RESUMO
La principal causa de muerte en personas con diabetes mellitus tipo 1 (DM1) es de origen cardiovascular (CV). La duración de la DM1 es uno de los predictores más importantes para infarto agudo de miocardio (IAM), junto con el colesterol de lipoproteínas de baja densidad (cLDL) y HbA1c. El desarrollo de DM1 antes de los 10 años de edad se asocia con un riesgo 90 veces mayor de IAM en mujeres. En la DM1 habría una mayor contribución de un estado de inflamación sistémica de bajo de grado. La combinación de electrocardiograma de ejercicio y una técnica de imagen proporciona valor diagnóstico para la detección de isquemia miocárdica y pronóstico. La evaluación del riesgo CV en el adulto mayor debe ser individualizado y categorizarlo según funcionalidad y comorbilidades a fin de fijar objetivos de control de factores glucémicos y no glucémicos personalizados. Las personas con enfermedad cardíaca conocida o múltiples factores de riesgo cardiovascular (FRCV) deben tener recomendaciones de ejercicio personalizadas; se recomienda el tratamiento intensificado de la glucemia y de los FRCV asociados. En la población pediátrica y adolescentes con DM1 es esencial la detección y tratamiento precoz de los FRCV a fin de prevenir o retrasar el inicio y progresión de eventos CV
The leading cause of death in type 1 diabetes mellitus (T1DM) is cardiovascular. The duration of diabetes is one of the most important predictors for acute myocardial infarction (AMI), along with low-density lipoprotein cholesterol (cLDL) and HbA1c. Being diagnosed of T1DM before age 10 is been associated with a 90 times higher risk of AMI in women. It has been proposed, that a low-grade systemic inflammation state to be great prompt contributor. The combination of exercise electrocardiogram and an imaging technique provides diagnostic value for myocardial ischemia detection and future prognosis. Cardiovascular risk assessment in the older adult should be individualized by categorizing it, according to functionality and patient's co morbidity and customized glycaemic and non-glycaemic targets. People with known heart disease or multiple cardiovascular risk factors should have personalized exercise recommendations, blood glucose intensified treatment and associated risk factors. In paediatric and adolescent population with T1DM, cardiovascular risk factors early screening, recognition and treatment has become essential to prevent or delay the onset and progression of cardiovascular events.
Assuntos
Humanos , Diabetes Mellitus Tipo 1 , Terapêutica , Glicemia , Doenças Cardiovasculares , DiagnósticoRESUMO
Peroxisomes perform various metabolic processes that are primarily related to the elimination of reactive oxygen species and oxidative lipid metabolism. These organelles are present in all major eukaryotic lineages, nevertheless, information regarding the presence of peroxisomes in opportunistic parasitic protozoa is scarce and in many cases it is still unknown whether these organisms have peroxisomes at all. Here, we performed ultrastructural, cytochemical, and bioinformatic studies to investigate the presence of peroxisomes in three genera of free-living amoebae from two different taxonomic groups that are known to cause fatal infections in humans. By transmission electron microscopy, round structures with a granular content limited by a single membrane were observed in Acanthamoeba castellanii, Acanthamoeba griffini, Acanthamoeba polyphaga, Acanthamoeba royreba, Balamuthia mandrillaris (Amoebozoa), and Naegleria fowleri (Heterolobosea). Further confirmation for the presence of peroxisomes was obtained by treating trophozoites in situ with diaminobenzidine and hydrogen peroxide, which showed positive reaction products for the presence of catalase. We then performed comparative genomic analyses to identify predicted peroxin homologues in these organisms. Our results demonstrate that a complete set of peroxins-which are essential for peroxisome biogenesis, proliferation, and protein import-are present in all of these amoebae. Likewise, our in silico analyses allowed us to identify a complete set of peroxins in Naegleria lovaniensis and three novel peroxin homologues in Naegleria gruberi. Thus, our results indicate that peroxisomes are present in these three genera of free-living amoebae and that they have a similar peroxin complement despite belonging to different evolutionary lineages.
Assuntos
Acanthamoeba castellanii/ultraestrutura , Balamuthia mandrillaris/ultraestrutura , Peroxinas/genética , Peroxissomos/ultraestrutura , Acanthamoeba castellanii/enzimologia , Acanthamoeba castellanii/genética , Balamuthia mandrillaris/enzimologia , Balamuthia mandrillaris/genética , Catalase/metabolismo , Microscopia Eletrônica de Transmissão , Peroxinas/metabolismo , Peroxissomos/enzimologia , Peroxissomos/genética , FilogeniaRESUMO
La prevalencia de diabetes mellitus (DM) actividad física es cada vez mayor asociada a bajos niveles de actividad física (AF) y aumento de sobrepeso-obesidad. Los beneficios de la AF incluyen la prevención de la DM, reducción de hemoglobina glicosilada y glucemia postprandial, mejoría del perfil cardiovascular (descenso Presión arterial y triglicéridos, aumento de colesterol HDL), descenso significativo de biomarcadores proinflamatorios. Además, la AF mejora la disfunción sexual, la función endotelial, el óxido nítrico biodisponible y la insulinosensibilad, incrementa la testosterona, mejora el humor y la autoestima, la ansiedad y la depresión. El ejercicio incrementa la producción de glucosa, la secreción de insulina compensatoria está alterada y se exacerba por una mayor secreción de catecolaminas. Las personas con insulinopenia marcada tienen riesgo de cetosis. El aumento de hipoglucemias está dado por una mayor captación de glucosa. La AF mejora la polineuropatía y la neuropatía autonómica cardíaca, previene la enfermad renal crónica y se asocia a menores niveles de retinopatía diabética. En pacientes con retinopatía preproliferativa y proliferativa o degradación macular, se desaconsejan las actividades que aumentan considerablemente la presión intraocular. Está contraindicado el ejercicio en caso de hemorragia vítrea. El requerimiento energético depende del tipo, intensidad y duración del ejercicio. Se debe considerar el cuidado del pie. Las recomendaciones son disminuir el tiempo sedentario, ejercicio aeróbico al menos 150 min/semana y ejercicio de resistencia. Al aumentar la intensidad o ante riesgo elevado se debe realizar chequeo que incluya electrocardiograma y test de esfuerzo. Considerar ecocardiograma bidimensional y doppler
Assuntos
Exercício Físico , Diabetes Mellitus Tipo 2 , Atividade MotoraRESUMO
One of the major problems faced for the development of a vaccine against Dengue virus is the lack of a suitable animal model. Although non-human primates do not show overt signs of disease, these animals develop viremia after the infection and are the best model to evaluate vaccine candidates against this pathogen. However, for that purpose, the screening of all animals is mandatory to discard those with previous natural immunity. The most common technique used in the screening is the plaque reduction neutralization test (PRNT). However, most recent studies points to the cell-mediated immunity (CMI) as an important player in the process of controlling Dengue virus (DENV) infections. Here we presented the results from the screening of 55 rhesus monkeys housed in an animal breeding facility at Quang Ninh province, Vietnam. We evaluated the neutralizing antibody response by PRNT and determined the levels of interferon γ (IFNγ)-secretion after the viral stimulation of monkey-peripheral blood mononuclear cells, by enzyme-linked immunosorbent assay (ELISA). We found no correspondence between PRNT and IFNγ-ELISA. In fact, 19 animals were positive only by IFNγ-ELISA. Moreover, to study the protective capacity of the CMI detected, three animals with positive response by IFNγ-ELISA and negative by PRNT were inoculated with an infective preparation of DENV-3 and, as a result, no viremia was detected during 10 days after the challenge. This fact points to the importance of screening non-human primates through a CMI assay together with PRNT. This procedure should discard those false-negative cases which would be protected after the viral challenge in the immunization schedule.
RESUMO
Our group has developed a subunit vaccine candidate against Dengue virus (DENV) based on two different viral regions, the domain III of the envelope protein and the capsid protein. The chimeric proteins for each serotype (DIIIC1-4), aggregated with the oligodeoxynucleotide 39 M, form the tetravalent formulation named Tetra DIIIC. Tetra DIIIC induces a protective immune response in mice when it is inoculated by intraperitoneal route. However, if children are the main targets for a DENV vaccine, then a needle-free route of administration should be attractive and advantageous. In this study, we evaluated for the first time, in vivo, a vaccine candidate against DENV based on recombinant proteins using the intranasal route. After three doses of Tetra DIIIC in mice, we measured the humoral immune response against the four DENV serotypes and the corresponding recombinant proteins. Moreover, the functionality of these antibodies was evaluated through a plaque reduction neutralization test. Finally, to assess the cellular immune response induced, we measured the IFN-γ-levels secreted by spleen cells after in vitro stimulation with DENV. The results presented in this study indicate that the intranasal immunization with Tetra DIIIC favors the generation of DENV-specific cell-mediated immunity. On the other hand, the immunization using intraperitoneal and intranasal routes, simultaneously, generate functional antibodies (anti-DIIIC and anti-DENV) and an in vitro response of IFN-γ secretion.
Assuntos
Vírus da Dengue/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia , Administração Intranasal , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Proteínas do Capsídeo/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Interferon gama/metabolismo , Leucócitos Mononucleares/imunologia , Camundongos Endogâmicos BALB C , Testes de Neutralização , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas de Subunidades Antigênicas/genética , Vacinas de Subunidades Antigênicas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Proteínas do Envelope Viral/imunologia , Ensaio de Placa Viral , Vacinas Virais/genéticaRESUMO
BACKGROUND: Growth hormone secretagogues (GHS), among other factors, regulate the release of GH. The biological activity of the secretagogue peptide A233 as a promoter of growth and innate immunity in teleost fish has previously been demonstrated, but its role in the immune system of mammals is not well understood. METHODS: The effect of the peptide was investigated in J774A.2 macrophage cells using a comparative proteomics approach after 6 and 12 h of peptide stimulation. RESULTS: The functional analysis of differentially modulated proteins showed that A233 peptide treatment appears to promote activation and ROS-dependent cytotoxic functions in macrophages and enhanced expression of antiviral protein complexes such as MAVS. In accordance with this hypothesis, we found that A233 treatment enhanced superoxide anion production and the IFN-γ level in J774A.2 cells and mouse splenocytes, respectively, and reduced viral load in a dengue virus mouse model of infection. CONCLUSIONS: The growth hormone secretagogue A233 peptide promotes activation of ROS-dependent cytotoxic functions and exerts immunomodulatory effects that enable an antiviral state in a dengue virus mouse model. GENERAL SIGNIFICANCE: The increase of IFN-γ level and the differential modulation of antiviral proteins by the A233 peptide suggest that the molecule could activate an innate immune response with a possible further impact in the treatment of acute and chronic diseases.
RESUMO
La fertilidad es la capacidad fisiológica de una mujer, de un hombre o de una pareja para producir un hijo vivo. Son múltiples los factores que pueden interferir en este complejo proceso. La diabetes mellitus -como enfermedad crónica que afecta el metabolismo- puede alterar dicho proceso en sus distintas etapas. En la siguiente revisión analizamos las evidencias existentes acerca de los distintos aspectos que relacionan la diabetes con las alteraciones de la fertilidad femenina.
Assuntos
Feminino , Diabetes Mellitus Tipo 1 , FertilidadeRESUMO
La fertilidad es la capacidad fisiológica de una mujer, de un hombre o de una pareja para producir un hijo vivo. Son múltiples los factores que pueden interferir en este complejo proceso. La diabetes mellitus -como enfermedad crónica que afecta el metabolismo- puede alterar dicho proceso en sus distintas etapas. En la siguiente revisión analizamos las evidencias existentes acerca de los distintos aspectos que relacionan la diabetes con las alteraciones de la fertilidad femenina.(AU)
Assuntos
Feminino , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , FertilidadeRESUMO
Periodic leg movements (PLMs) are a common sleep disorder in spinocerebellar ataxia type 2 (SCA2) being associated to higher disease severity and altered sleep patterns. To assess the efficacy and safety of lisuride for the treatment of PLMs in SCA2 patients, an open-label clinical trial was conducted in 12 SCA2 patients suffering from PLMs associated to other subjective sleep complaints. All subjects received 0.1 mg of oral lisuride daily for 4 weeks. Primary outcome measure was the change of PLMs index. Changes in the subjective sleep quality, other polysomnographical sleep parameters, Scale for the Assessment and Rating of Ataxia score, and saccadic velocity were assessed as secondary outcome parameters. Safety assessments included hemoglobin, hematocrit, cholesterol, creatinine, and TGP. A significant decrease in both the PLMs index and R stage latency were observed during the treatment, associated to subjective improvement of frequent awakenings, early insomnia, restless leg syndrome, and nocturnal limb paresthesias in most cases. Ataxia score and saccadic pathology were unchanged. No significantly adverse events were observed. Our study suggests the efficacy of dopamine agonist therapy in the treatment of PLMs in SCA2, improving various subjective sleep complaints. These findings serve to promote the adequate management of sleep-related disorders in SCA2, which could improve the life quality of the patients.
Assuntos
Agonistas de Dopamina/uso terapêutico , Perna (Membro)/fisiopatologia , Lisurida/uso terapêutico , Síndrome das Pernas Inquietas/tratamento farmacológico , Ataxias Espinocerebelares/tratamento farmacológico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia/métodos , Síndrome das Pernas Inquietas/etiologia , Sono/fisiologia , Ataxias Espinocerebelares/complicaçõesRESUMO
Electron dense granules (EDGs) were identified by transmission electron microscopy in Entamoeba histolytica trophozoites recovered from hamster liver lesions. Abundant granules were present in trophozoites recovered after 15 min of liver inoculation. Variation in the size and morphology of these EDGs was also observed. Numerous granules were present in the plasma membrane when these parasites were incubated for 5 min with MDCK monolayers. Release of these EDGs was suggested by the presence of granules in contact with the surface of the target cell plasma membrane. Parasite phagocytic invaginations were observed after 10 min of parasite-monolayer interaction. In these structures, scarce granules were seen. Granules secretion was corroborated by obtaining of a pellet of these small structures from the incubation of trophozoites with collagen supernatant. Collagenase and gellatinase activity of this pellet was identified in SDS-PAGE gels. EDGs were also present in amebic hamster liver lesions. Our observations corroborate that these granules are secreted and suggest that may participate in the cytopathic effect of E. histolytica both in vitro and in vivo.