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1.
J Clin Med ; 13(14)2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39064094

RESUMO

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disorder primarily targeting joints, significantly impacting patients' quality of life. The introduction of tumor necrosis factor-alpha (TNF-α) inhibitors has markedly improved RA management by reducing inflammation. However, these medications are associated with adverse skin reactions, which can vary greatly among patients due to genetic differences. Objectives: This study aimed to identify risk factors associated with skin adverse events by TNF-α in RA patients. Methods: A cohort study was conducted, encompassing patients with RA who were prescribed TNF-α inhibitors. This study utilized machine learning algorithms to analyze genetic data and identify markers associated with skin-related adverse events. Various machine learning algorithms were employed to predict skin and subcutaneous tissue-related outcomes, leading to the development of a risk-scoring system. Multivariable logistic regression analysis identified independent risk factors for skin and subcutaneous tissue-related complications. Results: After adjusting for covariates, individuals with the TT genotype of rs12551103, A allele carriers of rs13265933, and C allele carriers of rs73210737 exhibited approximately 20-, 14-, and 10-fold higher incidences of skin adverse events, respectively, compared to those with the C allele, GG genotype, and TT genotype. The machine learning algorithms used for risk prediction showed excellent performance. The risk of skin adverse events among patients receiving TNF-α inhibitors varied based on the risk score: 0 points, 0.6%; 2 points, 3.6%; 3 points, 8.5%; 4 points, 18.9%; 5 points, 36.7%; 6 points, 59.2%; 8 points, 90.0%; 9 points, 95.7%; and 10 points, 98.2%. Conclusions: These findings, emerging from this preliminary study, lay the groundwork for personalized intervention strategies to prevent TNF-α inhibitor-associated skin adverse events. This approach has the potential to improve patient outcomes by minimizing the risk of adverse effects while optimizing therapeutic efficacy.

2.
Mol Med Rep ; 8(4): 1235-41, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23933633

RESUMO

The aim of this study was to investigate the correlation between single nucleotide polymorphisms (SNPs) of the forkhead box J3 (FOXJ3) gene and rheumatoid arthritis (RA). For the association studies, 307 patients with RA and 476 control patients without RA were recruited. Eleven SNPs (rs2282404, rs2455084, rs1393009, rs7539485, rs4660616, rs510157, rs343386, rs12732892, rs343389, rs343376 and rs585320) were genotyped using direct sequencing and the resulting data were analyzed using the SNPStats, Haploview and Helixtree programs. Seven SNPs (rs2455084, rs1393009, rs7539485, rs4660616, rs510157, rs343386 and rs343389) were associated with RA in three alternative models (log­additive, dominant and recessive models; P<0.05). A strong linkage disequilibrium block, including all 11 SNPs, was constructed using the Gabriel method. Two haplotypes, TCCTTGTCTTT and TCTTCTGTCAC, were significantly associated with RA (P<0.05). In clinical characteristic analysis, the SNP rs585320 was also associated with the anti­cyclic citrullinated peptide. These results suggest that FOXJ3 may be associated with the development of RA.


Assuntos
Artrite Reumatoide/genética , Proteínas de Ciclo Celular/genética , Fatores de Transcrição Forkhead/genética , Adulto , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Autoanticorpos/sangue , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Peptídeos Cíclicos/imunologia , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA
3.
Neurochem Res ; 38(3): 620-31, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23283698

RESUMO

Prenatal exposure to alcohol has consistently been associated with adverse effects on neurodevelopment, which is collectively called fetal alcohol spectrum disorder (FASD). Increasing evidence suggest that prenatal exposure to alcohol increases the risk of developing attention deficit/hyperactivity disorder-like behavior in human. In this study, we investigated the behavioral effects of prenatal exposure to EtOH in offspring mice and rats focusing on hyperactivity and impulsivity. We also examined changes in dopamine transporter and MeCP2 expression, which may underlie as a key neurobiological and epigenetic determinant in FASD and hyperactive, inattentive and impulsive behaviors. Mouse or rat offspring born from dam exposed to alcohol during pregnancy (EtOH group) showed hyper locomotive activity, attention deficit and impulsivity. EtOH group also showed increased dopamine transporter and norepinephrine transporter level compared to control group in the prefrontal cortex and striatum. Prenatal exposure to EtOH also significantly decreased the expression of MeCP2 in both prefrontal cortex and striatum. These results suggest that prenatal exposure to EtOH induces hyperactive, inattentive and impulsive behaviors in rodent offspring that might be related to global epigenetic changes as well as aberration in catecholamine neurotransmitter transporter system.


Assuntos
Etanol/toxicidade , Animais , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/biossíntese , Epigênese Genética/efeitos dos fármacos , Feminino , Transtornos do Espectro Alcoólico Fetal/psicologia , Comportamento Impulsivo/induzido quimicamente , Proteína 2 de Ligação a Metil-CpG/metabolismo , Camundongos , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/biossíntese , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos
4.
Biomol Ther (Seoul) ; 20(2): 226-33, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24116300

RESUMO

Ethanol exposure during gestational period is related to growth retardation, morphological abnormality, and even in neurological abnormalities including attention deficit/hyperactivity disorder (ADHD)-like behaviors on offspring. However, relatively little is known about the effects of maternal ethanol consumption prior to conception on their offspring. In this study, we investi-gated whether maternal ethanol administration during preconceptional phase produces ADHD-like behaviors in the rat offspring. Sprague-Dawley (SD) female rats were administrated ethanol via intragastric intubation with dosing regimen of 6 g/kg daily for 10 consecutive days and treated female rats then mated with non-treated male SD rats after 8 weeks. Another group subjected to the same procedure as those conducted on ethanol treated group except the saline administration instead of ethanol. Offspring was tested for their ADHD-like behaviors using open field test, Y maze test and impulsivity test that is performed in the aversive electronic foot shock paradigm. Offspring of preconceptional ethanol treated (EtOH) group showed hyperlocomotive activity, attention deficit and impulsivity. And reduction of striatal dopamine transporter (DAT) level was observed by Western blot in the EtOH group, compared to control (Con) group, while the immunohistochemical analysis exhibited increased expression of norepinephrine transporter (NET) in the frontal cortex. These results suggest that maternal ethanol consumption in the preconceptional phase induces ADHD-like behaviors in offspring that might be related to the abnormal expression of DAT and NET in rat.

5.
Rheumatol Int ; 29(1): 43-6, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18493767

RESUMO

This study was performed to investigate the frequency of human leukocyte antigen (HLA)-B27 subtypes in the Korean population with spondyloarthropathy (SpA). We determined the HLA subtypes of 267 SpA patients who were positive for the B27 antigen (as determined by serology) by using a PEL-FREEZ kit (Dynal Biotech, Wisconsin, USA). Clinical features, including sex, peripheral joint involvement, and the presence of uveitis, were analyzed in a retrospective cohort study. Among 267 patients, 244 were B*2705-positive and 22 were B*2704-positive. One patient was positive for B*2704/2705. No other subtype was observed among the analyzed patients. We found that HLA-B*2705 was the predominant subtype in Koreans with SpA; this finding is remarkable because other Asians such as the Han or the Japanese exclusively have the B*2704 subtype. This result suggests that the clinical features and prevalence of SpA in Koreans may be similar to those observed in Europeans.


Assuntos
Povo Asiático , Antígeno HLA-B27/genética , Polimorfismo Genético/genética , Espondilite Anquilosante/genética , Adulto , Estudos Transversais , Feminino , Predisposição Genética para Doença , Antígeno HLA-B27/sangue , Antígeno HLA-B27/imunologia , Humanos , Coreia (Geográfico)/epidemiologia , Masculino , Espondilite Anquilosante/etnologia , Espondilite Anquilosante/imunologia , Adulto Jovem
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