Hemorheological profiles and chronic inflammation markers in transfusion-dependent and non-transfusion- dependent thalassemia.

The rheological properties of blood play an important role in regulating blood flow in micro and macro circulation. In thalassemia syndromes red blood cells exhibit altered hemodynamic properties that facilitate microcirculatory diseases: increased aggregation and reduced deformability, as well as a marked increase in adherence to the vascular endothelial cells. A personalized approach to treating thalassemia patients (transfusions, iron chelation, and splenectomy), has increased patients' life expectancy, however they generally present many complications and several studies have demonstrated the presence of high incidence of thromboembolic events.

Innovative screening test for the early detection of sickle cell anemia.

In this study, the capability of thermogravimetry in conjuction with a multivariate statistical analysis, was investigated for the screening of Sickle Cell Anemia (SCA), a hereditary disorder of hemoglobin characterized by severe hemolytic anemia with different severe clinical manifestations. SCA results from a mutation in the sixth codon of the beta globin gene, which results in the substitution of glutamic acid for valine and leads to the production of an altered form of hemoglobin, hemoglobin S (HbS). People with this disorder have atypical hemoglobin molecules which tend to aggregate together and form filaments inside the red blood cells.

An Innovative Multilevel Test for Hemoglobinopathies: TGA/Chemometrics Simultaneously Identifies and Classifies Sickle Cell Disease From Thalassemia.

Hemoglobinopathies are the most common genetic disorder wordlwide and because of migrations are become an emerging global health problem. Screening programmes for Sickle cell disease and Thalassemia have been implemented in some countries, but are not a common practice, due to a lack in the accuracy of the methods and to the costs of the analyses. The objective of this study was the application of the thermogravimetry coupled to chemometrics as new screening method to perform an early diagnosis of thalassemia and sickle cell disease.

Phenotypical and functional abnormalities of circulating neutrophils in patients with β-thalassemia.

β-Thalassemia is an inherited single gene disorder related to reduced synthesis of the β-globin chain of hemoglobin. Patients with β-thalassemia present variable clinical severity ranging from asymptomatic trait to severe transfusion-dependent anemia and multiple organs complications. Moreover, multiple immune abnormalities are a major concern in β-thalassemia patients.

COVID-19 Sepsis and Microcirculation Dysfunction.

The spreading of Coronavirus (SARS-CoV-2) pandemic, known as COVID-19, has caused a great number of fatalities all around the World. Up to date (2020 May 6) in Italy we had more than 28,000 deaths, while there were more than 205.000 infected.

Differential diagnosis of hereditary hemolytic anemias in a single multiscreening test by TGA/chemometrics.

A multi-screening test based on the coupling of thermogravimetry and chemometrics was optimized for the differential diagnosis of hereditary hemolytic anemias. The novel test is able to simultaneously perform a simple and fast diagnosis of sickle cell anemia, thalassemia, hereditary spherocytosis and hereditary elliptocytosis in a single analysis of a few microliters of non-pretreated whole blood. The thermogravimetric profile of blood from patients affected by such disorders was found to be characteristic of a specific anemic status or a disorder due to membrane defects.

Development of a novel test for the identification of hereditary erythrocyte membrane defects by TGA/Chemometrics.

Systematic screening for congenital erythrocyte disorders is not a common practice, due to a lack in the accuracy of the methods and to the costs of the analyses. As a consequence, the diagnosis is usually made when a severe complication occurs. This study introduces an innovative method to perform the screening of a hereditary disease characterized by erythrocyte membrane defects such as hereditary spherocytosis (HS) and hereditary elliptocytosis (HE).

Pregnancy in Thalassemia and Sickle Cell Disease: The Experience of an Italian Thalassemia Center.

The life expectancy of thalassemia patients has increased significantly in recent years being the most "elderly" patients approaching or are over 50 years old. Consequently, patients' perspectives have changed, leading them to longer-term planning with a consequent increase in their reproductive potential and desire to have children. Crucial points in the management of pregnancy in thalassemia are the iron chelation therapy before and during pregnancy, the antithrombotic prophylaxis, the management of transfusion therapy according to the modified transfusion requirement, a cardiologic monitoring for hemodynamic changes that expose an increased risk of heart failure.

HCV Infection in Thalassemia Syndromes and Hemoglobinopathies: New Perspectives.

Hepatitis C virus (HCV) infection is one of the most serious complications of transfusion therapy in the thalassemia and sickle cell disease (SCD) population before 1990; in fact, since 1990 serological tests were made available to detect infection in blood donors. The iron chelation therapy has improved the life expectancy of these patients and, consequently, a decrease in death due to heart disease may be observed, as well as an increase in liver disease due to the iron overload and HCV infection that lead to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Until few years ago, the recommended therapy for HCV treatment consisted of pegylated-interferon alpha plus ribavirin, a therapy with important side effects.

Hemorheological Alterations and Oxidative Damage in Sickle Cell Anemia.

Sickle cell anemia (SCA) is the most common hereditary disorder of hemoglobin (Hb) characterized by a mutation in the β globin gene, which leads to synthesis of HbS a hemoglobin which, under hypoxic conditions, gels and leading to the sickling of the red blood cells (RBC). The dehydration of the RBC increases the concentration of the intracellular Hb with an increase in the internal viscosity and consequently a decrease in the erythrocyte deformability. Sickle red blood cells due to their difficulty to flow through the microcirculation cause frequent vaso-occlusive episodes, tissue ischemia, and infarctions.

TGA/Chemometric Test Is Able to Detect the Presence of a Rare Hemoglobin Variant Hb Bibba.

In this study the TGA/Chemometric test was applied for diagnosis of a case of congenital hemolytic anemia for which the common first level diagnostic tests were not able to find the erythrocyte congenital defect. A 6 years old girl presented chronic hemolytic anemia characterized by hyperbilirubinemia, increased spleen, negative Coombs tests, normal hemoglobin values, decreased mean corpuscular volume (MCV), increased red cell distribution width (RDW), reticulocytes and lactate dehydrogenase (LDH), and altered erythrocyte morphology (ovalocytes, spherocytes, and rare schizocytes). The diagnostic protocols for differential diagnosis of hereditary hemolytic anemia were carried out by the investigation of the congenital hemolytic anemias due to defects of membrane proteins and the most common erythrocyte enzymes, but no defect was found.

Effect of hemorheological parameters on myocardial injury after primary or elective percutaneous coronary intervention.

Background: Abnormal blood viscosity favors atherosclerosis owing to endothelial dysfunction and changes in shear stress. Its effect on coronary microvasculature during percutaneous coronary intervention (PCI) is still unknown. We aimed to investigate the role of hemorheological parameters in the incidence of microvascular obstruction (MVO) and the periprocedural necrosis after primary or elective PCI, and secondarily, we evaluated their prognostic significance.

Update on thalassemia diagnosis: New insights and methods.

A novel approach based on Thermogravimetric analysis followed by Chemometrics (TGA/Chemometrics) is provided for Thalassemia diagnosis and a comprehensive study consisting of the coupled approach TGA/Chemometrics, the Complete Blood Count (CBC) and Red Blood Cell (RBC) indices is developed and results are compared. A number of 128 subjects were involved in this study included 16 thalassemia intermedia transfusion-dependent (TI-TD) patients, 18 thalassemia intermedia non transfusion-dependent (TI-NTD) patients, and 14 thalassemia major β (TM-TD) patients. Thalassemic patients were found to be clearly distinct from healthy donors as a function of a different thermal behavior.

Thermogravimetric analysis coupled with chemometrics as a powerful predictive tool for ß-thalassemia screening.

β-Thalassemia is a hemoglobin genetic disorder characterized by the absence or reduced β-globin chain synthesis, one of the constituents of the adult hemoglobin tetramer. In this study the possibility of using thermogravimetric analysis (TGA) followed by chemometrics as a new approach for β-thalassemia detection is proposed. Blood samples from patients with β-thalassemia were analyzed by the TG7 thermobalance and the resulting curves were compared to those typical of healthy individuals.

Glucose-6-phosphate dehydrogenase deficiency in Italian blood donors: prevalence and molecular defect characterization.

Background: In the countries with high G6PD deficiency prevalence, blood donors are not routinely screened for this genetic defect. G6PD deficiency is often asymptomatic, blood donors may be carriers of the deficiency without being aware of it. The aim of the study was to evaluate the prevalence of G6PD deficiency among the Italian blood donors.

The effects of insulin and insulin-like growth factors on tumor vascularization: new insights of insulin-like growth factor family in cancer.

It is currently believed that the development of a clinically relevant tumor needs new vessel formation provided by both angiogenesis (primary involving endothelial cells) and postnatal vasculogenesis (primary involving bone marrow-derived cells). Clearly, it is important to identify factors that help to enhance the growth and "health" of tumors, as well as their further vascularization. The Insulin and Insulin-like Growth Factors (IGFs) systems play a key role in cellular metabolism, differentiation, proliferation, transformation and apoptosis, during normal and malignant growth.

Hereditary spherocytosis and elliptocytosis associated with prosthetic heart valve replacement: rheological study of erythrocyte modifications.

The implantation of a prosthetic heart valve (HVP) in patients with hereditary spherocytosis (HS) and hereditary elliptocytosis (HE) is rare, and the changes in the structure and deformability of erythrocytes that follow implantation in these patients have been poorly described. In the present study, the erythrocytes in HS and HE patients with mechanical HVP were compared to the erythrocytes in patients with only congenital membrane defects, in terms of biochemical modifications and rheological behaviour. Integral and cytoskeletal erythrocyte membrane proteins were studied, and blood viscosity (shear rate/shear stress ratio), aggregation ratio [eta(1 s(-1))/eta(200 s(-1))], and red cell visco-elasticity were determined.

In vitro and in vivo analysis of neurotrophin-3 activation of Arf6 and Rac-1.

Arf GTP-binding proteins and Rho-family GTPases play key roles in regulating membrane remodeling and cytoskeletal reorganization involved in cell movement. Several studies have implicated neurotrophins and their receptors as upstream activators of these small GTP-binding proteins, however, the mechanisms and the cell type specificity of this neurotrophin activity are still under investigation. Here we describe the rationale and protocols used for the dissection of an NT3 activated pathway that leads to the specific activation of Arf6 and Rac1.

Sickle cell anaemia: haemorheological aspects.

The maintenance of erythrocyte shape and membrane integrity is bound to the modification of deformability and/or permeability. Usually, this features are not investigated with normal laboratory tests. The membrane stiffness, the cell geometry, and the viscoelasticity components are influencing factors on survival and functionality of the erythrocytes.

Neuroacanthocytosis associated with a defect of the 4.1R membrane protein.

Background: Neuroacanthocytosis (NA) denotes a heterogeneous group of diseases that are characterized by nervous system abnormalities in association with acanthocytosis in the patients' blood. The 4.1R protein of the erythrocyte membrane is critical for the membrane-associated cytoskeleton structure and in central neurons it regulates the stabilization of AMPA receptors on the neuronal surface at the postsynaptic density.

A kinase-deficient TrkC receptor isoform activates Arf6-Rac1 signaling through the scaffold protein tamalin.

Neurotrophins play an essential role in mammalian development. Most of their functions have been attributed to activation of the kinase-active Trk receptors and the p75 neurotrophin receptor. Truncated Trk receptor isoforms lacking the kinase domain are abundantly expressed during development and in the adult; however, their function and signaling capacity is largely unknown.

Semaphorin-3A is expressed by tumor cells and alters T-cell signal transduction and function.

An important aspect of tumor progression is the ability of cancer cells to escape detection and clearance by the immune system. Recent studies suggest that several tumors express soluble factors interfering with the immune response. Here, we show that semaphorin-3A (Sema-3A), a secreted member of the semaphorin family involved in axonal guidance, organogenesis, and angiogenesis, is highly expressed in several tumor cells.

Prosthetic heart valves' mechanical loading of red blood cells in patients with hereditary membrane defects.

Implantable cardiovascular devices such as prosthetic heart valves (PHVs) are widely applied clinical tools. Upon implantation, the patient can suffer from anemia as a result of red cell destruction and hemolysis can be more relevant whenever the patient is also affected by red cell disorders in which erythrocytes are more susceptible to mechanical stress such as hereditary spherocytosis (HS) and hereditary elliptocytosis (HE). Considering the typical morphological alterations observed in HS and HE, a study of the influence of cell geometry on the distribution of the shear stress on red cells in biological fluids was carried out.

5-Lipoxygenase regulates senescence-like growth arrest by promoting ROS-dependent p53 activation.

5-Lipoxygenase (5LO) is involved in the production of leukotrienes and reactive oxygen species (ROS) from arachidonic acid. Its strong activation has been associated with several diseases like cancer and neurodegeneration. Here we show that 5LO activity increases during senescence-like growth arrest induced by oncogenic ras or culture history in both human and mouse embryo fibroblasts.

5-lipoxygenase antagonizes genotoxic stress-induced apoptosis by altering p53 nuclear trafficking.

5-lipoxygenase (5-LO) promotes cancer cell proliferation and survival by unclear mechanisms. Here, we show that 5-LO expression and activity were induced by genotoxic agents in a p53-independent manner and antagonized p53- or genotoxic drug-induced apoptosis in a variety of cancer cells. 5-LO inhibited p53-governed transactivation of the pro-apoptotic genes bax and pig3 but not of p21(WAF1/CIP1) or mdm2.