Delayed multiorgan non-neoplastic damage after exposure to radiotherapy in infancy.
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Biomedical subjects
Publications and source records attributed to D Girelli.
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Loratadine is a new, highly selective, non sedating, H 1-receptor antagonist, without central nervous system activity. In a randomized double-blind, crossover study, we evaluated the effects of loratadine and placebo administered once daily in 184 food intolerant patients affected by urticaria-angioedema. The difference between loratadine and placebo treatment was significant in relieving symptoms. Adverse reactions reported in the treatment were mild, in fact somnolence was reported by 3.4%, dry mouth by 2.2% of patients.
Three groups of patients with chronic renal failure (CRF), 16 non-dialyzed, 16 undergoing haemodialysis (HD), 16 undergoing continuous ambulatory peritoneal dialysis (CAPD), and 48 controls were examined. We analyzed the fatty acid composition in membranes from erythrocytes and platelets and the platelet malondialdehyde (MDA) production as an index of thromboxane metabolism. Marked differences in erythrocytes fatty acid composition were observed between patients with CRF and controls and, particularly, among the three groups of patients with CRF. Patients on CAPD were characterized by an increase in oleic acid, while haemodialyzed had a marked increase in arachidonic acid. Platelet fatty acid composition showed similar differences, suggesting a 'systemic' membrane abnormality. Platelet MDA was increased in haemodialyzed and positively correlated with the platelet arachidonate content.
Since we have observed that monounsaturated fatty acids (MUFA) enriched diet modifies red cell membrane lipids and cation transport systems in normotensive subjects, we similarly evaluated a group of hypertensive patients undergoing an analogous dietary modification. In a group of 18 moderately hypertensive women, the diet was supplemented for two months with olive oil (about 45 g/day), which replaced an equal amount of seasoning fats. Before and after this period, red cell fatty acid composition was evaluated by gas-chromatography in order to verify diet compliance: a significant increase in oleic acid was observed, while the content of saturated and polyunsaturated fatty acids remained unchanged. After olive oil, maximal rates of Na-K pump (5580 +/- 329 vs 6995 +/- 390, p less than 0.001) and Na-K cotransport (Na-COT 544 +/- 52 vs 877 +/- 46, p less than 0.001: K-COT 790 +/- 76 vs 1176 +/- 66, p less than 0.001), cell Na content (9.58 +/- 0.4 vs 10.61 +/- 0.6, p less than 0.03) and passive permeability for Na (936 +/- 74 vs 1836 +/- 102, p less than 0.001) rose significantly. Although the reduction in maximal rate of the Li-Na CT after olive oil was not significant, it was the only cation transport parameter being correlated with the variations of membrane lipids, namely negatively with UFA (r = -0.528, p less than 0.05) and positively with SFA (r = 0.482, p less than 0.005). The change in maximal rate of Li-Na CT was also correlated with the variation of systolic and diastolic BP (r = 0.50, p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
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OBJECTIVE: To investigate the overall susceptibility of red blood cells (RBC) to lipid peroxidation from patients on continuous ambulatory peritoneal dialysis (CAPD). METHODS: The following parameters were measured: RBC malondialdehyde (MDA) production after oxidative stress with H2O2, RBC antioxidant enzymes glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), and RBC membrane lipid composition. The levels of plasma vitamin E and serum selenium were also assayed. PATIENTS: Eleven patients on continuous ambulatory peritoneal dialysis. Twenty-one healthy blood donors of similar age were used as normal controls. RESULTS: The MDA formation after H2O2 stimulation was normal in CAPD patients (0.79 +/- 0.1 mumol/gHb versus 0.78 +/- 0.1 in the control group). RBC from CAPD patients also showed a normal SOD activity, a more than adequate vitamin E status, and a peculiar pattern of membrane lipids, with reduced polyunsaturated fatty acids (p less than 0.001) and increased monounsaturated fatty acids (p less than 0.001). Both RBC GSH-Px activity, a selenium-dependent enzyme, and serum selenium levels were significantly lower in CAPD patients, and a significant positive correlation (r = 0.68; p less than 0.02) between the two parameters was found. CONCLUSIONS: This study found a normal sensitivity to oxidant stress in RBC from a group of CAPD patients, despite an impaired GSH-Px activity. The peculiar lipid pattern of RBC membrane, characterized by reduced PUFA and increased MUFA content, may contribute, in addition to adequate SOD activity and vitamin E status, to normal RBC lipid peroxidation.
The fatty acid composition and the glutathione-peroxidase activity (GSH-Px) of erythrocytes and platelets, the production of malondialdehyde (MDA) by platelets and the activity of the main systems of transmembrane cation transport in erythrocyte have been studied in 12 patients (5 males and 7 females) affected by retinitis pigmentosa (RP). A remarkable increase of saturated fatty acids (SFA), particularly of stearic acid (C18:0), has been noted in these patients. The reduced unsaturated/saturated fatty acids ratio (PUFA/SFA) observed in both erythrocytes and platelets and the decrease of arachidonic acid in platelets may depend by an active peroxidation process as documented by the increase of MDA. Platelet glutathione-peroxidase (PTL-GSH-PX) and plasma retinol were in the normal range, whereas erythrocyte glutathione-peroxidase (E-GSH-PX), MDA and plasma alfa-toco-pherol were increased in patients with RP. The activities of Na(+)-K+ pump, cotransport and Na(+)-Li+ countertransport were normal in RP erythrocytes.
The red cell represents a useful model for the study of general pathophysiological mechanisms, because of its availability and the relative easiness of the methodological approach due to the absence of nucleus and organelles. Particularly, most of the transmembrane ion transport systems, which control the homeostasis of intra- and extracellular electrolytes, have been firstly discovered in the red cell membrane. The pathophysiological importance of these transport systems is often extended to non haematological diseases like essential hypertension. Several reports from different laboratories have established that the red cell Na+/Li+ countertransport is stimulated in patients with essential hypertension. The regulation of Na+/Li+ countertransport, relationship with plasma and membrane lipids and the possibility of modulating its activity by dietary interventions, are focused in the last part of this review.
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We analyzed the erythrocyte membrane lipid composition in 11 non-diabetic CAPD patients on treatment for 3-78 months and in a control group of 12 subjects. The mean total values of both saturated fatty acids and unsaturated fatty acids were not statistically different in CAPD patients and in controls but the composition of fatty acids of in cell membranes was altered. In fact, CAPD patients had a higher percentage of monounsaturated fatty acids and a lower percentage of polyunsaturated fatty acids than controls. This increase MUFA/PUFA ratio might reflect either a preferential cell membrane uptake of MUFA or a relative PUFA deficiency due to an increased lipid peroxidation.
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Evidence exists of platelet activation and increased thromboxane B2 production in psoriasis. In 13 patients suffering from psoriasis, we determined the lipid composition of erythrocyte membrane, erythrocyte and platelet glutathione peroxidase activity (E-GSH-Px; Plt-GSH-Px), platelet MDA production and bleeding time. Compared with normal controls, psoriatics showed a significant increase in erythrocyte membrane arachidonic acid (AA) (p less than 0.001) and polyunsaturated fatty acids (PUFA) (p less than 0.001), platelet MDA production (p less than 0.01) and E- and Plt-GSH-Px activity (p less than 0.01; p less than 0.01). After 8 weeks of fish-oil supplementation (20 ml/day) we observed the following changes: a) marked amelioration of skin lesions; b) normalization of membrane lipid pattern and platelet MDA production; c) a further increase in E- and Plt-GSH-Px activity (p less than 0.01; p less than 0.01); d) significant prolongation of bleeding time (p less than 0.05). Our data demonstrate: 1) a generalized perturbation of membrane lipid pattern in psoriasis, characterized by an excess of AA; 2) an activation of AA metabolism in platelets suggested by increased MDA production and GSH-Px activity; 3) dietary fish-oil may normalize membrane lipid pattern and reduce platelet hyperactivity in psoriasis.
BACKGROUND: Raised serum uric acid (SUA) levels are associated with conditions at high risk for coronary heart disease. SUA levels can be partly modified by the diet, but little is known about the association of SUA with several dietary factors, particularly the quality of ingested lipids. METHODS: The associations between SUA levels and biological and dietary factors were investigated in a sample of 90 healthy subjects (45 males and 45 females; ages 55.6 +/- 18 years) living in Nove, a village near Vicenza (Veneto Region, northern Italy). A careful selection of subjects to exclude those with chronic or acute disease (influencing SUA directly or indirectly through their pharmacological treatments) was obtained with the collaboration of three general practitioners operating in Nove. RESULTS: SUA was higher among men than among women and higher among postmenopausal women than among women of child-bearing age (P < 0.01). Stepwise multiple linear regression analysis of the population as a whole showed that serum triglycerides and total RBC omega-6 PUFA were significant and independent predictors of a consistent proportion of serum uric acid variability (R = 0.59; R2 = 0.332; P < 0.001). Taking men and postmenopausal women together, the result was the same. CONCLUSIONS: Triglycerides and SUA are related even in the normal population and not only in "Syndrome X." Dietary enrichment with omega-6 PUFA might be useful for the negative modulation of SUA.
Cholesterol/phospholipids molar ratio and fatty acid composition have been estimated in erythrocyte membrane of 12 patients suffering from nephrotic syndrome and compared to values obtained in 23 normal subjects matched for sex and age. The membrane lipid composition has been correlated with the activity of erythrocyte Li-Na countertransport of the same subjects. The results show a significant increase in cholesterol/phospholipids ratio and total saturated fatty acids when erythrocytes of nephrotic patients are compared to normal erythrocytes, whereas total unsaturated fatty acids were lower in nephrotics (p less than 0.002). Li-Na countertransport was higher in nephrotics (p less than 0.001) and it was positively correlated with the total amount of saturated fatty acids of the erythrocyte membrane (r = +0.451; p less than 0.01). On the contrary, Li-Na countertransport was negatively correlated with the total amount of unsaturated fatty acids (r = -0.468; p less than 0.01).
The fatty acid composition of erythrocyte membrane, the glutathione-peroxidase activity of erythrocytes and platelets, the production of malondialdehyde by platelets and the activity of the main systems of transmembrane cation transport have been studied in 5 members of a family, 2 of whom affected by Laurence-Moon-Barter-Biedl Syndrome. A remarkable increase of polyunsaturated fatty acids (particularly arachidonic acid) and of cholesterol/phospholipid molar ratio has been noted. This pattern of membrane lipids was associated to an increment of malondialdehyde production and an increase activity of glutathione-peroxidase. Serum retinol and a-tocopherol were in the normal range, whereas serum selenium was low in 3 out of 5 members. Moreover, the alteration of membrane lipids was associated to a decrease of the maximal velocity of Li-Na countertransport. We speculate that the enrichment of polyunsaturated fatty acids on the cell membranes may represent a condition favoring the lipoperoxidation and therefore the development of the retinitis pigmentosa characteristic feature of Laurence-Moon-Barter-Biedl Syndrome.
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