Assuntos
Elementos Facilitadores Genéticos , Hemoglobina H/genética , alfa-Globinas/genética , Talassemia alfa/genética , Adulto , Alelos , Cromatina/genética , Cromatina/ultraestrutura , Cromossomos Humanos Par 16/genética , Cromossomos Humanos Par 16/ultraestrutura , Eritroblastos/patologia , Eritropoese , Feminino , Deleção de Genes , Regulação da Expressão Gênica , Genótipo , Hemoglobina E/genética , Hemoglobina H/análise , Humanos , Masculino , Linhagem , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Deleção de Sequência , Suriname/etnologia , alfa-Globinas/biossíntese , Talassemia alfa/sangue , Globinas beta/genéticaRESUMO
Sickle cell disease (SCD) is one of the most prevalent and severe monogenetic disorders. Previously, we generated iPS cell lines from SCD patients. Here, we generated iPS cell lines from three age-, ethnicity- and gender-matched healthy individuals as control cell lines. Cell reprogramming was performed using erythroblasts expanded from PBMC by a non-integrative method. SCD-iPSC controls expressed pluripotency markers, presented a normal karyotype, were able to differentiate into the three germ layers in embryoid body spontaneous differentiation and confirmed to be integration-free. The cell lines generated here may be used as matched healthy controls for SCD studies.
Assuntos
Anemia Falciforme , Técnicas de Reprogramação Celular , Eritroblastos , Células-Tronco Pluripotentes Induzidas/metabolismo , Anemia Falciforme/genética , Anemia Falciforme/metabolismo , Anemia Falciforme/patologia , Técnicas de Cultura de Células , Linhagem Celular , Eritroblastos/metabolismo , Eritroblastos/patologia , Humanos , Células-Tronco Pluripotentes Induzidas/patologiaRESUMO
Some of the most polluting activities occur in bovine skin processing. Tannery generates effluents containing high concentrations of heavy metals and organic compounds. The phases composing the leather production process generate a large volume of tannery effluents that are often discarded in aquatic environments without any previous treatment. However, the effect these xenobiotics have on adult representatives belonging to the class Amphibia remains unknown. Thus, the aim of the present study is to assess the geno- and cytotoxic effects of tannery effluent on adult male bullfrogs (Lithobates castesbeianus) exposed to it. Accordingly, the animals were divided into the following groups: negative control (tannery effluent-free water), positive control (cyclophosphamide), and effluent (water added with 5% tannery effluent). The animals were euthanized for blood collection, and erythrocyte analyses were conducted after 35 and 90 days of exposure. The micronuclei (MN) frequency and the frequency of other nuclear abnormalities in each of the animals in the experimental groups were assessed in 2000 erythrocytes. According to the present results, the exposure to tannery effluents increased MN frequency as well as other nuclear abnormalities (i.e., lobed nuclei, binucleated cell, kidney-shaped nuclei, notched nuclei, and apoptotic cell) in the erythrocytes of animals in the effluent group and in the positive control group after 35 and 90 exposure days. Thus, the current study corroborated the hypothesis that the tannery effluent has aneugenic and clastogenic potential in adult male bullfrogs (L. castesbeianus). The present study is the first to report such effect.
Assuntos
Eritrócitos/efeitos dos fármacos , Metais Pesados/toxicidade , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Mutagênicos/toxicidade , Curtume , Poluentes Químicos da Água/toxicidade , Animais , Dano ao DNA , Relação Dose-Resposta a Droga , Eritroblastos/química , Eritroblastos/efeitos dos fármacos , Eritroblastos/patologia , Eritrócitos/química , Eritrócitos/patologia , Eritrócitos Anormais/química , Eritrócitos Anormais/efeitos dos fármacos , Eritrócitos Anormais/patologia , Resíduos Industriais/análise , Masculino , Metais Pesados/análise , Testes para Micronúcleos , Estrutura Molecular , Mutagênicos/análise , Rana catesbeiana , Fatores de Tempo , Poluentes Químicos da Água/análiseRESUMO
BACKGROUND: The presence of nucleated red blood cells (NRBCs) in the peripheral blood of critically ill patients is associated with a poorer prognosis, though data on cardiovascular critical care patients is lacking. The aim of the present study was to assess the role of NRBCs as a predictor of intensive care unit (ICU) and in hospital all-cause mortality among cardiologic patients. METHODS: NRBCs were measured daily in consecutive cardiac ICU patients, including individuals with both coronary and non-coronary acute cardiac care. We excluded patients younger than 18 years, with cancer or hematological disease, on glucocorticoid therapy, those that were readmitted after hospital discharge and patients who died in the first 24 hours after admission. We performed a multiple logistic analysis to identify independent predictors of mortality. RESULTS: We included 152 patients (60.6 ± 16.8 years, 51.8% female, median ICU stay of 7 [4-11] days). The prevalence of NRBCs was 54.6% (83/152). The presence of NRBC was associated with a higher ICU mortality (49.4% vs 21.7%, P<0.001) as well as in-hospital mortality (61.4% vs 33.3%, p = 0.001). NRBC were equally associated with mortality among coronary disease (64.71% vs 32.5% [OR 3.80; 95%CI: 1.45-10.0; p = 0.007]) and non-coronary disease patients (61.45% vs 33.3% [OR 3.19; 95%CI: 1.63-6.21; p<0.001]). In a multivariable model, the inclusion of NRBC to the APACHE II score resulted in a significant improvement in the discrimination (p = 0.01). CONCLUSIONS: NRBC are predictors of all-cause in-hospital mortality in patients admitted to a cardiac ICU. This predictive value is independent and complementary to the well validated APACHE II score.
Assuntos
Cardiopatias/mortalidade , Adulto , Idoso , Cuidados Críticos , Estado Terminal , Eritroblastos/patologia , Contagem de Eritrócitos , Feminino , Cardiopatias/sangue , Cardiopatias/patologia , Cardiopatias/terapia , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Curva ROC , Análise de SobrevidaRESUMO
This study was undertaken to investigate the genomic instability on blood cells during 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis by means of single cell gel (comet) and micronucleus assays. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution through their drinking water for 4, 12, and 20 weeks. Ten animals were used as negative control. Although no histopathological abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure, genetic damage was found in blood cells as depicted by the mean tail moment and an increase of micronucleated polychromatic erythrocytes. After 12 and 20 weeks treatment, the same picture occurred, being the strong effect observed in the micronucleus induction. These periods correspond to pre-neoplastic lesions and well-differentiated squamous cell carcinomas, respectively. Taken together, our results support the idea that genomic instability on blood cells appears to be associated with the risk and progression of oral cancer, being a reliable tool for detecting early systemic conditions of malignancy.
Assuntos
4-Nitroquinolina-1-Óxido/toxicidade , Carcinógenos/toxicidade , Ensaio Cometa , Eritroblastos/metabolismo , Eritrócitos Anormais/metabolismo , Instabilidade Genômica/efeitos dos fármacos , Neoplasias da Língua/induzido quimicamente , Neoplasias da Língua/metabolismo , Animais , Eritroblastos/patologia , Eritrócitos Anormais/patologia , Masculino , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Valor Preditivo dos Testes , Ratos , Ratos Wistar , Fatores de Tempo , Neoplasias da Língua/patologiaRESUMO
The diagnosis of myelodysplastic syndromes (MDS) is based on peripheral cytopenias, bone marrow (BM) morphology and karyotyping. This may be difficult in cases with few dysplastic elements in BM and a normal karyotype. We examined the utility of flow cytometric analysis for the differential diagnosis between MDS and non-clonal disorders (NCD) presenting peripheral cytopenias. Quantitative assessment of CD45, CD16, CD13, CD11b, CD10 and CD64 in granulocytes and monocytes, and CD71 and glycophorin A in erythroblasts besides CD34+ cell count was performed in BM of 31 consecutive newly diagnosed patients with MDS, 11 patients with NCD and 11 healthy controls (BM donors). In MDS, the median number of phenotypic abnormalities found was 3 (1-8). The WPSS score showed a correlation with the total number of changes per case (r=0.48; p=0.002). Decreased SSC in promyelocytes correlated with the peripheral neutrophil count (r=-0.46; p=0.007). In NCD, the normal variation of antigen expression along granulocytic and erythroblast maturation was always maintained. In the discriminant analysis, SSC of CD34+ cells, together with that of promyelocytes and metamyelocytes were able to correctly classify 87% of the cases as clonal or non-clonal. Our quantitative approach permitted to detect at least one abnormality in antigen expression in every case of MDS. However, the most important parameters for differential diagnosis with NCD were the analysis of the granularity in immature cells, especially of the granulocytic series.
Assuntos
Antígenos CD/análise , Citometria de Fluxo/métodos , Síndromes Mielodisplásicas/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/patologia , Diferenciação Celular , Células Clonais , Diagnóstico Diferencial , Eritroblastos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos/patologia , Mutação , Síndromes Mielodisplásicas/genética , FenótipoRESUMO
Nuclear and cytoplasmic abnormalities were quantitated in bone marrow erythroblasts from 15 patients with iron deficient anemia, 5 beta-thalassemia homozygotes, 5 beta-thalassemia heterozygotes, 6 S/beta-thalassemia double heterozygotes and 9 controls. The frequency of dyserythropoietic changes in iron deficiency was 11.90 +/- 5.02% (mean +/- SD) which is significantly higher than 3.36 +/- 1.16% obtained for the control group. The degree of dyserythropoiesis was negatively correlated with hemoglobin level (rS = 0.757). The frequency of dyserythropoietic changes obtained for the beta-thalassemia heterozygotes (5.23 +/- 1.45%) and for S/beta-thalassemia (7.13 +/- 2.00%) was elevated compared with the controls (P less than 0.05 and P less than 0.01, respectively). The highest frequency of dyserythropoiesis (19.88 +/- 7.40%) occurred among beta-thalassemia homozygotes. In all cases studied the abnormalities were observed mainly in the late erythroblasts. In addition, a peculiar cytoplasmic inclusion was observed in Leishman-stained bone marrow or peripheral blood erythroblasts from beta-thalassemia homozygotes, which is probably the result of precipitation of excess alpha-chain. This abnormality of thalassemia erythroblasts in Leishman-stained smears had not been previously reported.
Assuntos
Anemia Hipocrômica/sangue , Eritroblastos/fisiologia , Índices de Eritrócitos , Eritropoese , Talassemia/sangue , Eritroblastos/patologia , Eritroblastos/ultraestrutura , Inclusões Eritrocíticas , Hematócrito , HumanosRESUMO
A case of dyserythropoietic congenital anemia type II (HEMPAS) in an infant 35 days of age is reported. Diagnosis was based upon morphological features of the erythroblasts, 25% of them were bi or multinucleated and a positive acidified serum test (pseudo HAM). The early and severe anemia which was present from the first days of life is emphasized. An additional and significant hemolytic factor with a relative tocopherol deficiency is suggested. A very important degree of hepatic hemosiderosis was found at necropsy. This finding reveals the very active dyserytropietic disorder in this case from the beginning of intrauterine file.