Accompanying Hemoglobin Polymerization in Red Blood Cells in Patients with Sickle Cell Disease Using Fluorescence Lifetime Imaging.

In recent studies, it has been shown that fluorescence lifetime imaging (FLIM) may reveal intracellular structural details in unstained cytological preparations that are not revealed by standard staining procedures. The aim of our investigation was to examine whether FLIM images could reveal areas suggestive of polymerization in red blood cells (RBCs) of sickle cell disease (SCD) patients. We examined label-free blood films using auto-fluorescence FLIM images of 45 SCD patients and compared the results with those of 27 control persons without hematological disease.

Sympathetic hypoactivity leads to hypocontractility of the corpus cavernosum in sickle cell mice: a mechanism contributing to priapism.

Priapism, a prevalent complication in sickle cell disease (SCD) patients, manifests as prolonged and painful erections unrelated to sexual arousal. The detailed mechanisms contributing to this condition, especially regarding sympathetic function in the corpus cavernosum that maintains penile flaccidity, remain to be elucidated. In this study, it was hypothesized that the pathways of the sympathetic nervous system would be down-regulated, thereby contributing to the development of ischemic priapism in sickle cell disease.

Impact of intravascular hemolysis on functional and molecular alterations in the urinary bladder: implications for an overactive bladder in sickle cell disease.

Patients with sickle cell disease (SCD) display an overactive bladder (OAB). Intravascular hemolysis in SCD is associated with various severe SCD complications. However, no experimental studies have evaluated the effect of intravascular hemolysis on bladder function.

Montreal cognitive assessment in Brazilian adults with sickle cell disease: The burdens of poor sociocultural background.

Sickle cell disease (SCD) patients are at higher risk of developing silent cerebral infarcts and overt stroke, which may reflect cognitive impairment, functional limitations, and worse quality of life. The cognitive function of Brazilian adult SCD patients ( = 124; 19-70 years; 56 men; 79 SS, 28 SC, 10 S/β, 7 S/β) was screened through Montreal Cognitive Assessment (MoCA) and correlated the results with possible predictive factors for test performance, including sociocultural, clinical, laboratory data and brain imaging. The Median MoCA score was 23 (8-30); 70% had a 25-or-less score, suggesting some level of cognitive impairment.

Nitric Oxide Resistance in Priapism Associated with Sickle Cell Disease: Mechanisms, Therapeutic Challenges, and Future Directions.

Patients with sickle cell disease (SCD) display priapism, a prolonged penile erection in the absence of sexual arousal. The current pharmacological treatments for SCD-associated priapism are limited and focused on acute interventions rather than prevention. Thus, there is an urgent need for new drug targets and preventive pharmacological therapies for this condition.

Hydroxyurea does not reverse functional alterations of the nitric oxide-cGMP pathway associated with priapism phenotype in corpus cavernosum from sickle cell mouse.

Sickle cell disease (SCD) is a genetic disorder that has been associated with priapism. The role of hydroxyurea, a common SCD therapy, in influencing the nitric oxide (NO)-cGMP pathway and its effect on priapism is unclear. To investigate the effect of hydroxyurea treatment on smooth muscle relaxation of corpus cavernosum induced by stimulation of the NO-cGMP pathway in SCD transgenic mice and endothelial NO synthase gene-deficient (eNOS-/-) mice, which are used as model of priapism associated with the low bioavailability of endothelial NO.

Safety and feasibility of the gene transfer of hemopexin for conditions with increased free heme.

Heme is a fundamental molecule for several biological processes, but when released in the extracellular space such as in hemolytic diseases, it can be toxic to cells and tissues. Hemopexin (HPX) is a circulating protein responsible for removing free heme from the circulation, whose levels can be severely depleted in conditions such as sickle cell diseases. Accordingly, increasing HPX levels represents an attractive strategy to mitigate the deleterious effects of heme in these conditions.

Estimated mortality rates of individuals with sickle cell disease in Brazil: real-world evidence.

Sickle cell disease (SCD) is a group of hereditary chronic diseases with a substantial impact on quality of life and morbimortality. In Brazil, it is 1 of the most common hereditary diseases; however, there are sparse epidemiological data for the country. Using data from death certificates, we aimed to estimate the median age at death, years of life lost because of SCD, and the median survival.

Comparative transcriptome analysis of endothelial progenitor cells of HbSS patients with and without proliferative retinopathy.

Among sickle cell anemia (SCA) complications, proliferative sickle cell retinopathy (PSCR) is one of the most important, being responsible for visual impairment in 10-20% of affected eyes. The aim of this study was to identify differentially expressed genes (DEGs) present in pathways that may be implicated in the pathophysiology of PSCR from the transcriptome profile analysis of endothelial progenitor cells. RNA-Seq was used to compare gene expression profile of circulating endothelial colony-forming cells (ECFCs) from HbSS patients with and without PSCR.

Association of variants in the (rs7137828), (rs2745572) and (rs35934224) genes as risk factors for primary open-angle glaucoma development in a Brazilian cohort.

Background: Primary open-angle glaucoma (POAG), the world's main cause of irreversible blindness, is an asymptomatic and neurodegenerative disease of multifactorial etiology with ethnic and geographic disparities. Multiethnic genome-wide association studies (GWAS) identified single nucleotide variants (SNVs) in , and loci as risk factors for POAG pathophysiology and/or endophenotypes. The aim of this case-control study was to investigate the association of the variants rs7137828 (), rs2745572 (), and rs35934224 (), as risk factors for POAG development, additionally to rs7137828 association with glaucoma clinical parameters in a Brazilian cohort from the Southeast and South regions.

Hemograms and serial hemogram-derived ratios in survivors and non-survivors of COVID-19 in Campinas, Brazil.

Introduction: The hemogram and hemogram-derivative ratios (HDRs) are becoming markers of the severity and mortality of COVID-19. We evaluated the hemograms and serial weekly HDRs [neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), neutrophil-platelet ratio (NPR) and systemic immune-inflammatory index (SII)] in the survivors and non-survivors of COVID-19.

Methods: We retrospectively reviewed the medical notes and serial hemograms of real-time reverse-transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19 adults hospitalized from April 2020 to March 2021 from the time of diagnosis to the 3 week of diagnosis.

Haptoglobin treatment contributes to regulating nitric oxide signal and reduces oxidative stress in the penis: A preventive treatment for priapism in sickle cell disease.

In sickle cell disease (SCD), reduced bioavailability of endothelial NO and cGMP results in reduced expression of phosphodiesterase type 5 (PDE5), thus impairing the penile erection control mechanism and resulting in prolonged penile erection (priapism). In SCD, reduced NO bioavailability is associated with excess plasma hemoglobin due to intravascular hemolysis and increased oxidative stress. Haptoglobin is the plasma protein responsible for reducing plasma hemoglobin levels, but in SCD, haptoglobin levels are reduced, which favors the accumulation of hemoglobin in plasma.

Epigenetic analysis in placentas from sickle cell disease patients reveals a hypermethylation profile.

Pregnancy in Sickle Cell Disease (SCD) women is associated to increased risk of clinical and obstetrical complications. Placentas from SCD pregnancies can present increased abnormal findings, which may lead to placental insufficiency, favoring adverse perinatal outcome. These placental abnormalities are well known and reported, however little is known about the molecular mechanisms, such as epigenetics.

Intravascular hemolysis leads to exaggerated corpus cavernosum relaxation: Implication for priapism in sickle cell disease.

Patients with sickle cell disease (SCD) display priapism. Clinical studies have shown a strong positive correlation between priapism and high levels of intravascular hemolysis in men with SCD. However, there are no experimental studies that show that intravascular hemolysis promotes alterations in erectile function.

Evaluation of the mechanisms of heme-induced tissue factor activation: Contribution of innate immune pathways.

Hemolytic diseases such as Sickle Cell Disease (SCD) are characterized by a natural propensity for both arterial and venous thrombosis. The ability of heme to induce tissue factor (TF) activation has been shown both in animal models of SCD, and in human endothelial cells and monocytes. Moreover, it was recently demonstrated that heme can induce coagulation activation in the whole blood of healthy volunteers in a TF-dependent fashion.

Resveratrol-nitric oxide donor hybrid effect on priapism in sickle cell and nitric oxide-deficient mouse.

Background: Children and adult with sickle cell disease (SCD) display priapism associated with low nitric oxide (NO) bioavailability and oxidative stress in penis.

Aim: This study aimed to evaluate the effects of hybrid compound RVT-FxMe, derived from resveratrol bearing a NO-donor subunit, on two murine model that display priapism phenotype, SCD transgenic mice and endothelial NO synthase gene-deficient (eNOS-/-) mice.

Methods: Wild-type, SCD, and eNOS-/- mice were treated with RVT-FxMe (25 mg/kg/d, 2 weeks).

Demographic history differences between Hispanics and Brazilians imprint haplotype features.

Admixture is known to greatly impact the genetic landscape of a population and, while genetic variation underlying human phenotypes has been shown to differ among populations, studies on admixed subjects are still scarce. Latin American populations are the result of complex demographic history, such as 2 or 3-way admixing events, bottlenecks and/or expansions, and adaptive events unique to the American continent. To explore the impact of these events on the genetic structure of Latino populations, we evaluated the following haplotype features: linkage disequilibrium, shared identity by descent segments, runs of homozygosity, and extended haplotype homozygosity (integrated haplotype score) in Latinos represented in the 1000 Genome Project along with array data from 171 Brazilians sampled in the South and Southeast regions of Brazil.

Association of (rs2472493) and (rs9913911) gene variants with primary open-angle glaucoma in a Brazilian population.

Purpose: Glaucoma is the world's leading cause of irreversible blindness, with primary open-angle glaucoma (POAG) being the most prevalent subtype. In recent years, there have been advances in knowledge about the genetics involved in POAG, but genetic studies in admixed populations, such as Brazilians, are still rare. This study aimed to evaluate the association of single nucleotide variants (SNV) of the (rs2472493) and (rs9913911) genes with POAG in a sample of the Brazilian population.

The landscape of hematology research in Brazil: an analysis of data from citation databases.

Introduction: Scientometrics is the field concerned with measuring and analyzing academic literature, using specific metrics and data from bibliometric databases. Hematology is a broad area of science and medicine, from which several landmark scientific discoveries have emerged.

Objective: The aim of this report is to provide a snapshot of the landscape of hematology research in Brazil, based on a comprehensive analysis of published studies in hematology whose authors were affiliated to Brazilian institutions from 1980 to 2020.

Effect of hydroxyurea therapy on intravascular hemolysis and endothelial dysfunction markers in sickle cell anemia patients.

Intravascular hemolysis (IH) contributes to the development of endothelial dysfunction (ED) in sickle cell anemia (SCA), and the effects of hydroxyurea (HU, the only approved drug that decreases the frequency and severity of vaso-oclussive crises) on IH and ED in SCA remain unclear. We evaluated and compared the markers of IH among steady-state adult Brazilians with SCA and HbAA individuals. Overall, this cross-sectional study enrolled 30 SCA patients not receiving HU therapy (HbSS), 25 SCA patients receiving HU therapy (HbSS_HU), and 32 HbAA volunteers (HbAA).