Pulmonary functions in Egyptian children with transfusion-dependent ß-thalassemia.

BACKGROUND: In ß-thalassemia, there are varying degrees of ineffective haematopoiesis, intermittent haemolysis and iron overload. Excess iron is deposited in organs such as the heart, the liver, the endocrine glands and the lungs. OBJECTIVES: To evaluate the pulmonary functions in asymptomatic beta thalassemic children on regular transfusion therapy and their relation to iron overload. METHODS: The study included 50 transfusion-dependent ß-thalassemic children and 50 apparently healthy children as control. All children had undergone pulmonary function tests (spirometry, lung volumes and diffusion capacities). In addition, test to determine the mean serum ferritin of the last 2 years and pre-transfusion haemoglobin and chest radiograph and echocardiography were performed for the thalassemic children only. RESULTS: A total of 70% of the thalassemic children had diffusion impairment, whereas 34% of them had associated restrictive abnormality. Thalassemic children with serum ferritin >2500 ng mL-1 had significantly lower values of forced vital capacity (FVC), forced expiratory volume at one second (FEV1), peak expiratory flow (PEFR), total lung capacity (TLC) and diffusing capacity of carbon monoxide (DLCO) (P < 0·05). Only diffusion impairment had a significant positive correlation with serum ferritin level. Restrictive impairment had significant positive correlations with age, duration of blood transfusion and serum ferritin level and a significant negative correlation with duration of chelation (P < 0·05). Having a serum ferritin >2500 ng mL-1 was the only predicting factor for diffusion impairment and the strongest predicting factor for restrictive dysfunction. CONCLUSION: Despite being asymptomatic, the majority of thalassemic children in this study suffered from diffusion impairment either alone or in combination with restrictive dysfunction. These pulmonary dysfunctions correlated significantly with body iron stores measured by serum ferritin.

Are D- and L-chiro-phosphoinositides substrates of phosphatidylinositol-specific phospholipase C?

Derivatives of chiro-inositol have been recently shown to mediate many important biological processes. This work addresses the question of whether phosphatidylinositol-specific phospholipase C (PI-PLC) could be involved in the generation of these chiro-inositol derivatives. Two diastereomers of the analog of phosphatidylinositol containing 1D- and 1L-chiro-inositol have been synthesized. 1D-2-O-(1,2-O-Dipalmitoyl-sn-glycero-3-phospho)-chiro-inositol (1D-chiro-PI) was synthesized in 12 steps starting from 1D-2,3,4,5-O-tetrakis(methoxymethylene)-myo-inositol by the inversion of the hydroxyl group at the 1-position of inositol followed by several protection/deprotection and phosphorylation steps. IL-2-O-(1,2-O-Dipalmitoyl-sn-glycero-3-phospho)-chiro-inositol (1L-chiro-PI) was synthesized in eight steps starting from 1L-chiro-inositol using regioselective silylation of the hydroxyl group at the 2-position of chiro-inositol in a key synthetic stage. Both diastereomers were subjected to cleavage by PI-PLC from Bacillus thuringiensis. The reaction of 1L-chiro-PI produced chiro-inositol 1,2-cyclic phosphate, however, at the rate of 10(-3) of that attained with the natural substrate, phosphatidylinositol. On the other hand, 1D-chiro-PI was found to be resistant to PI-PLC. These results suggest that the natural chiro-inositol derivatives should have the 1L-configuration if they are produced by PI-PLC, which is in contrast to the 1D-configuration reported by others. We therefore have isolated chiro-inositol from the total bovine liver lipid and determined its absolute configuration. The obtained chiro-inositol was found to be exclusively of the 1L-configuration, with the enantiomeric purity exceeding 99%.