Intravascular hemolysis, or the destruction of red blood cells in the circulation, can occur in numerous diseases, including the acquired hemolytic anemias, sickle cell disease and β-thalassemia, as well as during some transfusion reactions, preeclampsia and infections, such as those caused by malaria or Clostridium perfringens. Hemolysis results in the release of large quantities of red cell damage-associated molecular patterns (DAMPs) into the circulation, which, if not neutralized by innate protective mechanisms, have the potential to activate multiple inflammatory pathways. One of the major red cell DAMPs, heme, is able to activate converging inflammatory pathways, such as toll-like receptor signaling, neutrophil extracellular trap formation and inflammasome formation, suggesting that this DAMP both activates and amplifies inflammation. Other potent DAMPs that may be released by the erythrocytes upon their rupture include heat shock proteins (Hsp), such as Hsp70, interleukin-33 and Adenosine 5' triphosphate. As such, hemolysis represents a major inflammatory mechanism that potentially contributes to the clinical manifestations that have been associated with the hemolytic diseases, such as pulmonary hypertension and leg ulcers, and likely plays a role in specific complications of sickle cell disease such as endothelial activation, vaso-occlusive processes and tissue injury.

CONTEXT AND OBJECTIVE: Erectile dysfunction has been associated with cardiovascular diseases. The aim here was to evaluate cardiovascular risk through the Framingham Risk Score (FRS) criteria, C-reactive protein (CRP) assays and presence of metabolic syndrome (MS) in men with and without erectile dysfunction diagnosed within a healthcare program. DESIGN AND SETTING: A retrospective case-control study was conducted. The patients were selected from a healthcare program at the Hospital Israelita Albert Einstein, between January and December 2007. METHODS: 222 men were retrospectively selected, and they were divided into two groups: men with erectile dysfunction (n = 111) and men without erectile dysfunction (n = 111). The patients were stratified according to the International Index of Erectile Function-Erectile Function domain (IIEF-EF domain). CRP and FRS were analyzed and the two groups were compared. RESULTS: The CRP levels were significantly higher among men with erectile dysfunction (P = 0.04). Patients with erectile dysfunction also had high FRS (P = 0.0015). CRP and FRS did not correlate with the severity of erectile dysfunction. The presence of metabolic syndrome was greater among men with erectile dysfunction (P < 0.05). The severity of erectile dysfunction was directly associated with metabolic syndrome. CONCLUSION: Men with erectile dysfunction presented higher cardiovascular risk according to the FRS criteria and CRP measurements. Severe erectile dysfunction seemed to have a correlation with metabolic syndrome.

Laparoscopic pyeloplasty is a reproducible, highly effective, and minimally invasive treatment for uretero-pelvic junction obstruction. Surgical technique affects operative time and long-term success rates. Dismembered techniques seem to remain more effective after a long-term follow up. Surgical route does not seem to affect success rates.

Leukocyte recruitment and heterocellular aggregate formation drive the inflammatory vaso-occlusive processes associated with sickle cell anemia (SCA). We characterized neutrophils in a population of patients with SCA and investigated whether platelet-derived molecules can induce phenotypic alterations in this cell type. Imaging flow cytometry analysis demonstrated that the frequency of circulating CXCR4 hi neutrophils was significantly higher in steady-state SCA individuals than in healthy control individuals and that these cells presented increased CD11b activation and toll-like receptor-4 expression. SCA neutrophils display increased neutrophil-platelet aggregation, and CXCR4 hi neutrophils demonstrated augmented neutrophil-platelet aggregate frequency with a higher mean number of platelets adhered per neutrophil. Importantly, incubation of neutrophils with platelets significantly elevated their CXCR4 expression, while SCA plasma was found to induce CXCR4 hi neutrophil polarization significantly more than control plasma. SCA individuals had significantly increased plasma levels of serotonin (5-HT), and serotonin molecule and SCA plasma induced neutrophil CXCR4 expression in a serotonin-receptor-dependent manner. Thus, the augmented CXCR4 hi neutrophil population may contribute to mechanisms that promote vaso-occlusion in SCA; furthermore, circulating serotonin, derived from platelet activation, may play a role in the polarization of neutrophils, suggesting that serotonin-receptor antagonists or serotonin reuptake inhibitors could represent therapeutic approaches to reduce neutrophil activation in SCA. Despite being a monogenic disease, sickle cell anemia (SCA) incurs major damage to various organs and systems. The replacement of an adenine nitrogen base with a thymine nitrogen base in the hemoglobin β-globin gene results in the substitution of the apolar amino acid, valine (Val), in place of the polar amino acid, glutamic acid (Glu), at position six of the polypeptide chain, resulting in the production of the anomalous hemoglobin, hemoglobin S (HbS). HbS, when deoxygenated, polymerizes into elongated fibers that compromise the flexibility of erythrocytes, rendering them sickle-shaped, very susceptible to lysis and with different adhesive and physical properties 1,2. In addition to alterations in their erythrocytes, individuals with SCA display evidence of leukocyte, endothelial and platelet activation, as a result of processes of ischemia/reperfusion and intravascular hemolysis 3-5. These activated cells, in turn, direct the progression of inflammatory processes and participate in the vaso-occlusive events that characterize the disease. Among the leukocytes involved in the pathophysiology of SCA, neutrophils are particularly relevant, as these are the most abundant leukocytes in the circulation and, when activated, are recruited to vascular walls, in turn, forming aggregates with erythrocytes and/or platelets through interactions involving the integrin α M β 2 (Mac-1; CD11b/CD18) 6,7. Neutrophils are granular l...

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