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1.
Rev. patol. respir ; 22(supl.2): S202-S210, jul. 2019. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-188013

RESUMO

La piedra angular del tratamiento de la enfermedad pulmonar obstructiva crónica (EPOC) es la broncodilatación, y en los últimos años se ha desarrollado un importante número de moléculas que han ido cambiando paulatinamente la práctica clínica habitual en estos pacientes. Los fármacos multivalentes con más de un mecanismo de acción broncodilatador representan el próximo paso en materia de relajación del músculo liso bronquial, pero dada la creciente evidencia sobre el estrés oxidativo y estado inflamatorio generalizado de la EPOC, existe una clara tendencia a demostrar el beneficio de formulaciones antiinflamatorias respecto a un potencial control sintomático, y secundariamente la reducción de la importante carga económica que supone el consumo de recursos sanitarios. En este capítulo se pretende dar un resumen esquemático y actualizado sobre los fármacos en investigación en EPOC en las fases previas de su desarrollo clínico


Bronchodilators are the cornerstone of Chronic obstructive pulmonary disease (COPD) treatment, and in the last years an important number of new molecules have changed gradually the clinical practice in these patients. Multivalent drugs with more than one mechanism of action represent the next step in terms of bronchial smooth muscle relaxation, although, giving the growing evidence of oxidative stress and generalized inflammation in COPD, there is a clear tendency to test the potential benefit of new anti-inflammatory drugs for symptoms control in the first place and consequently the reduction of the high economic burden of this disease. This chapter aims to give a schematical and updated review of new drugs for COPD in the preclinical phases of their clinical development


Assuntos
Humanos , Drogas em Investigação/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Relaxamento Muscular/efeitos dos fármacos , Broncodilatadores/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Receptores do Fator de Necrose Tumoral/antagonistas & inibidores , Interleucina-1/antagonistas & inibidores , Interleucina-13/antagonistas & inibidores , Interleucinas/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Inibidores de Fosfodiesterase/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos
2.
Nutr. hosp ; 35(4): 841-846, jul.-ago. 2018. tab
Artigo em Inglês | IBECS | ID: ibc-179876

RESUMO

Background: iodine contributes to maintain the balance of the reduced and oxidized species and is also required for thyroid hormones synthesis as triiodothyronine (T3), which regulates energy metabolism in adults. Increased body mass index (BMI) is associated with inflammatory markers, oxidative stress, and abnormalities in adipocytokines secretions that are associated with obesity and chronic disease. Objective: the aim of the study is to investigate the association between ioduria, oxidative stress, total antioxidant status, adiponectin and interleukin-1 (IL-1) with BMI in healthy adults. Methods: a cross-sectional study was performed in 114 healthy adult volunteers, aged 25-44 years, divided according to their BMI in three groups: normal weight (BMI < 25), overweight (BMI ≤ 25 to < 30), obesity (BMI ≥ 30). Adiponectin and IL-1 were measured by immune-enzymatic assays; oxidative stress, by determination of malondialdehyde (MDA); and total antioxidant status (TAS) and ioduria were measured by colorimetric assays. Statistical association was done by Spearman’s test. Results: overweight and obese subjects have higher serum levels of MDA, TAS and IL-1 vs normal weight subjects. Moreover, overweight and obese subjects have lower levels of iodine and adiponectin vs normal weight subjects. MDA was positively related only with obese subjects (r = 0.787, p = 0.008) and TAS with overweight (r = 0.398, p = 0.049) and obese subjects (r = 0.448, p = 0.030). In contrast, a reverse correlation with ioduria was found in obese subjects (r = 0.463, p = 0.001). Adiponectin was negatively related only in obese subjects (r = -0.477, p = 0.001), while, IL-1 was positively related with the increase of BMI (overweight r = 0.287, p = 0.050; and obesity r = 0.515, p = 0.006).Conclusion: alteration in IL-1, adiponectin and oxidative stress levels were found to be related to overweight and obesity; also, iodine levels decreased when BMI increased, contributing to loss of redox equilibrium. All this data may play an important role in etiopathogenesis of chronic disease related to the increase of BMI


Antecedentes: el yodo contribuye a mantener el balance de especies reducidas y oxidadas y también es requerido para la síntesis de hormonas tiroideas como la triyodotironina (T3), que regula el metabolismo energético en el adulto. El incremento en el índice de masa corporal esta asociado con marcadores inflamatorios, estrés oxidativo y anormalidades en la secreción de adipocitocinas que están asociadas con la obesidad y enfermedades crónicas degenerativas. Objetivo: el objetivo del estudio es investigar la asociación entre yodaría, estrés oxidativo, estado antioxidante total, adiponectina, e interleucina 1, con el IMC en adultos saludables. Métodos: se realizo un estudio transversal con 114 adultos, 33 hombres y 81 mujeres, de entre 25 y 44 años, a los cuales se les midieron sus características clínicas, antropométricas y parámetros sociodemográficos. Los niveles de adiponectina e interleucina 1 se midieron por inmunoensayo; el estrés oxidativo, el estado antioxidante total y la yodaría, por métodos colorimétricos. Resultados: los sujetos con sobrepeso y obesidad tienen altos niveles de MDA, FRAP e IL-1 vs. los sujetos con peso normal. Sin embargo, los sujetos con sobrepeso y obesidad tienen bajos niveles de yodo y adiponectina vs. los sujetos con normopeso. El estrés oxidativo (MDA) se relacionó positivamente solo en sujetos obesos (r = 0,787, p = 0,008) y el estado antioxidante (FRAP) con sobrepeso (r = 0,398, p = 0,049) y obesidad (r = 0,448, p = 0,030). En contraste, se encontró una asociación entre yoduria y sujetos obesos (r = 0,463, r = 0,001). Los niveles de adiponectina se relacionaron negativamente solo en sujetos obesos (r = -0,477, p = 0,001), mientras que la IL-1 fue positivamente relacionada con el incremento de BMI (sobrepeso r = 0,287, p = 0,050; y obesidad r = 0,515, p = 0,006). Conclusión: La alteración en los niveles de interleucina-1, adiponectina y estrés oxidativo se relacionaron en sujetos con sobrepeso y obesidad; además, los niveles de yodo disminuyeron con el incremento del IMC, contribuyendo a la pérdida del equilibrio redox. Estos datos juegan un papel importante en la etiopatogenesis relacionada con enfermedades crónicas relacionadas con el incremento del IMC


Assuntos
Humanos , Masculino , Feminino , Adulto , Adiponectina/sangue , Índice de Massa Corporal , Interleucina-1/sangue , Iodo/urina , Estresse Oxidativo , Adipocinas/sangue , Estudos Transversais , Voluntários Saudáveis , Obesidade/sangue , Sobrepeso/sangue , Fatores Socioeconômicos
6.
Allergol. immunopatol ; 44(6): 542-546, nov.-dic. 2016. tab
Artigo em Inglês | IBECS | ID: ibc-157876

RESUMO

Background: Cytokines, including interleukin-1 (IL-1), seem to contribute towards the pathogenesis of juvenile idiopathic arthritis (JIA), so this study was designed to evaluate the associations of IL-1 gene cluster and IL-1 receptor (IL-1R) gene single nucleotide polymorphisms (SNPs) with JIA proneness in Iranian population. Materials and methods: Genomic DNA of 55 Iranian patients with JIA and 140 controls were extracted and typed for IL-1alpha gene at position −889, IL-1beta gene at positions −511 and +3962, IL-1R gene at position Pst-I 1970, and interleikin-1 receptor antagonist (IL-1Ra) gene at position Mspa-I 11100, using polymerase chain reaction with sequence-specific primers method, and compared between patients and controls. Results: The CC genotype of IL-1Ra at Mspa-I 11100 position was found to be more frequent in patients with JIA compared to healthy individuals (P=0.03), although the CT genotype at the same position was significantly higher in the control group in comparison with patients with JIA (P=0.02). No significant differences were observed between the two groups of case and control for IL-1alpha (−889 C/T), IL-1beta (−511 C/T and +3962 C/T) and IL-1R (Pst-1 1970 C/T). Conclusion: The results of the present investigation suggest that certain IL-1Ra gene variants are associated with individuals’ susceptibility to JIA. Nevertheless, further studies are required to establish the results of the current study (AU)


No disponible


Assuntos
Humanos , Artrite Juvenil/genética , Interleucina-1/análise , Polimorfismo de Nucleotídeo Único/genética , Irã (Geográfico)/epidemiologia , Marcadores Genéticos , Predisposição Genética para Doença , Estudos de Casos e Controles , Reação em Cadeia da Polimerase
7.
Allergol. immunopatol ; 44(1): 23-31, ene.-feb. 2016. ilus, graf
Artigo em Inglês | IBECS | ID: ibc-147480

RESUMO

Background: House dust mites (HDMs) faeces are the main factor involved in respiratory disorder. The true HDMs,Dermatophagoides pteronyssinus and D. farinae, detected in the samples collected from the house dust are the most important causes of allergic disorders such as asthma. Objective: The aim of this investigation was to study the curcuma and karkade amelioration of the allergenic immunological disorder, especially some cytokines, IgE and ROS, caused by the faeces of the dominant true HDM, D. pteronyssinus and D. farinae in valley and desert houses in EL-Minia Governorate, respectively. Methods: HDM cultures, faeces isolation, plant extraction and ELISA techniques were used. Male albino rats were classified into control, inhaled, and treated groups. Results: The present immunological study on the dominant allergenic true HDMs, D. pteronyssinus and D. farinae, revealed that significantly higher serum levels of TNF-α, IL-1β, IL-4, IL-13 and IgE were found in rats treated with both D. pteronyssinus and D. farinae faeces than the other groups. In addition, statistical analysis of ROS data showed significant difference between the curcuma- and karkade-treated groups and either the control or the faeces-treated groups (P < 0.05). Conclusions: Some immunological disturbances caused by repeated exposure to the faeces of two dominant allergenic true HDM species (D. pteronyssinus and D. farinae) in the valley and desert houses could be ameliorated by curcuma and karkade (AU)


No disponible


Assuntos
Animais , Masculino , Feminino , Ratos , Doenças do Sistema Imunitário/complicações , Doenças do Sistema Imunitário/diagnóstico , Doenças do Sistema Imunitário/imunologia , Asma/diagnóstico , Infestações por Ácaros/epidemiologia , Infestações por Ácaros/imunologia , Infestações por Ácaros/prevenção & controle , Ácaros/imunologia , Asma/imunologia , Asma/veterinária , Linfotoxina-alfa/imunologia , Linfotoxina-alfa/isolamento & purificação , Interleucina-4 , Interleucina-13/imunologia , Interleucina-13/isolamento & purificação , Interleucina-1/imunologia , Imunoglobulina E/análise , Imunoglobulina E/imunologia
8.
Med. oral patol. oral cir. bucal (Internet) ; 20(6): e737-e743, nov. 2015. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-144707

RESUMO

Background: Interleukin-1 (IL-1) is a proinflammatory cytokine that plays an important role in the pathogenesis of periodontitis, and so it might be useful to detect high-risk cases of peri-implantitis. It has been reported that IL-1 polymorphisms and smoking habit have a synergic effect, increasing the incidence of peri-implantitis. The aim of the present study was to evaluate the relationship between IL-1 gene polymorphisms and peri-implantitis in smoking patients. Material and Methods: A case-control study was performed in 27 patients with peri-implantitis and 27 patients with healthy implants. All patients included were smokers. IL-1A-C889T, IL-1B+C3953T and IL-1RN+T2018C were identified by polymerase chain reaction (PCR) amplification in order to establish a relation between these variables and the presence of peri-implantitis. A bivariate analysis was performed and odds-ratio (OR) were calculated. Results: The incidence of peri-implantitis was significantly higher in patients with previous history of periodontitis (p=0.024; OR=10.9). Both groups were similar regarding IL-1A-C889T, IL-1B+C3953T and IL-1RN+T2018C genotypes. No increased risk in heavy smokers with IL-1 polymorphism was found. Conclusions: IL-1 genotypes do not seem to be good predictors of peri-implantitis in the great majority of smoking patients. Furthermore, no synergic effect was found between IL-1 genotypes and heavy smokers. Patients with a previous history of periodontitis were more prone to peri-implantitis (AU)


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Interleucina-1 , Receptores Tipo I de Interleucina-1/análise , Receptores Tipo I de Interleucina-1/genética , Fumar/patologia , Tabagismo/complicações , Tabagismo/patologia , Peri-Implantite/complicações , Peri-Implantite/diagnóstico , Peri-Implantite/prevenção & controle , Peri-Implantite/fisiopatologia , Periodontite/complicações , Periodontite/patologia , Reação em Cadeia da Polimerase/métodos , Razão de Chances , Polimorfismo Genético
9.
Allergol. immunopatol ; 42(3): 212-215, mayo-jun. 2014. tab
Artigo em Inglês | IBECS | ID: ibc-122680

RESUMO

Background: Interleukin-1 (IL-1) seems to have an important role in early reactions towards microbes, while its genetic variability could affect this role in atopic patients who have a distressed immunity towards dermatological infections. Methods: Eighty-nine patients with atopic dermatitis (AD), who were referred to a main referral paediatric hospital, were enrolled in this study. Single nucleotide polymorphisms (SNP) of the following IL-1 cluster genes were assessed in this group of patients: IL-1α −889, IL-1β −511, IL-1β +3962, IL-1R Pst-I 1970, and IL-1RA Mspa-I 11100. The results were compared with a group of 140 healthy subjects from the same region. Results: Fourteen percent of the controls had TT homozygous genotype in IL-1R at position Pst-I 1970, while only 2% of the patients with AD had this genotype (p = 0.005, OR: 0.14, 95%CI: 0.02-0.64). The CC homozygous genotype was the most common genotype in IL-1α position −889 and IL-1β at position +3962 in both groups of patients with AD and the controls, while the TC heterozygous genotype was the most common genotype in IL-1β at position −511 and IL-1R at position Pst-I 1970, with no significant difference between the two groups. Conclusions: This study showed a significant negative association in the IL-1R Mspa-I 11100 TT homozygous genotype in the patients with AD (AU)


No disponible


Assuntos
Humanos , Dermatite Atópica/imunologia , Interleucina-1/imunologia , Polimorfismo de Nucleotídeo Único/imunologia , Citocinas/análise , Frequência do Gene
10.
J. investig. allergol. clin. immunol ; 23(7): 455-461, nov.-dic. 2013. tab
Artigo em Inglês | IBECS | ID: ibc-117660

RESUMO

Background: Allergic rhinitis is a complex polygenic disorder of the upper respiratory tract. Given that proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin (IL) 1 seem to play a role in the development of allergic rhinitis, we evaluated the associations between various single-nucleotide polymorphisms (SNPs) of the TNF and IL1 genes in a case-control study. Methods: The study population comprised 98 patients with allergic rhinitis. Genotyping was performed using polymerase chain reaction with sequence-specific primers for 2 TNFA promoter variants (rs1800629 and rs361525), 1 variant in the promoter region of IL1A (rs1800587), 2 SNPs in the IL1B gene (rs16944 and rs1143634), 1 variant in the IL1 receptor (rs2234650), and 1 in IL1RA (rs315952). Results: Patients who were homozygous for the T allele of rs16944 in IL1B had an 8.1-fold greater risk of allergic rhinitis than those with the C allele. In TNFA, a significant relationship was also detected between rs1800629 and rs361525 and allergic rhinitis. Except for rs1800587 in IL1A and rs315952 in IL1RA, significant differences were found between the patient and control groups for all other SNPs. Conclusions: We found that allelic variants in the TNFA and IL1 genes were not only associated with the risk of developing allergic rhinitis, but also affected disease course and severity (AU)


Antecedentes: La rinitis alérgica es una alteración poligénica compleja de las vías respiratorias. El TNF y la familia de la IL-1, como citoquinas proinflamatorias, parecen jugar un papel en el desarrollo de la rinitis alérgica. En este estudio de casos y controles, se evalúan las posibles asociaciones de diferentes polimorfismos de nucleótidos simples (SNPs) de los genes que regulan TNF- α e IL1. Métodos: Se estudiaron 19 pacientes con rinitis alérgica, los cuales fueron genotipados mediante PCR para primeras especie-específicos, para dos variantes del promotor del TNF- α (rs1800629 y rs361525), uno en el receptor de IL1 (rs2234650), dos SNPs en el gen de IL1ß (rs16944 y rs1143634), uno en el receptor de IL1 receptor (rs2234650) y IL1RA (rs315952). Resultados: En cuanto a los resultados obtenidos, los pacientes homicigotos para el alelo T de rs16944 en IL1ß mostraron un riesgo 8.1 veces mayor de tener rinitis alérgica que los que presentaban el alelo C. Con respecto al TNF- α, se observó una relación significativa entre los dos SNPs rs1800629 y rs361525 con la presentación de una rinitis alérgica. Excepto rs1800587, en IL1 α, y rs315952 en IL1RA, encuentran una diferencia significativa entre el grupo control y el de pacientes para el resto de los SNPs. Algunos SNPs se asociaron con el curso y con la gravedad de la enfermedad. Conclusiones: En conclusión, encontramos variantes genéticas de TNF-α y IL1 que se asocian con el riesgo de desarrollar una rinitis alérgica, y que también afectan al curso y gravedad de la enfermedad (AU)


Assuntos
Humanos , Rinite Alérgica Perene/imunologia , Polimorfismo de Nucleotídeo Único/imunologia , Fatores de Necrose Tumoral/imunologia , Interleucina-1/imunologia , Técnicas de Genotipagem/métodos , Predisposição Genética para Doença , Quimiocinas/imunologia
11.
J. investig. allergol. clin. immunol ; 23(7): 487-494, nov.-dic. 2013. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-117664

RESUMO

Background: Asthma is one of the most common chronic inflammatory diseases in developed countries. Susceptibility to asthma is associated with interaction between multiple genes and environmental factors. Several cytokines play a major role in the pathophysiology of the disease. Objective: We analyzed the distribution of cytokine gene polymorphisms in a group of patients with asthma and a control group in order to determine the effect of these variants, or their combinations, on the development of clinical phenotypes. Methods: We genotyped 22 single-nucleotide polymorphisms (SNPs) corresponding to 13 cytokine genes (IFNG, IL1A, IL1B, IL1R1, IL1RN, IL2, IL4, IL4R, IL6, IL10, IL12B, TGFB1, and TNFA) in 376 individuals (219 asthmatic patients and 157 controls). Genetic association was evaluated using genotype and allele models for different asthma phenotypes. Gene–gene interactions were explored using multifactor dimensionality reduction. Results: Genotype AC of IL12B -1188 was associated with the presence of asthma. A significant association was detected between 2 SNPs analyzed in TNFA (–308 and –238) and atopic asthma and severe-persistent asthma. The IL1B TT haplotype (3962T and –511T) was also associated with atopy and moderate-persistent asthma. Conclusion: Our data show that the presence of SNPs in IL12B, TNFA, and IL1B was significantly associated with asthma, atopy, and severity of asthma. We also highlight the importance of genetic context, haplotype, and gene–gene interaction analysis in genetic association studies (AU)


Introducción: El asma es una de las enfermedades inflamatorias crónicas más frecuentes en los países desarrollados. La susceptibilidad al asma viene determinada por la interacción entre múltiples genes y factores ambientales. En la fisiopatología de esta enfermedad las citocinas desempeñan un papel importante. Objetivo: El objetivo de este estudio fue analizar la distribución de varios polimorfismos en genes de citocinas en un grupo de pacientes con asma y en un grupo control para determinar la influencia que estas variantes, o sus combinaciones génicas, desempeñan en los fenotipos clínicos. Métodos: Se analizaron 22 SNP correspondientes a 13 genes codificantes de citocinas (IFNG, IL1A, IL1B, IL1R1, IL1RN, IL2, IL4, IL4R, IL6, IL10, IL12B, TGFB1, y TNFA) en 376 individuos, 219 sujetos asmáticos y 157 controles. Las asociaciones genéticas fueron evaluadas empleando modelos genotípicos y alélicos para los distintos fenotipos de asma. Las interacciones gen-gen se analizaron mediante la plataforma Multifactor Dimensionality Reduction Platform (MDR). Resultados: El genotipo AC de IL12B -1188 se asoció con la presencia de asma. Dos SNP analizados en el gen TNFA (TNFA-308, and TNFA-238) mostraron una asociación significativa con el asma atópica y con la presencia de asma persistente grave. El haplotipo TT de IL1B (3962T y -511T) también se asoció con la presencia de atopia y con asma persistente moderada. Conclusiones: Nuestros datos muestran que la presencia de estos SNP en los genes IL12B, TNFA y IL1B se asocian significativamente con el asma, la atopia y con la gravedad del asma. También recalcamos la importancia del contexto génico, haplotipos e interacciones gen-gen en los estudios de asociación génica (AU)


Assuntos
Humanos , Polimorfismo Genético , Asma/imunologia , Hipersensibilidade Imediata/imunologia , Interleucina-1/imunologia , Interleucina-12/imunologia , Suscetibilidade a Doenças/imunologia , Citocinas/análise
13.
Cient. dent. (Ed. impr.) ; 9(2): 35-44, mayo-ago. 2012. tab
Artigo em Espanhol | IBECS | ID: ibc-103912

RESUMO

Introducción El objetivo principal de la revisión fue determinar la asociación entre los polimorfismos de la interleukina 1 (IL-1) y la posible repercusión de los mismos en la severidad de la enfermedad periodontal. Material y método Se realizó una búsqueda bibliográfica de revisiones sistemáticas y estudios longitudinales publicados desde 1990 hasta el año2011 sobre los porlimorfismos de la IL-1 en las bases de datos: PubMed, EMBASE y Cochrane. Resultados De los artículos revisados que tratan de establecer correlación entre los polimorfismos de la IL-1 y la enfermedad periodontal,24 fueron estudios longitudinales y 1 un estudio retrospectivo. De los 25 estudios, 9establecen relación entre diferentes variables clínicas y los polimorfismos de la IL-1.Los 16 restantes intentan relacionar la presencia de ciertos polimorfismos de la IL-1con la presencia y/o ausencia de periodontitis. Discusión Existe una relación demostrada entre los polimorfismos de la IL-1 y la severidad de la enfermedad periodontal constada en numerosos estudios por el empeoramiento de las (..) (AU)


The principal aim of the review was to determine the association between interleukin 1(IL-1) and periodontitis, and the possible repercussions of the same for the severity of periodontal disease. Material and method A bibliographic search was conducted, looking for systematic reviews and longitudinal studies published between 1990 and 2011into IL-1 polymorfisms, in the following databases: PubMed, EMBASE and Cochrane. Results Of the articles reviewed that sought to establish a correlation between IL-1polymorphisms and periodontal disease, 24were longitudinal studies and 1 was a retrospective study. Of the 25 studies, 9established a relationship between different clinical variables and the IL-1 polymorphisms. The remaining 16 sought to relate the presence of certain polymorphisms to IL-1 with the presence and/or absence of (..) (AU)


Assuntos
Humanos , Periodontite/genética , Polimorfismo Genético , Interleucina-1/genética , Índice de Gravidade de Doença
15.
Reumatol. clín. (Barc.) ; 8(supl.1): 15-19, mar. 2012.
Artigo em Espanhol | IBECS | ID: ibc-147106

RESUMO

Los registros estiman que un tercio de los pacientes con artritis psoriásica (Aps) son «resistentes» a los bloqueantes del TNF-alfa. Por ello, la búsqueda de nuevos abordajes terapéuticos de la enfermedad es un objetivo que se puede considerar justificado. Actualmente las opciones terapéuticas que han probado su eficacia, son las vinculadas a la inhibición de la vía coestimuladora del linfocito T (abatacept y alefacept) y el bloqueo de la fracción P40 de la IL-12 e IL-23 (ustekinumab). Una novedosa vía de inhibición, que merece especial atención, es la que ofrece Apremilast. Esta molécula inhibe la fosfodiesterasa IV encargada de hidrolizar la adenosina monofosfato cíclica a adenosina monofosfato, lo que provoca un aumento de la cAMP. Este metabolito se relaciona con una disminución del TNF alfa. Capaz de provocar una modesta eficacia (respuesta ACR 20 del 43%), estudios posteriores han demostrado una mejoría en la escala visual analógica y en el SF36 respecto al grupo placebo. Actualmente hay en marcha 5 ensayos clínicos en fase III que evaluarán su eficacia en parámetros de inflamación y de progresión radiográfica. El espectro de posibilidades, ante el fracaso terapéutico con anti-TNF alfa, se amplía con la aparición de diversos reportes donde se ha mostrado eficacia en la utilización individual con agentes inhibidores del CD20 y de la IL-1. Se está demostrando en pacientes con artritis reumatoide (AR) la eficacia de las moléculas que inhiben la transducción de las señales de las citocinas (Anti-JAK), por lo que es posible que en un futuro sean utilizadas en pacientes con Aps (AU)


Registries estimate that one third of patients with psoriatic arthritis (PsA) are “resistant” to of TNF-alpha blockers. Therefore, the search for new approaches to treatment of this disease may be justified. Currently the treatment options that have proven effective are associated with inhibition of the T cell costimulatory pathway (abatacept and alefacept) and blocking the P40 fraction of IL-12 and IL-23 (ustekinumab). A novel pathway inhibition, which deserves special attention is offered by apremilast. This molecule inhibits phosphodiesterase IV, responsible for hydrolyzing cyclic adenosine monophosphate to adenosine monophosphate, which causes an increase in cAMP. This metabolite is associated with decreased TNF-alpha. It has a modest efficacy (ACR 20 response of 43%), and subsequent studies have shown an improvement in visual analog scale and the SF36 compared to placebo. Currently there are five clinical trials in phase III to assess its effectiveness in parameters of inflammation and radiographic progression. The spectrum of possibilities before treatment failure with anti-TNF alpha, is augmented by the appearance of several reports that show efficacy with the individual use of CD20 inhibitors and IL-1. In patients with rheumatoid arthritis (RA) the effectiveness of molecules that inhibit signal transduction of cytokines (Anti-JAK) has been proven, so it is possible that in the future they may be used in patients with PsA (AU)


Assuntos
Humanos , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/metabolismo , Artrite Psoriásica/patologia , Terapia de Alvo Molecular , Remodelação Óssea , AMP Cíclico/fisiologia , Citocinas/antagonistas & inibidores , Interleucina-1 , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Janus Quinases/antagonistas & inibidores , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Ativação Linfocitária , Depleção Linfocítica , Antígenos CD20 , Antirreumáticos/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Progressão da Doença , Resistência a Medicamentos , Inflamação , Oxazinas/uso terapêutico , Inibidores da Fosfodiesterase 4 , Piridinas/uso terapêutico , Subpopulações de Linfócitos T , Subpopulações de Linfócitos T/imunologia , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
16.
Med. oral patol. oral cir. bucal (Internet) ; 16(4): 467-472, jul. 2011. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-93033

RESUMO

Objective: In jawbones, ameloblastomas and odontogenic keratocysts share many clinical features in commonsuch as aggressiveness, high recurrence rates and radical management options. Understanding the pathogenesisand biological aspects of these tumors would improve the success of diagnose and treatment procedures. Theaim of this study was to exhibit the reasons of high recurrence rates and growth potentials of ameloblastomas andkeratocystic odontogenic tumours by investigating the expression of IL-1α and IL-6 and IL-1α -889 gene polymorphism.IL-1α and IL-6 are shown as very effective tissue degrading factors in bone remodelling.Study Design: This study included 25 cases of ameloblastomas, 41 cases of keratocystic odontogenic tumors (parakeratinizedodontogenic keratocysts) and 8 cases of orthokeratinized odontogenic keratocysts. All histologicalslides were stained immunohistochemically to show the expression of IL-1α and IL-6. Restriction fragment lengthanalysis was used to investigate the cytokine gene polymorphism.Results and Conclusions: The higher expression rates of IL-1α and IL-6 were associated with tumor size in ameloblastomasand with cyst wall thickness in keratocystic odontogenic tumors. This finding suggested us that thecytokines IL-1α and IL-6 play a role on aggressive behaviour of ameloblastomas and keratocystic odontogenictumors by making easy bone resorption. In addition, IL-1α (-889) T polymorphism was found consistent withincreased IL-1α expression but not seem as a risk factor on the development of these tumors (AU)


Assuntos
Humanos , Cistos Odontogênicos/patologia , Odontoma/patologia , Ameloblastoma/patologia , Interleucina-6/análise , Interleucina-1/análise , Neoplasias Bucais/diagnóstico , Biomarcadores Tumorais/análise , Polimorfismo de Nucleotídeo Único/fisiologia
17.
Reumatol. clín. (Barc.) ; 6(supl.3): 20-24, mar. 2011. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-148880

RESUMO

La artritis reumatoide (AR) es una enfermedad autoinmunitaria sistémica caracterizada por sinovitis y destrucción progresiva del cartílago articular y hueso subyacente, junto con diversas manifestaciones extraarticulares. Las citocinas actúan como mediadores solubles responsables del proceso inflamatorio. El bloqueo terapéutico mediante anticuerpos monoclonales de las citocinas proinflamatorias factor de necrosis tumoral-alfa y la interleucina 1ha demostrado una clara eficacia sobre la inflamación y las manifestaciones clínicas de la AR, si bien no son eficaces en todos los pacientes. Se presenta una revisión de nuevas citocinas relevantes en la fisiopatología de la AR que representan potenciales biomarcadores inflamatorios de la AR. El reto actual consiste en desarrollar biomarcadores que permitan un diagnóstico más precoz, marcadores pronósticos y nuevos candidatos terapéuticos. La administración combinada de varias de ellas podría permitir una aproximación personalizada de estas terapias (AU)


Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovitis and progressive destruction of the joint cartilage and underlying bone, together with diverse extra-articular manifestations. Cytokines act as soluble effector mediators of the inflammatory process. Therapeutic neutralization with monoclonal antibodies against the pro-inflammatory cytokines TNF-alpha and interleukin 1 (IL-1) has shown a clear efficacy on inflammation and clinical manifestations of RA, although a percentage of patients do not respond. This review covers new relevant cytokines in the RA physiopathology and potential biomarkers of inflammation. The current challenge is to develop biomarkers that enable an earlier diagnosis, as well as prognostic markers and new therapeutic candidates. Combined administration of several of these cytokines could eventually address a personalized treatment approach for each patient (AU)


Assuntos
Humanos , Artrite Reumatoide/fisiopatologia , Interleucinas/análise , Sinovite/fisiopatologia , Citocinas/análise , Mediadores da Inflamação/análise , Inflamação/fisiopatologia , Adipocinas/análise , Interleucina-1/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Receptores do Fator de Necrose Tumoral/antagonistas & inibidores
18.
Med. clín (Ed. impr.) ; 136(supl.1): 3-9, ene. 2011. tab
Artigo em Espanhol | IBECS | ID: ibc-141327

RESUMO

Los síndromes autoinflamatorios se caracterizan por episodios de inflamación recurrentes o persistentes sin aumento de los títulos de autoanticuerpos o de los linfocitos T antígeno específicos y en ausencia de infección. Inicialmente, se incluyeron los síndromes hereditarios de fiebre periódica, grupo de enfermedades monogénicas del sistema inmune innato caracterizadas por episodios febriles recurrentes, de diferentes características clínicas, duración e intervalo, acompañados de otros síntomas. Una complicación característica de este grupo es la amiloidosis secundaria. Los avances de los últimos años han permitido identificar genes susceptibles, nuevas proteínas y caracterizar mecanismos y vías patogénicas que permiten mejorar el diagnóstico y plantear tratamientos más eficaces. Entre estas vías destacan las alteraciones de los componentes del inflamasoma, grupo de proteínas citoplasmáticas que regulan la producción de varios mediadores de la respuesta inflamatoria. En los últimos años, el grupo inicial de enfermedades autoinflamatorias monogénicas se ha incrementado al incluirse varias enfermedades de herencia poligénica (AU)


Autoinflammatory syndromes are characterised by recurrent or persistent inflammation with no increase in the antibody titers or antigen-specific T lymphocytes, and absence of infection. Initially, they included the hereditary periodic fever syndromes, a group of innate immune system monogenic diseases characterised by recurrent febrile episodes, with different characteristics, duration and interval, accompanied by other symptoms. Secondary amyloidosis is a complication in this group. The advances in the last few years has led to the identification of susceptible genes, new proteins, and characterising mechanisms and pathogenic routes that have led to an improvement in the diagnosis and establishing more effective treatments. Among these routes, are the changes in the inflammasome components, a group of cytoplasmic proteins that regulate the production of several inflammatory response mediators. The initial group of monogenic autoinflammatory diseases have increased in the last few years, due to including several polygenic hereditary diseases (AU)


Assuntos
Humanos , Doenças Autoimunes/classificação , Doenças Hereditárias Autoinflamatórias/classificação , Doenças Hereditárias Autoinflamatórias/complicações , Inflamassomos/fisiologia , Inflamação/classificação , Citocinas/fisiologia , Proteínas do Citoesqueleto/genética , Imunidade Inata , Imunoglobulina D , Amiloidose/etiologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/fisiopatologia , Inflamassomos/antagonistas & inibidores , Inflamassomos/genética , Inflamação/imunologia , Inflamação/fisiopatologia , Proteínas do Sistema Complemento/fisiologia , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/epidemiologia , Febre Familiar do Mediterrâneo/genética , Febre Familiar do Mediterrâneo/fisiopatologia , Hipergamaglobulinemia/epidemiologia , Hipergamaglobulinemia/genética , Interleucina-1/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Ativação de Macrófagos , NF-kappa B/fisiologia , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Receptores Tipo I de Fatores de Necrose Tumoral/genética
19.
Med. clín (Ed. impr.) ; 136(supl.1): 22-28, ene. 2011. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-141330

RESUMO

El gen NLRP3 (antiguamente denominado CIAS1) codifica para la proteína criopirina (o Nalp3), perteneciente a la familia de receptores de tipo Nod (NLR) del sistema inmune innato. La criopirina forma parte de un complejo citosólico multiproteico denominado Nalp3-inflamasoma, que participa decisivamente en la respuesta inmune innata e inflamatoria mediante la detección de señales de peligro, exógenas y endógenas, y ciertas partículas inorgánicas (asbesto, sílice). La presencia de mutaciones en el gen NLRP3 que generan una criopirina hiperfuncionante es la base molecular común de los síndromes periódicos asociados a criopirina (CAPS), que engloban tres entidades clínicas de gravedad clínica creciente (síndrome autoinflamatorio familiar inducido por frío, síndrome de Muckle-Wells y síndrome CINCA-NOMID). Esta criopirina hiperfuncionante provoca la producción aumentada y no regulada de ciertas citocinas inflamatorias (IL-1β, IL-18, IL-33), y la administración in vivo de agentes bloqueadores de IL-1 provoca una excelente respuesta terapéutica en los pacientes afectados de CAPS (AU)


NLRP3 gene (formerly known as CIAS1) encodes for cryopyrin (Nalp3) protein, which belongs to the Nod-like family of innate immune receptors. Cryopyrin recruits different adaptor and effectors proteins into a cytosolic macromolecular complex termed Nalp3-inflammasome, which senses both several pathogen-associated and damage-associated molecular patterns as well as inorganic particles (asbestos, silica), and triggers innate immune and inflammatory responses. Gain-of-function NLRP3 mutations are the common molecular basis of cryopyrin-associated periodic syndromes (CAPS), which encompasses three clinical entities along a spectrum of disease severity (familial cold autoinflammatory syndrome, Muckle-Wells syndrome and CINCA-NOMID syndrome). This hypermorphic cryopyrin provokes an increased, unregulated secretion of different inflammatory cytokines (IL-1β, IL-18, IL-33) in patients with CAPS, and in vivo administration of IL-1 blocking agents results in excellent therapeutic responses in these patients (AU)


Assuntos
Humanos , Proteínas de Transporte/química , Proteínas de Transporte/genética , Proteínas de Transporte/fisiologia , Síndromes Periódicas Associadas à Criopirina/tratamento farmacológico , Síndromes Periódicas Associadas à Criopirina/genética , Síndromes Periódicas Associadas à Criopirina/fisiopatologia , Inflamassomos/fisiologia , Cromossomos Humanos Par 1/genética , Citocinas , Heterogeneidade Genética , Imunidade Inata , Inflamação , Interleucina-1/antagonistas & inibidores , Mutação , Linhagem , Estrutura Terciária de Proteína
20.
Med. clín (Ed. impr.) ; 136(supl.1): 29-33, ene. 2011.
Artigo em Espanhol | IBECS | ID: ibc-141331

RESUMO

En el tratamiento de los síndromes periódicos asociados a la criopirina (CAPS), clásicamente se han usado los antiinflamatorios no esteroideos, glucocorticoides y antihistamínicos, además de un sinfín de otras moléculas, con resultados poco alentadores. El conocimiento de su carácter genético y de su etiopatogenia relacionada con el inflamasoma y la producción de interleucina 1(IL1) ha permitido el desarrollo de nuevas terapias biológicas que consiguen no sólo mejorar la sintomatología y la calidad de vida de los pacientes, sino que logran el control de la inflamación subyacente. Las terapias anti_IL-1 han demostrado en los pacientes con CAPS tener una respuesta clínica espectacular, con normalización de los marcadores inflamatorios. Es posible que el uso de estas moléculas evite el desarrollo de complicaciones tardías derivadas de la inflamación crónica (AU)


Non-steroidal anti-inflammatories, corticoids and antihistamines, as well as a great many other molecules, have classically been used to control the symptoms of cryopyrin-associated periodic syndromes (CAPS), with very few encouraging results. Knowledge of its genetic character, and its aetiopathogenesis associated with inflammasome and the production of interlekin-1 (IL-1) has led to the development of new therapeutic weapons that have not just obtained improvements of the symptoms and quality of life of the patients, but also managed to control the underlying inflammation. Results show that anakinra, an IL-1 receptor antagonist molecule, improved the clinical symptoms and the inflammatory markers of patients with CAPS has motivated research with other molecules directed against IL-1: rilonacept and canakinumab. It is likely that the use of these molecules could prevent the development of the late complications associated with chronic inflammation (AU)


Assuntos
Humanos , Anti-Inflamatórios/uso terapêutico , Síndromes Periódicas Associadas à Criopirina/tratamento farmacológico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Interleucina-1/antagonistas & inibidores , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/imunologia , Receptores de Interleucina-1/antagonistas & inibidores , Anticorpos Monoclonais/uso terapêutico , Síndromes Periódicas Associadas à Criopirina/genética , Inflamassomos/antagonistas & inibidores , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Proteínas Recombinantes de Fusão/uso terapêutico
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