Polimorfismo do gene timidilato sintase e nível plasmático total de homocisteína em um grupo de pacientes turcos com artrite reumatoide: relação com a atividade da doença e toxicidade ao metotrexato

Resumo Introdução: Relata-se que o polimorfismo do gene timidilato sintase (TS) e a homocisteína têm relação com o metabolismo do metotrexato (MTX), com achados conflitantes. O objetivo deste estudo foi determinar os níveis de homocisteína e a frequência de polimorfismos de repetição tripla (TS3R) e dupla (TS2R) do gene TS em um grupo de pacientes turcos com AR e avaliar sua associação com a toxicidade ao MTX e a atividade da doença. Métodos: Foram incluídos no estudo 64 pacientes com AR e 31 indivíduos no grupo controle, com média de 48,7 ± 12,5 e 46,2 ± 13,4 anos. Foram obtidas as características demográficas e foi registrado o número de pacientes que relataram efeitos adversos ao MTX no grupo AR. Foram analisados os níveis de homocisteína e os polimorfismos TS2R/TS3R. Foi determinada a distribuição de genótipos de acordo com a toxicidade ao MTX e a atividade da doença. Resultados: Os dados demográficos foram semelhantes entre os pacientes e controles. Todos faziam suplementação de ácido fólico a uma dose média de 5 mg/semana. Dos 64 pacientes, 36 apresentaram efeitos adversos ao tratamento com MTX. Encontrou-se uma frequência de polimorfismos TS2R e TS3R semelhante nos grupos AR e controle. Encontrou-se que os polimorfismos TS2R e TS3R eram semelhantes em pacientes com e sem eventos adversos relacionados com o MTX. O nível médio de homocisteína também foi similar em pacientes com e sem polimorfismo do gene TS, mas era mais elevado (12,45 μmol/L vs. 10,7 μmol/L) em pacientes com do que sem efeitos adversos relacionados com o MTX. O nível médio de homocisteína se correlacionou com o VHS no grupo AR. Conclusões: Os níveis de homocisteína podem afetar a atividade da doença e a toxicidade ao MTX, mas os polimorfismos 2 R e 3 R no gene TS não se correlacionaram com a toxicidade ao MTX em pacientes com AR que recebem suplementação de ácido fólico. São necessários mais estudos para esclarecer os polimorfismos em outras enzimas que podem ser responsáveis pela toxicidade ao MTX em pacientes com AR

A novel missense mutation of the paired box 3 gene in a Turkish family with Waardenburg syndrome type 1

Purpose: Screening of mutations in the paired box 3 (PAX3) gene in three generations of a Turkish family with Waardenburg syndrome type 1 (WS1)

Two Acute Myeloblastic Leukemia Cases Concomitant with Hemophagocytic Lymphohistiocytosis and Review of the Literature

We present two patients with acute myeloblastic leukemia (FAB AML-M7 and AML-M2) complicated by hemophagocytic lymphohistiocytosis (HLH) and relevant literature review. To our knowledge, our first case is the first and youngest patient having AML-M7 associated with HLH reported in the literature. Our cases and cases in the literature highlight the high mortality rate of leukemia associated with HLH and the need for further investigation for the most appropriate therapy

The association between telomere length and ischemic stroke risk and phenotype.

The chronological age of a person is a key determinant of etiology and prognosis in the setting of ischemic stroke. Telomere length, an indicator of biological aging, progressively shortens with every cell cycle. Herein, we determined telomere length from peripheral blood leukocytes by Southern blot analyses in a prospective cohort of ischemic stroke patients (n = 163) and equal number of non-stroke controls and evaluated its association with various ischemic stroke features including etiology, severity, and outcome. A shorter telomere length (i.e. lowest quartile; ≤ 5.5 kb) was significantly associated with ischemic stroke (OR 2.95, 95% CI 1.70-5.13). This significant relationship persisted for all stroke etiologies, except for other rare causes of stroke. No significant association was present between admission lesion volume and telomere length; however, patients with shorter telomeres had higher admission National Institutes of Health Stroke Scale scores when adjusted for chronological age, risk factors, etiology, and infarct volume (p = 0.046). On the other hand, chronological age, but not telomere length, was associated with unfavorable outcome (modified Rankin scale > 2) and mortality at 90 days follow-up. The association between shorter telomere length and more severe clinical phenotype at the time of admission, might reflect reduced resilience of cerebral tissue to ischemia as part of biological aging

Nuchal Translucency Measurement Did Not Significantly Predict Trisomy Cases in Tertiary Referral Center

OBJECTIVE: We sought to determine the value of well defined screening method in predicting trisomy cases in our institution. STUDY DESIGN: Totally 300 amniocentesis cases were screened from prospectively collected database. Subjects were referred to amniocentesis according to the sequential results of first and second trimester screening tests. Each case had nuchal translucency measurement between 11th to 14th weeks of gestation. All values of NT measurement were analyzed to predict trisomy cases. RESUlTS:There were 7 trisomy cases , non of the screening methods significantly predicted trisomy cases (p>0.05) rather than the simply age (Area under curve 0.724, p=0.043). Mean NT did not differ between groups with normal and abnormal chromosomes(p>0.05). CONClUSION: This data led us to conclude that in our country there is still need for more accurate and standardized method to predict abnormal cases with higher sensitivity and specificiy to decrease invasive procedures

Melanocortin-4 Receptor Gene Mutations in a Group of Turkish Obese Children and Adolescents

Objective: Melanocortin-4 receptor (MC4R) mutations are the most common known cause of monogenic obesity. Data regarding MC4R mutations in Turkish subjects are limited. To determine the prevalence of MC4R mutations in a group of Turkish morbid obese children and adolescents

Biology of stem cells in human umbilical cord stroma: In situ and in vitro surveys

Cells in the umbilical cord stroma have gained attention in recent years; however, differentiation to certain lineages in humans has been demonstrated in few studies. Unlike bone marrow MSCs, human umbilical cord stroma cells (HUC-SCs) are far from being well characterized. This study attempts to describe proliferation, structural, and differentiation properties of these cells to account for their exceptional nature in many aspects. Cellular dynamics, cellular structure, and the degree of transformations during expansion and differentiation into mesenchymal and neuronal lineages were examined in vitro over a 10-month period. Comparisons with human bone marrow MSCs regarding differentiation were performed. HUCSCs in culture revealed two distinct cell populations, type 1 and type 2 cells, that possessed differential vimentin and cytokeratin filaments. Corresponding cells were encountered in cord sections displaying region-specific localization. alpha-Smooth muscle actin and desmin filaments, which were evident in cord sections, diminished through passages. No difference was noted regarding type 1 and type 2 cells in differentiation to chondrogenic, adipogenic, and osteogenic lineages, whereas a preferential differentiation was noted in neuronal lineage. Relative success was achieved by production of chondrocytic spheres and osteogenic monolayers, whereas adipocytes were immature compared with bone marrow MSCs. The presence of neuronal markers suggests that they transform into a certain state of maturity under neurogenic induction. Conclusively, HUCSCs retain their original phenotype in culture without spontaneous differentiation, have a limited lifespan, and bear multipotent stem cell characteristics. Given these characteristics, they may be generally considered progenitor cells if manipulated under appropriate conditions and deserve further study to be potentially used in cell-based therapies

Angiotensin Converting Enzyme Insertion/Deletion Gene Polymorphisms In Leukemic Hematopoiesis

Local bone marrow renin-angiotensin system (RAS) is an autocrine-paracrine system affecting normal and neoplastic hematopoiesis. Angiotensin converting enzyme (ACE) converts angiotensinogen-I to its physiologically active peptide angiotensinII, which stimulates proliferation and differentiation of hematopoietic stem cells through angiotensin II type 1 receptors. We investigated the ACE insertion/deletion (I/D) gene polymorphisms in patients with hematological malignancies including acute and chronic leukemia, myelodysplastic syndrome and multiple myeloma. Our results showed that 80.4% of the patients represented ID/II genotype, whereas it was 55.9% of the control group and 3.2 fold increased disease risk in the existence of insertion allele (ID/II). This is the first study demonstrating possible effects of ACE I/D gene polymorphism of the local bone marrow RAS components on leukemic hematopoiesis.WoSScopu