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1.
Biomedicines ; 11(12)2023 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-38137395

RESUMEN

This narrative review explores the complex relationship between aerobic exercise (AE) and neuropathic pain (NP), particularly focusing on peripheral neuropathies of mechanical origin. Pain, a multifaceted phenomenon, significantly impacts functionality and distress. The International Association for the Study of Pain's definition highlights pain's biopsychosocial nature, emphasizing the importance of patient articulation. Neuropathic pain, arising from various underlying processes, presents unique challenges in diagnosis and treatment. Our methodology involved a comprehensive literature search in the PubMed and SCOPUS databases, focusing on studies relating AE to NP, specifically in peripheral neuropathies caused by mechanical forces. The search yielded 28 articles and 1 book, primarily animal model studies, providing insights into the efficacy of AE in NP management. Results from animal models demonstrate that AE, particularly in forms like no-incline treadmill and swimming, effectively reduces mechanical allodynia and thermal hypersensitivity associated with NP. AE influences neurophysiological mechanisms underlying NP, modulating neurotrophins, cytokines, and glial cell activity. These findings suggest AE's potential in attenuating neurophysiological alterations in NP. However, human model studies are scarce, limiting the direct extrapolation of these findings to human neuropathic conditions. The few available studies indicate AE's potential benefits in peripheral NP, but a lack of specificity in these studies necessitates further research. In conclusion, while animal models show promising results regarding AE's role in mitigating NP symptoms and influencing underlying neurophysiological mechanisms, more human-centric research is required. This review underscores the need for targeted clinical trials to fully understand and harness AE's therapeutic potential in human neuropathic pain, especially of mechanical origin.

2.
Autoimmun Rev ; 22(8): 103362, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37230310

RESUMEN

OBJECTIVE: Vasculitis are a very heterogenous group of systemic autoimmune diseases, affecting large vessels (LVV), small vessels or presenting as a multisystemic variable vessel vasculitis. We aimed to define evidence and practice-based recommendations for the use of biologics in large and small vessels vasculitis, and Behçet's disease (BD). METHODS: Recommendations were made by an independent expert panel, following a comprehensive literature review and two consensus rounds. The panel included 17 internal medicine experts with recognized practice on autoimmune diseases management. The literature review was systematic from 2014 until 2019 and later updated by cross-reference checking and experts' input until 2022. Preliminary recommendations were drafted by working groups for each disease and voted in two rounds, in June and September 2021. Recommendations with at least 75% agreement were approved. RESULTS: A total of 32 final recommendations (10 for LVV treatment, 7 for small vessels vasculitis and 15 for BD) were approved by the experts and several biologic drugs were considered with different supporting evidence. Among LVV treatment options, tocilizumab presents the higher level of supporting evidence. Rituximab is recommended for treatment of severe/refractory cryoglobulinemic vasculitis. Infliximab and adalimumab are most recommended in treatment of severe/refractory BD manifestations. Other biologic drugs can be considered is specific presentations. CONCLUSION: These evidence and practice-based recommendations are a contribute to treatment decision and may, ultimately, improve the outcome of patients living with these conditions.


Asunto(s)
Síndrome de Behçet , Productos Biológicos , Vasculitis , Humanos , Síndrome de Behçet/tratamiento farmacológico , Vasculitis/tratamiento farmacológico , Rituximab/uso terapéutico , Terapia Biológica , Productos Biológicos/uso terapéutico
3.
Front Immunol ; 14: 1117699, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37138867

RESUMEN

Systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and Sjögren's syndrome (SS) are heterogeneous autoimmune diseases. Severe manifestations and refractory/intolerance to conventional immunosuppressants demand other options, namely biological drugs, and small molecules. We aimed to define evidence and practice-based guidance for the off-label use of biologics in SLE, APS, and SS. Recommendations were made by an independent expert panel, following a comprehensive literature review and two consensus rounds. The panel included 17 internal medicine experts with recognized practice in autoimmune disease management. The literature review was systematic from 2014 until 2019 and later updated by cross-reference checking and experts' input until 2021. Preliminary recommendations were drafted by working groups for each disease. A revision meeting with all experts anticipated the consensus meeting held in June 2021. All experts voted (agree, disagree, neither agree nor disagree) during two rounds, and recommendations with at least 75% agreement were approved. A total of 32 final recommendations (20 for SLE treatment, 5 for APS, and 7 for SS) were approved by the experts. These recommendations consider organ involvement, manifestations, severity, and response to previous treatments. In these three autoimmune diseases, most recommendations refer to rituximab, which aligns with the higher number of studies and clinical experience with this biological agent. Belimumab sequential treatment after rituximab may also be used in severe cases of SLE and SS. Second-line therapy with baricitinib, bortezomib, eculizumab, secukinumab, or tocilizumab can be considered in SLE-specific manifestations. These evidence and practice-based recommendations may support treatment decision and, ultimately, improve the outcome of patients living with SLE, APS, or SS.


Asunto(s)
Síndrome Antifosfolípido , Productos Biológicos , Lupus Eritematoso Sistémico , Síndrome de Sjögren , Humanos , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/tratamiento farmacológico , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/tratamiento farmacológico , Rituximab/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Terapia Biológica
4.
Artículo en Inglés | MEDLINE | ID: mdl-35206397

RESUMEN

The aim of this study was to evaluate the influence of the lockdown due to the COVID-19 pandemic, on eating and physical activity behavior, in a university population. A healthy diet such as the Mediterranean Diet (MD) pattern, rich in fruit and vegetables, can prevent degenerative diseases such as obesity, diabetes, cardiovascular diseases, etc. We conducted a cross-sectional study and data were collected by an anonymous online questionnaire. Participants completed a survey consisting of 3 sections: sociodemographic data; dietary behavior and physical activity; the Mediterranean Diet questionnaire (MEDAS-14) and the Emotional Eater Questionnaire (EEQ). A total of 168 participants completed the questionnaire: 66.7% were women, 79.2% were from Spain, 76.8% were students, 76.2% lived in their family home and 66.1% were of normal weight. During lockdown our population shopped for groceries 1 time or less per week (76.8%); maintained the same consumption of fruits (45.2%), vegetables (50.6%), dairy products (61.9%), pulses (64.9%), fish/seafood (57.7%), white meat (77.4%), red and processed meat (71.4%), pastries and snacks (48.2%), rice/pasta/potatoes (70.2%) and nuts (62.5%), spirits (98.8%) and sugary drinks (91.7%). Cooking time increased (73.2%) and the consumption decreased of low alcohol drinks (60.1%), spirits (75%) and sugary drinks (57.1%), and physical activity also diminished (49.4%). University Employees (UE) gained more weight (1.01 ± 0.02) than students (0.99 ± 0.03) (p < 0.05) during the confinement period. A total of 79.8% of the participants obtained a Medium/High Adherence to the MD during lockdown. Emotional and very emotional eaters were higher in the female group (p < 0.01). In the event of further confinement, strategies should be implemented to promote a balanced and healthy diet together with the practice of physical activity, taking special care of the female and UE groups.


Asunto(s)
COVID-19 , Dieta Mediterránea , Animales , COVID-19/epidemiología , Control de Enfermedades Transmisibles , Estudios Transversales , Dieta , Conducta Alimentaria/psicología , Femenino , Humanos , Estilo de Vida , Pandemias , SARS-CoV-2 , Encuestas y Cuestionarios , Universidades
5.
Materials (Basel) ; 13(4)2020 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-32085507

RESUMEN

Eucalyptus globulus Labill stands out as one of the hardwood species produced in Europe with prominent mechanical properties, which is undergoing a growing interest in extending added value. The development of engineered wood products with this species and its application in timber structures involving numerical finite element simulations requires knowledge of the mechanical properties for the different orthotropic material directions. The aim of the present study is to determine the main mechanical properties of E. globulus from small clear specimens, necessary for the development of finite element models. The work provides experimental results on the ultimate capacity and modulus of elasticity considering different stresses: tension parallel and perpendicular to the grain, compression parallel and perpendicular to the grain (in radial and tangential directions), shear and longitudinal static bending. The work is complemented with experimental data on timber-to-timber friction coefficients for 0°, 45°, and 90° orientation angles, which are useful in the modeling of traditional joints. Very high values of ultimate stress and modulus of elasticity for the different mechanical properties were obtained, highlighting the great potential of this species for structural applications.

6.
Eur J Case Rep Intern Med ; 6(6): 001117, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31293992

RESUMEN

INTRODUCTION: Behçet's disease (BD) is a chronic systemic condition characterized by recurrent oral and genital ulcers, neurological and vascular manifestations, ocular and skin lesions, and a positive pathergy test. Mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome is rare and consists of features of BD together with relapsing polychondritis. The treatment of this syndrome is similar that of BD and depends on disease expression and symptoms. CASE REPORT: We report the case of a 50-year-old man diagnosed with BD with relapsing polychondritis (MAGIC syndrome) which had evolved over approximately 35 years, with exuberant and frequent oral and genital ulcers. Various treatments were unsuccessful and had adverse effects. Lenalidomide was initiated at a dose of 5 mg per day with remission of oral and genital ulcers and no haematological or adverse effects. CONCLUSION: BD is a complex disorder with a variety of presentations. Its treatment can be challenging but sometimes off-label drugs, like lenalidomide, can be effective. LEARNING POINTS: Behçet's disease (BD) is a chronic systemic autoinflammatory disease whose treatment can be challenging and is dependent on disease expression and symptoms.Thalidomide can be effective for treating recurrent oral aphthae, but its use is limited by adverse effects, mostly sensory polyneuropathy.Lenalidomide is a more powerful thalidomide analogue with fewer adverse effects and may be effective for the treatment of BD.

7.
Molecules ; 23(8)2018 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-30071616

RESUMEN

Berry fruits are rich in nutrients and polyphenols, providing potential health benefits. Understanding the factors that affect their bioavailability is becoming of utmost importance for evaluating their biological significance and efficacy as functional food. In this study, the phytochemical composition and the total antioxidant capacity of different varieties of five berries (blackberry, blackcurrant, blueberry, raspberry, and strawberry) were evaluated after an in vitro gastrointestinal digestion process. The cultivar of each berry that showed the higher content of total phenols and flavonoids was selected to study its cytotoxic effect on human hepatoma cells. Digestion resulted in a high reduction (p ˂ 0.05) of total phenolic, flavonoid and anthocyanin contents and total antioxidant capacity, in the "IN" samples compared to the "OUT" extracts, which represent the "serum-available" and the "colon-available" fractions, respectively. Incubation of the digested fraction for 24 h didn't exert any effect on cellular viability, while a dose- and time-dependent cytotoxicity was observed after 48 h and 72 h of incubation for all the berries analyzed. Our results suggest that the approach proposed in this work may represent a rapid tool for evaluating and identifying new berries with increased phytochemical bioavailability, highlighting their antiproliferative agents after an in vitro digestion.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Frutas/química , Neoplasias Hepáticas/metabolismo , Arándanos Azules (Planta)/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Flavonoides/química , Flavonoides/farmacología , Fragaria/química , Humanos , Fenoles/química , Fenoles/farmacología , Polifenoles/química , Rubus/química
8.
BMJ Case Rep ; 20182018 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-29909388

RESUMEN

Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterised by vascular abnormalities, immune system activation and fibrosis. Lymphatic involvement in SSc was described more recently and starts in early stages. This report describes a 46-year-old patient who developed over the last 2 years asymmetric lymphedema in lower extremities. Compromise in lymphatic drainage was confirmed by lymphoscintigraphy. She also presented Raynaud's phenomenon, a scleroderma pattern in nailfold capillaroscopy, cutaneous thickening and anticentromere antibodies, which together resulted in a new diagnosis of limited cutaneous SSc. Treatment with methotrexate, prednisolone and lymphatic drainage resulted in lymphedema improvement. To our knowledge, this is the first case of grade 2 lymphedema in the setting of anticentromere-positive limited cutaneous SSc. We highlight the importance of considering rheumatic diseases in the differential diagnosis of lymphedema.


Asunto(s)
Linfedema/diagnóstico por imagen , Metotrexato/uso terapéutico , Prednisolona/uso terapéutico , Esclerodermia Limitada/diagnóstico , Femenino , Humanos , Linfedema/tratamiento farmacológico , Linfedema/etiología , Linfocintigrafia , Angioscopía Microscópica , Persona de Mediana Edad , Enfermedad de Raynaud/diagnóstico por imagen , Enfermedad de Raynaud/tratamiento farmacológico , Enfermedad de Raynaud/etiología , Esclerodermia Limitada/tratamiento farmacológico , Resultado del Tratamiento
9.
Pharmacol Res ; 131: 32-43, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29555333

RESUMEN

Ample epidemiological evidence suggests a strong correlation among diet, lifestyle factors and the onset and consolidation of dementia and Alzheimer's disease (AD). It has been demonstrated that AD, diabetes, obesity, insulin resistance, and cardiovascular disease are strongly interconnected pathologies. Preventive strategies and nutritional interventions seem to be promising approaches to delay neurocognitive decline and reduce the risk of AD and other non-psychiatric co-morbidities. In this regard, healthy dietary patterns, characterized by high intake of plant-based foods, probiotics, antioxidants, soy beans, nuts, and omega-3 polyunsaturated fatty acids, and a low intake of saturated fats, animal-derived proteins, and refined sugars, have been shown to decrease the risk of neurocognitive impairments and eventually the onset of AD. Here we review the role of some nutrients and, in particular, of healthy dietary patterns, such as the Mediterranean diet and other emerging healthy diets, DASH (Dietary Approach to Stop Hypertension) and MIND (Mediterranean-DASH dietIntervention for Neurodegenerative Delay), for the maintenance of cognitive performance, focusing specifically on human studies. The beneficial effects associated with overall diet composition, rather than single nutrient supplementations, for the prevention or the delay of AD and dementia are discussed.


Asunto(s)
Enfermedad de Alzheimer/etiología , Enfermedad de Alzheimer/prevención & control , Demencia/etiología , Demencia/prevención & control , Dietoterapia , Dieta Saludable , Enfermedad de Alzheimer/metabolismo , Demencia/metabolismo , Dietoterapia/métodos , Dieta Saludable/métodos , Dieta Mediterránea , Suplementos Dietéticos/análisis , Humanos , Hipertensión/etiología , Hipertensión/metabolismo , Hipertensión/prevención & control , Factores de Riesgo
10.
Food Chem Toxicol ; 112: 126-133, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29284135

RESUMEN

During the process of beeswax recycling, many industrial derivatives are obtained. These matrices may have an interesting healthy and commercial potential but to date they have not been properly studied. The aim of the present work was to evaluate the proximal and phytochemical composition, the antioxidant capacity and cytotoxic effects of two by-products from beeswax recycling process named MUD 1 and MUD 2 on liver hepatocellular carcinoma. Our results showed that MUD 1 presented the highest (P < .05) fiber, protein, carbohydrate, polyphenol and flavonoid concentration, as well as the highest (P < .05) total antioxidant capacity than the MUD 2 samples. MUD1 exerted also anticancer activity on HepG2 cells, by reducing cellular viability, increasing intracellular ROS levels and affecting mitochondrial functionality in a dose-dependent manner. We showed for the first time that by-products from beeswax recycling process can represent a rich source of phytochemicals with high total antioxidant capacity and anticancer activity; however, further researches are necessary to evaluate their potentiality for human health by in vivo studies.


Asunto(s)
Antioxidantes/farmacología , Polifenoles/farmacología , Reciclaje , Ceras/química , Antioxidantes/análisis , Cromatografía Líquida de Alta Presión , Ensayos de Selección de Medicamentos Antitumorales , Metabolismo Energético , Células Hep G2 , Miel , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Polifenoles/análisis , Especies Reactivas de Oxígeno/metabolismo , Espectrometría de Masa por Ionización de Electrospray
11.
Cancer Lett ; 411: 191-200, 2017 12 28.
Artículo en Inglés | MEDLINE | ID: mdl-29017913

RESUMEN

Among gynaecological cancers, ovarian cancer represents the leading cause of death in women. Current treatment for ovarian cancer entails surgery followed by combined chemotherapy with platinum and taxane, which are associated, particularly cisplatin, with severe side effects. While this treatment approach appears to be initially effective in a high number of patients, nearly 70% of them suffer a relapse within a few months after initial treatment. Therefore, more effective and better-tolerated treatment options are clearly needed. In recent years, several natural compounds (such as curcumin, epigallocatechin 3-gallate (EGCG), resveratrol, sulforaphane and Withaferin-A), characterized by long-term safety and negligible and/or inexistent side effects, have been proposed as possible adjuvants of traditional chemotherapy. Indeed, several in vitro and in vivo studies have shown that phytocompounds can effectively inhibit tumor cell proliferation, stimulate autophagy, induce apoptosis, and specifically target ovarian cancer stem cells (CSCs), which are generally considered to be responsible for tumor recurrence in several types of cancer. Here we review current literature on the role of natural products in ovarian cancer chemoprevention, highlighting their effects particularly on the regulation of inflammation, autophagy, proliferation and apoptosis, chemotherapy resistance, and ovarian CSC growth.


Asunto(s)
Productos Biológicos/uso terapéutico , Quimioprevención/métodos , Curcumina/uso terapéutico , Neoplasias Ováricas/terapia , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Curcumina/farmacología , Femenino , Humanos , Neoplasias Ováricas/patología , Neoplasias Ováricas/prevención & control
12.
Eur J Case Rep Intern Med ; 4(4): 000576, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-30755938

RESUMEN

TNF-α antagonists are used to treat various rheumatic diseases including sarcoidosis. However, there have been increasing reports of sarcoidosis in relation to treatment using these drugs. The pathogenesis of this reaction remains unknown. This is a report of a clinical case of sarcoidosis in Behçet's disease (DB) with mucocutaneous and intestinal involvement in treatment using adalimumab, with improvement after anti-TNF suspension and corticosteroid therapy. LEARNING POINTS: This clinical case demonstrates the efficacy of the anti-TNFa adalimumab in the treatment of Behçet with intestinal manifestations and not responsive to other therapeutics.To our knowledge it is the first time it is described a case of sarcoid reaction in a patient with Behçet treated with adalimumab.It shows how two complications of the use of immunosuppressants (sarcoid reaction and Legionella pneumophila pneumonia) in the same patient can difficult the correct diagnosis because of the many and overlapping clinical manifestations.

13.
Int J Rheum Dis ; 20(5): 622-627, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-24708170

RESUMEN

AIM: To explain the missing heritability after the genome-wide association studies era, sequencing studies allow the identification of low-frequency variants with a stronger effect on disease risk. Common variants in the interleukin 10 gene (IL10) have been consistently associated with Behçet's disease (BD) and the goal of this study is to investigate the role of low-frequency IL10 variants in BD susceptibility. METHODS: To identify IL10 low-frequency variants, a discovery group of 50 Portuguese BD patients were Sanger-sequenced in a 7.7 kb genomic region encompassing the complete IL10 gene, 0.9 kb upstream and 2 kb downstream, and two conserved regions in the putative promoter. To assess if the novel variants are BD- and/or Portuguese-specific, they were assayed in an additional group of BD patients (26 Portuguese and 964 Iranian) and controls (104 Portuguese and 823 Iranian). RESULTS: Rare IL10 coding variants were not detected in BD patients, but we identified 28 known single nucleotide polymorphisms with minor allele frequencies ranging from 0.010 to 0.390, and five novel non-coding variants in five heterozygous cases. ss836185595, located in the IL10 3' untranslated region, was also detected in one Iranian control individual and therefore is not specific to BD. The remaining novel IL10 variants (ss836185596 and ss836185602 in intron 3, ss836185598 and ss836185604 in the putative promoter region) were not found in the replication dataset. CONCLUSION: This study highlights the importance of screening the whole gene and regulatory regions when searching for novel variants associated with complex diseases, and the need to develop bioinformatics tools to predict the functional impact of non-coding variants and statistical tests which incorporate these predictions.


Asunto(s)
Síndrome de Behçet/genética , Interleucina-10/genética , Mutación , Polimorfismo de Nucleótido Simple , Adulto , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/inmunología , Estudios de Casos y Controles , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Humanos , Irán , Masculino , Persona de Mediana Edad , Tasa de Mutación , Fenotipo , Reacción en Cadena de la Polimerasa , Portugal , Factores de Riesgo , Adulto Joven
15.
Acta Reumatol Port ; 38(2): 104-12, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24141347

RESUMEN

INTRODUCTION: The objective of this study was to develop a Portuguese version of the World Health Organization fracture risk assessment tool (FRAX®). METHODS: All cases of hip fracture occurred at or after 40 years of age were extracted from the Portuguese National Hospital Discharge Register from 2006 to 2010. Age and sex-ranked population estimates and mortality rates were obtained from National Statistics. Age- and gender stratified incidences were computed and the average of the five years under consideration was taken. Rates for other major fractures were imputed from the epidemiology of Sweden, as undertaken for most national FRAX® models. All methodological aspects and results were submitted to critical appraisal by a wide panel of national experts and representatives of the different stakeholders, including patients. RESULTS: Hip fracture incidence rates were higher in women than in men and increased with age. The lowest incidence was observed in 40-44 years group (14.1 and 4.0 per 100,000 inhabitants for men and women, respectively). The highest rate was observed among the 95-100 age-group (2,577.6 and 3,551.8/100,000 inhabitants, for men and women, respectively). The estimated ten-year probability for major osteoporotic fracture or hip fracture increased with decreasing T-score and with increasing age. CONCLUSIONS: Portugal has one of the lowest fracture incidences among European countries. The FRAX® tool has been successfully calibrated to the Portuguese population, and can now be used to estimate the ten-year risk of osteoporotic fractures in this country. All major stakeholders officially endorsed the Portuguese FRAX® model and co-authored this paper.


Asunto(s)
Fracturas de Cadera/epidemiología , Modelos Estadísticos , Fracturas Osteoporóticas/epidemiología , Medición de Riesgo/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Portugal , Probabilidad , Organización Mundial de la Salud
16.
J Mol Med (Berl) ; 91(8): 1013-23, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23625463

RESUMEN

Behçet's disease (BD) is a complex disease with genetic and environmental risk factors implicated in its etiology; however, its pathophysiology is poorly understood. To decipher BD's genetic underpinnings, we combined gene expression profiling with pathway analysis and association studies. We compared the gene expression profiles in peripheral blood mononuclear cells (PBMCs) of 15 patients and 14 matched controls using Affymetrix microarrays and found that the neuregulin signaling pathway was over-represented among the differentially expressed genes. The Epiregulin (EREG), Amphiregulin (AREG), and Neuregulin-1 (NRG1) genes of this pathway stand out as they are also among the top differentially expressed genes. Twelve haplotype tagging SNPs at the EREG-AREG locus and 15 SNPs in NRG1 found associated in at least one published BD genome-wide association study were tested for association with BD in a dataset of 976 Iranian patients and 839 controls. We found a novel association with BD for the rs6845297 SNP located downstream of EREG, and replicated three associations at NRG1 (rs4489285, rs383632, and rs1462891). Multifactor dimensionality reduction analysis indicated the existence of epistatic interactions between EREG and NRG1 variants. EREG-AREG and NRG1, which are members of the epidermal growth factor (EGF) family, seem to modulate BD susceptibility through main effects and gene-gene interactions. These association findings support a role for the EGF/ErbB signaling pathway in BD pathogenesis that warrants further investigation and highlight the importance of combining genetic and genomic approaches to dissect the genetic architecture of complex diseases.


Asunto(s)
Síndrome de Behçet/genética , Factor de Crecimiento Epidérmico/genética , Glicoproteínas/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Neurregulina-1/genética , Adolescente , Adulto , Anfirregulina , Síndrome de Behçet/metabolismo , Familia de Proteínas EGF , Factor de Crecimiento Epidérmico/metabolismo , Epirregulina , Femenino , Perfilación de la Expresión Génica , Estudio de Asociación del Genoma Completo , Glicoproteínas/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Neurregulina-1/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Polimorfismo de Nucleótido Simple , Transducción de Señal , Adulto Joven
17.
Arthritis Rheum ; 64(8): 2761-72, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22378604

RESUMEN

OBJECTIVE: Independent replication of the findings from genome-wide association studies (GWAS) remains the gold standard for results validation. Our aim was to test the association of Behçet's disease (BD) with the interleukin-10 gene (IL10) and the IL-23 receptor-IL-12 receptor ß2 (IL23R-IL12RB2) locus, each of which has been previously identified as a risk factor for BD in 2 different GWAS. METHODS: Six haplotype-tagging single-nucleotide polymorphisms (SNPs) in IL10 and 42 in IL23R-IL12RB2 were genotyped in 973 Iranian patients with BD and 637 non-BD controls. Population stratification was assessed using a panel of 86 ancestry-informative markers. RESULTS: Subtle evidence of population stratification was found in our data set. In IL10, rs1518111 was nominally associated with BD before and after adjustment for population stratification (odds ratio [OR] for T allele 1.20, 95% confidence interval [95% CI] 1.02-1.40, unadjusted P [P(unadj) ] = 2.53 × 10(-2) ; adjusted P [P(adj) ] = 1.43 × 10(-2) ), and rs1554286 demonstrated a trend toward association (P(unadj) = 6.14 × 10(-2) ; P(adj) = 3.21 × 10(-2) ). Six SNPs in IL23R-IL12RB2 were found to be associated with BD after Bonferroni correction for multiple testing, the most significant of which were rs17375018 (OR for G allele 1.51, 95% CI 1.27-1.78, P(unadj) = 1.93 × 10(-6) ), rs7517847 (OR for T allele 1.48, 95% CI 1.26-1.74, P(unadj) = 1.23 × 10(-6) ), and rs924080 (OR for T allele 1.29, 95% CI 1.20-1.39, P = 1.78 × 10(-5) ). SNPs rs10489629, rs1343151, and rs1495965 were also significantly associated with BD in all tests performed. Results of meta-analyses of our data combined with data from other populations further confirmed the role of rs1518111, rs17375018, rs7517847, and rs924080 in the risk of BD, but no epistatic interactions between IL10 and IL23R-IL12RB2 were detected. Results of imputation analysis highlighted the importance of IL23R regulatory regions in the susceptibility to BD. CONCLUSION: These findings independently confirm, extend, and refine the association of BD with IL10 and IL23R-IL12RB2. These associations warrant further validation and investigation in patients with BD, as they may have implications for the development of novel therapies (e.g., immunosuppressive therapy targeted at IL-23p19).


Asunto(s)
Síndrome de Behçet/etnología , Síndrome de Behçet/genética , Interleucina-10/genética , Receptores de Interleucina-12/genética , Receptores de Interleucina/genética , Adulto , Alelos , Síndrome de Behçet/epidemiología , Estudios de Casos y Controles , Femenino , Estudio de Asociación del Genoma Completo , Haplotipos/genética , Humanos , Irán/epidemiología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Factores de Riesgo
18.
Acta Med Port ; 23(6): 1113-8, 2010.
Artículo en Portugués | MEDLINE | ID: mdl-21627887

RESUMEN

Panniculitis is an inflammation occurring within adipose tissue. This process is often associated with auto-immune diseases, infections, malignancy and others diseases of unknown cause. We report a 16-year-old woman with constitutional symptoms and relapsing nonsuppurative nodular panniculitis. The etiological study didn't identify any associated disease, on admission or in 2,5 years of follow-up. This is a case of Weber-Christian disease with a favourable corticosteroid therapy result. The authors present a Weber-Christian disease bibliographic revision.


Asunto(s)
Paniculitis Nodular no Supurativa , Adolescente , Femenino , Humanos , Paniculitis Nodular no Supurativa/diagnóstico , Paniculitis Nodular no Supurativa/etiología
19.
Acta Reumatol Port ; 31(4): 305-21, 2006.
Artículo en Portugués | MEDLINE | ID: mdl-17334043

RESUMEN

Links between rheumatic manifestations and neoplasms are today an evidence. Certain syndromes have epidemiologic studies confirming strong association with malignancy, such as dermatomyositis and polymyositis, hyperthrophic osteoarthropathy and Lambert - Eaton myasthenic syndrome. These disorders may mimic idiopathic conditions, difficulting diagnosis. Besides that, longstanding rheumatic syndromes may, in their course, behave like premalignant conditions, as a result of their pathophysiology or drugs used in their treatment. The mechanisms whereby the neoplasm leads to rheumatic symptoms are: direct invasion of the musculoskeletal system, synovial reaction of justa-articular bony or capsular carcinomatous, secondary gout and paraneoplastic manifestations. Neoplasms constitute an important admission cause in Internal Medicine wards and rheumatic manifestations are common causes of Internal Medicine and Rheumatology appointments. The objective of the present work is to review the literature concerning rheumatic syndromes more frequently associated with malignancy, characterizing features that may suggest the presence of a hidden neoplasm as well as the potential diagnostic and prognostic value of their presence in malignant diseases.


Asunto(s)
Neoplasias/complicaciones , Enfermedades Reumáticas/etiología , Humanos , Síndromes Paraneoplásicos/etiología , Enfermedades Vasculares/etiología
20.
Environ Res ; 96(1): 34-40, 2004 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15261782

RESUMEN

Organochlorine pesticides are lipophilic compounds that persist in the environment. Because of their lipid solubility and resistance to metabolism, some of these chemicals accumulate in human tissues. The largest area of intensive greenhouse agriculture in Europe is near the Mediterranean coast of Southern Spain, where this type of farming has greatly expanded since the 1960s. We determined and compared the levels of 15 organochlorine pesticides in the adipose tissue and blood of 200 women living in Southern Spain. Aldrin, dieldrin, endrin, lindane, methoxychlor, endosulfans, and DDT and its metabolites were identified. Detectable concentrations of p,p'-DDE were found in 100% of adipose tissue and serum samples. Among the remaining DDTs, p,p'-DDT was the most common, being detected in 39% of adipose tissue and 76.5% of serum samples, followed by endosulfans I and II, which also were found in both adipose tissue and serum samples but at lower concentrations. Endosulfans were followed in frequency by lindane, aldrin, and dieldrin. Endrin and methoxychlor were present at a much lower frequency compared to those of the other organochlorines. Serum concentrations of p,p'-DDE o,p'-DDD, and endosulfan -I, -sulfate, -lactone, and -diol were significantly correlated with their adipose tissue concentrations. No significant relationships were found between the serum and adipose tissue concentrations of the remaining nine compounds determined, raising doubts about the equivalent use of fat/serum samples for the exposure assessment of some pesticides in epidemiological studies. The results suggested that women of reproductive age in Southern Spain have been and are currently exposed to organochlorine pesticides. Because many of these chemicals can mobilize during pregnancy and lactation, further research is warranted to interpret the health consequences for the children of such exposure.


Asunto(s)
Exposición a Riesgos Ambientales/estadística & datos numéricos , Hidrocarburos Clorados , Insecticidas/metabolismo , Tejido Adiposo/metabolismo , Femenino , Humanos , Insecticidas/sangre , Persona de Mediana Edad , España/epidemiología , Salud de la Mujer
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