Severe transplantâ associated thrombotic microangiopathy in patients with hemoglobinopathies

Incidence and severity of transplantâ associated thrombotic microangiopathy (TAâ TMA) in patients with hemoglobinopathies receiving hematopoietic cell transplant is unknown. We report the outcomes for two patients with TAâ TMA who received eculizumab. A 2.5â yearâ old male with sickle cell disease developed TAâ TMAâ associated pericardial tamponade, severe hypertension, and acute kidney injury 2 months after transplant. A 7â yearâ old female with βâ thalassemia major developed TAâ TMAâ related acute kidney injury, severe hypertension, and seizures at 6 months after transplant. Both patients progressed to chronic kidney disease (CKD). In patients with hemoglobinopathies, preexisting endothelial dysfunction may place them at a greater risk for TAâ TMA and subsequent CKD.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137747/1/pbc26503.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137747/2/pbc26503_am.pd

Vascular Leakage in Dengue Hemorrhagic Fever Is Associated with Dengue Infected Monocytes, Monocyte Activation/Exhaustion, and Cytokines Production

The vascular leakage was shown by the increment of hematocrit (Hct), dengue viral infected monocyte, monocyte status, and cytokines production in patients infected with dengue virus. Dengue viral antigens were demonstrated in monocytes (CD14+) from peripheral blood mononuclear cells. The increased levels of Hct, interleukin- (IL-) 10, and tumor necrosis factor-alpha (TNF-α) were detected in dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) patients as compared with other febrile illnesses (OFIs). The highest levels of Hct and IL-10 were detected in DSS patients as compared with other groups (P<0.05) especially on one day before and after defervescence. The unstimulated and lipopolysaccharide- (LPS-) stimulated monocytes from DSS patients showed the significantly decreased of intracellular IL-1β and TNF-α. In addition, the lowest level of mean fluorescence intensity (MFI) of CD11b expression on monocytes surface in DSS patients was also demonstrated. Furthermore, the negative correlations between IL-10 levels and intracellular IL-1β and MFI of CD11b expression in unstimulated and LPS-stimulated monocytes were also detected. Nevertheless, not only were the relationships between the prominent IL-10 and the suppression of intracellular monocyte secretion, namely, IL-1β, TNF-α, demonstrated but also the effect of vascular leakage was observed

Vascular Endothelial Dysfunction in β-Thalassemia Occurs Despite Increased eNOS Expression and Preserved Vascular Smooth Muscle Cell Reactivity to NO

The hereditary β-thalassemia major condition requires regular lifelong blood transfusions. Transfusion-related iron overloading has been associated with the onset of cardiovascular complications, including cardiac dysfunction and vascular anomalies. By using an untransfused murine model of β-thalassemia major, we tested the hypothesis that vascular endothelial dysfunction, alterations of arterial structure and of its mechanical properties would occur despite the absence of treatments.Vascular function and structure were evaluated ex vivo. Compared to the controls, endothelium-dependent vasodilation with acetylcholine was blunted in mesenteric resistance arteries of β-thalassemic mice while the endothelium-independent vasodilator (sodium nitroprusside) produced comparable vessel dilation, indicating endothelial cell impairment with preserved smooth muscle cell reactivity to nitric oxide (NO). While these findings suggest a decrease in NO bioavailability, Western blotting showed heightened expression of aortic endothelial NO synthase (eNOS) in β-thalassemia. Vascular remodeling of the common carotid arteries revealed increased medial elastin content. Under isobaric conditions, the carotid arteries of β-thalassemic mice exhibited decreased wall stress and softening due to structural changes of the vessel wall.A complex vasculopathy was identified in untransfused β-thalassemic mice characterized by altered carotid artery structure and endothelial dysfunction of resistance arterioles, likely attributable to reduced NO bioavailability despite enhanced vascular eNOS expression

Circulating CD133+VEGFR2+ and CD34+VEGFR2+ cells and arterial function in patients with beta-thalassaemia major

Arterial dysfunction has been documented in patients with beta-thalassaemia major. This study aimed to determine the quantity and proliferative capacity of circulating CD133+VEGFR2+ and CD34+VEGFR2+ cells in patients with beta-thalassaemia major and those after haematopoietic stem cell transplantation (HSCT), and their relationships with arterial function. Brachial arterial flow-mediated dilation (FMD), carotid arterial stiffness, the quantity of these circulating cells and their number of colony-forming units (CFUs) were determined in 17 transfusion-dependent thalassaemia patients, 14 patients after HSCT and 11 controls. Compared with controls, both patient groups had significantly lower FMD and greater arterial stiffness. Despite having increased CD133+VEGFR2+ and CD34+VEGFR2+ cells, transfusion-dependent patients had significantly reduced CFUs compared with controls (p = 0.002). There was a trend of increasing CFUs across the three groups with decreasing iron load (p = 0.011). The CFUs correlated with brachial FMD (p = 0.029) and arterial stiffness (p = 0.02), but not with serum ferritin level. Multiple linear regression showed that CFU was a significant determinant of FMD (p = 0.043) and arterial stiffness (p = 0.02) after adjustment of age, sex, body mass index, blood pressure and serum ferritin level. In conclusion, arterial dysfunction found in patients with beta-thalassaemia major before and after HSCT may be related to impaired proliferation of CD133+VEGFR2+ and CD34+VEGFR2+ cells

Water soluble vitamins essential for the growth of Clarias

Meeting: Asian Finfish Nutrition Workshop, 23-26 Aug. 1983, Singapore, SGIn IDL-724