RESUMEN
The SARS-CoV-2 virus has emerged and rapidly evolved into a current global pandemic. Although bacterial and fungal coinfections have been associated with COVID-19, little is known about parasitic infection. We report a case of a COVID-19 patient who developed disseminated strongyloidiasis following treatment with high-dose corticosteroids and tocilizumab. Screening for Strongyloides infection should be pursued in individuals with COVID-19 who originate from endemic regions before initiating immunosuppressive therapy.
Asunto(s)
Infecciones por Coronavirus/parasitología , Diabetes Mellitus/parasitología , Hipertensión/parasitología , Enfermedades del Sistema Nervioso Periférico/parasitología , Neumonía Viral/parasitología , Strongyloides stercoralis/patogenicidad , Estrongiloidiasis/parasitología , Corticoesteroides/administración & dosificación , Anciano , Animales , Antihelmínticos/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Betacoronavirus/patogenicidad , COVID-19 , Coinfección , Connecticut , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/inmunología , Diabetes Mellitus/virología , Ecuador , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/inmunología , Hipertensión/virología , Factores Inmunológicos/administración & dosificación , Masculino , Pandemias , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/inmunología , Enfermedades del Sistema Nervioso Periférico/virología , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/inmunología , Neumonía Viral/virología , SARS-CoV-2 , Estrongiloidiasis/tratamiento farmacológico , Estrongiloidiasis/inmunología , Estrongiloidiasis/virologíaRESUMEN
Background: The COVID-19 pandemic has been causing varying severities of illness. Some are asymptomatic and some develop severe disease leading to mortality across ages. This contrast triggered us explore the causes, with the background that a vaccine for effective immunization or a drug to tackle COVID-19 is not too close to reality. We have discussed strategies to combat COVID-19 through immune enhancement, using simple measures including nutritional supplements. Discussion: A literature search on mortality-related comorbid conditions was performed. For those conditions, we analyzed the pro-inflammatory cytokines, which could cause the draining of the immune reservoir. We also analyzed the immune markers necessary for the defense mechanism/immune surveillance against COVID-19, especially through simple means including immune enhancing nutritional supplement consumption, and we suggest strategies to combat COVID-19. Major comorbid conditions associated with increased mortality include cardiovascular disease (CVD), diabetes, being immunocompromised by cancer, and severe kidney disease with a senile immune system. Consumption of Aureobasidium pullulans strain (AFO-202) beta 1,3-1,6 glucan supported enhanced IL-8, sFAS macrophage activity, and NK cells' cytotoxicity, which are major defense mechanisms against viral infection. Conclusion: People with co-morbid conditions who are more prone to COVID-19-related deaths due to immune dysregulation are likely to benefit from consuming nutritional supplements that enhance the immune system. We recommend clinical studies to validate AFO-202 beta glucan in COVID-19 patients to prove its efficacy in overcoming a hyper-inflammation status, thus reducing the mortality, until a definite vaccine is made available.
Asunto(s)
Betacoronavirus , Enfermedades Cardiovasculares/epidemiología , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Diabetes Mellitus/epidemiología , Suplementos Dietéticos , Neoplasias/epidemiología , Neumonía Viral/epidemiología , Neumonía Viral/inmunología , Insuficiencia Renal Crónica/epidemiología , Actinobacteria/química , Biomarcadores/sangre , COVID-19 , Enfermedades Cardiovasculares/inmunología , Comorbilidad , Infecciones por Coronavirus/dietoterapia , Infecciones por Coronavirus/mortalidad , Citocinas/sangre , Diabetes Mellitus/inmunología , Humanos , Huésped Inmunocomprometido , Neoplasias/inmunología , Pandemias , Neumonía Viral/dietoterapia , Neumonía Viral/mortalidad , Insuficiencia Renal Crónica/inmunología , SARS-CoV-2 , beta-Glucanos/farmacología , beta-Glucanos/uso terapéuticoRESUMEN
Poorly controlled diabetes mellitus leads to several comorbidities, including susceptibility to infections. Hyperglycemia increases phagocyte responsiveness, however immune cells from people with diabetes show inadequate antimicrobial functions. We and others have shown that aberrant production of leukotriene B4 (LTB4) is detrimental to host defense in models of bacterial infection. Here, we will unveil the consequences of high glucose in the outcome of Leishmania braziliensis skin infection in people with diabetes and determine the role of LTB4 in human phagocytes. We show that diabetes leads to higher systemic levels of LTB4, IL-6 and TNF-α in cutaneous leishmaniasis. Only LTB4 correlated with blood glucose levels and healing time in diabetes comorbidity. Skin lesions of people with leishmaniasis and diabetes exhibit increased neutrophil and amastigote numbers. Monocyte-derived macrophages from these individuals showed higher L. braziliensis loads, reduced production of Reactive Oxygen Species and unbalanced LTB4/PGE2 ratio. Our data reveal a systemic inflammation driven by diabetes comorbidity in opposition to a local reduced capacity to resolve L. braziliensis infection and a worse disease outcome.
Asunto(s)
Diabetes Mellitus/inmunología , Dinoprostona/metabolismo , Leishmania braziliensis/inmunología , Leishmaniasis Cutánea/metabolismo , Leucotrieno B4/metabolismo , Brasil , Células Cultivadas , Comorbilidad , Estudios Transversales , Diabetes Mellitus/metabolismo , Diabetes Mellitus/parasitología , Humanos , Interleucina-6/metabolismo , Leishmaniasis Cutánea/inmunología , Macrófagos/metabolismo , Macrófagos/parasitología , Fagocitos , Especies Reactivas de Oxígeno/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
PURPOSE OF REVIEW: An increasing body of evidence indicates that persons living with HIV (PLWH) display dysfunctional immunometabolism. Here, we provide an updated review of this topic and its relationship to HIV-associated immune stimuli and age-related disease. RECENT FINDINGS: HIV infection alters immunometabolism by increasing reliance on aerobic glycolysis for energy and productive infection and repurposing oxidative phosphorylation machinery for immune cell proliferation and survival. Recent studies in PLWH with diabetes mellitus or cardiovascular disease have identified an association with elevated T cell and monocyte glucose metabolism, respectively. Immunometabolic dysfunction has also been observed in PLWH in frailty and additional studies suggest a role for immunometabolism in non-AIDS defining cancers and neurocognitive disease. There is a plethora of HIV-associated immune stimuli that could drive immunometabolic dysfunction and age-related disease in PLWH, but studies directly examining their relationship are lacking. Immunometabolic dysfunction is characteristic of HIV infection and is a potential link between HIV-associated stimuli and age-related comorbidities.
Asunto(s)
Infecciones por VIH/inmunología , Infecciones por VIH/patología , Monocitos/metabolismo , Linfocitos T/metabolismo , Enfermedades Cardiovasculares/inmunología , Comorbilidad , Diabetes Mellitus/inmunología , Glucólisis/fisiología , Infecciones por VIH/complicaciones , Humanos , Inflamación/patología , Monocitos/inmunología , Neoplasias/inmunología , Fosforilación Oxidativa , Linfocitos T/inmunologíaRESUMEN
Characterized as a metabolic syndrome with multiple consequences for the lives of patients, diabetes mellitus is also classified as a chronic non-communicable disease of great scope in the world. It is a complex disease, with different points of view, including the relation between inflammatory process, obesity and insulin resistance due to the performance of the various immunoinflammatory mediators - called adipokines - on glycemic homeostasis. Recent studies have precisely addressed this aspect for the development of drugs that assist in the protection of pancreatic ß cells from the damages arising from oxidative stress and inflammatory process, in order to control the hyperglycemic picture, which is characteristic of diabetes mellitus.
Asunto(s)
Diabetes Mellitus/etiología , Mediadores de Inflamación/inmunología , Resistencia a la Insulina/inmunología , Diabetes Mellitus/inmunología , HumanosRESUMEN
ABSTRACT Characterized as a metabolic syndrome with multiple consequences for the lives of patients, diabetes mellitus is also classified as a chronic non-communicable disease of great scope in the world. It is a complex disease, with different points of view, including the relation between inflammatory process, obesity and insulin resistance due to the performance of the various immunoinflammatory mediators - called adipokines - on glycemic homeostasis. Recent studies have precisely addressed this aspect for the development of drugs that assist in the protection of pancreatic ß cells from the damages arising from oxidative stress and inflammatory process, in order to control the hyperglycemic picture, which is characteristic of diabetes mellitus.
RESUMO Caracterizado como uma síndrome metabólica de múltiplas consequências para a vida de seus portadores, o diabetes mellitus é também classificado como uma doença crônica não transmissível de grande abrangência no mundo. Trata-se de uma doença complexa, com diversos pontos de vista, dentre eles a relação entre processo inflamatório, obesidade e resistência à ação da insulina, devido à atuação dos diversos mediadores imunoinflamatórios, chamados de adipocinas, sobre a homeostase glicêmica. Recentes estudos têm abordado justamente este aspecto para o desenvolvimento de fármacos que auxiliem na proteção das células ß pancreáticas dos danos advindos do estresse oxidativo e processo inflamatório, de modo a controlar o quadro hiperglicêmico característico do diabetes mellitus.
Asunto(s)
Humanos , Resistencia a la Insulina/inmunología , Mediadores de Inflamación/inmunología , Diabetes Mellitus/etiología , Diabetes Mellitus/inmunologíaRESUMEN
Rhino-orbito-cerebral mucormycosis from dental origin is an acute infection caused by opportunistic fungi belonging to the order of Mucorales, which affects mainly diabetic and immunocompromised patients.We report the case of a 63-year old diabetic man who performed a dental extraction on himself by his own means and subsequently developed a rhino-orbito-cerebral mucormycosis with cutaneous and palatal affection. The species isolated in the mycological culture was Rhizopus sp.
Asunto(s)
Diabetes Mellitus/microbiología , Huésped Inmunocomprometido , Mucorales/química , Mucormicosis/microbiología , Diabetes Mellitus/inmunología , Humanos , Masculino , Mucormicosis/diagnósticoRESUMEN
Resumen La mucormicosis es una infección aguda causada por hongos oportunistas pertenecientes al orden de los mucorales, que afecta principalmente a pacientes diabéticos e inmunosuprimidos. Se reporta el caso de un hombre diabético de 63 años de edad, que se extrajo una pieza dental por sus propios medios y, posteriormente, desarrolló una mucormicosis rino-órbito-cerebral con afección cutánea y palatina. La especie aislada mediante cultivos micológicos fue Rhizopus sp.
Abstract Rhino-orbito-cerebral mucormycosis from dental origin is an acute infection caused by opportunistic fungi belonging to the order of Mucorales, which affects mainly diabetic and immunocompromised patients. We report the case of a 63-year old diabetic man who performed a dental extraction on himself by his own means and subsequently developed a rhino-orbito-cerebral mucormycosis with cutaneous and palatal affection. The species isolated in the mycological culture was Rhizopus sp.
Asunto(s)
Humanos , Masculino , Huésped Inmunocomprometido , Diabetes Mellitus/microbiología , Mucorales/química , Mucormicosis/microbiología , Diabetes Mellitus/inmunología , Mucormicosis/diagnósticoRESUMEN
Objetivo: estimar a cobertura vacinal contra gripe e pneumonia e a utilização do SUS para vacinação em adultos e idosos com diabetes autorreferida em São Paulo, SP, Brasil, em 2003, 2008 e 2015. Métodos: painel de estudos transversais do ISA-Capital. Resultados: entrevistaram-se 3.357, 3.271 e 4.043 pessoas em 2003, 2008 e 2015; as prevalências de diabetes mellitus foram de 5,0% (2003), 6,4% (2008) e 7,7% (2015); menos da metade das pessoas com diabetes vacinou-se contra gripe (47,2%) e pneumonia (17,9%) em 2003, com pequeno aumento em 2015 (59,2% e 26,1%, respectivamente); a maioria da população que se vacinou contra gripe e pneumonia o fez pelo SUS, 88,7% (2003) e 97,2% (2015) para gripe e 84,7% (2003) e 94,5% (2015) para pneumonia, sem diferença entre idade, sexo, escolaridade e raça. Conclusão: embora as coberturas vacinais tenham sido baixas na população com diabetes, a utilização do SUS foi elevada entre os vacinados.
Objetivo: estimar la cobertura de vacunas contra gripe y neumonía y la utilización del Sistema Único de Salud-SUS para vacunación en adultos y ancianos con diabetes autorreferida en la ciudad de São Paulo, Brasil, en 2003, 2008 y 2015. Métodos: datos del ISA-Capital. Resultados: entrevistados 3.357, 3.271 y 4.043 personas en 2003, 2008 y 2015; las prevalencias de diabetes mellitus fueron de 5,0% (2003), 6,4% (2008) y 7,7% (2015); menos de la mitad de las personas con diabetes mellitus se vacunaron contra gripe (47,2%) y neumonía (17,9%) en 2003, con un pequeño aumento en 2015 (59,2% y 26,1%, respectivamente); la mayoría de la población que se vacunó contra gripe y neumonía lo hizo a través del SUS: 88,7% (2003) y el 97,2% (2015) para la gripe y 84,7% (2003) y 94,5% (2015) para neumonía, sin diferencia entre edad, sexo, escolaridad y raza. Conclusión: Aunque las coberturas fueron bajas en la población con diabetes, la utilización del SUS fue elevada entre los vacunados.
Objective: to estimate the vaccination coverage against influenza and pneumonia and to analyze the utilization of Brazilian National Health System-SUS for vaccination in adults and elderly with self-reported diabetes in São Paulo, Brazil, in 2003, 2008 and 2015. Methods: Cross-sectional studies with data from the ISA-Capital (population-based household surveys). Results: 3,357, 3,271 and 4,043 were interviewed in 2003, 2008 and 2015; the prevalence of diabetes mellitus were 5.0% (2003), 6.4% (2008) and 7.7% (2015); fewer than half of people with diabetes, vaccinated against influenza (47.2%) and pneumonia (17.9%) in 2003, with a small increase in 2015 (59.2% and 26.1%, respectively); the majority of people who are vaccinated against influenza and pneumonia used SUS, 88.7% (2003) and 97.2% (2015) for influenza; 84.7% (2003) and 94.5% (2015) for pneumonia, without difference among age, sex, education level and ethnicity. Conclusion: despite the low vaccination coverage against influenza and pneumonia in the population with diabetes mellitus since 2003 the utilization of SUS to vaccination has been progressively expanding.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Anciano , Anciano de 80 o más Años , Neumonía , Sistema Único de Salud , Vacunación , Diabetes Mellitus/inmunología , Gripe Humana , Estudios TransversalesRESUMEN
Diabetic cardiomyopathy (DCM) is characterized by cardiac remodeling and impaired diastolic function that may lead to heart failure. The aim of this study was to evaluate oxidative stress, inflammatory cells, and fibrosis in both subendocardial (SEN) and interstitial (INT) areas of the myocardium. Male Wistar rats were allocated to 2 groups of 9 animals, a control (CT) group and streptozotocin-induced diabetes (DM). After 8 weeks, echocardiography morphometry, protein expression, and confocal microscopy in SEN and INT areas of the left ventricle (LV) were performed. The echocardiographic analysis showed that diabetes induction leads to cardiac dilation, hypertrophy, and LV diastolic dysfunction. As compared to CT, the induction of diabetes increased inflammatory cells and fibrosis in both SEN and INT areas of DM myocardium and increased ROS generation only in SEN. Comparing the SEN and INT areas in the DM group, inflammatory cells and fibrosis in SEN were greater than in INT. In conclusion, diabetic myocardium SEN area, wherein oxidative stress was more pronounced, is more susceptible to cardiac dysfunction than INT area. This finding can be important for the understanding of the heart remodeling process occurring in DCM and perhaps to engender targeted therapies to attenuate or revert DCM-related diastolic dysfunction.
Asunto(s)
Cardiomiopatías Diabéticas/metabolismo , Corazón/fisiología , Miocardio/metabolismo , Estrés Oxidativo/fisiología , Animales , Western Blotting , Diabetes Mellitus/inmunología , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patología , Diabetes Mellitus Experimental/inmunología , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Cardiomiopatías Diabéticas/inmunología , Ecocardiografía , Masculino , Miocardio/inmunología , Miocardio/patología , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Disfunción Ventricular Izquierda/inmunología , Disfunción Ventricular Izquierda/metabolismo , Disfunción Ventricular Izquierda/patologíaRESUMEN
Comorbid diabetes mellitus (DM) increases tuberculosis (TB) risk and adverse outcomes but the pathological interactions between DM and TB remain incompletely understood. We performed an integrative analysis of whole blood gene expression and plasma analytes, comparing South Indian TB patients with and without DM to diabetic and non-diabetic controls without TB. Luminex assay of plasma cytokines and growth factors delineated a distinct biosignature in comorbid TBDM in this cohort. Transcriptional profiling revealed elements in common with published TB signatures from cohorts that excluded DM. Neutrophil count correlated with the molecular degree of perturbation, especially in TBDM patients. Body mass index and HDL cholesterol were negatively correlated with molecular degree of perturbation. Diabetic complication pathways including several pathways linked to epigenetic reprogramming were activated in TBDM above levels observed with DM alone. Our data provide a rationale for trials of host-directed therapies in TBDM, targeting neutrophilic inflammation and diabetic complication pathways to address the greater morbidity and mortality associated with this increasingly prevalent dual burden of communicable and non-communicable diseases.
Asunto(s)
Complicaciones de la Diabetes , Diabetes Mellitus/epidemiología , Diabetes Mellitus/inmunología , Inmunidad , Tuberculosis/epidemiología , Tuberculosis/inmunología , Biomarcadores , Comorbilidad , Biología Computacional/métodos , Citocinas/sangre , Citocinas/metabolismo , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Susceptibilidad a Enfermedades , Femenino , Perfilación de la Expresión Génica , Humanos , Inmunidad/genética , India/epidemiología , Masculino , Proteoma , Proteómica/métodos , Vigilancia en Salud Pública , Factores de Riesgo , Transcriptoma , Tuberculosis/genética , Tuberculosis/metabolismoRESUMEN
Diabetes is prevalent among solid organ transplant recipients and is universal among islet transplant recipients. Whereas diabetes is often considered to result in an immune-compromised state, the impact of chronic hyperglycemia on host alloimmunity is not clear. Potential immune-modifying effects of obesity, autoimmunity, or diabetogenic agents like streptozotocin may confound understanding alloimmunity in experimental models of diabetes. Therefore, we sought to determine the role of chronic hyperglycemia due to insulinopenia on alloimmunity using the nonautoimmune, spontaneously diabetic H-2b-expressing C57BL/6 Ins2Akita mice (Akita). Akita mice harbor a mutated Ins2 allele that dominantly suppresses insulin secretion, resulting in lifelong diabetes. We used BALB/c donors (H-2d) to assess alloimmunization and islet transplantation outcomes in Akita recipients. Surprisingly, chronic hyperglycemia had little effect on primary T-cell reactivity after alloimmunization. Moreover, Akita mice readily rejected islet allografts, and chronic hyperglycemia had no impact on the magnitude or quality of intragraft T-cell responses. In contrast, allospecific IgM and IgG were significantly decreased in Akita mice after alloimmunization. Thus, whereas diabetes influences host immune defense, hyperglycemia itself does not cause generalized alloimmune impairment. Our data suggest that immune compromise in diabetes due to hyperglycemia may not apply to cellular rejection of transplants.
Asunto(s)
Diabetes Mellitus/inmunología , Rechazo de Injerto/inmunología , Hiperglucemia/inmunología , Inmunidad Celular/inmunología , Inmunidad Humoral/inmunología , Linfocitos T/inmunología , Animales , Diabetes Mellitus/cirugía , Insulina/genética , Trasplante de Islotes Pancreáticos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Mutación , Trasplante HomólogoRESUMEN
BACKGROUND: Current classification of diabetes mellitus (DM) is based on etiology and includes type 1 (T1DM), type 2 (T2DM), gestational, and other. Clinical and pathophysiological characteristics of T1DM and T2DM in the same patient have been designated as type 1.5 DM (T1.5DM). OBJECTIVES: The aim of this study was to classify pediatric patients with DM based on pancreatic autoimmunity and the presence or absence of overweight/obesity, and to compare the clinical, anthropometric, and biochemical characteristics between children in the different classes of DM. METHODS: A sample of 185 patients, recruited (March 2008-April 2015) as part of the Cohort of Mexican Children with DM (CMC-DM); ClinicalTrials.gov, identifier: NCT02722655. The DM classification was made considering pancreatic autoimmunity (via antibodies GAD-65, IAA, and AICA) and the presence or absence of overweight/obesity. Clinical, anthropometric and biochemical variables, grouped by type of DM were compared (Kruskal-Wallis or chi-squared test). RESULTS: The final analysis included 140 children; 18.57% T1ADM, 46.43% T1BDM, 12.14% T1.5DM, and 22.86% T2DM. Fasting C-Peptide (FCP), and hs-CRP levels were higher in T1.5DM and T2DM, and the greatest levels were observed in T1.5DM (p<0.001 and 0.024 respectively). CONCLUSIONS: We clearly identified that the etiologic mechanisms of T1DM and T2DM are not mutually exclusive, and we detailed why FCP levels are not critical for the classification system of DM in children. The findings of this study suggest that T1.5DM should be considered during the classification of pediatric DM and might facilitate more tailored approaches to treatment, clinical care and follow-up.
Asunto(s)
Autoanticuerpos/metabolismo , Péptido C/metabolismo , Proteína C-Reactiva/metabolismo , Diabetes Mellitus/clasificación , Páncreas/inmunología , Adolescente , Niño , Preescolar , Estudios Transversales , Diabetes Mellitus/epidemiología , Diabetes Mellitus/inmunología , Diabetes Mellitus/metabolismo , Femenino , Humanos , Lactante , Masculino , México/epidemiologíaRESUMEN
The present study characterized natural killer cells and cytokines in diabetic mothers, their placenta, and fetus. In the maternal blood from the hyperglycemic groups, the CD16(+)CD56(-) NK cells increased, whereas that of CD16(+)CD56(+) decreased in gestational diabetes mellitus [GDM] group. Cord blood from type 2 diabetes [DM-2] showed a higher proportion of CD16(+)CD56(-) and CD16(-)CD56(+). The placental extravillous layer of GDM and DM-2 showed an increase of CD16(+)CD56(-) cells and, irrespective of region, the proportion of CD16(-)CD56(+) cells was higher in mild gestational hyperglycemia [MGH] and GDM and lower in DM-2. IL-2 was lower in maternal blood and IFN-γ higher in maternal and cord blood from the GDM group. IL-17 was higher in maternal and cord blood from the DM-2 group. The placental extravillous layer of the MGH showed high levels of IL-4, IL-6, IL-10, IL-17, and IFN-γ and low levels of IL-1ß and IL-8, whereas the placental villous layer contained high levels of IL-17 and IFN-γ. The GDM group, irrespective of region, showed higher levels of IL-8. The DM-2 group, irrespective of region, placenta showed high levels of TNF-α, IL-17, and IFN-γ. The hyperglycemia produces an inflammatory environment with a high content of inflammatory cytokines and cells expressing CD16(+).
Asunto(s)
Citocinas/metabolismo , Diabetes Mellitus/inmunología , Diabetes Mellitus/metabolismo , Feto/inmunología , Feto/metabolismo , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Placenta/inmunología , Placenta/metabolismo , Adolescente , Adulto , Biomarcadores , Citocinas/sangre , Femenino , Estudios de Seguimiento , Humanos , Inmunofenotipificación , Persona de Mediana Edad , Fenotipo , Embarazo , Adulto JovenRESUMEN
Introdução: Apesar dos avanços no manejo do diabetes mellitus tipo 1 (DM1), 60% a 90% dos pacientes apresentam controle glicêmico inadequado e 10% a 30% relatam baixa adesão à insulina. Os objetivos dessa tese foram identificar fatores associados à elevada concentração de hemoglobina glicada (HbA1c) e à uma melhor percepção da adesão à insulina em pacientes com DM1 em dez cidades de grande porte no Brasil. Métodos: Foi realizado um estudo de corte transversal, multicêntrico, com pacientes ≥18 anos, com diagnóstico médico de DM1, atendidos em centros de saúde. Dados sócio demográficos, comportamentais, clínicos, de conhecimento sobre o diabetes e satisfação com o tratamento foram obtidos por meio de entrevistas. A HbA1c foi dosada para todos os participantes. Considerou-se controle glicêmico inadequado quando HbA1c >7,0%...
Introduction: Despite advances in managing diabetes mellitus type 1 (DM1), 60% to 90% of patients have poor glycemic control and 10% to 30% reported low adherence to insulin. The objectives of this thesis was to identify factors associated with high levels of glycated hemoglobin (HbA1c) and a better understanding of adherence to insulin in patients with type 1 diabetes in Brazil. Methods: We conducted a cross-sectional, multicenter study, with patients ≥18 years old, diagnosed with type 1 diabetes treated at health centers in 10 cities in Brazil. We obtained sociodemographic, behavioral and clinical data, knowledge about diabetes and satisfaction with treatment through interviews. We measured HbA1c for all participants. It was considered inadequate glycemic control when HbA1c >7.0%...
Asunto(s)
Humanos , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Diabetes Mellitus/inmunología , Diabetes Mellitus/mortalidad , Diabetes Mellitus/patología , Diabetes Mellitus/prevención & control , Diabetes Mellitus/terapia , Insulina/análisis , Insulina/sangreRESUMEN
Diabetes is associated with increased glucose levels and accumulation of glycated products. It is also associated with impairment in the immune response, such as increased susceptibility to infections. In this study, we assessed the possible interactions between TLR4 and RAGE signalling on apoptosis and on the expression of inflammatory cytokines in PBMC from individuals with and without diabetes. PBMCs were isolated from seven diabetic patients and six individuals without diabetes and stimulated in vitro with bacterial LPS (1 µg/ml) associated or not with BSA-AGE (200 µg/ml). This stimulation was performed for 6 h, both in the presence and in the absence of inhibitors of TLR4 (R. sphaeroides LPS, 20 µg/ml) and RAGE (blocking monoclonal antibody). Apoptosis at early and late stages was assessed by the annexin-V/PI staining using flow cytometry. Regulation of TNF-α and IL-10 gene expression was determined by RT-qPCR. PBMCs from diabetes patients tended to be more resistant apoptosis. There were no synergistic or antagonistic effects with the simultaneous activation of TLR4 and RAGE in PBMCs from either diabetes or non-diabetes group. Activation of TLR4 is more potent for the induction of TNF-α and IL-10; RAGE signalling had a negative regulatory effect on TNF-α expression induced by LPS. TLR and RAGE do not have relevant roles in apoptosis of PBMCs. The activation of TLR has greater role than RAGE in regulating the gene expression of IL-10 and TNF-α.
Asunto(s)
Apoptosis/inmunología , Diabetes Mellitus/inmunología , Regulación de la Expresión Génica/inmunología , Leucocitos Mononucleares/inmunología , Receptor para Productos Finales de Glicación Avanzada/inmunología , Receptor Toll-Like 4/inmunología , Adulto , Anticuerpos Bloqueadores/inmunología , Anticuerpos Monoclonales/inmunología , Femenino , Productos Finales de Glicación Avanzada/metabolismo , Productos Finales de Glicación Avanzada/farmacología , Humanos , Inflamación/inmunología , Interleucina-10/biosíntesis , Lipopolisacáridos , Masculino , Persona de Mediana Edad , Receptor para Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Albúmina Sérica Bovina/farmacología , Transducción de Señal/inmunología , Receptor Toll-Like 4/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
OBJECTIVE: To compare knowledge, attitudes, and risks related to pet contact in households with and without immunocompromised children. STUDY DESIGN: A questionnaire was distributed to parents of children diagnosed with cancer (immunocompromised; n=80) or diabetes (immunocompetent; n=251) receiving care at the Children's Hospital of Eastern Ontario. Information was collected on knowledge of pets as sources of disease, concerns regarding pet-derived pathogens, and pet ownership practices. Data were analyzed with multivariable logistic regression. RESULTS: The questionnaire was completed by 65% (214 of 331) of the individuals to whom it was given. Pet ownership was common; 45% of respondents had a household pet when their child was diagnosed, and many (households with a child with diabetes, 49%; households with a child with cancer, 20%) acquired a new pet after diagnosis. Most households that obtained a new pet had acquired a pet considered high risk for infectious disease based on species/age (diabetes, 73%; cancer, 77%). Parents of children with cancer were more likely than parents of children with diabetes to recall being asked by a physician/staff member if they owned a pet (OR, 5.9) or to recall receiving zoonotic disease information (OR, 5.3), yet these interactions were reported uncommonly (diabetes, ≤13%; cancer, ≤48%). Greater knowledge of pet-associated pathogens was associated with recalled receipt of previous education on this topic (OR, 3.9). Pet exposure outside the home was reported frequently for children in non-pet-owning households (diabetes, 48%; cancer, 25%). CONCLUSION: Improved zoonotic disease education is needed for pet-owning and non-pet-owning households with immunocompromised children, with ongoing provision of information while the children are at increased risk of disease. Additional efforts from pediatric and veterinary healthcare professionals are required.
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Diabetes Mellitus/inmunología , Conocimientos, Actitudes y Práctica en Salud , Huésped Inmunocomprometido/inmunología , Neoplasias/inmunología , Mascotas , Encuestas y Cuestionarios , Zoonosis/epidemiología , Adolescente , Animales , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Ontario/epidemiología , Factores de Riesgo , Zoonosis/transmisiónRESUMEN
PROBLEM: Impaired pregnancy in non-obese diabetic (NOD) mice was related to limited vascular remodeling and autoimmune background. Vasoactive intestinal peptide (VIP) has anti-inflammatory and immunosuppressant effects, so we explored its ability to modulate the immune microenvironment at the early maternal-placental interface and improve pregnancy in NOD mice. METHOD OF STUDY: Implantation sites were isolated from pregnant NOD mice at gestational day 9.5 and were incubated with VIP for evaluation of cytokine or transcription factor expression by RT-PCR, immunoblotting, and immunohistochemistry. Alternatively, pregnant mice were injected with VIP at day 6.5 and studied at day 9.5. RESULTS: VIP and VPAC receptors were detected in viable implantation sites. VIP immunostaining was found predominantly on trophoblast giant cells. The in vitro treatment of viable implantation sites with VIP increased IL-10, TGF-ß, and Foxp3 expression. Sites with resorption processes presented lower VIP expression, reduced suppressant markers, and increased IL-17 and RORγT expression compared with viable sites and VIP reduced RORγT expression. Pregnant mice treated with VIP at day 6.5 presented an even distribution of viable implantation sites with an increased expression of IL-10, TGF- ß, and Foxp3. CONCLUSION: VIP induces an immunosuppressant profile at the early maternal-placental interface of NOD mice and improves pregnancy outcome.
Asunto(s)
Diabetes Mellitus/inmunología , Tolerancia Inmunológica , Complicaciones del Embarazo/inmunología , Útero/metabolismo , Péptido Intestinal Vasoactivo/metabolismo , Animales , Células Cultivadas , Microambiente Celular , Citocinas/genética , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Edad Gestacional , Humanos , Intercambio Materno-Fetal , Ratones , Ratones Endogámicos NOD , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/genética , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Técnicas de Cultivo de Órganos , Embarazo , Resultado del Embarazo , Receptores de Tipo II del Péptido Intestinal Vasoactivo/metabolismo , Útero/inmunología , Útero/patología , Péptido Intestinal Vasoactivo/inmunologíaRESUMEN
OBJECTIVE: This study investigated the susceptibility of 198 clinical isolates of Candida species against caspofungin, amphotericin B, itraconazole, and fluconazole. STUDY DESIGN: Suspensions of the microorganisms were spread on Roswell Park Memorial Institute (RPMI) agar plates. Etest strips were placed on the plates, and the minimal inhibitory concentration (MIC) was read after incubation (48 h at 37 °C). Data were analyzed by a factorial analysis of variance and a 2 × 2 post hoc test (α = .05). RESULTS: C glabrata showed the highest MIC values (P < .001) against caspofungin, itraconazole, and fluconazole. For amphotericin B, the MIC values of C tropicalis and C glabrata (P = .0521) were higher than those of C albicans (P < .001). Itraconazole was the least effective antifungal; 93.3% of the C glabrata isolates, 3.3% of the C albicans, and 1.3% of the C tropicalis were resistant. All microorganisms were susceptible to caspofungin and amphotericin B. CONCLUSIONS: Caspofungin and amphotericin B should be recommended as an effective alternative for the management of oral Candida infections when treatment with topical or other systemic drugs has definitely failed.