Zinc improved erythrocyte deformability and aggregation in patients with beta-thalassemia: An in vitro study.

BACKGROUND: Thalassemia patients have reduced red cell deformability and decreased plasma zinc levels in their blood. OBJECTIVE: This study aimed to evaluate the effects of zinc (Zn) on the hemorheological parameters and antioxidant enzyme activities in ß-thalassemia major (TM) and healthy volunteers (HV). METHODS: Hemorheological parameters were measured using LORCA (laser-assisted optical rotational cell analyzer) after adjusting the hematocrit to 40%. Zinc sulfate (ZnSO4.7H2O) was used for Zn incubation with a concentration of 0.5µg/dl. Oxidative stress and antioxidant status were determined using commercial kits. RESULTS: Data showed that after Zn incubation, EImax, the area under the EI-osmolarity curve (Area), and Omax decreased in TM. However, no significant difference was observed in the osmotic deformability parameters of HV. The increased elongation index was obtained at different shear stresses for TM and HV, and SS1/2 decreased in both groups. The AMP and aggregation index (AI) decreased in TM, and the required time for half of the maximum aggregation (t1/2) increased in HV. However, Zn did not affect oxidative parameters in both groups. CONCLUSIONS: This study showed that Zn incubation increased deformability and decreased aggregation in thalassemic erythrocytes. It means that Zn supplementation will contribute to microcirculation in thalassemia patients.

Nitrite may serve as a combination partner and a biomarker for the anti-cancer activity of RRx-001.

BACKGROUND: RRx-001 is an anti-cancer immunotherapeutic that increases the sensitivity of drug resistant tumors via multiple mechanisms which involve binding to hemoglobin and enhancing nitrite reductase activity of deoxyhemoglobin. OBJECTIVE: In the present study, the effect of clinically used doses of RRx-001 on erythrocyte deformability was examined. METHODS: A dose dependent effect of RRx-001 (1-1000 micro molar) on erythrocyte deformability was measured by ektacytometer under hypoxia (n = 8). Low dose RRx-001 (20 micro molar) in the presence of ODQ (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one), L-NAME (L-NG-Nitroarginine methyl ester) or nitrite were examined both in normoxia and hypoxia. Intracellular nitric oxide (NO) levels were measured fluorometrically with DAF-FM-DA. RESULTS: Higher doses of RRx-001 (100, 1000 micro molar) significantly decreased erythrocyte deformability under hypoxia (p < 0.01; p < 0.05, respectively). RRx-001 (20 micro molar), alone or in combination with ODQ or L-NAME, did not change deformability. However, RRx-001 and nitrite caused an increase in deformability (p < 0.01) under hypoxia. RRx-001 induced NO production was more pronounced in the presence of nitrite (p < 0.05). CONCLUSIONS: Co-administration of RRx-001 and nitrite under hypoxic conditions results in a significant increase in erythrocyte deformability that is related to increased NO production. We suggest that measurement of serum nitrite level in RRx-001 treated cancer patients should be routinely undertaken and supplemented if levels are low for maximal activity.

Acute and long-term effects of hyperbaric oxygen therapy on hemorheological parameters in patients with various disorders.

Inhalation of 100% oxygen in a hyperbaric chamber has been accepted as a useful treatment for patients with various pathologies who suffer from hypoxia. The oxidative effects of hyperbaric oxygen (HBO) on RBCs have been investigated in animals but there is not enough data on hemorheological parameters in patients following HBO treatment (HBOT).In this study, we investigated the effect of HBO on hemorheological and haematological parameters during treatment. Red blood cell (RBC) deformability and aggregation, blood and plasma viscosity and superoxide dismutase activity were investigated in patients who underwent HBOT. Hematological parameters were determined by an electronic hematology analyzer. A Laser-assisted Optical Rotational Cell Analyzer (LORCA) was used to measure RBC deformability. RBC aggregation was measured for cells in autologous plasma and for cells resuspended in PBS containing Dextran70 (3% ) by using a Myrenne Aggregometer. A Wells-Brookfield cone/plate rotational viscometer was used for viscosity measurements. According to our results, a significant decrement of the hematocrit and the RBC count was observed after the 20th session of HBOT compared to the baseline, but none of the hemorheological parameters changed significantly. Our results showed that HBOT did not cause any significant changes in hemorheological parameters, thereby not representing any problems for the patients.

Genes and molecular mechanisms involved in the epileptogenesis of idiopathic absence epilepsies.

Idiopathic absence epilepsies (IAE), that have high prevalence particularly among children and adolescents, are complex disorders mainly caused by genetic factors. Childhood absence epilepsy and juvenile absence epilepsy are among the most common subtypes of IAEs. While the role of ion channels has been the primary focus of epilepsy research, the analysis of mutation and association in both patients with absence epilepsies and animal models revealed the involvement of GABA receptors and calcium channels, but also of novel non-ion channel proteins in inducing spike wave discharges (SWD). Functional studies on a mutated variant of these proteins also support their role in the epileptogenesis of absence seizures. Studies in animal models point to both the thalamus and cortex as the origin of SWDs: the abnormalities in the components of these circuits leading to seizure activity. This review examines the current research on mutations and susceptibility alleles determined in the genes that code for the subunits of GABA receptors (GABRG2, GABRA1, GABRB3, GABRA5, GABA(B1) and GABA(B2)), calcium channels (CACNA1A, CACNA1G, CACNA1H, CACNA1I, CACNAB4, CACNAG2 and CACNG3), and novel non-ion channel proteins, taking into account the results of functional studies on these variants.

Hypothalamic hamartoma associated with a craniopharyngeal canal.

Hypothalamic hamartoma is a rare congenital lesion. We present the case of a 7-year-old girl who suffered from precocious puberty, the cause of which was diagnosed by using MR imaging and CT as pedunculated hypothalamic hamartoma associated with a large craniopharyngeal canal and sellar spine mimicking pituitary duplication.

Effect of antioxidant vitamin treatment on the time course of hematological and hemorheological alterations after an exhausting exercise episode in human subjects.

This study examined the effects of a 2-mo antioxidant vitamin treatment on acute hematological and hemorheological alterations induced by exhausting exercise; both sedentary and trained individuals were employed. Eighteen young male, human subjects (9 sedentary, 9 trained by regular exercise) participated in the study and performed an initial maximal aerobic cycle ergometer exercise with frequent blood sampling over a 24-h period and analysis of hematological and hemorheological parameters. All subjects were treated with an antioxidant vitamin A, C, and E regimen, supplemented orally for 2 mo, and then subjected to a second exercise test and blood sampling at the end of this period. In the sedentary group during the first testing period (before vitamin treatment), white blood cell counts and granulocyte percentages were increased at 2 h after the exercise test and remained elevated for 4-12 h. Red blood cell (RBC) deformability and aggregation were also altered by exercise in the sedentary group before vitamin treatment. However, none of these parameters in the sedentary group were altered by exercise after the 2-mo period of antioxidant vitamin treatment. With the exception of a transient rise in granulocyte percentage, these parameters were also not affected in the trained subjects before the vitamin treatment. Significant increases of RBC lipid peroxidation observed 12 h after the exercise test in both sedentary and trained subjects were also totally prevented by vitamin treatment. Our results indicate that antioxidant vitamin treatment is effective in preventing the inflammation-like response and coincident adverse hemorheological changes after an episode of exhausting exercise, and suggest that such changes may be related to exercise-induced death events.