RESUMO
PURPOSE: Chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by pathogenic variants of genes encoding the enzyme complex NADPH oxidase. In countries where tuberculosis (TB) is endemic and the Bacillus Calmette-Guérin (BCG) vaccine is routinely administered, mycobacteria are major disease-causing pathogens in CGD. However, information on the clinical evolution and treatment of mycobacterial diseases in patients with CGD is limited. The present study describes the adverse reactions to BCG and TB in Mexican patients with CGD. METHODS: Patients with CGD who were evaluated at the Immunodeficiency Laboratory of the National Institute of Pediatrics between 2013 and 2024 were included. Medical records were reviewed to determine the clinical course and treatment of adverse reactions to BCG and TB disease. RESULTS: A total of 79 patients with CGD were included in this study. Adverse reactions to BCG were reported in 55 (72%) of 76 patients who received the vaccine. Tuberculosis was diagnosed in 19 (24%) patients. Relapse was documented in three (10%) of 31 patients with BGC-osis and six (32%) of 19 patients with TB, despite antituberculosis treatment. There was no difference in the frequency of BCG and TB disease between patients with pathogenic variants of the X-linked CYBB gene versus recessive variants. CONCLUSIONS: This report highlights the importance of considering TB in endemic areas and BCG complications in children with CGD to enable appropriate diagnostic and therapeutic approaches to improve prognosis and reduce the risk of relapse.
Assuntos
Vacina BCG , Doença Granulomatosa Crônica , NADPH Oxidase 2 , Tuberculose , Humanos , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/epidemiologia , Doença Granulomatosa Crônica/complicações , Vacina BCG/efeitos adversos , Masculino , Feminino , Criança , Tuberculose/epidemiologia , Tuberculose/imunologia , Pré-Escolar , Lactente , Adolescente , NADPH Oxidase 2/genética , Estudos de Coortes , Mycobacterium bovis , México/epidemiologia , Antituberculosos/uso terapêutico , NADPH Oxidases/genéticaRESUMO
The purpose of this study is to determine the activation of the extrinsic and intrinsic apoptotic pathways in the cerebellum of rats exposed to amygdaloid electrical kindling. Western blot analyses were carried out for caspase-8 and caspase-9, Bid, Bax, and Bcl-2 in the cerebellum and immunohistochemistry of Bid, Bax, cytochrome C, and VDAC (voltage-dependent anion channels) in the cerebellar cortex of Wistar male rats with 0, 15, and 45 kindling stimulations. In the experimental group of 45 stimuli, we observed an increase in protein activation of caspase-9 and truncated Bid and Bax, in addition to a decrease in expression of pro-caspase-8 and the anti-apoptotic protein Bcl-2, determined by Western blot. Moreover, we observed a cytosolic immunopositivity for cytochrome C and a mitochondrial immunolocalization for truncated Bid and Bax in the group of 45 stimuli. In this work, we found an increase of caspase-8, a cysteine-protease that can activate caspase-3 triggering extrinsic apoptosis by signaling of death receptors. However, it also can activate the intrinsic pathway releasing Bid, which performs mitochondrial translocation of Bax, inactivating Bcl-2 and allowing the release of cytochrome C through the opening of the mitochondrial permeability transition pore, promoting the activation of caspase-9 which activates caspase-3, the main executor caspase of apoptosis. Therefore, it is concluded that there is an activation of the intrinsic and extrinsic apoptotic pathways in the cerebellum of rats exposed to the kindling model. Apoptosis signaling pathways can be analyzed as an important developing object of research about the epileptic activity. Graphical Abstract.
Assuntos
Proteínas Reguladoras de Apoptose/genética , Apoptose/fisiologia , Cerebelo/fisiologia , Excitação Neurológica , Tonsila do Cerebelo/fisiologia , Animais , Proteínas Reguladoras de Apoptose/biossíntese , Córtex Cerebelar/fisiologia , Eletrodos Implantados , Imuno-Histoquímica , Masculino , Ratos , Ratos WistarRESUMO
BACKGROUND: Allergic rhinitis and asthma are the more frequent allergic diseases. Dermatophagoides pteronyssinus is one of the more clinically relevant causes of allergic diseases. OBJECTIVE: To standardize the biological potency Allergenic Bioequivalent Units (BAU) of Dermatophagoides pteronyssinus allergen extracts of three national laboratories. METHODS: This experimental, prospective, transversal, quantitative study included patients allergic to house dust mites. According to the FDA protocol, allergenic extracts of Dermatophagoides pteronyssinus from three Mexican manufacturers, were injected intradermally in threefold dilutions, until get an midpoint orthogonal diameters 50 mm erythema sum. Statistical analysis was done using logistic regression, one-way analysis of variance and Bonferroni test. RESULTS: We included 20 adult patients, 11 women and 9 men, aged between 16 and 45 years. Four patients had allergic asthma and rhinitis and 16 only had allergic rhinitis. There were no systemic anaphylactic reactions. Correlation coefficients of linear regression of the dose/response were to Allerstand r=0.55, Allergomex r=0.54 and Allerquim r=0.57(p=0.001). Dilutions calculated for 100,000 BAU/ml for each extract were Allerstand 1:26295, Allergomex 1:26341 and Allerquim 1:73993. The protein concentration (mcg/mL) was: Allergomex: 63, Allerquim 65, Allerstand 154. CONCLUSIONS: It was established the biological potency for each tested extract. We have found significant differences in the biological equivalence among the extracts from the three manufacturers. The procedure showed an adequate safety profile.
Assuntos
Alérgenos/imunologia , Alérgenos/uso terapêutico , Produtos Biológicos/imunologia , Produtos Biológicos/uso terapêutico , Dermatophagoides pteronyssinus/imunologia , Imunoterapia , Adolescente , Adulto , Alérgenos/farmacocinética , Animais , Produtos Biológicos/farmacocinética , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Equivalência Terapêutica , Adulto JovemRESUMO
BACKGROUND: Hypersensitivity reactions to insulin are infrequent, yet of clinical importance. The mechanisms of hypersensitivity involved can be of three types: I, III and IV. OBJECTIVE: To describe the pathophysiology of hypersensitivity to insulin, its clinical features and diagnostic and therapeutic approach, that help identify the cases of allergy to insulin and begin a treatment, or if necessary, to refer patients to a specialists or appropriate medical attention. METHODS: An electronic search of papers related to insulin hypersensitivity was performed in PubMed and the articles selected were those considered the most relevant for this review. RESULTS: Thirty eight papers about pathophysiology, mechanisms of injury and the different types of insulin involved in hypersensitivity reactions were included. Likewise, information for the diagnosis of insulin hypersensitivity and some options of treatment for first contact physicians or the referral of patients to specialists in endocrinology and allergy were included. CONCLUSIONS: Insulin hypersensitivity has a low prevalence and diverse clinical manifestations. The different types of insulin suitable allow the majority of cases of hypersensitivity to continue the treatment in a efficient and flexible manner.