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2.
Pan Afr Med J ; 25: 240, 2016.
Artigo em Francês | MEDLINE | ID: mdl-28293356

RESUMO

Homozygous sickle cell disease is one of the most frequent haemoglobinopathies in Morocco. Sickle cell disease is characterized by a large clinical and biological expression variability which depends on modulating genetic and environmental factors. Clinical manifestation includes regenerative anemia whose severity may vary among individuals. In the absence of treatment, it results in premature death. Sickle cell disease is characterized by a large clinical and biological expression variability which depends on genetic and environmental factors. A severe clinical picture marked by high early transfusion frequency, severe infectious complications and early mortality. A constant inflammatory condition characterized by elevated inflammatory proteins and compromised nutritional status. The objective of this study is to determine the hematological parameters profile in moroccan patients with homozygous sickle cell (SS) disease during stationary phases. We conducted a cross-sectional descriptive study of 87 patients with sickle cell (SS) disease. We performed a biological study based on: Hemogram with morphological assessment of red blood cells stained with MGG and automated reticulocyte counting; Hemoglobin electrophoresis test performed on alkaline agarose gel (pH 8.8) and densitometric integration. The average age is 13.22 years ± 16.36, ranging betrween 0.6 and 36 years, with a sex ratio (M/F) of 1.175. Biological effects of anemia were intense in 88.5% of patients; 67.8% of patients had normocytic anemia compared with 29.9% with microcytosis, and 2.3% with macrocytosis. The degree of anisocytosis was related to the degree of anemia, very evocative in patients with homozygous S/S (95.4%). Reticulocytosis was observed in 81.6% of patients; 52.9% of patients had thrombocytosis. Leukocytosis was observed in 64.4% of patients; 80.5% of patients had neutropenia. The parameters of the hemogram will serve as a basis for comparison during crises and will make it possible to evaluate the effectiveness of patient management. High white blood cell count, platelets and MCHC seem to be determinant of sickle cell anemia severity in Morocco. The haematological profile of moroccan patients with sickle cell disease exhibits data similar to those reported in literature relating to patients with leucocytosis from Central Africa. The results of our study suggest that sickle cell anemia is the most common health problem in Morocco and they are similar to those for major sickle cell syndrome.


Assuntos
Anemia Falciforme/fisiopatologia , Contagem de Células Sanguíneas/métodos , Leucocitose/epidemiologia , Neutropenia/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Marrocos , Reticulocitose/fisiologia , Índice de Gravidade de Doença , Trombocitose/epidemiologia , Adulto Jovem
4.
J Infect Dis ; 209(1): 140-9, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-23922378

RESUMO

Low reticulocytosis, indicating reduced red blood cell (RBC) output, is an important feature of severe malarial anemia. Evidence supports a role for Plasmodium products, especially hemozoin (Hz), in suppressed erythropoiesis during malaria, but the mechanism(s) involved remains unclear. Here, we demonstrated that low reticulocytosis and suppressed erythropoietin (Epo)-induced erythropoiesis are features of malarial anemia in Plasmodium yoelii- and Plasmodium berghei ANKA-infected mice, similar to our previous observations in Plasmodium chabaudi AS-infected mice. The magnitude of decreases in RBC was a reflection of parasitemia level, but low reticulocytosis was evident despite differences in parasitemia, clinical manifestation, and infection outcome. Schizont extracts and Hz from P. falciparum and P. yoelii and synthetic Hz suppressed Epo-induced proliferation of erythroid precursors in vitro but did not inhibit RBC maturation. To determine whether Hz contributes to malarial anemia, P. yoelii-derived or synthetic Hz was administered to naive mice, and the development of anemia, reticulocytosis, and RBC turnover was determined. Parasite-derived Hz induced significant decreases in RBC and increased RBC turnover with compensatory reticulocytosis, but anemia was not as severe as that in infected mice. Our findings suggest that parasite factors, including Hz, contribute to severe malarial anemia by suppressing Epo-induced proliferation of erythroid precursors.


Assuntos
Anemia/parasitologia , Eritropoese/fisiologia , Hemeproteínas/farmacologia , Malária/sangue , Reticulocitose/fisiologia , Análise de Variância , Anemia/sangue , Anemia/metabolismo , Animais , Contagem de Eritrócitos , Eritropoese/efeitos dos fármacos , Feminino , Macrófagos/química , Macrófagos/parasitologia , Malária/parasitologia , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/química , Monócitos/parasitologia , Plasmodium , Reticulocitose/efeitos dos fármacos , Esquizontes/fisiologia
5.
Intern Med ; 52(13): 1509-12, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23812200

RESUMO

Case 1. The laboratory findings of a hematological analysis of a 53-year-old woman with palpitations and dyspnea revealed the following: red blood cell (RBC) count: 9.4×10(5)/µL with 60.0‰ reticulocytes; Hb: 3.7 g/dL; mean corpuscular volume (MCV): 124.5 fL; white blood cell (WBC) count: 2,800/µL with 10.0% myeloblasts. Case 2. Similarly, a 42-year-old man with dizziness had a RBC count of 1.63×10(6)/µL with 24.0% reticulocytes, an Hb level of 6.0 g/dL, an MCV of 120.2 fL and a WBC count of 3,100/µL with 4.0% myeloblasts. Bone marrow aspirates in both patients confirmed a diagnosis of acute erythroid leukemia (AEL), which can present as marked macrocytic anemia with an MCV in excess of 120 fL and hemolysis.


Assuntos
Anemia Macrocítica/diagnóstico , Hemólise/fisiologia , Leucemia Eritroblástica Aguda/diagnóstico , Reticulocitose/fisiologia , Adulto , Anemia Macrocítica/sangue , Anemia Macrocítica/complicações , Diagnóstico Diferencial , Feminino , Humanos , Leucemia Eritroblástica Aguda/sangue , Leucemia Eritroblástica Aguda/complicações , Masculino , Pessoa de Meia-Idade
6.
Blood ; 121(13): 2553-62, 2013 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-23361909

RESUMO

B-cell lymphoma 11A (BCL11A) downregulation in human primary adult erythroid progenitors results in elevated expression of fetal γ-globin. Recent reports showed that BCL11A expression is activated by KLF1, leading to γ-globin repression. To study regulation of erythropoiesis and globin expression by KLF1 and BCL11A in an in vivo model, we used mice carrying a human ß-globin locus transgene with combinations of Klf1 knockout, Bcl11a floxed, and EpoR(Cre) knockin alleles. We found a higher percentage of reticulocytes in adult Klf1(wt/ko) mice and a mild compensated anemia in Bcl11a(cko/cko) mice. These phenotypes were more pronounced in compound Klf1(wt/ko)::Bcl11a(cko/cko) mice. Analysis of Klf1(wt/ko), Bcl11a(cko/cko), and Klf1(wt/ko)::Bcl11a(cko/cko) mutant embryos demonstrated increased expression of mouse embryonic globins during fetal development. Expression of human γ-globin remained high in Bcl11a(cko/cko) embryos during fetal development, and this was further augmented in Klf1(wt/ko)::Bcl11a(cko/cko) embryos. After birth, expression of human γ-globin and mouse embryonic globins decreased in Bcl11a(cko/cko) and Klf1(wt/ko)::Bcl11a(cko/cko) mice, but the levels remained much higher than those observed in control animals. Collectively, our data support an important role for the KLF1-BCL11A axis in erythroid maturation and developmental regulation of globin expression.


Assuntos
Proteínas de Transporte/genética , Eritropoese/genética , Genes de Troca/genética , Globinas/genética , Fatores de Transcrição Kruppel-Like/genética , Proteínas Nucleares/genética , Animais , Proteínas de Ligação a DNA , Embrião de Mamíferos , Eritropoese/fisiologia , Desenvolvimento Fetal/genética , Regulação da Expressão Gênica no Desenvolvimento , Rearranjo Gênico/genética , Rearranjo Gênico/fisiologia , Genes de Troca/fisiologia , Humanos , Camundongos , Camundongos Mutantes , Camundongos Transgênicos , Proteínas Repressoras , Reticulocitose/genética , Reticulocitose/fisiologia , Baço/citologia , Baço/embriologia , Baço/metabolismo
7.
Acta Biol Hung ; 62(2): 122-32, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21555264

RESUMO

Stimulated erythropoiesis and reticulocytosis can be induced by daily bleeding, or by phenylhydrazine (PHZ) treatment. We compared the in vivo effects of PHZ and bleeding treatment on haematological, energy and redox status parameters in red blood cells (RBC) of rats. The results showed that all followed haematological parameters were significantly lower in bleeding, compared to PHZ-treated rats. PHZ induced even 2.58-fold higher reticulocytosis as compared to bleeding treatment. Although PHZ induced higher reticulocytosis, respiration intensity and energy production was lower than in bleeding-induced reticulocytes. These alterations were the consequence of increased superoxide anion and peroxynitrite concentrations in PHZ-treated rats. Bleeding treatment resulted in increased activity of an antioxidative enzyme, superoxide dismutase. In conclusion, differences in these two experimental models for reticulocytosis may be used as tools for appropriate pharmacological testing of redox-active substances considering energy and redox processes, as well as apoptosis pathways.


Assuntos
Metabolismo Energético/efeitos dos fármacos , Eritrócitos/metabolismo , Hemorragia/metabolismo , Oxidantes/farmacologia , Fenil-Hidrazinas/farmacologia , Reticulocitose/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Eritrócitos/efeitos dos fármacos , Masculino , Modelos Animais , Nitritos/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ácido Peroxinitroso/metabolismo , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Reticulócitos/citologia , Reticulócitos/efeitos dos fármacos , Reticulócitos/metabolismo , Reticulocitose/fisiologia , Superóxido Dismutase/metabolismo
8.
Biol Res ; 44(2): 161-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22513419

RESUMO

Hypobaric hypoxia is of interest due to an increase of human populations working at high altitude. Testicular damage is related to the physiological response (neoangiogenesis) to increased intrascrotal blood flow as temperature rises. Hypoxia is a stress factor with overproduction of reactive oxygen species (ROS). The effect of hypoxia in mice reproductive parameters is analyzed. Animals were exposed to simulated hypoxia of 4,200 meters above sea level (m.a.s.l.) in a chamber for 33.2 days, both to continuous (HH) or intermittent hypoxia (HI) with an intermittency period of 4 days hypoxia /4 days normoxia (500 m.a.s.l.). The anti-inflammatory drug Ibuprofen was administered to a group of mice to control vasodilation and increased blood flow. Melatonin was administered to another group of mice as a potent ROS scavenger. Animals in both HH and HI exposure were compared to normoxic non-treated controls. There was a hematological response in hypoxia, with an increase in hematocrit and reticulocytosis. There was also increased teratozoospermia. This damage was more pronounced in HH than HI, suggesting that alternating normoxic periods permits compensation for the effects of hypoxia. In both hypoxia systems, the level of lipoperoxidation and the instability of DNA increased. In HH, there was a reduction of teratozoospermia in melatonin-treated mice. Ibuprofen presented a protective effect on the same parameters as melatonin with both HI and HH. The quality of sperm DNA, fragmentation, unpacking and DNA stability diminished. In conclusion, reproductive damage elicited by HH or HI was partially ameliorated by simultaneous treatment with antiflogistic and/or antioxidant agents.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/uso terapêutico , Hipóxia/fisiopatologia , Ibuprofeno/uso terapêutico , Melatonina/uso terapêutico , Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia , Altitude , Animais , Epididimo/citologia , Epididimo/fisiologia , Hematócrito , Masculino , Camundongos , Espécies Reativas de Oxigênio , Reticulocitose/fisiologia , Contagem de Espermatozoides
9.
Biol. Res ; 44(2): 161-167, 2011. tab
Artigo em Inglês | LILACS | ID: lil-602972

RESUMO

Hypobaric hypoxia is of interest due to an increase of human populations working at high altitude. Testicular damage is related to the physiological response (neoangiogenesis) to increased intrascrotal blood flow as temperature rises. Hypoxia is a stress factor with overproduction of reactive oxygen species (ROS). The effect of hypoxia in mice reproductive parameters is analyzed. Animals were exposed to simulated hypoxia of 4,200 meters above sea level (m.a.s.l.) in a chamber for 33.2 days, both to continuous (HH) or intermittent hypoxia (HI) with an intermittency period of 4 days hypoxia /4 days normoxia (500 m.a.s.l.). The anti-inflammatory drug Ibuprofen was administered to a group of mice to control vasodilation and increased blood flow. Melatonin was administered to another group of mice as a potent ROS scavenger. Animals in both HH and HI exposure were compared to normoxic non-treated controls. There was a hematological response in hypoxia, with an increase in hematocrit and reticulocytosis. There was also increased teratozoospermia. This damage was more pronounced in HH than HI, suggesting that alternating normoxic periods permits compensation for the effects of hypoxia. In both hypoxia systems, the level of lipoperoxidation and the instability of DNA increased. In HH, there was a reduction of teratozoospermia in melatonin-treated mice. Ibuprofen presented a protective effect on the same parameters as melatonin with both HI and HH. The quality of sperm DNA, fragmentation, unpacking and DNA stability diminished. In conclusion, reproductive damage elicited by HH or HI was partially ameliorated by simultaneous treatment with antiflogistic and/or antioxidant agents.


Assuntos
Animais , Masculino , Camundongos , Hipóxia/fisiopatologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/uso terapêutico , Ibuprofeno/uso terapêutico , Melatonina/uso terapêutico , Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia , Altitude , Epididimo/citologia , Epididimo/fisiologia , Hematócrito , Espécies Reativas de Oxigênio , Reticulocitose/fisiologia , Contagem de Espermatozoides
10.
Jpn J Vet Res ; 58(1): 17-27, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20645582

RESUMO

The present study characterizes canine reticulocyte exosomes. Exosomes are small membrane vesicles involved in membrane remodeling that are released from reticulocytes during the final maturation step of red blood cells. The vesicles collected from reticulocyte culture supernatants by differential centrifugation contained major exosomal proteins including heat shock protein cognate 70 (Hsc70) and transferrin receptors (TfR), consistent with the definition of the exosome. In addition, the Na,K-ATPase alpha-subunit and stomatin, a lipid raft-associated protein, were extruded by the exosome pathway, possibly leading to the absence of these proteins in erythrocytes, while the major protein constituents of erythrocyte membranes, spectrin and band 3 were retained in reticulocytes and not expelled into exosomes. The Na,K-ATPase alpha-subunit, as well as TfR and about half of the stomatin contained in exosomes, was obtained in a detergent-soluble fraction that was distinct from the lipid raft microdomain. Moreover, Na,K-ATPase and a portion of stomatin were distributed differently to Hsc70, TfR, stomatin, and ganglioside GM1 in vesicles separated with sucrose density gradient centrifugation. These results demonstrate that a heterogeneous group of exosomes participates in the loss of Na,K-ATPase and membrane remodeling during reticulocyte maturation in dogs.


Assuntos
Receptores da Transferrina/metabolismo , Reticulócitos/fisiologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Animais , Cães , Reticulócitos/citologia , Reticulocitose/fisiologia , ATPase Trocadora de Sódio-Potássio/isolamento & purificação
11.
Blood ; 115(10): 2021-7, 2010 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-20038785

RESUMO

The transition of reticulocytes into erythrocytes is accompanied by extensive changes in the structure and properties of the plasma membrane. These changes include an increase in shear resistance, loss of surface area, and acquisition of a biconcave shape. The processes by which these changes are effected have remained largely undefined. Here we examine how the expression of 30 distinct membrane proteins and their interactions change during murine reticulocyte maturation. We show that tubulin and cytosolic actin are lost, whereas the membrane content of myosin, tropomyosin, intercellular adhesion molecule-4, glucose transporter-4, Na-K-ATPase, sodium/hydrogen exchanger 1, glycophorin A, CD47, Duffy, and Kell is reduced. The degradation of tubulin and actin is, at least in part, through the ubiquitin-proteasome degradation pathway. In regard to the protein-protein interactions, the formation of membrane-associated spectrin tetramers from dimers is unperturbed, whereas the interactions responsible for the formation of the membrane-skeletal junctions are weaker in reticulocytes, as is the attachment of transmembrane proteins to these structures. This weakness, in part, results from the elevated phosphorylation of 4.1R in reticulocytes, which leads to a decrease in shear resistance by reducing its interaction with spectrin and actin. These observations begin to unravel the mechanistic basis of crucial changes accompanying reticulocyte maturation.


Assuntos
Diferenciação Celular , Membrana Celular/fisiologia , Reticulócitos/fisiologia , Actinas/metabolismo , Animais , Diferenciação Celular/fisiologia , Células Cultivadas , Proteínas do Citoesqueleto/metabolismo , Proteínas do Citoesqueleto/fisiologia , Membrana Eritrocítica/fisiologia , Hematopoese/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Complexo de Endopeptidases do Proteassoma/metabolismo , Complexo de Endopeptidases do Proteassoma/fisiologia , Reticulócitos/ultraestrutura , Reticulocitose/fisiologia , Transdução de Sinais/fisiologia , Tubulina (Proteína)/metabolismo , Ubiquitina/metabolismo
12.
Hematology ; 13(1): 68-70, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18534070

RESUMO

Sickle cell disease (SCD) is associated with an increased incidence of deep vein thrombosis and pulmonary embolism which contributes to the morbidity and mortality associated with it. The predisposition to thrombosis has been attributed to the different blood components including platelets, the coagulation system and recently damaged red cells. This article discusses the possible role of reticulocytes in promoting thrombus formation in individuals with SCD and suggests a similar pathogenetic mechanism in thromboembolism associated with other hemolytic states.


Assuntos
Anemia Falciforme/complicações , Hemólise/fisiologia , Reticulocitose/fisiologia , Tromboembolia/etiologia , Anemia Falciforme/sangue , Anemia Falciforme/fisiopatologia , Humanos , Fatores de Risco , Tromboembolia/sangue , Tromboembolia/fisiopatologia
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