Reduced sensitivity of the ferroportin Q248H mutant to physiological concentrations of hepcidin

Ferroportin Q248H mutation has an allele frequency of 2.2–13.4% in African populations and is associated with a mild tendency to increased serum ferritin in the general population. Some investigators have reported that ferroportin Q248H is degraded after exposure to hepcidin in exactly the same manner as wild-type ferroportin, but supraphysiological concentrations of hepcidin were used. The aim of our study was to determine whether ferroportin Q248H may have reduced sensitivity to physiological concentrations of hepcidin. The sensitivity of ferroportin Q248H to hepcidin was determined in 293T cells transiently expressing ferroportin using immunoblotting and fluorescence analysis. Ferritin concentrations were measured in these cells and also in human primary monocytes derived from humans with different ferroportin genotypes. The effect of Q248H on serum iron measures was examined in patients with sickle cell anemia. Immunoblotting and fluorescence analysis showed decreased sensitivity of ferroportin Q248H to physiological concentrations of hepcidin. Lower ferritin concentrations were observed after incubation with iron and hepcidin in 293T cells expressing ferroportin Q248H and in primary monocytes from ferroportin Q248H subjects. In sickle cell anemia, ferroportin Q248H heterozygotes had lower serum ferritin concentrations than wild-type subjects, consistent with enhanced iron release by macrophage ferroportin Q248H. A clinical benefit of ferroportin Q248H was suggested by lower echocardiographic estimates of pulmonary artery pressure in patients carrying mutant alleles. In conclusion, our results suggest that ferroportin Q248H protein is resistant to physiological concentrations of hepcidin and that this mutation has discernible effects on iron metabolism-related clinical complications of sickle cell anemia. They provide a mechanistic explanation for the effect of ferroportin Q248H on iron status in individuals of African descent and suggest that these changes in iron metabolism may be beneficial under certain disease-specific circumstances.(ClinicalTrials.gov Identifier:{"type":"clinical-trial","attrs":{"text":"NCT00011648","term_id":"NCT00011648"}}NCT00011648).     

Pleiotropic effects of intravascular haemolysis on vascular homeostasis

The breakdown of senescent or defective red blood cells releases red cell contents, especially haemoglobin, which scavenges nitric oxide (NO) and decomposes to haem and free iron. These are potent oxidants, all of which have promoted the evolution of inducible and vasculoprotective compensatory pathways to rapidly clear and detoxify haemoglobin, haem and iron. Chronic haemolytic red cell disorders as diverse as sickle cell disease, thalassaemia, unstable haemoglobinopathy, cytoskeletal defects and enzymopathies have been linked to a clinical constellation of pulmonary hypertension, priapism, leg ulceration and possibly cerebrovascular disease and thrombosis. Besides free haemoglobin, haemolysis has been associated with extracellular arginase that limits substrate availability to NO synthase, endogenous inhibitors of NO synthase activity, and inappropriate activation of haemostatic pathways. This article reviews the haemolytic disorders that have been reported to manifest vascular complications, and explores the speculative possibility that haemolysis mediates some of the vascular complications of inflammation and diabetes.     

Application of constant-current coulometry for estimation of plasma total antioxidant capacity and its relationship with transition metal contents

Simple and express coulometric method for the evaluation of the total antioxidant capacity (TAC) of human plasma based on the reaction with electrogenerated bromine is applied. TAC of plasma from patients with different ethiology of chronic renal failure was observed. The levels of antioxidant capacity for venous and arterial plasma are authentically different (15+/-1 kCl/L versus 11.7+/-0.7 kCl/L, p<0.01). The application of Vitamin E and ximedon as an antioxidant treatment significantly increase TAC level of plasma. Free liposoluble antioxidants in plasma in alpha-tocopherol units was determined. Redox potential of plasma is measured and its correlation with lg(TAC) is obtained. Transition metal contents of Fe, Cu, Mn, Ni, and Cr in plasma of patients with chronic renal failure is significantly higher than that for a control group. Correlation analysis has shown negative linear regression between TAC value and transition metals concentration in plasma. This confirms interrelation of processes with participation of free radicals, antioxidants and transition metals as donors of electrons in chain radical processes. Moreover, it shows utility of common parameters, TAC for example, for estimation of efficiency of antioxidant defense system in living organism, in particular its antioxidant status.     

Superior vena cava patency syndrome in a patient with chronic mediastinal compression

There are adduced the literature data and own observation of rare disease of main thoracic cavity veins-syndrome of disorder passability of vena cava superior (SDPVCS). The most frequent causes of SDPVCS occurrence, informative methods of diagnosis, mane methods of treatment were enlighted.     

The influence of walking speed on dynamic loading on the human musculoskeletal system

PURPOSE: A study was conducted to investigate the effects of walking speed on the magnitude of the heel strike initiated shock waves that propagate throughout the human musculoskeletal system. METHODS: Subjects walking on a treadmill at various speeds were used to acquire the experimental data regarding the heel strike-initiated shock waves. Fifteen young healthy men participated in this study. Each one walked on the treadmill at five various speeds, and their associated cadences, while the heel strike induced shock waves were recorded at the tibial tuberosity for each speed during a 16-s period at a sampling rate of 1 kHz. RESULTS: The obtained data reveal a significant increase in the dynamic loading experienced by the human musculoskeletal system with an increase in the walking speed. CONCLUSION: The analysis of the recorded acceleration suggests that an increase in walking speed contributes to an increase in dynamic loading on the human musculoskeletal system. Further, the evidence indicates that dynamic loading increases with the increase in speed at five times the rate of the ground reaction force increase.     

Mesodiencephalic modulation (transcranial electrostimulation of the brain) in neurology and psychiatry

The paper outlines the results of mesodiencephalic modulation (MDM) as therapy in adults and children with neurological and mental diseases in the out- and inpatient setting. MDM is a method of transcranial electric therapy that normalizes the performance of the hypothalamohypophyseal and opioid systems of the brain, which ultimately improves the body's adaptive response in disease.     

The pulmonary microangiopathy in patients with tuberculosis coexisting with diabetes mellitus

There were done histologic, electron-microscopic investigations of the lungs preparations in 47 patients with destructive tuberculosis (DT) and diabetes mellitus, the operations were performed, the signs of the disseminated microangiopathy were revealed. This complication negatively influence the DT course before and after the operation, and the final result of operation also.     

Effect of freon-114B2 (1,2-dibromotetrafluoroethane) on the seasonal rhythm of energy activity in rat liver mitochondria]

In the experiments with white rats it was found, that the inhalation of freon 114B2 at CL16, CL50, CL84 levels caused the changes in seasonal values of the energy activity in mitochondria. The action of the freon 114B2 caused disturbances in regulation of the mitochondria activity and desynchronization of seasonal rhythms of their energy activity.