RESUMEN
BACKGRAUND: There is evidence that the adverse effects of metamizole occur due to the effect of the drug on the hematopoietic stem/progenitor cells, and therefore, the disruption of hematopoiesis. Therefore, our study aimed to evaluate the effects of metamizole on hematopoietic stem/progenitor cells using cell culture techniques. MATERIAL AND METHODS: In our study, samples were taken from stem cell products of healthy allogeneic stem cell transplant donors. The colony-forming unit (CFU) assay was used for the cells obtained from these samples. In addition, the drug effects on cell proliferation were evaluated with the MTT. Furthermore, the cell colonies were labelled with immunofluorescent antibodies and the effects of metamizole on cell types formed in culture were evaluated. RESULTS: We determined that metamizole negatively affects the proliferation of cells, especially starting from 10 µM. As a result of the evaluation of colonization, we saw that the number of colonies decreased with increasing concentrations. Granulocyte-macrophage colonies were more affected at increasing concentrations than other colonies. As a result of the evaluations of our in vitro study, it was also shown as an important finding that the individual effects of the drug were highly variable. CONCLUSION: CFU method can be used as a suitable method to investigate the effects of drugs and toxic substances on hematopoiesis. We also think it may be suitable for pre-analysing hematopoietic side effects in new drug research. In addition, using stem cell samples in studies may contribute more easily to the in vitro simulation of hematopoietic differentiations (Fig. 7, Ref. 29). Text in PDF www.elis.sk Keywords: metamizole, hematopoietic progenitor cells, hematopoiesis, CFU assay, adverse effect.
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Dipirona , Células Madre Hematopoyéticas , Dipirona/farmacología , Células Madre Hematopoyéticas/fisiología , Hematopoyesis , Ensayo de Unidades Formadoras de Colonias , Diferenciación Celular , Células CultivadasRESUMEN
In this study, it was aimed to analyze behavioral changes of adrenergic receptors (ARs) in first three passages and osteogenic/adipogenic differentiation of mesenchymal stem cells (MSCs) derived from placenta fetal membrane (FM) and bone marrow (BM). It was also aimed to evaluate effects of receptor blockade on differentiation. We obtained first three passages of MSCs from placenta and BM samples. For cell identification, the cells were analyzed by flow cytometry using CD34, CD45 and CD3, CD105 antibodies in each passage. The effects of propranolol and phenoxybenzamine at incremental doses were analyzed by MTT. In addition, cell cultures were separately maintained with the blockers or without after second passage. After each passage and differentiation, α1A, α1B, α2A, α2B, ß1, ß2, ß3 AR-mRNA expressions analyzed by RT-qPCR technique. BMP6 and PPARG mRNA expressions only after differentiation and passage 3 were analyzed. A microscopic examination was also performed. Our results showed that AR expression behaviors were different in MSCs obtained from different tissue sources. In particular, α1A-AR and α2A-AR were expressed with considerably high coefficients in differentiation under blocker effect in BM-derived MSCs. No such coefficients were observed in any group of placental MSCs. In addition, it was found that the blockers stimulated adipogenesis in BM-derived MSCs during osteogenic differentiation. MSCs exhibit protein expressions that vary according to source of tissue and differentiation. Given that MSCs from different sources are used for repair and modulation, our study makes implications of this variable expression intriguing in the clinical practice.
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Células Madre Mesenquimatosas , Osteogénesis , Células de la Médula Ósea , Diferenciación Celular/genética , Células Cultivadas , Femenino , Humanos , Células Madre Mesenquimatosas/metabolismo , Osteogénesis/genética , Placenta/metabolismo , Embarazo , ARN Mensajero/metabolismo , Receptores Adrenérgicos/metabolismoRESUMEN
The endothelium is a single-layered structure that responds to physical and chemical signals with various factors it synthesizes. In the early days of its discovery, as the inner wall of the vessels, the endothelium was thought to be a simple barrier that lays on the surface. Over time it is discovered that endothelium maintains body homeostasis with the molecules it synthesizes, despite its simple single-layer structure. It has been accepted as an important organ that contributes to the maintenance of vascular tone, cell adhesion, inflammation, vascular permeability and coagulation. Any imbalance in these physiological and pathological events causes endothelial dysfunction. This can cause many diseases such as atherosclerosis, hypertension, diabetes, or it can occur because of these. Endothelial related disorders may also complicate hematopoietic stem cell transplantation (HSCT), which is used to treat various hematologic and neoplastic diseases. These life-threatening complications include graft-versus-host disease, hepatic veno-occlussive disease, transplant-associated thrombotic microangiopathy and diffuse alveolar hemorrhage. They share a similar pathophysiology involving endothelial cells with different clinical presentations. Therefore, current researche on the issue is putting the endothelium under the spotlight for novel markers and treatment options that should be used to monitor or treat at least some of these complications following HSCT.
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Endotelio/metabolismo , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , HumanosRESUMEN
Graft versus host disease (GVHD) is still the most important cause of mortality and morbidity after allogeneic stem cell transplantation. Though perfect response rates are not achieved, steroids are still the first-line treatment. In the face of the presence of the drugs approved by FDA in recent years for acute and chronic GVHD as second-line therapy in the steroid-refractory group, there exists no standard approach. Extracorporeal photopheresis (ECP) with an immunomodulatory effect, is favored in the treatment of both acute and chronic steroid refractory GVHD as it does not increase the risk of relapses or infections. Having a low profile of side effects, ECP is also generally well-tolerated by patients. Being a time requiring procedure, the fact is that it is not able to be practiced in all health centers and requires central venous catheters in patients unfit for venous access may be enumerated among its shortcomings. No complete standard is available with respect to ECP application frequency-time; it varies from one center to another. The Turkish Society of Apheresis established the Turkish ECP (TECP) group and sought some answers to the questions regarding the use of ECP in the treatment of GVHD, and issued a position statement.
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Eliminación de Componentes Sanguíneos/métodos , Enfermedad Injerto contra Huésped/terapia , Fotoféresis/métodos , Enfermedad Aguda , Enfermedad Crónica , Humanos , TurquíaRESUMEN
Aluminum phosphide (AIP) is a fumigant commonly used in agricultural areas. AIP is frequently misused for suicidal purposes because it is easily accessible. AIP poisoning causes severe metabolic acidosis, resistant hypotension, acute respiratory distress syndrome, and multiorgan failure with cardiogenic shock. Despite supportive management and intensive care, most patients die following AIP ingestion because there is no specific antidote. In this case report we present a 15-year-old female who presented with vomiting, coma and epigastric pain. She developed resistant metabolic acidosis and hypotension due to AIP poisoning. Although supportive treatment did not result in clinical improvement, she was successfully treated with automated red blood cell exchange. Automated red blood cell exchange is a procedure which is used to exchange the patient erythrocyte mass with donor red blood cell. Although automated red blood cell exchange is a preferred treatment method in the complications of sickle cell anemia, some blood diseases and infectious diseases such as malaria and babesiosis, there is little information about its use in poisoning. To the best of our knowledge, this is the first child with AIP poisoning who was treated with automated red blood cell exchange.
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Acidosis , Hipotensión , Fosfinas , Intoxicación , Adolescente , Compuestos de Aluminio , Niño , Eritrocitos , Femenino , HumanosRESUMEN
BACKGROUND AND AIM: The incidence of fetomaternal complications during pregnancy is high for women with sickle cell disease (SCD), which is the most common hematologic genetic disorder worldwide. Prophylactic red blood cell exchange (pRBCX) has been shown to be efficient, safe, and feasible for preventing complications. The aim of this study was to observe maternal, perinatal, and neonatal outcomes of pregnancies in which pRBCX was. METHOD: This was a single-center, retrospective, cross-sectional study, which recruited 46 consecutive adult pregnant women with SCD between January 2012 and June 2019. Obstetric features, SCD-related complications, and fetomaternal outcomes were compared between the 27 patients who received prophylactic exchange and the 19 who did not (therapeutic exchange was performed in 7 and was not performed in 12 cases). RESULTS: Painful crises, preeclampsia, and preterm birth rates were significantly higher in the group that did not receive prophylactic exchange (control group; P = .001, P = .024, and P = .027, respectively). There was one maternal mortality in the control group (P = .41). Incidence of adverse fetal or maternal complications was significantly higher in the control group (P = .044 and P = .007, respectively). CONCLUSIONS: Our center's experience over a 7.5-year period, as described above, demonstrates that pRBCX in SCD affects the course of pregnancy positively by ameliorating negative fetomaternal outcomes.
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Anemia de Células Falciformes/terapia , Transfusión de Eritrocitos/métodos , Complicaciones Hematológicas del Embarazo/terapia , Adulto , Anemia de Células Falciformes/prevención & control , Estudios Transversales , Femenino , Humanos , Embarazo , Complicaciones Hematológicas del Embarazo/prevención & control , Resultado del Embarazo , Estudios RetrospectivosRESUMEN
Ovarian cancer remains one of the most frequent causes of cancer-related death in women. Many patients with ovarian cancer suffer from de novo or acquired resistance to chemotherapy. Here, we report that RAB25 suppresses chemotherapy-induced mitochondrial apoptosis signaling in ovarian cancer cell lines and primary ovarian cancer cells. RAB25 blocks chemotherapy-induced apoptosis upstream of mitochondrial outer membrane permeabilization by either increasing antiapoptotic BCL-2 proteins or decreasing proapoptotic BCL-2 proteins. In particular, BAX expression negatively correlates with RAB25 expression in ovarian cancer cells. BH3 profiling assays corroborated that RAB25 decreases mitochondrial cell death priming. Suppressing RAB25 by means of RNAi or RFP14 inhibitory hydrocarbon-stapled peptide sensitizes ovarian cancer cells to chemotherapy as well as RAB25-mediated proliferation, invasion and migration. Our data suggest that RAB25 is a potential therapeutic target for ovarian cancer.
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Apoptosis , Resistencia a Antineoplásicos , Neoplasias Ováricas/metabolismo , Proteínas de Unión al GTP rab/fisiología , Adulto , Anciano , Ciclo Celular , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Humanos , Persona de Mediana Edad , Mitocondrias , Invasividad Neoplásica , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Transducción de Señal , Proteínas de Unión al GTP rab/metabolismoRESUMEN
BACKGROUND: Chronic myeloid leukemia (CML) is a disease resulting from BCR-ABL gene fusion. It is possible to monitor treatment by molecular testing for BCR-ABL. The lymphocyte-to-monocyte ratio (LMR) is a commonly used marker associated with prognosis in various neoplasms. This study was performed to evaluate the relevance of absolute lymphocyte count (ALC), absolute monocyte count (AMC), and LMR in predicting molecular response status in patients with chronic phase CML. METHODS: Samples submitted to our hematology laboratory for BCR-ABL testing between April 2012 and October 2018 were retrospectively reviewed. Concurrent hemogram testing together with the results of quantitative reverse transcriptase-polymerase chain reaction were noted. Data were grouped according to molecular response status and the ALC, AMC, and LMR were compared among patient groups. RESULTS: A total of 224 samples from 95 patients were included in the study. Analysis revealed differences between groups when newly diagnosed patients were compared with patients undergoing treatment, regardless of response status. However, analyzing the groups according to molecular response status failed to reveal differences in ALC, AMC, or LMR. CONCLUSIONS: ALC, AMC, and LMR are not potential biomarkers for predicting molecular response status in patients with chronic phase CML.
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Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Recuento de Leucocitos , Linfocitos/citología , Monocitos/citología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The profile of leukocytes in bronchoalveolar lavage (BAL) fluid provides important information for diagnosing various lung diseases. A differential cell count of BAL is conventionally performed by evaluating centrifuged samples under a light microscope and enumerating the stained cells. Another rarely used method to identify BAL leukocytes is flow cytometry (FCM). However, there are no guidelines for standardizing this method and related literature is limited. This study aimed to evaluate the accuracy of FCM for identifying BAL leukocytes. METHODS: The BAL samples accepted to the hematology laboratory between 2014 - 2018 were retrospectively evaluated via light microscopy (LM) by a hematologist; while flow cytometric analyses with a monoclonal antibody panel composed of CD45/CD14/CD16 were noted by another doctor. The percentages of macrophages, lymphocytes, neutrophils and eosinophils determined by both methods were recorded for analysis. Correlations between the results from LM and FCM were investigated. In addition, compatibility between LM and FCM for denoting pathological values for each cell type was checked. RESULTS: Among 140 reviewed BAL samples, 76 were included for further analysis. Comparisons revealed strong correlations between FCM and LM for identifying macrophages, lymphocytes, neutrophils, and eosinophils. In addition, regarding the normal cutoff values for each leukocyte type, FCM and LM were similar in the identification of pathological changes of all cell types except eosinophils. CONCLUSIONS: Flow cytometry was found to be feasible for use instead of LM and might become a more widely used technique to analyze BAL fluid in the future.
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Anticuerpos Monoclonales/análisis , Líquido del Lavado Bronquioalveolar/citología , Citometría de Flujo/métodos , Enfermedades Pulmonares/diagnóstico , Neoplasias Pulmonares/diagnóstico , Anticuerpos Monoclonales/inmunología , Líquido del Lavado Bronquioalveolar/inmunología , Eosinófilos/citología , Eosinófilos/inmunología , Estudios de Factibilidad , Femenino , Humanos , Recuento de Leucocitos , Leucocitos/citología , Leucocitos/inmunología , Macrófagos/citología , Macrófagos/inmunología , Masculino , Microscopía/métodos , Persona de Mediana Edad , Neutrófilos/citología , Neutrófilos/inmunología , Patología Clínica/instrumentación , Patología Clínica/métodos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Sickle cell disease (SCD) is a life-threatening chronic condition primarily caused by genetic mutation. The disease is characterized by intermittent vaso-occlusive events and chronic hemolytic anemia. Acute complications in patients with SCD are difficult to manage due to the pathophysiological nature of the disease. Transfusion therapy is the cornerstone of management of acute complications and significantly reduces SCD morbidity and mortality. Red cell exchange (RCE), which is characterized by low iron accumulation and volume overload, has been widely used for transfusion therapy in recent years.
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Anemia de Células Falciformes/terapia , Transfusión de Eritrocitos/métodos , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/genética , HumanosRESUMEN
BACKGROUND AND OBJECTIVE: Assessment of Hemoglobin S trait donors has gained importance together with the increased allogeneic peripheral stem cell transplant activity for sickle cell disease in the regions where the disease is prevalent. Outcomes of Granulocyte-Colony Stimulating Factor (G-CSF) administration are obscure for hemoglobin S trait donors. This study aims at investigating the incidence of hemoglobin S carrier status and outcomes of G-CSF administration among donors who live in Eastern Mediterranean region. MATERIAL AND METHOD: The cross-sectional, single-center cohort study was performed with 147 donors between January 2013 and March 2017. Prevalence of hemoglobin S trait was estimated and subjects with or without Hemogobin S trait were compared with regard to stem cell characteristics, early and late clinical outcomes after G-CSF administration. RESULTS: Eleven out of 147 donors (7.48%) were found as hemoglobin S trait. G-CSF administration was successfully completed and yielded good harvesting results in hemoglobin S trait donors. No statistically significant difference was found between groups with regard to early and late side effects, stem cell characteristics. Blood pressures and QTc values were within normal ranges in both groups. Groups were similar with regard to CD34 values. CONCLUSION: G-CSF seems safe in hemoglobin S trait donors. Their being eligible as donors would increase the chance of the patients for allogeneic stem cell transplantation in high prevalence regions. Further studies are required to reveal the safety profile of G-SCF in hemoglobin S carriers in different regions.
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Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética/métodos , Rasgo Drepanocítico , Donantes de Tejidos , Adulto , Estudios de Cohortes , Estudios Transversales , Femenino , Hemoglobina Falciforme , Humanos , Masculino , Región Mediterránea , Persona de Mediana EdadRESUMEN
BACKGROUND AND AIM: Today, voluntary donation of peripheral blood stem cells by healthy donors for allogeneic hemopoietic cell transplantation is common worldwide. Such donations are associated with small but measurable risks of morbidity and mortality. Most complications are associated with citrate infusion during cell collection. We studied the effects of citrate infusion on the QTc and other vital parameters during and after peripheral stem cell apheresis in volunteers. METHOD: To ensure that donors were healthy, screening included taking a detailed medical history, physical examination, and laboratory measurements of plasma calcium and magnesium. Corrected QT (QTc) values were assessed using a 12-lead electrocardiographic platform that derived QTc values automatically. RESULTS: In all, 141 apheresis procedures were performed. The mean QTc values at baseline, at 2 and 4 h during the procedure, and at 30 min after the procedure, were 347.6 ± 59.5, 349.9 ± 52.8, 391.8 ± 54.0, and 404.8 ± 59.2 ms, respectively. The baseline and 2 h QTcs did not differ significantly, but the baseline QTc did differ significantly from the 4 h and 30 min after the procedure values. The plasma levels of calcium and magnesium did not significantly differ before and after the procedure. CONCLUSION: QTc prolongation may develop during leukopheresis, particularly if the procedure takes more than 2 h. Thus, to enhance donor safety, QTc measurement should be standard for all donors. In addition, any family history of sudden death should be noted, to prevent the development of possible fatal arrhythmia in susceptible donors.
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Eliminación de Componentes Sanguíneos/métodos , Electrocardiografía/normas , Células Madre de Sangre Periférica/citología , Adolescente , Adulto , Ácido Cítrico/administración & dosificación , Estudios Transversales , Femenino , Voluntarios Sanos , Humanos , Leucaféresis , Masculino , Anamnesis , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Donantes de Tejidos , Adulto JovenRESUMEN
Previous studies showed that bone marrow-derived mesenchymal stem cells (BMSCs) could ameliorate a variety of immune-mediated and inflammatory diseases due to their immunomodulatory and anti-inflammatory effects. In this study, we developed a mouse model of ovalbumin (OVA) induced allergic inflammation in the upper airways and evaluated the effects of the intraperitoneal administration of BMSCs on allergic inflammation. Twenty-five BALB/c mice were divided into five groups; group I (control group), group II (sensitized and challenged with OVA and treated with saline-placebo group), group III (sensitized and challenged with OVA and treated with 1 × 106 BMSCs), group IV (sensitized and challenged with OVA and treated with 2 × 106 BMSCs), and group V (sensitized and challenged with phosphate buffered saline (PBS) and treated with 1 × 106 BMSCs). Histopathological features (number of goblet cells, eosinophils and mast cells, basement membrane, epithelium thickness, and subepithelial smooth muscle thickness) of the upper and lower airways and BMSCs migration to nasal and lung tissue were evaluated using light and confocal microscopes. Levels of cytokines in the nasal lavage fluid and lung tissue supernatants were measured using enzyme-linked immunosorbent assay (ELISA). Confocal microscopic analysis showed that there was no significant amount of BMSCs in the nasal and lung tissues of group V. However, significant amount of BMSCs were observed in group III and IV. In OVA-induced AR groups (group II, III, and IV), histopathological findings of chronic asthma, such as elevated subepithelial smooth muscle thickness, epithelium thickness, and number of goblet and mast cells, were determined. Furthermore, the number of nasal goblet and eosinophil cells, histopathological findings of chronic asthma, and IL-4, IL-5, IL-13, and NO levels was significantly lower in both BMSCs-treated groups compared to the placebo group. Our findings indicated that histopathological findings of chronic asthma were also observed in mice upon AR induction. BMSCs migrated to the nasal and lung tissues following intraperitoneal delivery and ameliorated to the airway remodeling and airway inflammation both in the upper and lower airways via the inhibition of T helper (Th) 2 immune response in the murine model of AR.
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Trasplante de Células Madre Mesenquimatosas/métodos , Rinitis Alérgica/terapia , Alérgenos/efectos adversos , Animales , Biomarcadores/metabolismo , Citocinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Inyecciones Intraperitoneales , Masculino , Ratones , Ratones Endogámicos BALB C , Mucosa Nasal/inmunología , Mucosa Nasal/metabolismo , Mucosa Nasal/patología , Ovalbúmina/efectos adversos , Distribución Aleatoria , Rinitis Alérgica/etiología , Rinitis Alérgica/inmunología , Rinitis Alérgica/patologíaRESUMEN
OBJECTIVES: To investigate the association between endothelial progenitor cells (EPCs) and Takayasu arteritis (TA). Subjects andMethods: A total of 39 subjects were included in this study: 12 subjects had been diagnosed with active TA, 11 had active Behçet disease (BD), and 16 were healthy controls. The EPCs, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels of all the subjects were measured. MedCalc 15.8 software (MedCalc, Belgium) was used for all statistical analyses. RESULTS: The level of EPCs was higher in TA patients (4.25 ± 2.56) than in the BD group (2.27 ± 2.0) and the healthy controls (2.12 ± 1.2) (p = 0.015). TA patients with acrotism (n = 4) had higher levels of EPCs compared to TA patients without acrotism (n = 8) (6.50 ± 1.73 vs. 3.12 ± 2.16, p = 0.02). A positive correlation was found between EPCs and the ESR (r = 0.723, p = 0.0079) and between EPCs and CRP in patients with TA (r = 0.769, p < 0.0034). CONCLUSION: High levels of circulating EPCs were correlated with the CRP level and the ESR in patients with TA. These cells could be a marker for acrotism and inflammation in patients with TA.
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Síndrome de Behçet/sangre , Síndrome de Behçet/epidemiología , Células Progenitoras Endoteliales/metabolismo , Arteritis de Takayasu/sangre , Arteritis de Takayasu/epidemiología , Adulto , Factores de Edad , Biomarcadores , Sedimentación Sanguínea , Proteína C-Reactiva/análisis , Estudios Transversales , Femenino , Humanos , Masculino , Factores Sexuales , Fumar/epidemiología , TurquíaRESUMEN
BACKGROUND: Sickle cell disease (SCD) is associated with chronic hemolysis and painful episodes. Pregnancy accelerates sickle cell complications, including prepartum and postpartum vasoocclusive crisis, pulmonary complications, and preeclampsia or eclampsia. Fetal complications include preterm birth and its associated risks, intrauterine growth restriction, and a high rate of perinatal mortality. The purpose of this study was to evaluate pregnancy outcomes in patients with SCD who underwent planned preventive red blood cell exchange (RBCX). STUDY DESIGN AND METHODS: We retrospectively evaluated the complications of SCD in 37 pregnant patients. Patients with SCD who had undergone prophylactic RBCX were compared with a control group who had not undergone RBCX during pregnancy. RESULTS: Forty-three exchange procedures were performed in 24 patients. The control group comprised 13 patients with a mean age of 27.4 ± 3.3 years who had not undergone RBCX during pregnancy. Four of the five patients who developed a vasoocclusive crisis died. There was a significant difference in maternal mortality between the study and control groups (p = 0.011). There was also a significant difference in the incidence of vasoocclusive crisis between the study and control groups. One fetal death occurred in the 20th gestational week in a patient in the control group, although there were no postpartum complications in either the babies or the mothers in the control group. CONCLUSION: This study has demonstrated that prophylactic RBCX during pregnancy is a feasible and safe procedure for prevention of complications. Given the decrease in the risks of transfusion, RBCX warrants further study.
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Anemia de Células Falciformes/terapia , Transfusión de Eritrocitos/métodos , Complicaciones Hematológicas del Embarazo/terapia , Síndrome Torácico Agudo/etiología , Síndrome Torácico Agudo/mortalidad , Anemia de Células Falciformes/complicaciones , Arteriopatías Oclusivas/etiología , Arteriopatías Oclusivas/mortalidad , Arteriopatías Oclusivas/prevención & control , Cesárea , Estudios Transversales , Estudios de Factibilidad , Femenino , Sangre Fetal/química , Muerte Fetal , Humanos , Recién Nacido , Isquemia/etiología , Isquemia/prevención & control , Trabajo de Parto Inducido , Complicaciones del Trabajo de Parto/prevención & control , Embarazo , Complicaciones Hematológicas del Embarazo/mortalidad , Complicaciones Hematológicas del Embarazo/prevención & control , Resultado del Embarazo , Estudios Retrospectivos , Adulto JovenRESUMEN
Despite the presence of many therapeutic regimens like imatinib and other tyrosine kinase inhibitors, the development of resistance, intolerance, and side effects makes chronic myeloid leukemia (CML) therapy challenging. Thus, there is a need to discover novel drugs for CML patients. In this study, we attempted to assess apigenin, a common plant dietary flavonoid, in terms of its cytotoxic, apoptotic, and cytostatic effects on imatinib-sensitive and resistant Philadelphia-positive CML cells. We analyzed apigenin's effects on cell proliferation, apoptosis, caspase-3 activity, loss of mitochondrial membrane potential, and cell cycle progression in K562 and K562/IMA3 cells. Furthermore, we described genes and gene networks that are modulated in CML in response to apigenin. Results of our study revealed that apigenin has cytotoxic and apoptotic effects on both cell types. We also displayed that apigenin induced G2/M arrest in K562 cells while arresting K562/IMA3 cells in S phase especially at the highest apigenin concentration. The expression analysis identified a set of genes that were regulated by apigenin in K652 and K562/IMA3 cells. Association of modulated genes with biological functional groups identified several networks affected by apigenin including cell survival, proliferation, cell death, cell cycle, and cell signalling pathways.
Asunto(s)
Antineoplásicos/farmacología , Apigenina/farmacología , Benzamidas/farmacología , Resistencia a Antineoplásicos , Piperazinas/farmacología , Pirimidinas/farmacología , Apoptosis/efectos de los fármacos , Caspasa 3/genética , Caspasa 3/metabolismo , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Humanos , Mesilato de Imatinib , Células K562 , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacosRESUMEN
OBJECTIVES: Behçet's disease (BD) is a systemic disorder characterised by vasculitis. Endothelial progenitor cells are derived from the bone marrow and contribute to new vessel formation. The aim of this study was to investigate the level of endothelial progenitor cells in BD and BD-associated conditions. METHODS: A total of 74 subjects were included in this study, of whom 44 and 30 subjects were patients with BD or healthy subjects, respectively. Endothelial progenitor cells were defined and measured by flow cytometry according to the expression of CD146, CD31 and CD34. We separated BD patients according to the active disease, pathergy test results, thrombosis and gender. MedCalc 12.5 software programme was used for statistical analyses. RESULTS: The level of endothelial progenitor cells was comparable in patients with BD and healthy subjects (p=0.849). It was also comparable in patients with active or inactive BD (p=0.320). The level of endothelial progenitor cells was higher in patients with thrombosis (p=0.04). There was no statistical significant difference between pathergy positive and negative patients (p=0.969). The level of endothelial progenitor cells was not correlated with age, C-reactive protein, erythrocyte sedimentation rate, white blood cells and disease duration (p>0.05). CONCLUSIONS: The level of endothelial progenitor cells was significantly higher in BD patients with thrombosis. On the other hand, they were not associated with disease activity, pathergy test and other conditions. EPCs may be a useful marker for thrombosis in patients with BD. In our opinion, this is the most expected result in this study.
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Síndrome de Behçet/sangre , Síndrome de Behçet/patología , Células Endoteliales/patología , Células Madre/patología , Trombosis/sangre , Trombosis/patología , Adulto , Síndrome de Behçet/complicaciones , Sedimentación Sanguínea , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trombosis/complicaciones , Adulto JovenRESUMEN
Patients with sickle cell disease (SCD) are prone to develop thrombosis and infection due to their inflammatory and immune deficiency state. These patients require red cell exchange therapy for treatment or prevention of hemoglobin S associated complications. Owing to vascular access problems, adult patients need central venous catheterization (CVC) for exchange procedures. Procedure related complications have been reported for long-term CVCs in pediatric patients. However, short-term CVC complications in adult patients are not clear. This report represents the results of documented complications of short-term CVCs in patients with SCD who undergo apheresis. A total of 142 non-tunneled catheters with average median diameter of 9 F (range 8-16 F) were implanted for apheresis. The catheters were mainly inserted through the right internal jugular vein (66.2 %). Total days of catheter were 412. Results were reported as a complication rate and event according to 1,000 catheter days and compared to a control group including 37 healthy stem cell donors. In the patient group, 1 (1 %) hematoma and 1 (1 %) infection were observed for internal jugular vein catheterization (3.7 hemorrhages and 3.7 infections according to 1,000 catheter days), whereas four (8.9 %) cases of thrombosis and 1 (2.2 %) infection (27 and 6.9 according to 1,000 catheter days) developed in femoral vein. There was a significant difference in terms of thrombosis (P = 0.009). In the control group, only individual developed thrombosis in internal jugular vein. Short-term CVC inserted through to the internal jugular vein seems to be safer than femoral vein in patients with SCD.
Asunto(s)
Anemia de Células Falciformes , Eliminación de Componentes Sanguíneos/efectos adversos , Catéteres Venosos Centrales/efectos adversos , Hemorragia , Infecciones , Trombosis , Adolescente , Adulto , Anemia de Células Falciformes/epidemiología , Anemia de Células Falciformes/terapia , Femenino , Hemorragia/epidemiología , Hemorragia/etiología , Humanos , Infecciones/epidemiología , Infecciones/etiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trombosis/epidemiología , Trombosis/etiologíaRESUMEN
Increased thrombocyte activation leads to a higher likelihood of coagulation in sickle-cell disease. On the other hand, chronic inflammation and endothelial cell activation promote vaso-occlusion. The effect of circulating microparticles derived from erythrocytes, monocytes, thrombocytes, and endothelial cells on the vaso-occlusive process is unclear. This study aims to analyze the relationship between sickle-cell disease and miscellaneous organ complications by defining the circulating microparticles during the steady-state and painful crisis periods in 45 patients with sickle-cell disease. Microparticle analysis was conducted using an eight-parameter flow cytometric method, using CD61 PERCP, CD142PE, CD106 FITC, CD14 APC-H7, CD235a FITC, and Annexin-V APC monoclonal antibodies. Microparticle levels of sickle-cell patients were found to be significantly higher during both painful crisis and steady-state situations compared with the control group (for all, p < 0.001). Among these microparticles, levels of erythrocyte microparticles (eMPs) were significantly higher during crisis than in the steady-state period (eMP steady state vs. painful crisis: 7.59 ± 12.24 vs. 7.59 ± 12.24, respectively; p < 0.01). Microparticles, including eMPs, were not affected by hydroxyurea treatment. Their level did not reflect the high frequency of crisis (>3 times/year). Thrombocyte microparticle levels were found to be higher in patients with nephropathia than in those without (48.05 ± 40.23 vs. 7.67 ± 6.75, respectively; p < 0.049). Circulating microparticles seem to be involved in the pathogenesis of sickle-cell disease. eMPs may help with the management of crisis. Thrombocyte microparticles might predict renal damage induced by vaso-occlusion.