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BACKGROUND: Mesenchymal stem cell infusion and vitamin D supplementation may have immunomodulatory actions that could prolong the preservation of residual insulin secretion in patients with type 1 diabetes (T1D). Intervention with these agents after onset of T1D could favor the development of a remission phase, with potential clinical impact. We aimed to compare the presence of clinical remission (CR), glycemic control and daily insulin requirement at 6, 12, 18, 24 and 36 months after the diagnosis of T1D using IDAA1c in patients who received therapy with adipose tissue-derived mesenchymal stem cell (ASC) infusion and vitamin D supplementation and a control group. METHODS: This retrospective cohort study analyzed data from the medical records of patients with T1D diagnosed between 15 and 40 years. Partial CR was defined as an IDAA1c index < 9. Patients in the intervention group received an infusion of adipose tissued-derived mesenchymal stem cells (ASCs) within 3 months after diagnosis and supplementation with 2000 IU of cholecalciferol for 1 year, started on the day following the infusion. Partial CR was also determined using the ISPAD criteria, to assess its agreement with IDAA1c. RESULTS: A total of 28 patients were evaluated: 7 in the intervention group (group 1) and 21 in the control group (group 2). All patients in group 1 evolved with partial CR while only 46.7% of patients in group 2 had this outcome. Group 1 had a higher frequency of CR when evaluated with IDAA1c and ISPAD criteria. The mean duration of CR varied between the two criteria. Although HbA1c was similar between groups during follow-up, group 1 had a lower total daily insulin requirement (p < 0.005) at all time points. At 36 months, group 1 used 49% of the total daily insulin dose used by group 2 with similar glycemic control. CONCLUSION: The intervention with infusion of ASC + vitamin D supplementation was associated with partial CR at 6 months. Although there were no differences in CR established by the IDAA1c and ISPAD criteria after three years of follow-up, patients who underwent intervention had nearly the half insulin requirement of controls with conventional treatment, with similar glycemic control. TRIAL REGISTRATION: 37001514.0.0000.5257.
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To evaluate safety and therapeutic effect along 12 months of allogenic adipose tissue-derived stromal/stem cells (ASCs) transplantation with cholecalciferol (VITD) in patients with recent-onset type 1 diabetes (T1D). Prospective, phase II, open trial, pilot study in which patients with recent onset T1D received ASCs (1xKgx106 cells) and VITD 2000UI/day for 12 months (group 1) and were compared to controls with standard insulin therapy (group 2). Adverse events, C-peptide area under the curve (CPAUC), insulin dose, HbA1c and frequency of FoxP3+ in CD4+ or CD8+ T-cells(flow cytometry) were evaluated at baseline(T0), after 3(T3), 6(T6) and 12 months(T12). Eleven patients completed follow up (7:group 1;4:group 2). Group 1 had lower insulin requirement at T3(0.24±0.18vs0.53±0.23UI/kg,p=0.04), T6(0.24±0.15vs0.66±0.33 UI/kg,p=0.04) and T12(0.39±0.15vs0.74±0.29 UI/Kg,p=0.04).HbA1c was lower at T6 (50.57±8.56vs72.25±10.34 mmol/mol,p=0.01), without differences at T12 (57.14±11.98 in group 1 vs. 73.5±14.57 mmol/min in group 2, p=0.16). CPAUC was not significantly different between groups at T0(p=0.07), higher in group 1 at T3(p=0.04) and T6(p=0.006), but similar at T12(p=0.23). IDAA1c was significantly lower in group 1 than group 2 at T3,T6 and T12 (p=0.006, 0.006 and 0.042, respectively). IDDA1c was inversely correlated to FoxP3 expression in CD4 and CD8+ T cells at T6 (p<0.001 and p=0.01, respectively). In group 1, one patient had recurrence of a benign teratoma that was surgically removed, not associated to the intervention. ASCs with VITD without immunosuppression were safe and associated lower insulin requirements, better glycemic control, and transient better pancreatic function in recent onset T1D, but the potential benefits were not sustained.
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Diabetes Mellitus Tipo 1 , Humanos , Diabetes Mellitus Tipo 1/terapia , Colecalciferol/uso terapêutico , Hemoglobinas Glicadas , Projetos Piloto , Estudos Prospectivos , Seguimentos , Insulina/metabolismo , Tecido Adiposo/metabolismo , Suplementos Nutricionais , Células-Tronco/metabolismo , Fatores de Transcrição ForkheadRESUMO
ABSTRACT Objective: Adipose tissue-derived stromal/stem cells (ASCs) and vitamin D have immunomodulatory actions that could be useful for type 1 diabetes (T1D). We aimed in this study to investigate the safety and efficacy of ASCs + daily cholecalciferol (VIT D) for 6 months in patients with recent-onset T1D. Materials and methods: In this prospective, dual-center, open trial, patients with recent onset T1D received one dose of allogenic ASC (1 x 106 cells/kg) and cholecalciferol 2,000 UI/day for 6 months (group 1). They were compared to patients who received chol-ecalciferol (group 2) and standard treatment (group 3). Adverse events were recorded; C-peptide (CP), insulin dose and HbA1c were measured at baseline (T0), after 3 (T3) and 6 months (T6). Results: In group 1 (n = 7), adverse events included transient headache (all), mild local reactions (all), tachycardia (n = 4), abdominal cramps (n = 1), thrombophlebitis (n = 4), scotomas (n = 2), and central retinal vein occlusion at T3 (n = 1, resolution at T6). Group 1 had an increase in basal CP (p = 0.018; mean: 40.41+/-40.79 %), without changes in stimulated CP after mixed meal (p = 0.62), from T0 to T6. Basal CP remained stable in groups 2 and 3 (p = 0.58 and p = 0.116, respectively). Group 1 had small insulin requirements (0.31+/- 0.26 UI/kg) without changes at T6 (p = 0.44) and HbA1c decline (p = 0.01). At T6, all patients (100%; n = 7) in group 1 were in honeymoon vs 75% (n = 3/4) and 50% (n = 3/6) in groups 2 and 3, p = 0.01. Conclusions: Allogenic ASC + VIT D without immunosuppression was safe and might have a role in the preservation of β-cells in patients with recent-onset T1D. ClinicalTrials.gov: NCT03920397.
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Humanos , Células-Tronco/citologia , Colecalciferol/uso terapêutico , Transplante de Células-Tronco Mesenquimais , Diabetes Mellitus Tipo 1/tratamento farmacológico , Projetos Piloto , Tecido Adiposo/citologia , Estudos ProspectivosRESUMO
The Rhipicephalus (Boophilus) microplus tick is a major concern for the livestock market worldwide, as it causes serious economic damage. Plant-derived acaricides are an attractive alternative to control this ectoparasite and limit the development of resistance. Therefore, the aim of this study was to evaluate the acaricidal activity of Furcraea foetida leaf extract against engorged female R. (B.) microplus ticks. Our in vitro bioassays showed that the crude extract of leaves from F. foetida caused hemorrhagic swelling and skin lesions in the ticks, and three days of treatment caused 100% mortality. Dose-response assay indicated that this toxicity effect was dose-dependent. Similar effects were observed when the crude extract from F. foetida leaves was denatured by boiling at 100°C. These results suggest that the toxicity of the leaf extract might be associated with thermostable biomolecules. Together, our results show for the first time that the crude extract of F. foetida leaves has acaricidal activity against engorged female R. (B.) microplus ticks and it acts in a dose-dependent manner.
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Misturas Complexas/análise , Misturas Complexas/toxicidade , Rhipicephalus/efeitos dos fármacos , AcaricidasRESUMO
PURPOSE: The aim of this study was to sequence the coding region of the PAX4 gene in a Brazilian cohort with clinical manifestations of monogenic diabetes. PATIENTS AND METHODS: This study included 31 patients with autosomal dominant history of diabetes, age at diagnosis ≤40 years, BMI <30 kg/m2, and no mutations in GCK or HNF1A, HNF4A, and HNF1B. Screening of the PAX4 coding region was performed by Sanger sequencing. In silico algorithms were used to assess the potential impact of amino acid substitutions on protein structure and function. Additionally, PAX4-MODY family members and 158 control subjects without diabetes were analyzed for the identified mutation. RESULTS: The molecular analysis of PAX4 has detected one missense mutation, p.Arg164Gln (c.491G>A), segregating with diabetes in a large Brazilian family. The mutation was absent among the control group. The index case is a woman diagnosed at 32 years of age with polyneuropathy and treated with insulin. She did not present diabetic renal disease or retinopathy. Family members with the PAX4 p.Arg164Gln mutation have a heterogeneous clinical manifestation and treatment response, with age at diagnosis ranging from 24 years to 50 years. CONCLUSION: To the best of our knowledge, this is the first study to report a PAX4-MODY family in Brazil. The age of PAX4-MODY diagnosis in the Brazilian family seems to be higher than the classical criteria for MODY. Our results reinforce the importance of screening large monogenic diabetes families for the understanding of the clinical manifestations of rare forms of diabetes for the specific and personalized treatment.
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Objective: To evaluate the short term safety and potential therapeutic effect of allogenic adipose tissue-derived stromal/stem cells (ASCs) + cholecalciferol in patients with recent-onset T1D. Methods: Prospective, phase II, open trial, pilot study in which patients with recent onset T1D received ASCs (1 × 106 cells/kg) and cholecalciferol 2000 UI/day for 3 months (group 1) and were compared to controls with standard insulin therapy (group 2). Adverse events, C-peptide (CP), insulin dose, HbA1c, time in range (TIR), glucose variability (continuous glucose monitoring) and frequency of CD4+FoxP3+ T-cells (flow cytometry) were evaluated at baseline (T0) and after 3 months (T3). Results: 13 patients were included (8: group 1; 5: group 2). Their mean age and disease duration were 26.7 ± 6.1 years and 2.9 ± 1.05 months. Adverse events were transient headache (n = 8), mild local reactions (n = 7), tachycardia (n = 4), abdominal cramps (n = 1), thrombophlebitis (n = 4), mild floaters (n = 2), central retinal vein occlusion (n = 1, complete resolution). At T3, group 1 had lower insulin requirement (0.22 ± 0.17 vs. 0.61±0.26IU/Kg; p = 0.01) and HbA1c (6.47 ± 0.86 vs. 7.48 ± 0.52%; p = 0.03) than group 2. In group 1, 2 patients became insulin free (for 4 and 8 weeks) and all were in honeymoon at T3 (vs. none in group 2; p = 0.01). CP variations did not differ between groups (-4.6 ± 29.1% vs. +2.3 ± 59.65%; p = 0.83). Conclusions: Allogenic ASCs + cholecalciferol without immunosuppression was associated with stability of CP and unanticipated mild transient adverse events in patients with recent onset T1D. ClinicalTrials.gov registration: NCT03920397.
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Tecido Adiposo/citologia , Colecalciferol/uso terapêutico , Diabetes Mellitus Tipo 1/terapia , Suplementos Nutricionais , Transplante de Células-Tronco Mesenquimais , Vitaminas/uso terapêutico , Adolescente , Adulto , Biomarcadores/sangue , Glicemia/metabolismo , Brasil , Colecalciferol/efeitos adversos , Terapia Combinada , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Suplementos Nutricionais/efeitos adversos , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Projetos Piloto , Estudos Prospectivos , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento , Vitaminas/efeitos adversos , Adulto JovemRESUMO
ABSTRACT Objective We aimed to identify the frequency of monogenic diabetes, which is poorly studied in multiethnic populations, due to GCK or HNF1A mutations in patients with suggestive clinical characteristics from the Brazilian population, as well as investigate if the MODY probability calculator (MPC) could help patients with their selection. Subjects and methods Inclusion criteria were patients with DM diagnosed before 35 years; body mass index < 30 kg/m2; negative autoantibodies; and family history of DM in two or more generations. We sequenced HNF1A in 27 patients and GCK in seven subjects with asymptomatic mild fasting hyperglycemia. In addition, we calculated MODY probability with MPC. Results We identified 11 mutations in 34 patients (32.3%). We found three novel mutations. In the GCK group, six cases had mutations (85.7%), and their MODY probability on MPC was higher than 50%. In the HNF1A group, five of 27 individuals had mutations (18.5%). The MPC was higher than 75% in 11 subjects (including all five cases with HNF1A mutations). Conclusion Approximately one third of the studied patients have GCK or HNF1A mutations. Inclusion criteria included efficiency in detecting patients with GCK mutations but not for HNF1A mutations (< 20%). MPC was helpful in narrowing the number of candidates for HNF1A screening.
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Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Adulto Jovem , Diabetes Mellitus Tipo 2 , Fator 1-alfa Nuclear de Hepatócito/genética , Glucoquinase/genética , Mutação/genética , Linhagem , Fenótipo , Brasil , Estudos Transversais , ProbabilidadeRESUMO
Objective We aimed to identify the frequency of monogenic diabetes, which is poorly studied in multiethnic populations, due to GCK or HNF1A mutations in patients with suggestive clinical characteristics from the Brazilian population, as well as investigate if the MODY probability calculator (MPC) could help patients with their selection. Subjects and methods Inclusion criteria were patients with DM diagnosed before 35 years; body mass index < 30 kg/m2; negative autoantibodies; and family history of DM in two or more generations. We sequenced HNF1A in 27 patients and GCK in seven subjects with asymptomatic mild fasting hyperglycemia. In addition, we calculated MODY probability with MPC. Results We identified 11 mutations in 34 patients (32.3%). We found three novel mutations. In the GCK group, six cases had mutations (85.7%), and their MODY probability on MPC was higher than 50%. In the HNF1A group, five of 27 individuals had mutations (18.5%). The MPC was higher than 75% in 11 subjects (including all five cases with HNF1A mutations). Conclusion Approximately one third of the studied patients have GCK or HNF1A mutations. Inclusion criteria included efficiency in detecting patients with GCK mutations but not for HNF1A mutations (< 20%). MPC was helpful in narrowing the number of candidates for HNF1A screening.
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Diabetes Mellitus Tipo 2/genética , Glucoquinase/genética , Fator 1-alfa Nuclear de Hepatócito/genética , Mutação/genética , Adolescente , Adulto , Brasil , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Linhagem , Fenótipo , Probabilidade , Adulto JovemRESUMO
O levantamento e a análise do estado da arte da produção do conhecimento referente aos estudos do lazer no Brasil a partir de suas características internas e da conjuntura mais ampla permitiram localizar quatro grandes ciclos da produção do conhecimento. Neste trabalho, aprofundamos a investigação sobre o primeiro ciclo, orientadas pelo entendimento de que a explicação para a produção de ideias deve ser buscada nas características da formação social brasileira no período. Buscamos reconhecer, no movimento contraditório das forças produtivas e das relações de produção em desenvolvimento no Brasil, os interesses pelo controle e preenchimento do tempo livre com conteúdos culturais diversificados. No processo de desenvolvimento da indústria como força motriz do desenvolvimento brasileiro, verificamos configurarse no período uma política educacional de caráter conformador dos interesses da classe operária aos interesses da burguesia brasileira.
The survey and analysis of the state of art in the production of knowledge regarding the studies of leisure in Brazil from its internal characteristics helped to find four large cycles. In this work we further research the first cycle guided by the understanding that the explanation for the production of ideas should be found in the characteristics of the Brazilian social formation in the period. We try to recognize, in the contradictory movement of productive forces and from the relations of the development productions in Brazil, the interests for the control and the filling of spare time with diverse cultural content. In the process of developing industry as a springboard for Brazilian development, it is checked, in the period, the configuration of an education policy in a manner that complies with the interests of the working class to the interests of the Brazilian bourgeoisie.
El levantamiento y análisis del estado del arte de la producción del conocimiento referente a los estudios del entretenimiento en Brasil a partir de sus particularidades internas y de la coyuntura más amplia permitieron localizar cuatro grandes ciclos de la producción del conocimiento. En este trabajo profundizamos la investigación sobre el primer ciclo, orientadas por la comprensión de que la explicación para la producción de ideas debe ser buscada en las características de la formación social brasilera en el periodo. Buscamos reconocer, en el movimiento contradictorio de las fuerzas productivas y de las relaciones de producción en desarrollo en el Brasil, los intereses por el control y relleno del tempo libre con contenidos culturales diversificados. En el proceso de desarrollo de la industria como fuerza motriz del desarrollo brasilero, verificamos configurarse en el periodo una política educacional de carácter conformador de los intereses de la clase operaria a los intereses de la burguesía brasilera.
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MedicinaRESUMO
INTRODUÇAO: O diagnóstico da tuberculose pleural permanece um desafio, pois a sensibilidade dos testes tradicionais é baixa. O exame histopatológico da pleura é o método mais preciso, com até 80 por cento de sensibilidade. A dosagem da adenosina deaminase foi introduzida mais recentemente, mas sua utilidade no diagnóstico da tuberculose pleural no Brasil não foi suficientemente esclarecida. OBJETIVO: Verificar a sensibilidade e a especificidade de um método experimental de dosagem da atividade da adenosina deaminase em uma série de pacientes com derrame pleural investigados entre agosto de 1998 e novembro de 2002 no Rio de Janeiro (RJ). RESULTADOS: De 137 casos, em 111 havia amostras de líquido pleural disponíveis, das quais 83 pertenciam a pacientes com tuberculose pleural. Entre os 67 pacientes testados com tuberculose pleural, 10 apresentavam co-infecção pelo vírus da imunodeficiência humana (14,9 por cento). O valor de corte da adenosina deaminase de 35U/L foi determinado por uma curva receiver operator characteristic. A sensibilidade, especificidade, e razões de verossimilhança positiva e negativa da adenosina deaminase foram de 92,8 por cento, 93,2 por cento, 25,8 e 13,9, respectivamente. A média de adenosina deaminase no grupo com tuberculose pleural foi de 84,7 ± 43,1 U/L e no grupo com outras doenças de 15,9 ±11,1 U/L. Não houve diferença significativa na dosagem da adenosina deaminase entre pacientes com tuberculose pleural co-infectados ou não pelo vírus da imunodeficiência humana. CONCLUSAO: A dosagem da adenosina deaminase no líquido pleural é um método sensível e específico para o diagnóstico da tuberculose pleural e seu uso rotineiro pode reduzir a necessidade de realização de biópsias pleurais na abordagem inicial de um derrame pleural. O valor de corte de 35U/L para a adenosina deaminase é recomendado.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Adenosina Desaminase , Líquido da Lavagem Broncoalveolar , Infecções por HIV , Derrame Pleural , Tuberculose Pleural , Idoso de 80 Anos ou mais , Biomarcadores , Sensibilidade e EspecificidadeRESUMO
O tema geral deste trabalho é a psiquiatria brasileira, no período de 1930 a 1950, a partir da análise das dimensões do institucional, do saber e da prática. No período de 1930 a 1950 a assistência psiquiatrica pública expande-se para todos os Estados do pais, com a criação de serviços psiquiatricos patrocinada pelo governo federal. A criação do Serviço Nacional de Doenças Mentais e a formulação do plano psiquiatrico para a União, em 1941, é o marco estratégico do período, do ponto de vista institucional
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Serviços de Saúde Mental , Unidade Hospitalar de Psiquiatria/história , Psiquiatria/história , BrasilAssuntos
Masculino , Feminino , Humanos , Gravidez/psicologia , Gravidez/estatística & dados numéricosRESUMO
An experimental model for acquired and congenital ocular toxoplasmosis as well as a model to induce experimental autoimunne uveitis (EAU) was investigated in Calomys callosus. Toxoplasma gondii, ME-49 strain, was used to infect males and pregnant and not pregnant-females while S-antigen, a major glycoprotein of the retinal photoreceptor cell, was used to induce EAU. The ocular lesions elicited by T. gondii were characterized by the presence of cysts, free tachyzoites and inflammatory cells in the retina or related tissues. In the congenital form, 40 per cent of the fetus presented ocular lesions, i.e., presence of cysts in the retina, vitreous, and extra-retinal tissues. In the acquired form, 75 per cent of the females and 50 per cent of the males presented unilateral ocular cysts both at 21 and 47 days post-infection. It was also demonstrated that S-antigen was not uveitogenic in the C. callosus model. No lesion was observed in the animals exclusively immunized with this retinal component, even when jacalin was used as addicional adjuvant for polyclonal response to the retinal antigen. It can be concluded that C. callosus may constitue in a promising model for study both acquired and congenital ocular toxoplasmosis, particularly when it is important to make sure that a non autoimmune process is involved in the genesis of the ocular infection.
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Animais , Camundongos , Arvicolinae/parasitologia , Toxoplasma/parasitologia , Toxoplasmose Ocular/parasitologia , Uveíte/parasitologiaRESUMO
Foram estudados os efeitos resultantes da adição da beta-propiolactona (BPL) ao sangue total e soro nas dosagens de íons, na capacidade de fixação do ferro (TIBC), nas mucoproteínas, na eletroforese de proteínas e em algumas provas de funções hepáticas e pancreáticas. A adição desta substância ao sangue pode levar à hemólise, com conseqüentes alterações de análises bioquímicas. De todos os testes estudados apenas as dosagens de mucoproteínas nas alíquotas de soro contendo BPL apresentaram alterações com significado estatístico. Os autores recomendam o uso da BPL antes da realização das análises bioquímicas de rotina em soros de indivíduos infectados pelo HIV ou pertencentes a grupos de risco.
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Humanos , Análise Química do Sangue , HIV , Propiolactona/farmacologia , Eletroforese das Proteínas Sanguíneas , Fígado/fisiologia , Infecções por HIV/prevenção & controle , Íons , Ferro/metabolismo , Mucoproteínas , Pâncreas/fisiologiaRESUMO
Os autores fazem um relatorio sucinto de pesquisa que realizaram sobre a formacao de terapeutas de grupo, intitulada 'As formacoes dos especialistas em tecnicas grupais como possivel alternativas para suprimento das necessidades na area de saude mental'. Essa pesquisa contou com os auspicios do CNPq e apoio do IBRAPSI, Instituto Brasileiro de Psinalise, Grupos e Instituicoes. A principio, justificam a eleicao do tema e a hipotese inicial do trabalho, que consiste no levantamento de dispositivos contidos nas diversas propostas teoricas e tecnicas e seu possivel interesse para as praticas terapeuticas de grupo. Descrevem a metodologia utilizada e fazem uma critica as escolas de formacao grupalista. Finalmente, tecem consideracoes sobre a pratica grupal, enfatizando seu aspecto de analisador institucional.