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1.
PLoS One ; 15(8): e0237543, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32776978

RESUMO

Sickle cell disease (SCD) impacts liver and kidney function as well as skin integrity. These complications, as well as the hyperinflammatory state of SCD, could affect serum albumin. Serum albumin has key roles in antioxidant, anti-inflammatory and antithrombotic pathways and maintains vascular integrity. In SCD, these pathways modulate disease severity and clinical outcomes. We used three independent SCD adult cohorts to assess clinical predictors of serum albumin as well its association with mortality. In 2553 SCD adult participants, the frequency of low (<35 g/L) serum albumin was 5%. Older age and lower hemoglobin (P <0.001) were associated with lower serum albumin in all three cohorts. In age and hemoglobin adjusted analysis, higher liver enzymes (P <0.05) were associated with lower serum albumin. In two of the three cohorts, lower kidney function as measured by Glomerular Filtration Rate (P<0.001) was associated with lower serum albumin. Lower serum albumin predicted higher risk of tricuspid regurgitation velocity ≥ 2.5 m/s (OR = 1.1 per g/L, P ≤0.01). In all three cohorts, patients with low serum albumin had higher mortality (adjusted HR ≥2.9, P ≤0.003). This study confirms the role of serum albumin as a biomarker of disease severity and prognosis in patients with SCD. Albumin as a biomarker and possible mediator of SCD severity should be studied further.


Assuntos
Anemia Falciforme/mortalidade , Biomarcadores/sangue , Hemoglobinas/análise , Albumina Sérica/análise , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/patologia , Estudos de Coortes , Feminino , Humanos , Masculino , Prognóstico , Taxa de Sobrevida
2.
PLoS One ; 15(6): e0234151, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32520956

RESUMO

OBJECTIVES: To examine interocular asymmetry of foveal avascular zone (FAZ) and parafoveal capillary density metrics in sickle cell retinopathy (SCR) using optical coherence tomography angiography (OCT-A). METHODS: This cross-sectional, retrospective study evaluated SCR patients and unaffected controls who underwent 3x3mm macular OCT-A imaging using a spectral domain-OCT system. FAZ (area, perimeter, and acircularity index) and parafoveal capillary density metrics were computed for both eyes of each participant. In unaffected controls, interocular difference in FAZ and parafoveal capillary density metrics were evaluated using Bland-Altman plots. SCR patients with interocular difference outside the upper 97.5% and lower 2.5% limits of agreement from controls were defined as having interocular asymmetry. Area under receiver operating characteristic curve (AROC) was also performed to determine the ability of the absolute interocular difference to differentiate between subjects with SCR-including non-proliferative SCR (NP-SCR) and proliferative SCR (P-SCR)-and unaffected controls. RESULTS: Thirty-one patients with SCR (21 NP-SCR and 10 P-SCR) and 14 race-matched and age-matched controls were included for analysis. Interocular asymmetry was seen for all FAZ and parafoveal capillary density metrics in NP-SCR and P-SCR subjects. SCR subjects showed greater disease severity in the left-eye for FAZ and parafoveal capillary density metrics. CONCLUSIONS: NP-SCR and P-SCR patients demonstrated quantifiable interocular asymmetry in FAZ and parafoveal capillary density metrics compared to unaffected subjects, with left-eye predominance in disease severity.


Assuntos
Anemia Falciforme/patologia , Capilares/fisiologia , Fóvea Central/fisiologia , Doenças Retinianas/patologia , Adulto , Anemia Falciforme/complicações , Área Sob a Curva , Estudos de Casos e Controles , Estudos Transversais , Olho/diagnóstico por imagem , Feminino , Fóvea Central/irrigação sanguínea , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Doenças Retinianas/etiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Tomografia de Coerência Óptica , Adulto Jovem
5.
PLoS One ; 15(4): e0229959, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32243480

RESUMO

Sickle cell disease (SCD) is characterized by deoxygenation-induced polymerization of hemoglobin in red blood cells, leading to hemolytic anemia, vaso-occlusion, and the development of multiple clinical complications. To characterize the clinical burden associated with differences in hemoglobin concentration and hemolysis measures, a systematic literature review of MEDLINE, EMBASE, and related meta-analyses was undertaken. For quantitative analyses related to hemoglobin concentration, pooled results were analyzed using random effects models to control for within-and between-study variability. To derive risk ratios associated with hemoglobin concentration change, we combined ratios of means from select studies, which reported hazard and odds ratios in meta-analyses for hemoglobin concentration-related outcomes and changes between groups. Forty-one studies were identified for inclusion based on relating hemoglobin concentration to clinical outcomes. Meta-analyses demonstrated that mean hemoglobin concentration was significantly lower in patients with cerebrovascular disease (0.4 g/dL), increased transcranial Doppler velocity in cerebral arteries (0.6 g/dL), albuminuria (0.6 g/dL), elevated estimated pulmonary artery systolic pressure (0.9 g/dL), and in patients that subsequently died (0.6 g/dL). In a risk reduction meta-analysis, modeled increased hemoglobin concentrations of 1 g/dL or greater resulted in decreased risk of negative clinical outcomes of 41% to 64%. In conclusion, chronic anemia is associated with worse clinical outcomes in individuals with SCD and even modest increases in hemoglobin concentration may be beneficial in this patient population. This systematic review has been registered on Prospero (Registration number CRD42018096860; https://www.crd.york.ac.uk/prospero/).


Assuntos
Anemia Falciforme/sangue , Transtornos Cerebrovasculares/sangue , Hemoglobinas/metabolismo , Nefropatias/sangue , Anemia/sangue , Anemia/epidemiologia , Anemia/patologia , Anemia Falciforme/mortalidade , Anemia Falciforme/patologia , Transtornos Cerebrovasculares/epidemiologia , Transtornos Cerebrovasculares/patologia , Hemoglobina Falciforme/genética , Hemoglobina Falciforme/metabolismo , Hemólise , Humanos , Nefropatias/epidemiologia , Nefropatias/patologia , Razão de Chances , Ultrassonografia Doppler Transcraniana
6.
Nat Med ; 26(4): 535-541, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32284612

RESUMO

Base editing by nucleotide deaminases linked to programmable DNA-binding proteins represents a promising approach to permanently remedy blood disorders, although its application in engrafting hematopoietic stem cells (HSCs) remains unexplored. In this study, we purified A3A (N57Q)-BE3 base editor for ribonucleoprotein (RNP) electroporation of human-peripheral-blood-mobilized CD34+ hematopoietic stem and progenitor cells (HSPCs). We observed frequent on-target cytosine base edits at the BCL11A erythroid enhancer at +58 with few indels. Fetal hemoglobin (HbF) induction in erythroid progeny after base editing or nuclease editing was similar. A single therapeutic base edit of the BCL11A enhancer prevented sickling and ameliorated globin chain imbalance in erythroid progeny from sickle cell disease and ß-thalassemia patient-derived HSPCs, respectively. Moreover, efficient multiplex editing could be achieved with combined disruption of the BCL11A erythroid enhancer and correction of the HBB -28A>G promoter mutation. Finally, base edits could be produced in multilineage-repopulating self-renewing human HSCs with high frequency as assayed in primary and secondary recipient animals resulting in potent HbF induction in vivo. Together, these results demonstrate the potential of RNP base editing of human HSPCs as a feasible alternative to nuclease editing for HSC-targeted therapeutic genome modification.


Assuntos
Anemia Falciforme/patologia , Edição de Genes , Terapia Genética/métodos , Células-Tronco Hematopoéticas/metabolismo , Proteínas Repressoras/genética , gama-Globinas/genética , Anemia Falciforme/terapia , Animais , Antígenos CD34/metabolismo , Sistemas CRISPR-Cas , Células Cultivadas , Estudos de Viabilidade , Feminino , Edição de Genes/métodos , Marcação de Genes/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/patologia , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos Transgênicos , Cultura Primária de Células , Proteínas Repressoras/metabolismo , Talassemia beta/patologia , Talassemia beta/terapia , gama-Globinas/metabolismo
8.
Lancet Haematol ; 7(4): e329-e341, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32220342

RESUMO

Sickle cell disease is a life-threatening inherited condition designated as a public health priority by WHO. Increased longevity of patients with sickle cell disease in high-income, middle-income, and low-income countries present unprecedented challenges for all settings; however, a globally standardised solution for patient transition from paediatric to adult sickle cell disease health care is unlikely to address the challenges. We established a task force of experts from a multicountry (the USA, Europe, Middle East, and Africa) consortium. We combined themes from the literature with viewpoints from members of the task force and invited experts to provide a global overview of transition care practice, highlighting barriers to effective transition care and provide baseline recommendations that can be adapted to local needs. We highlighted priorities to consider for any young person with sickle cell disease transitioning from paediatric to adult health care: skills transfer, increasing self-efficacy, coordination, knowledge transfer, linking to adult services, and evaluating readiness (the SICKLE recommendations). These recommendations aim to ensure appropriate benchmarking of transition programming, but multisite prospective studies are needed to address this growing public health need.


Assuntos
Anemia Falciforme/patologia , Comitês Consultivos , Criança , Assistência à Saúde , Humanos , Gestão do Conhecimento , Autoeficácia , Transição para Assistência do Adulto
9.
Subcell Biochem ; 94: 297-322, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32189305

RESUMO

Sickle cell hemoglobin (HbS) is an example of a genetic variant of human hemoglobin where a point mutation in the ß globin gene results in substitution of glutamic acid to valine at sixth position of the ß globin chain. Association between tetrameric hemoglobin molecules through noncovalent interactions between side chain residue of ßVal6 and hydrophobic grooves formed by ßAla70, ßPhe85 and ßLeu88 amino acid residues of another tetramer followed by the precipitation of the elongated polymer leads to the formation of sickle-shaped RBCs in the deoxygenated state of HbS. There are multiple non-covalent interactions between residues across intra- and inter-strands that stabilize the polymer. The clinical phenotype of sickling of RBCs manifests as sickle cell anemia, which was first documented in the year 1910 in an African patient. Although the molecular reason of the disease has been understood well over the decades of research and several treatment procedures have been explored to date, an effective therapeutic strategy for sickle cell anemia has not been discovered yet. Surprisingly, it has been observed that the oxy form of HbS and glutathionylated form of deoxy HbS inhibits polymerization. In addition to describe the residue level interactions in the HbS polymer that provides its stability, here we explain the mechanism of inhibition in the polymerization of HbS in its oxy state. Additionally, we reported the molecular insights of inhibition in the polymerization for glutathionyl HbS, a posttranslational modification of hemoglobin, even in its deoxy state. In this chapter we briefly consider the available treatment procedures of sickle cell anemia and propose that the elevation of glutathionylation of HbS within RBCs, without inducing oxidative stress, might be an effective therapeutic strategy for sickle cell anemia.


Assuntos
Anemia Falciforme/metabolismo , Hemoglobinas/química , Hemoglobinas/metabolismo , Anemia Falciforme/genética , Anemia Falciforme/patologia , Anemia Falciforme/terapia , Eritrócitos/química , Eritrócitos/metabolismo , Eritrócitos/patologia , Hemoglobinas/genética , Humanos , Polimerização
10.
J Fr Ophtalmol ; 43(4): 319-323, 2020 Apr.
Artigo em Francês | MEDLINE | ID: mdl-32093957

RESUMO

We aimed to describe the epidemiological, etiological and clinical features, treatment and clinical course of sickle cell retinopathy in children and to determine the risk factors for serious involvement. METHODS: This was a retrospective study including all children diagnosed with sickle cell retinopathy. Epidemiological, clinical and therapeutic characteristics, as well as clinical course, were analysed retrospectively by chart review. Two groups were defined: Group 1 (Goldberg stage 1 and 2); Group 2 (Goldberg stage 3, 4 and 5). In order to identify factors independently associated with severe sickle cell retinopathy, we conducted a logistic regression analysis in descending order. RESULTS: The frequency of sickle cell retinopathy was 14.48%. Forty-two patients (84 eyes) were included; among them 23 boys and 19 girls, aged 10 to 17 with a mean age of 14±1.98 years. Twenty patients were of genotype SS, 11 patients of genotype SC, 8 Sß and 3 SO Arab. The three patients in group 2 were all of SS genotype. The majority of patients (32) had an HbF level of less than 15%. All our patients had sickle cell retinopathy distributed as follows: 62% at stage 1; 31% at stage 2; 5% at stage 3 and 2% at stage 4. Multivariate analysis revealed a single risk factor independently linked to severe involvement - an HbF level<15%. CONCLUSION: Retinopathy is a frequent complication of sickle cell disease which may lead to blindness. The HbF level is negatively correlated with severe involvement.


Assuntos
Anemia Falciforme/epidemiologia , Doenças Retinianas/epidemiologia , Adolescente , Idade de Início , Anemia Falciforme/complicações , Anemia Falciforme/genética , Anemia Falciforme/patologia , Criança , Progressão da Doença , Feminino , Genótipo , Humanos , Masculino , Doenças Retinianas/etiologia , Doenças Retinianas/genética , Doenças Retinianas/patologia , Estudos Retrospectivos , Fatores de Risco
11.
Clin Appl Thromb Hemost ; 26: 1076029619895111, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31942811

RESUMO

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) was introduced as a potential inflammatory marker in sickle cell disease (SCD). This study aimed to evaluate the impact of hydroxyurea (HU) treatment on the value of NLR and some inflammatory mediators in SCD. METHODS: The hematological parameters and clinical events were analyzed in 35 children with SCD under HU treatment and followed up for 1 year and in 20 healthy controls. Enzyme-linked immunosorbent assay was performed for the evaluation of proinflammatory cytokines, including interleukin (IL) 6, IL-8, high-sensitivity C-reactive protein (hs-CRP), and tumor necrosis factor α (TNF-α). RESULTS: Hydroxyurea significantly improves most of the hematological parameters in children with SCD. The percentages of hemoglobin fraction S, serum levels of TNF-α and IL-6 were significantly decreased when compared to baseline value but did not reach the value of the healthy control. The HU treatment led to a significant decrease in NLR compared to the baseline values and reached healthy control values. Neutrophil-to-lymphocyte ratio was positively correlated with hs-CRP, TNF-α, and IL-8 serum levels and negatively correlated with percentage of fetal hemoglobin and hematocrit values. The cutoff value of NLR to expect a response to HU among SCD was 3.0, with 76% specificity and 85% sensitivity (area under the curve: 0.85, P < .0001). In conclusion, hydroxyurea induced a decrease in NLR and inflammatory cytokines, which represent a biomarker of inflammation in SCD. The calculation of NLR is a straightforward and cheap method for SCD outcome prediction in young children.


Assuntos
Anemia Falciforme/patologia , Hidroxiureia/farmacologia , Inflamação/diagnóstico , Linfócitos/citologia , Neutrófilos/citologia , Adolescente , Anemia Falciforme/tratamento farmacológico , Biomarcadores/sangue , Contagem de Células , Criança , Pré-Escolar , Citocinas/metabolismo , Feminino , Humanos , Hidroxiureia/uso terapêutico , Inflamação/tratamento farmacológico , Masculino , Prognóstico
12.
Acta Haematol ; 143(2): 163-175, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31307033

RESUMO

BACKGROUND/AIMS: We surveyed sickle cell disease (SCD) patients who transitioned from pediatric care at Texas Children's Hematology Center (TCHC) to adult care to determine the characteristics of patients with an adult SCD provider, continuation rates of pre-transition therapies, and patient perceptions of the transition process. METHODS: A cross-sectional study was conducted by telephone survey of 44 young adults with SCD, aged 19-29 years, who transitioned from TCHC to adult care within the last 15 years. RESULTS: Findings of the 23-item questionnaire revealed that transitioned patients with current adult providers (68.2%) were more likely to have seen a provider within 6 months of transition (p = 0.023) and to have been on hydroxyurea and/or monthly blood transfusions pre-transition (p = 0.021) than transitioned patients without a provider; 83% of patients on pre-transition hydroxyurea reported continuing hydroxyurea after transition. Transition challenges included inadequate preparation, difficulty finding knowledgeable adult providers, and lack of healthcare insurance/coverage. CONCLUSION: Transition to adult providers is predicted by establishing care with an adult SCD provider within 6 months of transition and being on pre-transition disease-modifying therapy. Transition may be improved if pediatric hematology centers assist and verify adult provider contact within 6 months of transition and engage patients of all disease severity during transition.


Assuntos
Anemia Falciforme/patologia , Adulto , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/economia , Anemia Falciforme/psicologia , Transfusão de Sangue , Estudos Transversais , Feminino , Humanos , Hidroxiureia/uso terapêutico , Cobertura do Seguro , Masculino , Inquéritos e Questionários , Adulto Jovem
13.
Am J Hematol ; 95(2): 205-211, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31763707

RESUMO

70 years ago, Linus Pauling, the legendary genius of 20th century chemistry, published his famous work on the molecular cause of sickle cell disease, a paper that gave birth to what is now called molecular medicine. In this paper, Pauling left important questions unanswered that have motivated an enormous amount of scientific and clinical research since then. This retrospective discusses the basic science studies that have answered those questions directly related to the kinetics and thermodynamics of hemoglobin S polymerization.


Assuntos
Anemia Falciforme , Hemoglobina Falciforme , Polimerização , Anemia Falciforme/história , Anemia Falciforme/metabolismo , Anemia Falciforme/patologia , Hemoglobina Falciforme/história , Hemoglobina Falciforme/metabolismo , História do Século XX , Humanos , Publicações Periódicas como Assunto/história
15.
Pediatr Blood Cancer ; 67(2): e27830, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31135090

RESUMO

INTRODUCTION: Understanding factors that affect the decisions of caregivers of African children to enroll their children in clinical trials would lead to more fully informed consent. METHODS: During the NOHARM study (NCT01976416), a placebo-controlled clinical trial of hydroxyurea for Ugandan children with sickle cell anemia (SCA), 206 caregivers were given a semistructured questionnaire about factors that influenced participation in the study and their perceptions of study benefits and risks. Factors were further assessed with focus group discussions. RESULTS: Caregivers identified education provided during the recruitment process (44%), the child's current poor state of health (35%), and the possibility of improvement in the child's health (16%) as their primary initial reasons for deciding to participate in the NOHARM trial. Concerns regarding the drug or participation in a research study, including the stated concern of death by several caregivers, were outweighed by the possibility of improvement in the child's health. During the study, 72% of caregivers cited improved health as an advantage of study participation, while disadvantages cited included the potential side effects of hydroxyurea, most of which did not occur during the trial. DISCUSSION: Our study findings highlight the generally poor state of health of Ugandan children with SCA, the desperation by caregivers for anything that could improve the child's health, and the inevitable improvements in care that result from strict adherence to a study protocol, even a protocol based on local guidelines. Studies in this vulnerable population must be careful not to portray improved care as a primary incentive for participation.


Assuntos
Anemia Falciforme/tratamento farmacológico , Cuidadores/psicologia , Tomada de Decisões , Conhecimentos, Atitudes e Prática em Saúde , Consentimento dos Pais/estatística & dados numéricos , Participação do Paciente/psicologia , Medição de Risco/métodos , Anemia Falciforme/patologia , Antidrepanocíticos/uso terapêutico , Criança , Ensaios Clínicos Fase III como Assunto , Humanos , Hidroxiureia/uso terapêutico , Participação do Paciente/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Inquéritos e Questionários
16.
Blood Cells Mol Dis ; 81: 102397, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31864103

RESUMO

Sickle cell disease (SCD) is characterized by frequent and unpredictable vaso-occlusive episodes (VOEs) that lead to severe pain, organ damage, and early death. Lack of reliable biomarkers that objectively define VOEs remains a critical barrier to improving the care for SCD patients. VOEs result from a complex interplay of cell-cell interactions that promote micro-vascular occlusion. Earlier studies demonstrated that sickle erythrocytes are more adherent than non-sickle erythrocytes and established a direct link between adhesion and frequency of VOEs. We developed a standardized, flow-based adhesion bioassay to assess the adhesive properties of SCD blood samples. The current study provides a cross-sectional analysis of steady state adhesion in SCD patients presenting at monthly out-patient hematology visits. Steady state adhesion varied from patient-to-patient. Adhesion positively correlated with reticulocyte percent and WBC count although there was no significant relationship between adhesion and platelets or hemoglobin in this study. Additionally, steady state adhesion indices were significantly lower in SCD subjects receiving hydroxyurea therapy when compared to the untreated group. The well-plate based microfluidic flow adhesion bioassay described in this report may provide a platform to identify SCD subjects with severe disease phenotypes, predict impending VOEs, and monitor response to current and developing therapies.


Assuntos
Anemia Falciforme/complicações , Adesão Celular , Molécula 1 de Adesão de Célula Vascular/metabolismo , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/diagnóstico , Anemia Falciforme/patologia , Bioensaio/normas , Contagem de Células Sanguíneas , Estudos Transversais , Humanos , Hidroxiureia/farmacologia , Hidroxiureia/uso terapêutico , Padrões de Referência , Doenças Vasculares/etiologia
17.
J Pediatr Hematol Oncol ; 42(2): 92-99, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31851069

RESUMO

OBJECTIVE: The aim of this study was to compare optical coherence tomography (OCT) findings in pediatric patients with sickle cell disease (SCD) and healthy individuals and to investigate associations between these data and the patients' systemic findings. MATERIALS AND METHODS: The study included 108 eyes of 54 patients with SCD with no visual symptoms and a control group consisting of 110 eyes of 55 healthy subjects with no systemic or ocular pathology. After best-corrected visual acuity assessment, the study participants underwent a complete ophthalmologic examination including intraocular pressure. After examination and pupil dilation induced with 1% tropicamide, 9×9 mm macular sections were obtained with spectral-domain OCT. The macular sections were evaluated according to Early Treatment Diabetic Retinopathy Study (ETDRS) map and internal and external retinal thicknesses were measured using the software included in the OCT device. RESULTS: The patient group showed significantly more foveal flattening, temporal thinning, and vascular tortuosity than the control group (P<0.0001 for all). Foveal width was significantly greater in the patient group (1592.39±175.56 µm) compared with the control group (1391.01±175.56 µm) (P<0.0001), whereas foveal depth was significantly lower in the patient group (121.15±26.83 µm) than in the control group (146.1±12.25 µm) (P<0.0001). The mean total retinal thickness was 253.53±22.31 µm in the patient group and 261.03±18.48 µm in the control group (P=0.007). Similarly, central retinal thickness was significantly lower in the patient group (219.35±10.53 µm) compared with the control group (235.32±12.51 µm) (P<0.0001). DISCUSSION: Our study shows that pediatric patients with SCD may have subclinical retinal involvement and that temporal thinning, in particular, is an important OCT finding. This strongly suggests that OCT imaging would be a beneficial addition to routine ophthalmologic examination in the diagnosis and follow-up of this patient group.


Assuntos
Anemia Falciforme/complicações , Doenças Retinianas/diagnóstico , Tomografia de Coerência Óptica/métodos , Adolescente , Anemia Falciforme/diagnóstico por imagem , Anemia Falciforme/patologia , Estudos de Casos e Controles , Criança , Feminino , Seguimentos , Humanos , Masculino , Ensaios Clínicos Controlados não Aleatórios como Assunto , Prognóstico , Estudos Prospectivos , Doenças Retinianas/diagnóstico por imagem , Doenças Retinianas/etiologia
18.
Lipids Health Dis ; 18(1): 225, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31861992

RESUMO

BACKGROUND: Hypocholesterolemia is the most frequently encountered lipid abnormality in sickle cell disease (SCD). We enrolled pediatric patients to determine the relationships between lipid profile and parameters of hemolysis, oxidative stress and chronic inflammation in SCD. METHODS: The study involved 35 pediatric SCD patients and 19 healthy controls. Patients were crisis-free and had not received transfusions for the last 3 months. Total cholesterol, triglyceride, HDL-C, LDL-C, VLDL-C, apolipoprotein A1, apolipoprotein B, LCAT, LDH, bilirubin, haptoglobin, iron, ferritin, hemin, serum amyloid A (SAA), myeloperoxidase (MPO), uric acid, ALT and GGT levels were evaluated in patients' blood. RESULTS: Patients had hypocholesterolemia depicted by lower levels of total cholesterol, HDL-C, LDL-C, as well as Apolipoprotein A1 and Apolipoprotein B compared to controls. The chronic hemolysis of SCD was evident in patients by higher LDH and bilirubin and almost undetectable haptoglobin levels. Hemin levels (as a measure of oxidized heme) were significantly increased in patients with SCD. Inflammation markers, SAA and MPO, were significantly increased in the patients as well. There were negative correlations between HDL-C and LDH, and Apo A1 and SAA. Hemin was positively correlated to MPO. CONCLUSION: Hemolysis was associated with decreased HDL -C, and Inflammation was linked to decreased apolipoprotein A1 levels in our SCD patients. Therefore, we suggest that the HDL particle is altered during the course of the disease. The altered HDL in SCD may become dysfunctional and result with a slowing down of the reverse cholesterol transport.


Assuntos
Anemia Falciforme/sangue , Apolipoproteína A-I/sangue , Colesterol/sangue , Inflamação/sangue , Adolescente , Adulto , Anemia Falciforme/metabolismo , Anemia Falciforme/patologia , Apolipoproteína A-I/genética , Apolipoproteínas B/sangue , Bilirrubina/sangue , Biomarcadores/sangue , Criança , Colesterol/metabolismo , HDL-Colesterol/sangue , LDL-Colesterol/sangue , VLDL-Colesterol/sangue , Feminino , Hemólise , Humanos , Inflamação/metabolismo , Inflamação/patologia , L-Lactato Desidrogenase/sangue , Lipídeos/sangue , Masculino , Peroxidase/sangue , Proteína Amiloide A Sérica/metabolismo , Triglicerídeos/sangue , Adulto Jovem
19.
Molecules ; 24(24)2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31842406

RESUMO

Sickle cell disease (SCD) is a group of inherited disorders affecting red blood cells, which is caused by a single mutation that results in substitution of the amino acid valine for glutamic acid in the sixth position of the ß-globin chain of hemoglobin. These mutant hemoglobin molecules, called hemoglobin S, can polymerize upon deoxygenation, causing erythrocytes to adopt a sickled form and to suffer hemolysis and vaso-occlusion. Until recently, only two drug therapies for SCD, which do not even fully address the manifestations of SCD, were approved by the United States (US) Food and Drug Administration. A third treatment was newly approved, while a monoclonal antibody preventing vaso-occlusive crises is also now available. The complex nature of SCD manifestations provides multiple critical points where drug discovery efforts can be and have been directed. These notwithstanding, the need for new therapeutic approaches remains high and one of the recent efforts includes developments aimed at inhibiting the polymerization of hemoglobin S. This review focuses on anti-sickling approaches using peptide-based inhibitors, ranging from individual amino acid dipeptides investigated 30-40 years ago up to more promising 12- and 15-mers under consideration in recent years.


Assuntos
Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos , Desenho de Fármacos , Peptídeos , Anemia Falciforme/metabolismo , Anemia Falciforme/patologia , Antidrepanocíticos/química , Antidrepanocíticos/uso terapêutico , Hemoglobina Falciforme/metabolismo , Humanos , Peptídeos/química , Peptídeos/uso terapêutico
20.
Biomed Res Int ; 2019: 2757450, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31886191

RESUMO

Background: Parvovirus B19 (B19 V) infection had been reported to be more frequent with serious clinical outcomes in patients with sickle cell disease (SCD) than in the general population. There is a wide variation in data among the existing literature regarding the seroprevalence of B19 V in patients with SCD. These data require further summary and analyses for better accuracy. This systematic review and meta-analysis was done to estimate the seroprevalence of B19 V in patients with SCD. Methods: This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases of MEDLINE/PubMed, Virtual Health Library (VHL), ScienceDirect, Google Scholar, and OpenGrey were used for the systematic search. The random-effects model was used to estimate the pooled prevalence with the corresponding 95% confidence interval (CI) using OpenMeta Analyst software. Publication bias was estimated based on Begg's test, Egger's test, and examination of the funnel plot. Subgroup analyses and metaregression were used to explore the moderators of heterogeneity between studies. Results: A total of 18 studies including 2890 patients were analyzed. The overall IgG seroprevalence of B19 V infection among patients with SCD was found to be 48.8% (95% CI 39.5%-58.0%). Evidence of publication bias was not detected. Evidence of acute viral infection detected by positive IgM antibodies among the screened SCD patients was found in 8.30% (95% CI 5.20%-11.4%) of them. There was a statistically significant association between seroprevalence of B19 V and geographical areas. Conclusion: There was a high prevalence of B19 V in patients with SCD. Healthcare providers need to be aware of the magnitude of B19 V infection in patients with SCD to ensure effective management. This review could provide a comprehensive view of B19 V prevalence in this susceptible population.


Assuntos
Anemia Falciforme/sangue , Anticorpos Antivirais/sangue , Eritema Infeccioso/sangue , Estudos Soroepidemiológicos , Anemia Falciforme/imunologia , Anemia Falciforme/patologia , Anemia Falciforme/virologia , Anticorpos Antivirais/imunologia , Eritema Infeccioso/imunologia , Eritema Infeccioso/patologia , Eritema Infeccioso/virologia , Humanos , Parvovirus B19 Humano/imunologia , Parvovirus B19 Humano/patogenicidade
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