RESUMO
INTRODUCTION: Environmental factors causing oxidative stress are known to be associated with asthma morbidity. The antioxidative gene NFE2L2 has been implicated in asthma development in mice models. In humans, the SNPs -617C/A and -653G/A, located at the promoter region of NFE2L2 gene, have been found associated with the susceptibility to develop diverse chronic-degenerative diseases. OBJECTIVE: To determine if there is association of the -617C/A and -653G/A NFE2L2 SNPs and childhood-onset asthma in a Mexican population. MATERIALS AND METHODS: In a case-control study 242 unrelated patients with diagnosis of asthma and 358 ethnically- and sex-matched healthy individuals were included. The -617C/A and -653G/A NFE2L2 genotyping was carried out using the TaqMan allelic discrimination assay. RESULTS: The risk allele of both polymorphisms showed a high frequency in our sample (-617A: 24% and -653A: 40%), similarly to those previously reported in Asiatic populations (-617A: 24-29% and -653A: 42-52%; p > 0.05). In contrast, the -617A allele frequency was higher than that reported in a European-African admixed population (10%, p < 0.001). The allelic and genotypic frequencies from both polymorphisms showed no significant differences among cases and controls in female and male samples. Likewise, haplotype analysis found no association between NFE2L2 gene variants and the disease. CONCLUSIONS: Despite the experimental evidence suggesting that NFE2L2 gene is involved in asthma pathogenesis, the -617C/A and -653G/A SNPs were not associated with childhood-onset asthma.
Assuntos
Asma/genética , Fator 2 Relacionado a NF-E2/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Idade de Início , Alelos , Asma/epidemiologia , Criança , Pré-Escolar , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Masculino , México/epidemiologia , Fator 2 Relacionado a NF-E2/fisiologiaRESUMO
BACKGROUND: Budesonide/formoterol maintenance and reliever therapy (Symbicort SMART) improves asthma control compared with fixed-dose inhaled corticosteroid/long-acting beta(2)-agonist (ICS/LABA) regimens, but its efficacy has not been assessed in comparison with sustained high-dose salmeterol/fluticasone (Seretide) plus a short-acting beta(2)-agonist (SABA). METHODS: Patients (N=2309) with symptomatic asthma (aged 12 years; forced expiratory volume in 1s 50% predicted), who had experienced an asthma exacerbation in the previous year, were randomised to receive budesonide/formoterol 160/4.5 microg two inhalations twice daily and as needed, or one inhalation of salmeterol/fluticasone 50/500 microg twice daily plus terbutaline as needed, for 6 months. RESULTS: Time to first severe exacerbation, the pre-specified primary outcome, was not significantly prolonged (risk ratio 0.82; 95% confidence interval 0.63, 1.05). Budesonide/formoterol maintenance and reliever therapy reduced total exacerbations from 31 to 25 events/100 patients/year (P=0.039), and exacerbations requiring hospitalisation/emergency room (ER) treatment from 13 to 9 events/100 patients/year (P=0.046). The treatments showed no difference in measures of lung function or asthma symptoms. The mean dose of ICS received was lower using budesonide/formoterol maintenance and reliever therapy (792 microg/day budesonide [1238 microg/day beclomethasone dipropionate (BDP) equivalent] versus 1000 microg/day fluticasone [2000 microg/day BDP equivalent] with salmeterol/fluticasone therapy; P<0.0001). Both treatments were well tolerated. CONCLUSION: In the treatment of uncontrolled asthma, budesonide/formoterol maintenance and reliever therapy reduces the incidence of severe asthma exacerbations and hospitalisation/ER treatment with similar daily symptom control compared with sustained high-dose salmeterol/fluticasone plus SABA. This benefit is achieved with substantially less ICS exposure.
Assuntos
Albuterol/análogos & derivados , Androstadienos/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Budesonida/uso terapêutico , Etanolaminas/uso terapêutico , Administração por Inalação , Adolescente , Agonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuterol/uso terapêutico , Asma/fisiopatologia , Azidas/uso terapêutico , Criança , Doença Crônica , Método Duplo-Cego , Esquema de Medicação , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Combinação Fluticasona-Salmeterol , Fumarato de Formoterol , Hospitalização , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Testes de Função Respiratória , Serotonina/análogos & derivados , Serotonina/uso terapêutico , Resultado do TratamentoRESUMO
Chronic obstructive pulmonary disease (COPD) is a common, preventable and treatable condition that has a complex pathophysiology and an even more complex immunopathological process. The purpose of this review was to analyze COPD immunopathological aspects, which was addressed by undertaking a literature search for the most relevant documents indexed in the PubMed database over the last 10 years. Different conclusions could be drawn: in COPD immunopathology there are immune and non-immune inflammatory changes with oxidative stress imbalance, there are alterations in the protease/anti-protease ratio caused by direct and indirect genetic and epigenetic-environmental defects; COPD produces irreversible tissue damage and chronic inflammation with tissue repair alteration, which induces chronic obstruction of the airway, bronchitis and systemic damage. Most common resulting comorbidities include cardiovascular disease, metabolic syndrome, osteoporosis, depression, musculoskeletal dysfunction, increased biological age, lung cancer and other types of malignancies. In the conception of COPD, recognizing that it is a non-transmittable and preventable disease is indispensable.
La enfermedad pulmonar obstructiva crónica (EPOC) es una enfermedad común, prevenible y tratable que presenta una fisiopatología compleja y un proceso inmunopatológico aún más complicado. El objetivo de esta revisión fue analizar los aspectos inmunopatológicos de la EPOC, para lo cual se llevó a una cabo una pesquisa bibliográfica de los documentos más relevantes indexados en la base de datos PubMed durante los últimos 10 años. Diversos aspectos pudieron concluirse: en la inmunopatología de la EPOC existen cambios inflamatorios, inmunológicos y no inmunológicos con un desequilibrio en el estrés oxidativo, así como alteraciones en la relación proteasas/antiproteasas debidas a efectos genéticos, epigenéticos, ambientales directos e indirectos. La EPOC produce daño tisular irreversible e inflamación crónica con alteración de la reparación tisular que induce obstrucción crónica de la vía aérea, bronquitis, enfisema y daño sistémico. Las comorbilidades resultantes más comunes son enfermedad cardiovascular, síndrome metabólico, osteoporosis, depresión, disfunción músculo esquelética, incremento de la edad biológica, cáncer pulmonar y otros tipos de neoplasias. En la concepción de la EPOC es indispensable reconocer que es una enfermedad no transmisible y prevenible.
Assuntos
Doença Pulmonar Obstrutiva Crônica/imunologia , Envelhecimento/imunologia , Bronquite/epidemiologia , Comorbidade , Citocinas/fisiologia , Humanos , Inflamassomos/imunologia , Inflamação , Pulmão/microbiologia , Linfócitos/patologia , Microbiota , Células Mieloides/patologia , Neoplasias/epidemiologia , Neoplasias/imunologia , Estresse Oxidativo , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/patologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Enfisema Pulmonar/epidemiologia , Músculos Respiratórios/fisiopatologiaRESUMO
Secondary immunodeficiencys, previously presented in immunocompetent individuals. The lack of primary or secondary response to the presence of a foreign antigen, in the case of infections is a sentinel data in the diagnosis of immunodeficiency (can be primary or secondary), in the case of a self antigen may generate the presence of Cancer. Cancer has shown an increase in the prevalence and incidence globally. Most current medical treatments in cancer are focused primarily on immunomodulatory actions (immunosuppression / immune stimulation or both). Knowledge of key concepts from the perspective of innate and acquired immunity lead to cancer development, engaging immune surveillance and escape mechanisms of this that contribute to better understand the origin, behavior and treatment of neoplasm's. These treatments can cause immunological disorders such as allergy, anaphylaxis, lack of response immunogenicity care fields specialist in allergy and clinical immunology.
Las inmunodeficiencias secundarias aparecen en individuos previamente inmunocompetentes. La falta de respuesta primaria o secundaria a un antígeno extraño, en el caso de infecciones, es un dato centinela en el diagnóstico de inmunodeficiencia (puede ser primaria o secundaria); en el caso de un antígeno propio podría generar cáncer. Éste ha mostrado un aumento en la prevalencia e incidencia en forma global. La mayor parte de los tratamientos médicos actuales en cáncer se enfocan, fundamentalmente, a acciones inmunomoduladoras (inmunosupresióninmunoestimulación o ambos). El conocimiento de los conceptos clave, desde la perspectiva de la inmunidad innata y adquirida, conduce al desarrollo de cáncer, involucrándose a la vigilancia inmunológica y los mecanismos de escape de ésta, que contribuyen a comprender mejor el origen, comportamiento y tratamiento de las neoplasias. Los tratamientos pueden originar alteraciones inmunológicas como: alergia, anafilaxia, falta de respuesta por inmunogenicidad, campos de atención del especialista en Alergia e Inmunología clínica.
Assuntos
Síndromes de Imunodeficiência/complicações , Neoplasias/imunologia , Imunidade Adaptativa/imunologia , Humanos , Imunidade Inata/imunologia , Síndromes de Imunodeficiência/imunologia , Neoplasias/terapiaRESUMO
BACKGROUND: Systemic lupus erythematous is an autoimmune disease of multifactorial etiology with genetic predisposition. Its pathogenesis involved more than 100 genes. CD24 gene can mediate various functions such as their costimulatory activity in the clonal expansion of T cells. The single nucleotide polymorphism, resulting in a non-conservative replacement of alanine to valine (CD24v) precedes immediately GPI anchorage site (position ω-1), determines CD24 loss activity. CD24v has been associated with multiple sclerosis and systemic lupus erythematous in other populations. OBJECTIVE: To find the presence of CD24v in Mexican patients with systemic lupus erythematous. MATERIAL AND METHOD: A study of fenotyping of CD24v included 65 subjects, 32 cases (systemic lupus erythematous): 28 women and 4 men; and 32 controls: 9 women and 23 men; cases and controls from patients with systemic lupus erythematous in National Medical Center 20 de Noviembre ISSSTE, Mexico City, services of Clinical Immunology and Rheumatology. RESULTS: In cases, 19 patients had a wild homozygous genotype, 12 were heterozygous and only one patient showed homozygous polymorphism. In controls, 17 showed wild heterozygous genotypes; 14 were heterozygous and 1 was found to be polymorphic homozygote. With odds ratio: 0.84 and chi-squared of 0.17; therefore there was no statistically significant difference. CONCLUSIONS: Study population showed that there is no statistically significant difference between systemic lupus erythematous cases and controls with respect to the presence of CD24v.
Antecedentes: el lupus eritematoso sistémico es un padecimiento autoinmunitario, de origen multifactorial, con predisposición genética; más de 100 genes participan en su etiopatogenia. El gen de CD24 puede mediar varias funciones, como su actividad coestimuladora en la expansión clonal de las células T. El polimorfismo de un simple nucleótido de CD24, que resulta en un reemplazo no conservador de alanina a valina (CD24v), que precede inmediatamente al sitio de anclaje GPI (posición ω-1), condiciona la pérdida de actividad de CD24. Se ha descrito que CD24v está asociado con esclerosis múltiple y lupus eritematoso sistémico en otras poblaciones. Objetivo: encontrar la existencia de CD24v en pacientes mexicanos con lupus eritematoso sistémico. Material y método: estudio de genotipificación de CD24v en el que se incluyeron 64 sujetos, 32 casos con lupus eritematoso sistémico: 28 mujeres y 4 hombres; y 32 controles: 9 mujeres y 23 hombres; todos eran pacientes con lupus eritematoso sistémico del Centro Médico Nacional 20 de Noviembre, del ISSSTE, atendidos en los servicios de Inmunología Clínica y Reumatología. Resultados: de los casos, 19 pacientes tenían genotipo homocigoto silvestre, 12 con genotipo heterocigotos y sólo un paciente mostró el polimorfismo en estado homocigoto. De los controles, 17 sujetos mostraron genotipos heterocigotos silvestres, 14 eran heterocigotos y sólo en uno se encontró que era homocigoto polimórfico. Se obtuvo una razón de momios de 0.84 y chi cuadrada de 0.17, por lo que no hubo diferencia estadísticamente significativa. Conclusiones: se demostró que no hay diferencia estadísticamente significativa entre pacientes con lupus eritematoso sistémico y controles respecto a la existencia de CD24v.
RESUMO
Asthma is characterized by chronic airway inflammation, which induces airway remodelling of the extracellular matrix over time. Matrix metalloproteinases (MMPs) are involved in this process, and single-nucleotide polymorphisms (SNPs) in MMP genes may influence their mRNA expression levels or abilities to bind substrates and inhibitors, thereby contributing to asthma predisposition and severity. MMP-9 is highly expressed in airways and many studies support its involvement in asthma pathogenesis; however the contribution of MMP-9 SNPs is controversial. To investigate whether MMP-9 SNPs are associated with childhood-onset asthma in Mexican patients we conducted a case-control study including 403 children with clinical asthma diagnoses and 426 healthy controls from Mexico. The cases and controls were matched by ethnicity and gender. We found that the SNPs rs2274755, rs17577, and rs3918249 were associated with asthma risk. The most significant associations were with rs2274755 (OR=2.10, 95% CI 1.31-3.39, P=0.001) and rs17577 (OR=2.07, 95% CI 1.29-3.30, P=0.001); which were in strong linkage disequilibrium. Both SNPs were also associated with atopic asthma (OR=2.38, 95% CI 1.44-3 · 96, P=0.0005). The SNP rs3918249 exhibited a female gender-dependent association with asthma (OR=1.66, 95% CI 1.14-2.43, P=0.007). Our results suggest that MMP-9 polymorphisms could play a role in the susceptibility to childhood-onset asthma.
Assuntos
Asma/genética , Metaloproteinase 9 da Matriz/genética , Polimorfismo Genético , Adolescente , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , México , Polimorfismo de Nucleotídeo Único , RiscoRESUMO
BACKGROUND: Odontogenic necrotizing fasciitis of the neck is a fulminant infection of odontogenic origin that quickly spreads along the fascial planes and results in necrosis of the affected tissues. It is usually polymicrobial, occurs frequently in immunocompromised patients, and has a high mortality rate. CASE PRESENTATION: A 69-year old Mexican male had a pain in the maxillar right-canine region and a swelling of the submental and submandibular regions. Our examination revealed local pain, tachycardia, hyperthermia (39°C), and the swelling of bilateral submental and submandibular regions, which also were erythematous, hyperthermic, crepitant, and with a positive Godet sign. Mobility and third-degree caries were seen in the right mandibular canine. Bacteriological cultures isolated streptococcus pyogenes and staphylococcus aureus. The histopathological diagnosis was odontogenic necrotizing fasciitis of the submental and submandibular regions. The initial treatment was surgical debridement and the administration of antibiotics. After cultures were negative, the surgical wound was treated with a growth factor-enriched autologous plasma eight times every third day until complete healing occurred. CONCLUSIONS: The treatment with a growth factor-enriched autologous plasma caused a rapid healing of an extensive surgical wound in a patient with odontogenic necrotizing fasciitis. The benefits were rapid tissue regeneration, an aesthetic and a functional scar, and the avoidance of further surgery and possible complications.
RESUMO
Trigger and risk factors in asthma are multiple, the most relevant at the time are: genetic, infectious (viral, bacterial, fungi and parasites), environmental (allergens, smoking, irritants, pollutants of cars, industries, work environment, etc.) and obesity. Asthma severity meets influenced by the age, sex, pregnancy, immunological system immaturity and the atopic march. The pathogeny of the inflammatory allergic process more than an imbalance Th1/Th2, mast cells, eosinophils and IgE, today includes the important participation of other elements such as: Th17 or IL-17, IL-23, IL-25, IL-27, Tregs, TLRs, NODs, MAs, DCs, bronchial epithelial cells, chemokines, neurokinins, ICAM-1, NO (iNO). Besides other elements that influence the inflammatory response amplification and the remodeling of the airway epithelium.
Assuntos
Asma/etiologia , Fatores Etários , Asma/imunologia , Asma/microbiologia , Humanos , Fatores de RiscoRESUMO
There is a great deal of evidence that points to the association of the tumor necrosis factor-alpha (TNF-alpha) gene as a common genetic factor in the pathogenesis of diseases that are caused by inflammatory and/or autoimmune etiologies. Two single nucleotide polymorphisms (SNPs) identified in the TNF-alpha promoter region have been associated with disease susceptibility and severity. We investigated whether -308G/A and -238G/A TNF-alpha polymorphisms were associated with asthma, systemic lupus erythematosus (SLE), and juvenile rheumatoid arthritis (JRA) in a pediatric Mexican population. In a case-control study of 725 patients (asthma: 226, JRA: 171, and SLE: 328) and 400 control subjects, the participants were analyzed using the allelic discrimination technique. The genotype distribution of both TNF-alpha polymorphisms was in Hardy-Weinberg equilibrium in each group. However, there were significant differences in the allele frequency of TNF-alpha-308A between the patients and the healthy controls. This allele was detected in 2.9% of the controls, 6.0% of asthmatic and JRA patients (p = 0.002 and p = 0.0086), and 6.7% of SLE patients (p = 0.00049); statistical significance was maintained after ancestry stratification (asthma: p = 0.0143, JRA: p = 0.0083, and SLE: p = 0.0026). Stratification by gender showed that the risk for the -308A allele in asthma and JRA was greater in females (OR = 4.16, p = 0.0008 and OR = 4.4, p = 0.0002, respectively). The TNF-alpha -238A allele showed an association only with JRA in males (OR = 2.89, p = 0.004). These results support the concept that the TNF-alpha gene is a genetic risk factor for asthma, SLE, and JRA in the pediatric Mexican population.
Assuntos
Artrite Juvenil/genética , Asma/genética , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Adolescente , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , México , Fatores de Risco , Fatores SexuaisRESUMO
La apoptosis (muerte celular programada) es un mecanismo que implica un suicidio fisiológico para mantener la homeostasia celular en una variedad de tejidos. Fas (APO-1; CD95) es una importante vía celular responsable de la inducción de la apoptosis en diversos tejidos. La eosinofilia en la sangre periférica y en los tejidos es característica de los padecimientos alérgicos, como el asma. En estos padecimientos, la apoptosis del eosinófilo está sobrerregulada a través de IL-5 y GM-CSF. Para inducir apoptosis en el eosinófilo se han utilizado los glucocorticoides, teofilina y algunos macrólidos, procedimiento que puede representar un mecanismo para promover la solución de la inflamación en los padecimientos alérgicos.
Assuntos
Apoptose , Asma , Eosinofilia , Hipersensibilidade , Granulócitos , Inflamação , NecroseRESUMO
El origen de la alegria responde a diversos factores y depende de la interacción de situaciones ambientales en individuos genéticamente susceptibles. El riesgo de contraer un padecimiento alérgico y la tendencia a desarrollar alergía en forma temprana, están fuertemente influidos por factores genéticos e historia familiar de padecimientos alérgicos. La genética de la atopia, sin embargo, no se ha comprendido totalmente. Aunque se asocie con aberraciones bioquímicas e inmunológicas junto con genes en los cromosomas, 5 y 11, los factores del medio ambiente juegan un papel principal en el desarrollo del padecimiento alérgico. Los mecanismos de éstos en forma individual son desconocidos, y se necesita más información sobre la dinámica de producción y de contaminantes en interiores, tasas de descomposición y factores ambientales que favorecen o crean las fuentes de contaminación del aire en interiores
Assuntos
Humanos , Meio Ambiente , Exposição Ambiental , Hipersensibilidade Imediata/etiologia , Hipersensibilidade Imediata/genética , Alérgenos/efeitos adversos , Fatores de RiscoRESUMO
La prolactina es una hormona hipofisiaria con diversas funciones, entre ellas, inmunorreguladoras. Los pacientes con prolactinemia cursan con hiperprolactinemia. Se comunican dos casos de pacientes con prolactinemia asociada a enfermedades autoinmunitarias: el primero, masculino con eslcerosis múltiple y, el segundo, una mujer con lupus eritematoso sistémico. En ambos, el tratamiento de la hiperprolactinemia se hizo con bromocriptina, misma que se relacionó con una evolución satisfactoria y permitió reducir las dosis de medicamentos inmunosupresores. El tratamiento con bromocriptina en el paciente con esclerosis múltiple se relacionó con la recuperación de las funciones neurológicas y en la paciente con lupus eritematoso sistémico, al suspenderlo, con recaída. En los padecimientos autoinmunitarios se deberá valorar la función hipofisiaria para descartar alteraciones que pudieran condicionar hiperprolactinemia, que sin duda exacerba dichos problemas
Assuntos
Humanos , Masculino , Feminino , Adulto , Autoimunidade , Bromocriptina/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Hiperprolactinemia/tratamento farmacológico , Hiperprolactinemia/imunologia , Lúpus Eritematoso Sistêmico/tratamento farmacológicoRESUMO
A 17 pacientes con diagnóstico de vasculitis primaria idiopática se les realizó valoración inmunitaria y de anticuerpos antivirales. Se comparó su biometría hemática y sus anticuerpos antivirales con 25 testigos sanos. Todos los pacientes y testigos HIV y HBV resultaron negativos. Se demostró actividad viral por IgM en ocho pacientes: cinco con púrpura vascular, una con enfermedad de Takayazu, una con poliarteritis nodosa y la otra con eritema nodoso. Ningún testigo tuvo IgM positiva. Se detectaron 14 anormalidades en la biometría hemática de los pacientes y en cuatro testigos. Los pacientes exhibieron respuestas de anticuerpos IgG menores que los testigos, alteraciones en subpoblaciones linfocitarias y complejos inmunitarios circulantes. El 47 por ciento de los pacientes tenía infección viral activa, pero la característica predominante fue una respuesta inmunitaria anormal en 82 por ciento
Assuntos
Humanos , Masculino , Feminino , Adulto , Antivirais , Vasculite/sangue , Vasculite/classificação , Vasculite/imunologia , Vasculite/virologia , Viroses , Viroses/sangue , Viroses/complicaçõesRESUMO
El virus de Epstein Barr (EBV) se ha relacionado con diversos padecimientos. Se comunica el caso de tres pacientes en quienes el virus Epstein Barr se manifestó con un curso clínico poco frecuente: Caso 1: hipergammaglobulinemia policlonal, femenina de 47 años de edad con lupus eritematoso sistémico y datos clínicos de mononucleosis infecciosa, pero con evolución hacia una forma crónica de gammopatía policlonar, con IgM predominante contra VEB. Caso 2: encefalitis con desmielinización, masculino de 32 años de edad que presentó alteraciones neurológicas centrales, anticuerpos IgM para VEB y lesión demielinizante en imagen de resonancia magnética. Caso 3: leucoplaquia vellosa, masculino de 40 años de edad con tumoración amigdalina, y anticuerpos IgM persistentes contra VEB. El tratamiento antiviral e inmunomodulador (específico para cada caso), condicionó una respuesta clínica satisfactoria en los tres pacientes