Contribuição genética para o entendimento da fisiopatologia da doença de crohn / Genetic contribution to understanding the pathophysiology of crohn's disease

A Doença de Crohn (DC) integra o grupo das Doenças Inflamatórias Intestinais (DII) e apresenta aspectos multifatoriais, os quais dificultam a correta compreensão de sua fisiopatologia. Apesar de forte componente genético de susceptibilidade, com mais de 200 loci associados, esse explica apenas 1/3 dos eventos, evidenciando a relevância de outros fatores. Assim, objetivou-se avaliar a relação entre a genética, fisiopatologia e a ocorrência da DC. Foi realizada uma revisão bibliográfica na base de dados MEDLINE, utilizando os descritores “Crohn’s disease”, “Genetic Markers” e “Pathology”, no período de 2016 a 2021. Foram encontrados 35 artigos, dos quais 18 foram selecionados para compor esse estudo de acordo com os critérios de inclusão e exclusão. Dentre os distúrbios genéticos associados à etiologia complexa da DC, destacam-se: redução de peptídeos intestinais com função de barreira antimicrobiana, desenvolvimento de microbiota pró-inflamatória, polimorfismos nos genes NOD2, ATG16L1 e IRGM relacionados à autofagia e miRNAs desregulados (ex: miR-100, miR-142-3p e miR-146a). Tais fatores contribuem para o estado inflamatório do trato gastrointestinal e possivelmente para a carcinogênese. Têm sido encontrados padrões de metilação específico na DC com diferentes locais de metilação alterada (VMP1, CARD9, WNT2B), incluindo genes relevantes do sistema imune adaptativo e inato (TNFSF4, ITGB2), todos associados a sua etiofisiopatogenia. Conclui-se que as produções científicas entre 2016 e 2021 resultaram em avanços relevantes para a compreensão da fisiopatologia da DC, mas sua etiologia e patogênese, apesar das diversas teorias propostas, permanecem desconhecidas e muitos aspectos ainda necessitam de investigação

Papel do profissional de enfermagem no teste do pezinho no Programa Nacional de Triagem Neonatal: uma revisão integrativa

Objetivo: Identificar o papel do profissional de enfermagem no Programa Nacional de Triagem Neonatal para fomentar discussões acerca do tema com o propósito de construir mecanismos futuros para a melhoria desse programa. Métodos: Revisão integrativa cuja questão norteadora é: Qual é o papel do profissional de enfermagem no teste do pezinho no Programa Nacional de Triagem Neonatal?  Resultados: Foram encontradas cem produções, que após análise e adequação ao tema, restaram oito. Emergiram três categorias de análise temática: (I) Erros técnicos nas coletas de amostras; (II) Desvalorização do exame pelos profissionais; (III) Falta de conhecimento técnico-científico dos profissionais de enfermagem acerca do exame. Conclusão: Os profissionais de enfermagem devem informar a necessidade da realização do teste de triagem, explicar os benefícios do diagnóstico precoce e o período adequado para realização. Estas medidas preventivas irão atingir o objetivo principal que é evitar a morbimortalidade infantil

Oxidative stress in sickle cell disease: An overview of erythrocyte redox metabolism and current antioxidant therapeutic strategies

Erythrocytes have an environment of continuous pro-oxidant generation due to the presence of hemoglobin (Hb), which represents an additional and quantitatively significant source of superoxide (O2 •-) generation in biological systems. To counteract oxidative stress, erythrocytes have a self-sustaining antioxidant defense system. Thus, red blood cells uniquely function to protect Hb via a selective barrier allowing gaseous and other ligand transport as well as providing antioxidant protection not only to themselves but also to other tissues and organs in the body. Sickle hemoglobin molecules suffer repeated polymerization/depolymerization generating greater amounts of reactive oxygen species, which can lead to a cyclic cascade characterized by blood cell adhesion, hemolysis, vaso-occlusion, and ischemia-reperfusion injury. In other words, sickle cell disease is intimately linked to a pathophysiologic condition of multiple sources of pro-oxidant processes with consequent chronic and systemic oxidative stress. For this reason, newer therapeutic agents that can target oxidative stress may constitute a valuable means for preventing or delaying the development of organ complications. © © 2013 Elsevier Inc. All rights reserved

The relationship between of ACE I/D and the MTHFR C677T polymorphisms in the pathophysiology of type 2 diabetes mellitus in a population of Brazilian obese patients

ABSTRACT Objectives This study aimed to evaluate the frequencies of the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) and methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphisms in obese patients with and without type 2 diabetes mellitus (T2DM). Subjects and methods These polymorphisms were analyzed by polymerase chain reaction in 125 patients with obesity, 47 (T2DM) and 78 (Control Group). Results No significant difference was found on comparing the T2DM and Control Groups in respect to the genotypic frequencies of the polymorphisms - (II: 13.3% vs. 12.0%; ID: 37.8% vs. 37.3; DD: 48.9% vs. 50.7%; CC: 36.2% vs. 39.0%; CT: 46.8% vs. 49.3%; TT: 17.0% vs. 11.7%), and alleles (I: 32.2% vs. 30.7%; D: 67.8% vs. 69.3%; C: 59.6% vs. 63.6%; T: 40.4% vs. 36.4%) and their synergisms in the pathophysiology of T2DM. On analyzing the T2DM Group, there were no significant differences in the presence of complications. In this population of Brazilian obese patients, no correlation was found between the ACE and MTHFR polymorphisms in the development of T2DM. Conclusion Analyzing only the group with diabetes, there was also no relationship between these polymorphisms and comorbidities

Perfil de beta talassemia heterozigota obtido a partir de análise data mining em banco de dados The profile of beta thalassemia obtained by data mining analysis in a database

<abstract language="eng">Variations in the phenotypic expression of heterozygous beta thalassemia reflect the formation of different populations. To better understand the profile of heterozygous beta-thalassemia of the Brazilian population, we aimed at establishing parameters to direct the diagnosis of carriers and calculate the frequency from information stored in an electronic database. Using a Data Mining tool, we evaluated information on 10,960 blood samples deposited in a relational database. Over the years, improved diagnostic technology has facilitated the elucidation of suspected beta thalassemia heterozygote cases with an average frequency of 3.5% of referred cases. We also found that the Brazilian beta thalassemia trait has classic increases of Hb A2 and Hb F (60%), mainly caused by mutations in beta zero thalassemia, especially in the southeast of the country

Relationship between oxidative stress, glutathione S-transferase polymorphisms and hydroxyurea treatment in sickle cell anemia

This study evaluated the oxidative stress and antioxidant capacity markers in sickle cell anemia (SCA) patients with and without treatment with hydroxyurea. We assessed GSTT1, GSTM1 and GSTP1 polymorphisms in patients and a control group. The study groups were composed of 48 subjects without hemoglobinopathies and 28 SCA patients, 13 treated with HU [SCA (+ HU)], and 15 SCA patients not treated with HU [SCA (- HU)]. We observed a significant difference for GSTP1 polymorphisms in SCA patients with the V/V genotype that showed higher glutathione (GSH) and Trolox equivalent antioxidant capacity (TEAC) (p = 0.0445 and p = 0.0360), respectively, compared with the I/I genotype. HU use was associated with a 35.2% decrease in the lipid peroxidation levels of the SCA (+ HU) group (p<0.0001). Moreover, the SCA (+ HU) group showed higher TEAC as compared to the control group (p = 0.002). We did not find any significant difference in glutathione-S-transferase (GST) activity between the groups (p = 0.76), but the catalase (CAT) activity was about 17% and 30% decreased in the SCA (+ HU) and SCA (HU) groups, respectively (p<0.00001). Whereas the plasma GSH levels were similar to 2 times higher in the SCA patients than the control group (p = 0.0005). HU use has contributed to higher CAT activity and TEAC, and lower lipid peroxidation in patients under treatment. These findings may explain the influence of HU in ameliorating oxidative stress on SCA subjects. (C) 2011 Elsevier B.V. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Serum melatonin level and oxidative stress in sickle cell anemia

This study evaluated serum melatonin levels in patients with sickle cell anemia (SCA) and compared the results to lipid peroxidation by determining thiobarbituric acid-reactive substances (TBARS) and Trolox equivalent antioxidant capacity (TEAC). The group studied was composed of 15 SCA patients and 24 subjects without hemoglobinopathies. The average melatonin level was significantly reduced in the SCA patients (p<0.001) when compared to the control group. The SCA patients showed significantly higher values for TBARS and TEAC when compared to values obtained for the control group (p<0.001 and p<0.01). Results from the correlation analysis in the SCA group were not statistically significant for any parameters except for TBARS and TEAC levels, which had a positive correlation (r = 0.51; p = 0.04), suggesting the participation of melatonin in antioxidant defense. The use of melatonin could be a possible therapeutic target for improving antioxidant defense and to reduce oxidative damage, alleviating symptoms associated with SCA. (C) 2010 Elsevier B.V. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Severity of Brazilian sickle cell disease patients: severity scores and feasibility of the Bayesian network model use

The integration of the several clinical and laboratory dimensions and the influence of each parameter on the sickle cell disease (SCD)-related mortality is useful for predicting the phenotype of an individual. This study evaluated the feasibility of the SCD severity calculator use to measure disease severity in Brazilian patients. The study group was composed of 500 SCD patients (440 HbSS and 60 HbSC) diagnosed by molecular biology. We observed a decrease in severity scores in 72 SCD patients assessed before and after the hydroxyurea (HU) use. Furthermore, the HU influenced the increase of mean corpuscular volume (MCV) and HbF concentration, and the decrease of leukocytes and total bilirubin. We found 180 (36.0%) patients with intermediate phenotype, 170 (34.0%) mild phenotype and 150 (30.0%) with severe phenotype. Patients with ages &gt;40 years had higher mean score (0.778 +/- 0.177) than patients between 18 and 40 years (0.562 +/- 0.152) and patients between 5 and 17 years (0.322 +/- 0.145). We observe that there is a tendency of individuals with leg ulcers, avascular necrosis and cardiac complications with increasing age. Correlation analysis showed relations between severity scores with leukocytes, reticulocytes, bilirubin, lactate dehydrogenase, HbS, hemoglobin and hematocrit (p &lt; 0.05). Several comparisons involving age groups, SCD genotype and phenotypic classification had satisfactory results and this classification will be used for future studies involving genetic polymorphisms, response to treatment with HU and oxidative stress markers in SCD.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq