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1.
J Epidemiol Glob Health ; 13(2): 266-278, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37129837

RESUMO

Over a period of about 9 months, we conducted three serosurveys in the two major cities of Cameroon to determine the prevalence of SARS-COV-2 antibodies and to identify factors associated with seropositivity in each survey. We conducted three independent cross-sectional serosurveys of adult blood donors at the Central Hospital in Yaoundé (CHY), the Jamot Hospital in Yaoundé (JHY) and at the Laquintinie Hospital in Douala (LHD) who consented in writing to participate. Before blood sampling, a short questionnaire was administered to participants to collect their sociodemographic and clinical characteristics. We included a total of 743, 1202, and 1501 participants in the first (January 25-February 15, 2021), second (May 03-28, 2021), and third (November 29-December 31, 2021) surveys, respectively. The adjusted seroprevalence increased from 66.3% (95% CrI 61.1-71.3) in the first survey to 87.2% (95% CrI 84.0-90.0) in the second survey, and 98.4% (95% CrI 96.8-99.7) in the third survey. In the first survey, study site, participant occupation, and comorbid conditions were associated with SARS-CoV-2 seropositivity, whereas only study site remained associated in the second survey. None of the factors studied was significantly associated with seropositivity in the third survey. Together, the data suggest a rapid initial spread of SARS-CoV-2 in the study population, independent of the sociodemographic parameters assessed.


Assuntos
COVID-19 , Adulto , Humanos , COVID-19/epidemiologia , Estudos Transversais , SARS-CoV-2 , Estudos Soroepidemiológicos , Cidades/epidemiologia , Doadores de Sangue , Camarões/epidemiologia , Anticorpos Antivirais
2.
Vox Sang ; 117(7): 920-928, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35298840

RESUMO

BACKGROUND AND OBJECTIVES: We had previously developed an Africa-specific donor health questionnaire (ASDHQ) based on local risk factors and designed a scoring scheme. This study assessed the performance of a new donor health questionnaire by comparing the human immunodeficiency virus (HIV) status in accepted versus deferred donors by ASDHQ and comparing the rate of risk deferrals with historical data. MATERIALS AND METHODS: Data were collected during a cross-sectional study conducted over 15 months at three referral-hospital-based blood services in Cameroon. ASDHQ was administered to blood donors aged 18-65 years in the same screening conditions as the routine questionnaire. The main outcomes of the study were ASDHQ sensitivity and specificity with regard to HIV laboratory testing as well as donor deferral rates for each of the routine screening algorithms and for ASDHQ. RESULTS: Overall, 71/11,120 (0.6%) were confirmed as HIV positive. The mean ASDHQ score was 95.80 ± 4.4 in HIV-negative donors and 94.80 ± 4.4 in HIV-positive donors (p = 0.05). The optimal cut-off provided by the receiver operating characteristic (ROC) curve for the best performance of ASDHQ was 95.04. Using this optimal cut-off, the ASDHQ sensitivity and specificity were 57% and 53%, respectively (area under curve = 0.58 [0.51, 0.64], p = 0.028). Using ASDHQ, the HIV prevalence was 0.7% in deferred donors and 0.6% in accepted donors. CONCLUSION: ASDHQ might be efficient only in specific conditions that maximize truthful donor responses, requiring each blood service to create an environment of trust and transparency to increase donor compliance and improve the accuracy of the questionnaire.


Assuntos
Infecções por HIV , Soropositividade para HIV , Doadores de Sangue , Camarões/epidemiologia , Estudos Transversais , Seleção do Doador , HIV , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Humanos , Inquéritos e Questionários
3.
Front Genet ; 12: 595702, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33790942

RESUMO

BACKGROUND: Renal dysfunctions are associated with increased morbidity and mortality in sickle cell disease (SCD). Early detection and subsequent management of SCD patients at risk for renal failure and dysfunctions are essential, however, predictors that can identify patients at risk of developing renal dysfunction are not fully understood. METHODS: In this study, we have investigated the association of 31 known kidney dysfunctions-related variants detected in African Americans from multi-ethnic genome wide studies (GWAS) meta-analysis, to kidney-dysfunctions in a group of 413 Cameroonian patients with SCD. Systems level bioinformatics analyses were performed, employing protein-protein interaction networks to further interrogate the putative associations. RESULTS: Up to 61% of these patients had micro-albuminuria, 2.4% proteinuria, 71% glomerular hyperfiltration, and 5.9% had renal failure. Six variants are significantly associated with the two quantifiable phenotypes of kidney dysfunction (eGFR and crude-albuminuria): A1CF-rs10994860 (P = 0.02020), SYPL2-rs12136063 (P = 0.04208), and APOL1 (G1)-rs73885319 (P = 0.04610) are associated with eGFR; and WNT7A-rs6795744 (P = 0.03730), TMEM60-rs6465825 (P = 0.02340), and APOL1 (G2)-rs71785313 (P = 0.03803) observed to be protective against micro-albuminuria. We identified a protein-protein interaction sub-network containing three of these gene variants: APOL1, SYPL2, and WNT7A, connected to the Nuclear factor NF-kappa-B p105 subunit (NFKB1), revealed to be essential and might indirectly influence extreme phenotypes. Interestingly, clinical variables, including body mass index (BMI), systolic blood pressure, vaso-occlusive crisis (VOC), and haemoglobin (Hb), explain better the kidney phenotypic variations in this SCD population. CONCLUSION: This study highlights a strong contribution of haematological indices (Hb level), anthropometric variables (BMI, blood pressure), and clinical events (i.e., vaso-occlusive crisis) to kidney dysfunctions in SCD, rather than known genetic factors. Only 6/31 characterised gene-variants are associated with kidney dysfunction phenotypes in SCD samples from Cameroon. The data reveal and emphasise the urgent need to extend GWAS studies in populations of African ancestries living in Africa, and particularly for kidney dysfunctions in SCD.

4.
Vox Sang ; 116(6): 637-644, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33314185

RESUMO

INTRODUCTION: The COVID-19 pandemic, caused by a novel coronavirus, has already affected over 99 062 people in 53 African countries and killed 3082. The pandemic threatens blood supply but we do not yet know its impact on blood donations or on the perceptions and expectations of donors. METHODS: We conducted a cross-sectional study in four hospital-based blood services in Cameroon, using a survey design and focusing on the subjective and cultural aspects of donors. Using a semi-structured questionnaire, we collected the participants' responses as to their understanding of COVID-19 and of current protection measures, and their expectations. Data on trends of blood donations were collected retrospectively for the period from 1st January to 30th April 2019 and the same period in 2020. RESULTS: Of 494 donors included, 432 (87·4%) were enrolled from fixed blood collection sites and 62 (12·6%) were contacted by phone. A total of 464 (93·9%) participants believed that the COVID-19 is a lung disease, but some declared it to be imaginary (7·7%), a foreign disease (8·3%) or a blood-borne disease (3·2%). The participants reported that the distribution of face masks and hydroalcoholic solutions (92·5%), social distancing and hygiene (6·3%) are the most important measures that need to be in place for safe donation. The number of blood donations dropped by 21·5% between 2019 and 2020. CONCLUSION: Most of the donors know COVID-19, its transmission routes and manifestations. In the absence of barrier measures, they perceive blood donation as a threat to their health. Distribution of masks and hydroalcoholic solution might motivate more donors and improve the blood supply.


Assuntos
Doadores de Sangue/psicologia , Doadores de Sangue/estatística & dados numéricos , COVID-19/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Pandemias , Adolescente , Adulto , Camarões/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inquéritos e Questionários , Adulto Jovem
5.
Vox Sang ; 115(8): 686-694, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32468573

RESUMO

BACKGROUND AND OBJECTIVE: In the WHO Universal test and treat strategy, false-positive HIV blood donors and patients may be unnecessarily put under antiretroviral treatment and false-negative subjects may be lost to follow-up. This study assessed the false positivity rate of the Cameroonian national HIV screening testing algorithm and the benefit of a confirmation test in the enrolment of patients and donors in the HIV care programme. METHODS: We included initial HIV reactive blood donors and patients in a cross-sectional study conducted in two Cameroonian hospitals. Samples were retested according to the Cameroon national algorithm for HIV diagnosis. A positive or discordant sample was retested with the Geenius Bio-Rad HIV 1&2 (Bio-Rad, Marnes-la-Coquette, France) for confirmation. The Geenius HIV-1-positive results with 'poor' profiles were retested for RNA as well as the Geenius indeterminate results. RESULTS: Of the 356 participants, 190/225 (84·4%) patients and 76/131 (58%) blood donors were declared positive with the national algorithm; 257 participants (96·6%) were confirmed HIV-1-positive. The study revealed that about 34/1000 blood donors and patients are false-positive and unnecessarily put on treatment; 89/1000 blood donors and patients declared discordant could have been included immediately in the HIV care programme if confirmatory testing was performed. The second test of the algorithm had a false-negative rate of 3%. Eleven samples (3·1%) were Geenius poor positive and NAT negative. CONCLUSION: The universal test and treat strategy may identify and refer more individuals to HIV care if a third rapid confirmatory test is performed for discordant cases.


Assuntos
Doadores de Sangue , Infecções por HIV/diagnóstico , Soropositividade para HIV/diagnóstico , Adolescente , Adulto , Algoritmos , Camarões , Estudos Transversais , Feminino , Anticorpos Anti-HIV/sangue , HIV-1/imunologia , HIV-2/imunologia , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Testes Sorológicos , Organização Mundial da Saúde , Adulto Jovem
6.
Blood ; 130(20): 2215-2223, 2017 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-28931524

RESUMO

The hyperhemolysis paradigm that describes overlapping "hyperhemolytic-endothelial dysfunction" and "high hemoglobin-hyperviscous" subphenotypes of sickle cell disease (SCD) patients is based on North American studies. We performed a transversal study nested in the CADRE cohort to analyze the association between steady-state hemolysis and vascular complications of SCD among sub-Saharan African patients. In Mali, Cameroon, and Ivory Coast, 2407 SCD patients (1751 SS or sickle ß-zero-thalassemia [Sß0], 495 SC, and 161 sickle ß+-thalassemia [Sß+]), aged 3 years old and over, were included at steady state. Relative hemolytic intensity was estimated from a composite index derived from principal component analysis, which included bilirubin levels or clinical icterus, and lactate dehydrogenase levels. We assessed vascular complications (elevated tricuspid regurgitant jet velocity [TRV], microalbuminuria, leg ulcers, priapism, stroke, and osteonecrosis) by clinical examination, laboratory tests, and echocardiography. After adjustment for age, sex, country, and SCD phenotype, a low hemoglobin level was significantly associated with TRV and microalbuminuria in the whole population and with leg ulcers in SS-Sß0 adults. A high hemolysis index was associated with microalbuminuria in the whole population and with elevated TRV, microalbuminuria, and leg ulcers in SS-Sß0 adults, but these associations were no longer significant after adjustment for hemoglobin level. In conclusion, severe anemia at steady state in SCD patients living in West and Central Africa is associated with elevated TRV, microalbuminuria, and leg ulcers, but these vascular complications are not independently associated with indirect markers of increased hemolysis. Other mechanisms leading to anemia, including malnutrition and infectious diseases, may also play a role in the development of SCD vasculopathy.


Assuntos
Anemia Falciforme/complicações , Anemia Falciforme/epidemiologia , Hemólise , Doenças Vasculares/etiologia , Doenças Vasculares/patologia , Adolescente , África/epidemiologia , Albuminúria/etiologia , Anemia Hemolítica , Biomarcadores , Criança , Pré-Escolar , Feminino , Hemoglobinas/análise , Humanos , Lactente , Úlcera da Perna/etiologia , Masculino , Insuficiência da Valva Tricúspide/etiologia , Adulto Jovem
7.
Health sci. dis ; 18(1): 74-77, 2017.
Artigo em Francês | AIM (África) | ID: biblio-1262775

RESUMO

But. La drépanocytose a pour maitre symptôme la douleur, laquelle nécessite une thérapeutique analgésiante dont la référence demeure la morphine. C'est un antalgique de troisième palier, classe thérapeutique peu utilisée sur le continent africain selon des études menées par l'OMS. Notre étude avait pour but de décrire la prise en charge de la douleur du patient drépanocytaire hospitalisé pour crises vaso-occlusives au service d'hémato-oncologie de l'Hôpital Central de Yaoundé. Méthodes. Nous avons mené une étude prospective, descriptive du 1er janvier au 30 juin 2014. Des drépanocytaires connus d'au moins 6 ans hospitalisés pour crise vaso-occlusive étaient recrutés. Les analgésiques utilisés et leur posologie étaient relevés pour chacun. La douleur avant et après l'administration des antalgiques était évaluée avec une Échelle Visuelle Analogique (EVA) ou une Échelle Numérique (EN) et la satisfaction du patient aux analgésiques reçus, notée. Résultats. Nous avons recruté 73 drépanocytaires homozygotes âgés de 7 à 53 ans et d'âge moyen égal à 23,04 ±8,35 ans pour un sex ratio de 1,21. Les antalgiques des paliers 1 et 2 ont été prescrits et administrés respectivement à 97.30% et 94.50%, le kétoprofène et le tramadol étant utilisés en première intention. Aucun antalgique de palier 3 n'a été utilisé. L'analgésie complète a été obtenue après quatre jours ou plus. 49 patients (67.1%) ont attribué les mentions d'appréciation les plus basses au traitement analgésique reçu et seuls 4 (5.5%) l'ont estimé excellent. Dans 53,42% des cas il a fallu soixante minutes ou plus pour que les différents produits prescrits soient disponibles. Pour tous les patients, aucun traitement n'a permis d'obtenir une analgésie dans les 30 minutes suivant son administration. Conclusion. La majorité des sujets drépanocytaires est insatisfaite du traitement antalgique reçu. Des sessions de formation du personnel sont nécessaires


Assuntos
Anemia Falciforme , Camarões , Dor , Manejo da Dor , Pacientes
8.
BMC Hematol ; 14(1): 5, 2014 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-24517107

RESUMO

BACKGROUND: Transfusion-transmissible infections (TTIs) pose a major health risk in Cameroon given the high prevalence of such pathogens and increased demands for blood donations in the local communities. This study aims at establishing the prevalence of commonly encountered TTIs among blood donors and transfusion-related complications among recipients in an urban center of Cameroon. METHODS: A total of 477 blood donors and 83 blood recipients were recruited by consecutive sampling at the Laquintinie Hospital in Douala (LHD), Cameroon. Serum samples from blood donors were tested by quantitative enzyme-linked immunosorbent assays (ELISA) and/or using various Rapid diagnostic test (RDT) for presence of Hepatits B (HBV) viral antigens, and antibodies to human immunodeficiency (HIV-1/2), Hepatits B (HCV) and Treponema pallidum. Recipient's medical records were also analyzed for possible transfusion-associated complications. RESULTS: The male/female sex ratio of the blood donors was 4/1 with a mean age of 30.2 (Sd = 8.3) years. Of all blood donors, 64/467 (13.7%) were infected by at least one of the four TTIs. Infected volunteer donors represented 8.3% while infected family donors comprised 14.3% of the donor population. The prevalence of HCV, HIV, HBV and T. pallidum were 1.3%, 1.8%, 3.5%, and 8.1%, respectively. More than half of the blood recipients were female (78.3%) and the mean age was 20.6 (SD = 16.1) years. The causes of severe anemia indicative of transfusion in recipients varied with wards (postpartum hemorrhage, caesarean section, uterine or cervical lacerations, abortions, urinary tract infections, severe malaria, vaso-occlusive attacks, wounds and gastrointestinal bleeding). The most frequent complications were chills and hematuria, which represented 46.1% of all observed complications. Other complications such as nausea, vomiting, jaundice, sudden diarrhea, anxiety, tachycardia, or hyperthermia were also found in recipients. Three cases of deaths occurred during the study, including a girl of less than one year. CONCLUSION: This study confirms the presence of blood-borne infectious diseases in blood donors at the LHD, identifying T. pallidum as the greatest threat to blood safety in the region, and hematuria as the most common immunological complications in blood recipients.

9.
Leuk Lymphoma ; 55(1): 74-7, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23566160

RESUMO

Granulocyte-colony stimulating factors (G-CSFs) enhance bone marrow (BM) recovery after autologous stem cell transplant (ASCT) in patients with lymphoma and myeloma. Few publications exist that discuss the use of filgrastim biosimilars after ASCT. We conducted a single-center retrospective study in patients with lymphoma and myeloma treated at Brest Hospital to assess the cost reductions related to and the efficiency and safety of filgrastim biosimilars. We identified 65 patients with lymphoma or myeloma treated with filgrastim biosimilars for ASCT and compared 19 parameters of these patients, including BM recovery, side effects, infectious complications and treatment costs, with published historical data on a cohort of 50 patients treated with classic filgrastim. We observed a significant reduction of G-CSF costs in both groups but did not observe a change in total hospitalization costs (representing less than 2% of the costs) between groups. Additionally, we did not observe differences between the two groups in BM recovery, infectious complications, side effects or the other studied parameters. In this retrospective study, the absence of differences between groups after ASCT in lymphoma and myeloma led us to believe that these drugs could be safely and effectively used for such indications without a significant impact on hospitalization costs. A prospective study should be conducted to confirm our results.


Assuntos
Medicamentos Biossimilares/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Adulto , Idoso , Medicamentos Biossimilares/economia , Custos de Medicamentos , Feminino , Filgrastim , Fator Estimulador de Colônias de Granulócitos/economia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Proteínas Recombinantes/economia , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
10.
Clin Kidney J ; 6(1): 15-20, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27818746

RESUMO

BACKGROUND: Little is known about the renal profiles of individuals with sickle cell disease (SCD) in equatorial Africa, the global epicenter of SCD. We evaluated the kidney function, urinalysis abnormalities and their correlates in a group of Cameroonians homozygous for SCD. METHODS: This was a cross-sectional study of 4-month duration involving 72 homozygous SCD patients (39 men, 54%), recruited during routine visit or vaso-occlusive crisis at the Yaoundé Central Hospital in Cameroon. Clinical and laboratory data were used to evaluate the renal and urinalysis parameters, and potential effects of SCD-related clinical and hematological variables on those parameters investigated through linear and logistic regression models. RESULTS: The mean serum creatinine increased with increasing age, translating into a decreasing estimated glomerular filtration rate (eGFR) with age (P < 0.001). One patient (1.4%) had an eGFR of <60 mL/min and nine others (12.5%) had 60 ≤ eGFR ≤ 90 mL/min. The eGFR was lower in women and decreased with increasing systolic blood pressure. The prevalence of proteinuria (>200 mg/g) was 93% and the main urinalysis abnormalities were leukocyturia (77.8%), albuminuria (40.3%), hematuria (13.9%) and cristalluria (9.7%). None of the predictive clinical, hematological and urinary factors studied was associated with proteinuria or albuminuria, while hematuria and leukocyturia were associated with increasing age and male gender. CONCLUSIONS: Cameroonians homozygous for SCD present a high prevalence of proteinuria and urinalysis abnormalities, and a slight renal impairment. Age, blood pressure variables and gender seem to be the main determinants. Urinalysis abnormalities and kidney function assessment should be an active pursuit in women with SCD.

11.
Health sci. dis ; 14(2): 1-5, 2013.
Artigo em Inglês | AIM (África) | ID: biblio-1262662

RESUMO

Sickle cell anemia (SCA) is an autosomal recessive genetic blood disorder; characterized by red blood cells that assume an abnormal; rigid; sickle shape and often shows itself by chronic hemolytic anemia. Patients are exposed to multiple blood transfusions throughout their life with a higher risk of contacting viruses such as major human immunodeficiency virus (HIV). The aim of this study was to estimate the prevalence HIV infection in sickle cell patient accounting the number of received transfusions. Patients and methods:This was a cross sectional analytical study performed on the sickle cell patients of the sickle cell clinic of the Yaounde Central Hospital from July 2008 to January 2009. Sociodemographic data; transfusion history were recorded. A serological testing with ELISA method was done Results: Hundred and eight (108) patients were enrolled after obtaining informed consent. More than half (52.78) was male and the mean age of patients was 21+/-9 years (5-47). HIV antibodies were found in six patients (5;6). Five of 6 infected patients were Female (p = 0.028). All HIV positive patients have already been transfused and HIV seropositivity increased with the number of blood transfusions (r = 0.24; P 0.05). Conclusion: These results show the vulnerability of the polytransfused patients with sickle cell anemia towards HIV infection and the necessity of strengthening the transfusional safety policy


Assuntos
Anemia , Transfusão de Sangue , Infecções por HIV , Prevalência
12.
Am J Trop Med Hyg ; 83(4): 906-8, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20889889

RESUMO

Poor laboratory equipment and few human resources have made it difficult to implement microscopic diagnosis of pulmonary tuberculosis (TB) on a large scale basis worldwide. Three hundred sputum samples from patients in Cameroon were studied by using the CyScope®, a new light-emitting, diode-based, fluorescence microscope, to compare auramine-rhodamine fluorescence with the conventional Ziehl-Neelsen staining method. Five fluorescence protocols were tested to reduce manipulation time. Smear positivity for acid-fast bacilli with the Ziehl-Neelsen staining method was 27.7% (83 of 300) compared with 33.3% (100 of 300) with the fluorescent method. Staining time with the modified fluorescence protocol could be reduced from 21 minutes to 10 minutes. This study confirmed that the fluorescence staining method is more sensitive than the Ziehl-Neelsen staining method. It is suggested that the training of laboratory technicians on fluorescence microscopy should be scaled up for increased disease control.


Assuntos
Microscopia de Fluorescência/economia , Microscopia de Fluorescência/instrumentação , Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Tuberculose/diagnóstico , Benzofenoneídio/química , Reações Falso-Negativas , Humanos , Rodaminas/química , Sensibilidade e Especificidade , Coloração e Rotulagem , Fatores de Tempo
13.
Afr J Reprod Health ; 13(3): 47-52, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20690261

RESUMO

We conducted a cross sectional retrospective study to determine anti-D and D-negative phenotype rates among Cameroonian women of reproductive age (15-44 years), in order to evaluate the importance of D alloimmunization. Analysis of the haematology laboratory records from January 2006 to December 2007 harvested 225 results for red blood cell alloantibody screening and 2460 D phenotypes. Anti-D rate was found to be high at 4% and not linked to women's parity. Three hundred and fifty two (14.3%) women were found to be D-negative. Anti-D rates significantly decreased with age from 18.8% among teenagers (15-19) to 7.8% among older women (35-44) (p = 0.001). The number of women submitted to both irregular antibody screening and type D phenotype determination was not strong enough (50) to analyse the link between anti-D rate and antigen D distribution in our study.


Assuntos
Isoanticorpos/sangue , Sistema do Grupo Sanguíneo Rh-Hr/imunologia , Adolescente , Adulto , Fatores Etários , Camarões/epidemiologia , Estudos Transversais , Feminino , Humanos , Programas de Rastreamento , Prevalência , Estudos Retrospectivos , Imunoglobulina rho(D) , Adulto Jovem
14.
Leuk Res ; 32(5): 743-54, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-17980427

RESUMO

Regulation of normal hematopoiesis by neuropeptide substance P (SP) and its amino terminal fragment, SP(1-4), has been reported. Endogenous erythroid colony (EEC) formation without erythropoietin is characteristic of polycythemia vera (PV), a chronic myeloproliferative disorder. We investigated the effect(s) of SP and SP(1-4) on EEC formation from PV BM mononuclear cells (BMMCs) and purified CD36+ erythroid progenitors. We found a potent in vitro inhibitory effect of SP and SP(1-4) on PV EEC formation for both BMMCs and CD36+ erythroid progenitors. The influence of SP and SP(1-4) on PV progenitor erythroid differentiation and cell viability was also investigated, and the impact of neurokinin receptors and G proteins in the inhibition were analyzed by quantitative PCR and with specific inhibitors. This progenitor inhibition was: (1) not mediated by accessory cells; (2) characterized by an increase in cell death and inhibition of the EPOindependent terminal erythroid differentiation; and (3) not mediated by the same neurokinin receptor. NK-1R and NK-2R antagonists completely abrogated the SP inhibitory effect but not SP(1-4)-induced inhibition. Furthermore, the truncated form of the NK-1R was predominant over the full-length mRNA and could mediated the SP inhibitory effect on PV CD36+ erythroid progenitors. Different G proteins were also implicated according to the erythroid differentiation stage of the PV cells. The observation of an inhibitory effect of SP and its related peptide, SP(1-4), on PV EEC formation at physiological concentrations (10-8M) suggests that neuropeptides represent a way to downregulate pathologic expansion of PV progenitors.


Assuntos
Células Precursoras Eritroides/efeitos dos fármacos , Eritropoetina/fisiologia , Fragmentos de Peptídeos/farmacologia , Policitemia Vera/tratamento farmacológico , Substância P/farmacologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Precursoras Eritroides/fisiologia , Proteínas de Ligação ao GTP/fisiologia , Humanos , Policitemia Vera/sangue , RNA Mensageiro/análise , Receptores de Taquicininas/genética
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