrou uma significante redução nos níveis de BDNF em amígdala e hipocampo. CONCLUSÃO: Em conclusão, propõe-se que a administração de ouabaína diminuiu os níveis de BDNF em amígdala e hipocampo quando avaliados sete dias após a injeção, suportando a hipótese da participação da Na/K ATPase no transtorno bipolar

The Combined Deficiency of Immunoproteasome Subunits Affects Both the Magnitude and Quality of Pathogen- and Genetic Vaccination-Induced CD8+ T Cell Responses to the Human Protozoan Parasite Trypanosoma cruzi

The beta1i, beta2i and beta5i immunoproteasome subunits have an important role in defining the repertoire of MHC class I-restricted epitopes. However, the impact of combined deficiency of the three immunoproteasome subunits in the development of protective immunity to intracellular pathogens has not been investigated. Here, we demonstrate that immunoproteasomes play a key role in host resistance and genetic vaccination-induced protection against the human pathogen Trypanosoma cruzi (the causative agent of Chagas disease), immunity to which is dependent on CD8+ T cells and IFN-gamma (the classical immunoproteasome inducer). We observed that infection with T. cruzi triggers the transcription of immunoproteasome genes, both in mice and humans. Importantly, genetically vaccinated or T. cruzi-infected beta1i, beta2i and beta5i triple knockout (TKO) mice presented significantly lower frequencies and numbers of splenic CD8+ effector T cells (CD8+CD44highCD62Llow) specific for the previously characterized immunodominant (VNHRFTLV) H-2Kb-restricted T. cruzi epitope. Not only the quantity, but also the quality of parasite-specific CD8+ T cell responses was altered in TKO mice. Hence, the frequency of double-positive (IFN-gamma+/TNF+) or single-positive (IFN-gamma+) cells specific for the H-2Kb-restricted immunodominant as well as subdominant T. cruzi epitopes were higher in WT mice, whereas TNF single-positive cells prevailed among CD8+ T cells from TKO mice. Contrasting with their WT counterparts, TKO animals were also lethally susceptible to T. cruzi challenge, even after an otherwise protective vaccination with DNA and adenoviral vectors. We conclude that the immunoproteasome subunits are key determinants in host resistance to T. cruzi infection by influencing both the magnitude and quality of CD8+ T cell responses

Dinâmicas socioecológicas no semiárido baiano a partir do acesso a água : O caso da família Farias

A dinâmica socioecológica dos camponeses do semiárido brasileiro vem mudando há algumas décadas em decorrência do acesso a programas e políticas públicas para a convivência com o semiárido. Este trabalho apresenta o resultado da avaliação socioecológica em um agroecossistema no semiárido baiano após o acesso a tecnologias de captação e armazenamento de água da chuva, visando contribuir com a discussão sobre a sustentabilidade de agroecossistemas no semiárido brasileiro. Para construção desses dados foram utilizadas as metodologias e ferramentas de um Diagnóstico Rural Participativo. As tecnologias de captação e armazenamento de água da chuva possibilitaram mudanças significativas na vida dessas famílias, permitindo o acesso além da água para consumo humano e ampliando esse acesso para a água de produção, permitindo o cultivo de espécies e a criação de animais que garantem a manutenção da família no tempo e no espaço.The socioecological dynamics of the Brazilian semi-arid farmers has changed a few decades as a result of access to programs and policies for coexistence with the semiarid region. This paper presents the results of socio-ecological evaluation in a semi-arid agroecosystem in Bahia after access to rainwater capture and storage technologies, to contribute to the discussion about the sustainability of agro-ecosystems in the Brazilian semiarid region. Construction of such data the methodologies and tools of a Participatory Rural Appraisal. The capture and rainwater storage technologies enabled significant changes in the lives of these families, allowing access in addition to drinking water and expanding such access for the production of water, allowing the cultivation of species and breeding that guarantee family maintenance in time and space.Eje A6: Desarrollo Rural, Movimientos Sociales, Estado y AgroecologíaFacultad de Ciencias Agrarias y Forestale

Dinâmicas socioecológicas no semiárido baiano a partir do acesso a água : O caso da família Farias

A dinâmica socioecológica dos camponeses do semiárido brasileiro vem mudando há algumas décadas em decorrência do acesso a programas e políticas públicas para a convivência com o semiárido. Este trabalho apresenta o resultado da avaliação socioecológica em um agroecossistema no semiárido baiano após o acesso a tecnologias de captação e armazenamento de água da chuva, visando contribuir com a discussão sobre a sustentabilidade de agroecossistemas no semiárido brasileiro. Para construção desses dados foram utilizadas as metodologias e ferramentas de um Diagnóstico Rural Participativo. As tecnologias de captação e armazenamento de água da chuva possibilitaram mudanças significativas na vida dessas famílias, permitindo o acesso além da água para consumo humano e ampliando esse acesso para a água de produção, permitindo o cultivo de espécies e a criação de animais que garantem a manutenção da família no tempo e no espaço.The socioecological dynamics of the Brazilian semi-arid farmers has changed a few decades as a result of access to programs and policies for coexistence with the semiarid region. This paper presents the results of socio-ecological evaluation in a semi-arid agroecosystem in Bahia after access to rainwater capture and storage technologies, to contribute to the discussion about the sustainability of agro-ecosystems in the Brazilian semiarid region. Construction of such data the methodologies and tools of a Participatory Rural Appraisal. The capture and rainwater storage technologies enabled significant changes in the lives of these families, allowing access in addition to drinking water and expanding such access for the production of water, allowing the cultivation of species and breeding that guarantee family maintenance in time and space.Eje A6: Desarrollo Rural, Movimientos Sociales, Estado y AgroecologíaFacultad de Ciencias Agrarias y Forestale

Phenolic composition and cell-based biological activities of ten coloured potato peels (Solanum tuberosum L.)

The present study provides an in-depth characterisation of the non-anthocyanin and anthocyanin phenolic compounds of potato peels from ten coloured potato varieties. Furthermore, the underexplored bioactive potential (antioxidant, cytotoxic and anti-inflammatory capacities) of the studied peels is comprehensively analysed. Among non-anthocyanin phenolics, caffeic and a caffeoylquinic acid were found in the highest concentrations in all samples, which also showed the presence of O-glycosylated flavonol derivatives and polyamine derivatives. Acylated anthocyanins were identified in red and purple varieties, being pelargonidin, peonidin, and malvidin the most prominent aglycones. All samples revealed antioxidant and antitumor activities, and no toxic effect. The extract of the Rosemary variety presented the best antioxidant and antitumor outcomes and was the only sample to reveal anti-inflammatory activity. These results are valuable for the food-industry by adding value to an important bio-residue, particularly concerning its potential as natural ingredients in novel food and pharmaceutical formulations.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support by national funds FCT/ MCTES to CIMO (UIDB/00690/2020); the national funding by FCT, P.I., through the institutional scientific employment program-contract for L. Barros, Maria Inês Dias and C. Pereira contracts; to FEDER-Interreg España-Portugal programme through the project TRANSCoLAB 0612_TRANS_CO_LAB_2_P; to the European Regional Development Fund (ERDF) through the Regional Operational Program North 2020, within the scope of Project Mobilizador Norte-01-0247-FEDER-024479: ValorNatural ®; and also to the Ministry of Education, Science and Technological Development of Republic of Serbia (451-03-68/2020-14/200007). GIP-USAL is financially supported by the Spanish Government through the project AGL2015-64522-C2-2-R. S. Sampaio acknowledges CAPES Foundation (Ministry of Education, Brazil) for her PhD grant no. 99999.001423/2015-00.info:eu-repo/semantics/publishedVersio

Low medication adherence in patients with Short Bowel Syndrome dependent on parenteral nutrition

Study design: Cross-sectional. Aim: We aimed to investigate adherence to oral medications in patients with severe Short Bowel Syndrome (SBS). Casuistic and Methods: Ten patients with severe intestinal failure attending a specialized unit in a university hospital were enrolled in this study. All patients received intermittent parenteral nutrition for at least 4 months. The participants (six men and four women) had 56 ± 13 years and body mass index of 18 ± 3 kg/m2. Information related to the use of medications at home was recorded, and adherence behavior was assessed by using the Morisky Medication Adherence Scale. Results: Four patients (40%) had high medication adherence. Among patients with low medication adherence, unintentional behavior was observed in two patients, intentional behavior was observed in one patient, and an association of unintentional with intentional behavior was identified in three patients. Conclusion: Outside the hospital setting, most patients with SBS have low adherence to oral medications. These results suggest the development and implementation of targeted strategies aimed to promote awareness and adherence to medication treatmentModelo do estudo: Transversal. Objetivo do estudo: Avaliar a adesão de pacientes com Síndrome do Intestino Curto ao tratamento medicamentoso por via oral. Casuística e Métodos: O estudo inclui 10 pacientes com Síndrome do Intestino Curto (SIC) acompanhados em unidade especializada de um hospital universitário. Todos os pacientes recebiam nutrição parenteral por no mínimo quatro meses. A casuística consistia em seis homens e quatro mulheres, com idade de 56 ± 13 anos e Índice de Massa Corporal de 18 ± 3kg/m2. Foram registradas informações sobre o uso de medicamentos no domicílio. A adesão ao tratamento medicamentoso foi avaliada pelo teste de Morisky e foi identificada a natureza do comportamento em relação à não adesão. Resultados Apenas 40% dos pacientes foram classificados como “mais aderentes”. Dentre os “menos aderentes”, a baixa adesão por associação do comportamento intencional e não intencional foi observada em três casos; dois pacientes apresentavam apenas o comportamento intencional e o comportamento não intencional foi documentado em um paciente. Conclusões: A maioria dos pacientes tem baixa adesão ao tratamento medicamentoso por via oral durante o período em que eles permanecem em seus domicílios. Tais resultados sugerem o desenvolvimento e a implementação de estratégias que visem à percepção da relevância do uso correto dos medicamentos e a promoção da adesão ao tratamento medicamentos

SARS-CoV-2 reinfection: report of two cases in Southeast Brazil

From February 26, 2020 to March 11, 2021, coronavirus disease 2019 (COVID-19) pandemic resulted in 11,439,558 cases and 277,102 deaths in Brazil. Among them, 2,195,130 cases and 63,965 deaths occurred in Sao Paulo State, Southeast Brazil. The recent emergence and rise of new variants of SARS-CoV-2 is of concern because of their higher transmissibility and possible association with more severe disease. Cases of SARS-CoV-2 reinfections have been described since December 2020 in Brazil. This report describes two cases of COVID-19 reinfection, that occurred five and six months after the first infection, during the second wave of the pandemic in Sao Paulo State. Both patients presented mild symptoms in the two COVID-19 episodes and different lineages of SARS-CoV-2 were identified: B.1.1.33 and B.1.1.28 lineages in case 1 and B1.1.128 and P. 2 lineages in case 2

Early onset of obesity induces reproductive deficits in female rats

The incidence of obesity is increasing rapidly all over the world and results in numerous health detriments, including disruptions in reproduction. However, the mechanisms by which excess body fat interferes with reproductive functions are still not fully understood. After weaning, female rats were treated with a cafeteria diet or a chow diet (control group). Biometric and metabolic parameters were evaluated in adulthood. Reproductive parameters, including estradiol, progesterone, LH and prolactin during the proestrus afternoon, sexual behavior, ovulation rates and histological analysis of ovaries were also evaluated. Cafeteria diet was able to induce obesity in female rats by increasing body and fat pad weight, which resulted in increased levels of triglycerides, total cholesterol, LDL and induced insulin resistance. The cafeteria diet also negatively affected female reproduction by reducing the number of oocytes and preantral follicles, as well as the thickness of the follicular layer. Obese females did not show preovulatory progesterone and LH surges, though plasma estradiol and prolactin showed preovulatory surges similar to control rats. Nevertheless, sexual receptiveness was not altered by cafeteria diet. Taken together, our results suggest that the cafeteria diet administered from weaning age was able to induce obesity and reduce the reproductive capability in adult female rats, indicating that this obesity model can be used to better understand the mechanisms underlying reproductive dysfunction in obese subjects. (C) 2012 Elsevier Inc. All rights reserved.Fundacao Araucaria de Apoio ao Desenvolvimento Cientifico e Tecnologico do Estado do ParanaFundacao Araucaria de Apoio ao Desenvolvimento Cientifico e Tecnologico do Estado do ParanaConselho Nacional para o Desenvolvimento Cientifico e Tecnologico (CNPq)Conselho Nacional para o Desenvolvimento Cientifico e Tecnologico (CNPq)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Secretaria de Ciencia, Tecnologia e Ensino Superior do Estado do ParanaSecretaria de Ciencia, Tecnologia e Ensino Superior do Estado do Paran

Partial and simultaneous remission of nephritis and autoimmune hemolytic anemia in patients with lupus after treatment with biological agent: a case report

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease, systemic, of unknown cause and autoimmune nature. It features variable prognosis, depending on the affected organ or system. The renal impairment is the condition most often related to morbidity and mortality. This manuscript aims to contribute to the further evidence that early diagnosis of lupus associated with quickly aggressive therapy could increase the success outcome rate. Also, immediate recognition of therapeutic failures and change the treatment strategy must be applied. In this regard, a new therapeutic option seems to be the biological drug rituximab described in this study and which it is emphasised because of its possible and still supposed ability to act as a rescue agent for nephritis and hemolytic lupus anaemia, simultaneously, with effectiveness and safety. This article presents the case of female lupus patient with both severe refractory hematologic disorder and renal impairment, which had an evolution of the simultaneous restoration of urine output, and clinical and laboratory improvement of autoimmune anaemia after rituximab administration. The persistence of renal damage could not be ruled out, so the response to treatment was considered to be partialO Lúpus Eritematoso Sistêmico (LES) é uma doença inflamatória crônica, sistêmica, de causa desconhecida e de natureza autoimune. Apresenta prognóstico variável, dependente do órgão ou sistema acometido, sendo o comprometimento renal uma das condições mais frequentemente relacionadas à morbimortalidade. O presente manuscrito propõe-se a contribuir como mais um indício de que o diagnóstico precoce e a terapia agressiva inicial, no lúpus, elevam sobremaneira o índice de sucesso clinico. Falhas no tratamento devem ser reconhecidas de imediato, com rápida mudança de estratégia, quando necessário. Neste sentido, uma nova opção terapêutica parece ser o agente biológico rituximab, descrito neste estudo e para o qual é dada ênfase devido à sua possível e ainda suposta capacidade de atuar como agente de resgate para a nefrite e para a anemia hemolítica lúpicas, simultaneamente, com efetividade e segurança. Apresenta-se o caso de paciente lúpica com acometimento renal e hematológico grave e refratário, que evoluiu simultaneamente com restabelecimento do débito urinário e melhora clínico-laboratorial da anemia autoimune após administração de rituximab, resposta considerada parcial, posto que a existência de dano renal persistente não pode ser descartad

Associations of the TNF-alpha-308 G/A, IL6-174 G/C and AdipoQ 45 T/G polymorphisms with inflammatory and metabolic responses to lifestyle intervention in Brazilians at high cardiometabolic risk

Background: Cytokines secreted by the adipose tissue influence inflammation and insulin sensitivity, and lead to metabolic disturbances. How certain single-nucleotide polymorphisms (SNPs) interfere on lifestyle interventions is unclear. We assessed associations of selected SNPs with changes induced by a lifestyle intervention. Methods: This 9-month intervention on diet and physical activity included 180 Brazilians at high cardiometabolic risk, genotyped for the TNF-alpha -308 G/A, IL-6 -174 G/C and AdipoQ 45 T/G SNPs. Changes in metabolic and inflammatory variables were analyzed according to these SNPs. Individuals with at least one variant allele were grouped and compared with those with the reference genotype. Results: In the entire sample (66.7% women; mean age 56.5 +/- 11.6 years), intervention resulted in lower energy intake, higher physical activity, and improvement in anthropometry, plasma glucose, HOMA-IR, lipid profile and inflammatory markers, except for IL-6 concentrations. After intervention, only variant allele carriers of the TNF-alpha -308 G/A decreased plasma glucose, after adjusting for age and gender (OR 2.96, p = 0.025). Regarding the IL-6 -174 G/C SNP, carriers of the variant allele had a better response of lipid profile and adiponectin concentration, but only the reference genotype group decreased plasma glucose. In contrast to individuals with the reference genotype, carriers of variant allele of AdipoQ 45 T/G SNP did not change plasma glucose, apolipoprotein B, HDL-c and adiponectin concentrations in response to intervention. Conclusion: The TNF alpha -308 G/A SNP may predispose a better response of glucose metabolism to lifestyle intervention. The IL-6 -174 G/C SNP may confer a beneficial effect on lipid but not on glucose metabolism. Our findings reinforce unfavorable effects of the AdipoQ 45 T/G SNP in lipid profile and glucose metabolism after intervention in Brazilians at cardiometabolic risk. Further studies are needed to direct lifestyle intervention to subsets of individuals at cardiometabolic risk.State of Sao PauloState of Sao Paul