Depletion of total antioxidant capacity in type 2 diabetes

The purpose of the study was to examine the relationship between antioxidant depletion, glycemic control, and development of chronic complications in a controlled population of type 2 diabetic patients. Fifty age-matched type 2 diabetic patients receiving sulfonylureas but not insulin treatment were screened and assigned to two groups based on the presence or absence of proteinuria. A third group of normal subjects without diabetes were also enrolled in the study. All subjects in the three groups were Egyptians who were matched for body weight, and the two diabetic groups were also age-matched. Plasma glucose and fructosamine levels were higher in the two groups of diabetic patients versus the control group, but lipid peroxide levels were higher only in the patients with proteinuria. Compared with the control group, the total antioxidant capacity was depleted in the two diabetic groups, but the depletion was more severe in patients with proteinuria. Thus, the mean Trolox equivalent antioxidant capacity (TEAC) of the control group was 2.7+/-0.45, versus 1.7+/-0.5 (P < .001) in the patients without proteinuria. Furthermore, the TEAC measured in patients with proteinuria, who also had more diabetic complications, was lower (1.4+/-0.5, P < .001) than the TEAC in patients without urinary protein. In conclusion, a depletion of the total antioxidant capacity is associated with a higher incidence of diabetic complications.     

Effects of treadmill exercise test on oxidative/antioxidative parameters and DNA damage.

OBJECTIVE: We investigated the acute effects of treadmill exercise test (TET) on total peroxide, total antioxidant capacity (TAC), oxidative stress index (OSI) and DNA damage levels in voluntary and untrained healthy subjects. METHODS: A total of 113 untrained healthy subjects were included in the study. All subjects maintained a similar diet and physical activity for a week before the test. Blood samples were obtained before and after TET. Total peroxide, TAC, vitamin C and DNA damage were measured. The DNA damage was analyzed by using the Comet assay and OSI was calculated using total peroxide and TAC values. RESULTS: Treadmill exercise test leads to the increase of total peroxide (12 +/- 3 micromol H2O2/L to 14 +/- 3 micromol H2O2/L, p<0.001), OSI (0.72 +/- 0.18 AU to 0.81 +/- 0.22 AU, p<0.001), and to the decrease of TAC (1.78 +/- 0.16 mmol Trolox Eq./L to 1.72 +/- 0.15 mmol Trolox Eq./L, p<0.001) and vitamin C levels (98 +/- 4.2 micromol/L to 95 +/- 3.4 micromol/L, p<0.001). There was not significant difference in DNA damage. CONCLUSION: Our findings demonstrate that TET increases oxidants, decreases TAC and vitamin C namely, the balance shift towards oxidative side, but this stress is not enough to produce DNA damage.     

Evidence of postprandial absorption of olive oil phenols in humans

BACKGROUND AND AIM: Olive oil phenols are potent antioxidants in vitro. If this were to be also demonstrated in vivo, it would help to explain the beneficial effects of this typical ingredient of the Mediterranean diet. This study was designed to determine the presence in lipoprotein fractions of two phenolic compounds peculiar to extra virgin olive oil, namely tyrosol and OH-tyrosol, and whether their absorption induces an antioxidant effect in vivo. METHODS AND RESULTS: Two trials were performed. In the first (Long-term), 14 healthy volunteers followed two diets, each for one month. The only difference between the diets was that the first supplied 50 g of extra virgin olive oil per day, where-as the second one supplied 50 g of refined olive oil with no simple phenols, as demonstrated by GC-MS analysis. There were no changes in LDL oxidizability and tyrosol and OH-tyrosol were not recovered in lipoproteins and plasma from fasting samples drawn at the end of each diet period. In the second study (Postprandial), eight healthy volunteers received an oral fat load consisting of 100 g of extra virgin olive oil. Blood was drawn at times 0', 30', 60', 120', 240', 360', and major plasma lipoprotein classes were separated. The concentration of tyrosol, OH-tyrosol and vitamin E was determined in lipoprotein fractions. Plasma antioxidant capacity was measured by a crocin-bleaching test and expressed as mM Trolox C equivalents. Tyrosol and OH-tyrosol were recovered in all lipoprotein fractions, except VLDL, with concentrations peaking between 60' and 120'. However, a very high variability in tyrosol and OH-tyrosol absorption was observed among subjects. Vitamin E content of LDL and HDL did not vary significantly throughout the study. Plasma antioxidant capacity increased significantly at time 120' (baseline 0.96 mM Trolox; 120' 1.19 mM Trolox; p = 0.02), and then returned almost to baseline values after 360' (1.1 mM Trolox). CONCLUSIONS: These findings suggest that phenolic compounds in olive oil are absorbed from the intestine, though not through a pathway dependent on chylomicron formation, and may exert a significant antioxidant effect in vivo, probably in the postprandial phase.     

Serum melatonin level and oxidative stress in sickle cell anemia

This study evaluated serum melatonin levels in patients with sickle cell anemia (SCA) and compared the results to lipid peroxidation by determining thiobarbituric acid-reactive substances (TBARS) and Trolox equivalent antioxidant capacity (TEAC). The group studied was composed of 15 SCA patients and 24 subjects without hemoglobinopathies. The average melatonin level was significantly reduced in the SCA patients (p<0.001) when compared to the control group. The SCA patients showed significantly higher values for TBARS and TEAC when compared to values obtained for the control group (p<0.001 and p<0.01). Results from the correlation analysis in the SCA group were not statistically significant for any parameters except for TBARS and TEAC levels, which had a positive correlation (r=0.51; p=0.04), suggesting the participation of melatonin in antioxidant defense. The use of melatonin could be a possible therapeutic target for improving antioxidant defense and to reduce oxidative damage, alleviating symptoms associated with SCA.     

HbE Level and Red Cell Parameters in Heterozygous HbE With and Without α<Superscript>0</Superscript>-Thalassemia Trait

We compared hemoglobin (Hb) E levels and red cell parameters between heterozygous HbE with and without α⁰-thalassemia trait and also determine their appropriated cut-off points for differentiating these two groups. High performance liquid chromatography analysis results and mean levels of red blood cell (RBC) parameters, including RBC count, total Hb, hematocrit, MCV, MCH and MCHC of heterozygous HbE with α⁰-thalassemia trait (n?=?183) and without α⁰-thalassemia trait (n?=?1437) were reviewed and compared. The α⁰-thalassemia status in these samples was detected by real-time PCR with SYBR Green1 and high resolution melting analysis. Mean levels of HbE, total Hb, MCV, MCH and MCHC of heterozygous HbE with α⁰-thalassemia trait were significantly lower than those of heterozygous HbE without α⁰-thalassemia trait (P?<?0.001). In addition, HbE level at a cut-off value of?<?24% was superior to MCV (<?80 fL) and MCH (<?27 pg) for differentiating the heterozygous HbE with and without α⁰-thalassemia trait with 100% sensitivity and 87.2% specificity. Despite certain limitations of this study like missing RDW and reticulocyte counts, and not testing for α⁺-thalassemia and Hb Constant Spring, we conclude that the HbE level at a cut-off point of?<?24% is a useful marker for initial discrimination between heterozygous HbE with and without α⁰-thalassemia trait.     

Reduced venous endothelial responsiveness after oral lipid overload in healthy volunteers

The aim of this study was to investigate endothelial venous function, inflammatory markers, and systemic oxidative stress after an oral lipid overload (OLO). We studied 18 healthy adults (9 men; age, 29.2 +/- 0.9 years; body mass index, 22.3 +/- 0.4 kg/m(2)). Blood samples were collected in the fasting state and 3, 4, and 5 hour after the OLO (1000 kcal, 58% fat) for metabolic variables, oxidative stress, inflammatory markers, adiponectin, and resistin. Changes in vein diameter to phenylephrine, acetylcholine, and sodium nitroprusside (dorsal hand vein technique) were measured before and after the OLO. Oral lipid overload increased triglycerides (61 +/- 6 vs 134 +/- 17 mg/dL, P < .001), insulin (7.2 +/- 0.8 vs 10.7 +/- 1.3 muU/mL, P < .05), and resistin (5.38 +/- 0.5 vs 6.81 +/- 0.7 ng/mL, P < .05) and reduced antioxidant capacity (plasma total antioxidant capacity: 186.7 +/- 56 vs 161.8 +/- 50 U Trolox per microliter plasma, P < .01), vascular reactivity (171.3 +/- 85 vs 894.4 +/- 301 ng/mL, P < .001), and maximum acetylcholine venodilation (105.9% +/- 9% vs 61.0% +/- 7%, P < .05). No changes were observed for sodium nitroprusside. Post-OLO triglycerides were positively correlated with phenylephrine dose (rho = 0.38, P < .05) and resistin (rho = 0.43, P < .01) and negatively correlated with the maximum acetylcholine venodilation (rho = -0.36, P < .05). In conclusion, an OLO impaired venoconstriction responsiveness in healthy subjects, probably because of a reduction in the antioxidant capacity.     

Evaluation of systemic oxidative status and mononuclear leukocytes DNA damage in children with caustic esophageal stricture

Esophageal stricture (ES) due to accidentally caustic digestions is a common problem in children. Mucosal damage and repeated dilatations lead to chronic inflammation and finally ES. We investigated the oxidative status and DNA damage of children with ES. Five children with ES were compared with the same age- and sex-matched healthy subjects. Oxidative status of plasma was evaluated by measuring myeloperoxidase (MPO) activity, and total peroxide (TP) level. Anti-oxidative status of the plasma was evaluated by measuring catalase (CAT) activity, and total antioxidant response (TAR). We used the Single Cell Gel Electrophoresis (also called Comet Assay) to measure DNA strand break in peripheral blood mononuclear leukocytes. Mean MPO activity and TP levels in the ES group were significantly higher than the control group (0.83 +/- 0.35, 0.09 +/- 0.03 and 0.98 +/- 0.38, 0.34 +/- 0.20, P = 0.009 and P = 0.047 respectively). There was no significant difference in CAT activity and TAR levels between the two groups (P = 0.347). DNA damage in patients with ES was increased compared to control subjects (108.8 +/- 51.2 and 57.6 +/- 31.2 arbitrary units, respectively), but this difference was not significant statistically (P= 0.09). This study shows that systemic oxidative stress and alteration at the nuclear level occur in patients with ES, as a result of multiple dilatations and tissue injury. On the other hand, these results support that patients with ES may benefit from antioxidant treatment.     

Role of interleukin-3 and signaling pathways on beta-thalassemia/HbE erythroid progenitor cell in culture

In order to study the role of the cytokine interleukin-3 (IL-3) and its signaling pathways in erythropoiesis of beta-thalassemia/HbE erythroid progenitor cells, CD34 positive cells were isolated from peripheral blood of patients and healthy subjects. After culturing the cells in the presence or absence of IL-3, cell viability was measured by trypan blue staining and apoptotic cells were analyzed by flow cytometry. After 7 days of culture the highest percent erythroid progenitor cell viability was obtained with cells from healthy subjects, while the lowest percentage was found in those from splenectomized beta-thalassemia/HbE. Viability of beta-thalassemia/HbE erythroid progenitor cells in the presence of IL-3 was higher than that of nonsupplemented cells. In addition, specific inhibitors of protein kinase C (Ro-318220), phospholipase C (U-73122) and Janus kinase 2 (AG-490) were used to investigate the involvement of signaling pathways in erythropoiesis. Percent apoptosis of erythroid progenitor cells from splenectomized beta-thalassemia/HbE subjects treated with RO-318220 was higher than those of nonsplenectomized beta-thalassemia/HbE and healthy subjects. Treatment with U-73122 resulted in enhanced percent apoptotic cells from normal and beta-thalassemia/HbE subjects. All these effects were independent of IL-3 treatment.     

Plasma total anti-oxidant status in young survivors of myocardial infarction]

Free oxygen radicals are involved in the endothelial lesion process which leads to the formation of the atheroma plaque and thrombosis. There is some evidence that antioxidant therapy may be beneficial in coronary heart disease prevention. Our objective was to study the plasma total anti-oxidant status in young survivors of acute myocardial infarction. POPULATION: 23 patients, mean age 35.2 years (22-40) admitted for acute myocardial infarction from January 1995 to June 1998 (20 males). RISK FACTORS: Tobacco smoking 22/23, systemic arterial hypertension 4/23, hypercholesterolemia 17/23, positive family history for coronary heart disease 5 patients, previous history of angina 4 patients, none of these patients had diabetes mellitus. The location of the infarct was anterior in 12 patients, inferior in 10 patients and non-Q wave in one patient. Blood samples were drawn after overnight fasting and the plasma total antioxidant status (TAS) was determined by a colorymethric method (Trolox equivalent). The mean time elapsed since the acute myocardial infarction until sample collection was 16.5 +/- 10.7 months. RESULTS: 18 patients had low TAS values, mean 1.23 +/- 0.11 mmol/L (below the reference values: 1.3-1.77 mmol/L). CONCLUSIONS: In this group of patients, the plasma total antioxidant capacity was globally decreased, which may constitute a risk factor for coronary heart disease.     

Antioxidant enzyme activities in healthy Chinese adults: influence of age, gender and smoking

OBJECTIVE: Specific antioxidant enzymes play a vital role in regulating and maintaining oxidant species. The aim of this study was to determine these antioxidant enzyme activities (i.e. catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx)) in erythrocytes from a group of healthy Chinese subjects and to study the influence of age, gender and smoking habits on the enzyme activities. METHODOLOGY: Chinese healthy subjects (n = 276) were grouped according to their age range, gender differences and smoking habits. Antioxidant enzyme activities were measured spectrophotometrically using standard kinetic methods. RESULTS: There was a significant decrease in erythrocyte GPx activity in ever-smokers compared with non-smokers (47.10 +/- 1.33 mU/g haemoglobin (Hb) vs. 51.41 +/- 1.64 mU/g Hb, P < 0.05). Age-related significant increases in erythrocyte CAT and SOD activities were found in non-smokers but not in ever-smokers. There was no age-related difference in erythrocyte GPx activity in either non-smokers or ever-smokers. Among those >60 years old, erythrocyte CAT and GPx activities were significantly lower in ever-smokers than in non-smokers (29.70 +/- 3.07 mU/g Hb vs. 41.63 +/- 4.92 mU/g Hb (P < 0.05), and 47.55 +/- 2.00 mU/g Hb vs. 55.30 +/- 3.60 mU/g Hb (P < 0.05), respectively). It was also found that females had higher erythrocyte GPx activity than males but this difference did not reach significance in non-smokers. CONCLUSION: From the results of this study, it is concluded that oxidative stress seems to be present in elderly ever-smokers among the Chinese population.     

Urinary excretion of oxidative metabolites of bilirubin in subjects with Gilbert syndrome

BACKGROUND AND AIM: Bilirubin is a potent endogenous antioxidant substance. Recent data suggest a direct relationship exists between urinary excretion of biopyrrins, a novel group of bilirubin oxidative metabolites, and severity of oxidative stress. The aim of this study was to evaluate urinary excretion of biopyrrins in subjects with Gilbert syndrome. METHODS: The study included patients with Gilbert syndrome (n = 33) and healthy blood donors (n = 25). In all subjects complete biochemical tests were conducted along with analysis of urinary excretion of biopyrrins. Linear and logistic regression analyses were used for multiple adjustments of possible confounders/modifiers. RESULTS: As expected, high serum bilirubin levels were found in the Gilbert syndrome group as compared to controls (27.8 +/- 9.7 vs 9.9 +/- 3.0 micromol/L, P < 0.001). In contrast, urinary levels of biopyrrins were substantially lower in the Gilbert syndrome group as compared to normobilirubinemic control subjects (19.9 +/- 26.0 vs 90.2 +/- 139.1 U/g urinary creatinine, P < 0.001). The Gilbert syndrome group also had very low prevalence odds ratios for urinary biopyrrins above the median of the control values even after adjustment for possibly confounding factors (odds ratio 0.18, 95% confidence interval 0.33-0.94; P = 0.042). CONCLUSIONS: An inverse relationship was demonstrated between serum bilirubin level and urinary excretion of biopyrrins, which is presumably due to antioxidative effects of elevated serum bilirubin levels in Gilbert syndrome.     

Evidence of local exercise-induced systemic oxidative stress in chronic obstructive pulmonary disease patients.

Chronic inactivity may not be the sole factor involved in the myopathy of chronic obstructive pulmonary disease (COPD) patients. One hypothesis is that exercise-induced oxidative stress that leads to muscle alterations may also be involved. This study investigated whether exercise localised to a peripheral muscle group would induce oxidative stress in COPD patients. Eleven COPD patients (FEV1 1.15+/-0.4 L (mean+/-SD)) and 12 healthy age-matched subjects with a similar low quantity of physical activity performed endurance exercise localised to a peripheral muscle group, the quadriceps of the dominant leg. The authors measured plasma levels of thiobarbituric reactive substances (TBARs) as an index of oxidative stress, the release in superoxide anion (O2*-) by stimulated phagocytes as an oxidant, and blood vitamin E as one antioxidant. Quadriceps endurance was significantly lower in the COPD patients compared with healthy subjects (136+/-16 s versus 385+/-69 s (mean+/-SEM), respectively). A significant increase in TBARs 6 h after quadriceps exercise was only found in the COPD patients. In addition, significantly higher O2*- release and lower blood vitamin E levels were found in COPD patients than in controls at rest. This blood vitamin E level was significantly correlated with the resting level of plasma TBARs in the COPD patients. This study mainly showed that quadriceps exercise induced systemic oxidative stress in chronic obstructive pulmonary disease patients and that vitamin E levels were decreased in these patients at rest. The exact relevance of these findings to chronic obstructive pulmonary disease myopathy needs to be elucidated.     

Discriminant function using red cell indices to distinguish between HbC and HbE traits

Summary Values for MCV, MCH, MCHC and red cell distribution width (RDW) derived from subjects with HbC and HbE traits using a Technicon H*1 automated blood count analyser were compared. Significantly higher MCH, MCHC and RDW values were found in those with HbC trait. By use of a simple discriminant function (MCHC²× RDW/1000), 19/20 subjects with HbC trait gave a value ≥ 16.3, and 20/21 subjects with HbE trait gave a value ≤ 16.2. The function described may be of value as an adjunct to electrophoresis in intralaboratory quality control.     

Oral amino acid administration decreases oxidative stress and improves brachial reactivity in elderly individuals

BACKGROUND: Atherosclerosis is a major cause of death in elderly individuals. Endothelial dysfunction is recognized as a key early event in atherogenesis. In the present study, we evaluated the possible beneficial effect of amino acid administration on endothelial regulation in elderly subjects. METHODS: A total of 25 healthy elderly subjects were administered essential amino acids (EAA) for 4 months. Before and after EAA administration, each subject underwent brachial reactivity investigation with and without an intra-arterial infusion of 4 micromol/min of N(G)-monomethyl-l-arginine (L-NMMA), an inhibitor of nitric oxide (NO) synthase. RESULTS: At baseline, age correlated with free plasma insulin growth factor-1 IGF-1 (r = -0.48; P < .01), plasma Trolox equivalent antioxidant capacity (TEAC) (r = -0.40; P < .04), and thiobarbituric acid-reactive substances (TBARS) (r = 0.42, P < .04), and homeostasis model assessment (HOMA) index (r = 0.45, P < .03), as well as with changes in diameter (r = -0.49, P < .01) and flow (r = -0.43, P < .03). Administration of EAA was associated with a significant increase in plasma TEAC (P < .001) and decline in plasma TBARS (P < .001) and with improvement in changes in diameter (7.15 +/-1.10 v 8.98 +/-1.80, P < .001) and flow (5.6 +/-1.2 v 6.4 +/- 1.2, P < .03). These latter two associations were independent of changes in HOMA index (P < .04 for both correlations). The beneficial effects of EAA administration on brachial reactivity were partly attenuated by L-NMMA. CONCLUSIONS: Administration of EAA may improve brachial reactivity in elderly persons and may also protect against the development of atherosclerosis via the rise in plasma-free IGF-1 levels.     

Age-dependent change of uric acid level in the dermis using cutaneous microdialysis

BACKGROUND: We had proposed the usefulness of cutaneous microdialysis for the study of antioxidants in the skin. OBJECTIVE: We designed a study analyzing the level of uric acid in the skin, one of the major antioxidants, for an age-dependent change. METHODS: 16 healthy male volunteers were divided into two groups according to age. Eleven subjects were in their 3rd decade, under 30 years of age (young group) and the others were their 8th decade (old group), over 70 years of age. Dialysate samples were analyzed using high-performance liquid chromatography analysis. RESULTS: In the young group the mean level of uric acid was 31.9+/-16.1 microg/ml, while in old group it was 13.4+/-5.2 microg/ml. CONCLUSION: This result demonstrated an in vivo state of antioxidant level in the human skin and the age-dependent difference was concordant with other in vitro or ex vivo studies; therefore, cutaneous microdialysis could be used in analysis and monitoring studies including human antioxidants and anti-aging.     

Malondialdehyde and nitric oxide behaviour in patients with myocardial infarction

INTRODUCTION AND OBJECTIVES: The aim of this study was to determine the potential usefulness of malondialdehyde and nitric oxide as sensors of metabolic damage produced during acute coronary ischaemics events. METHODS: Serum malondialdehyde and nitric oxide levels were determined as thiobarbituric acid derivative and nitrites respectively in 15 male patients who were admitted to the emergency ward of the Hospital General del Sur de Maracaibo, because of acute stage of myocardial infarction. RESULTS: Our results show, upon follow-up and afterwards 30 days a highly significant increase in the malondialdehyde level during the acute phase of myocardial infarction (1.87 +/- 0.29 vs 45.47 +/- 8.67 mM; p < 2.01 10-5) that returns to normal levels 30 days after myocardial infarction when compared with healthy subjects of the same age (1.87 +/- 0.29 vs 4.58 +/- 1.43 mM). As for nitric oxide, levels also increased significantly during the acute phase of myocardial infarction (41.25 +/- 3.59 vs 164.63 +/- 12.7, p < 2.13 10-10 mM) and diminished significantly when compared with healthy adults of the same age 30 days after the acute event (41.25 +/- 3.59 vs 40.85 +/- 4.50 mM). CONCLUSIONS: Our results show that serum levels of malondialdehyde and nitric oxide increased significantly during acute infarction, coming back to normal levels 30 days after infarction, which suggest that both substances are potential tools to predict cardiac function recovery.     

Postprandial cholecystokinin secretion in elderly with protein-energy undernutrition.

OBJECTIVE: Malnutrition is currently observed in aged people, and cholecystokinin is an important peripheral satiety signal. The aim of this study was to examine the effect of aging and protein-energy malnutrition on postprandial cholecystokinin (CCK) release. DESIGN: Non-randomized, cross-sectional comparison by age group. SETTING: Gastroenterology section of a teaching hospital. PARTICIPANTS: Twenty-one human volunteers divided into three groups: young healthy subjects (Group 1: mean 29 years, n = 7), aged healthy subjects (Group 2, mean 80 years, n = 7), and aged subjects with an important degree of malnutrition (Group 3, mean 84.6 years, n = 7). INTERVENTION: Each subject ingested a standardized liquid meal after an overnight fast. MAIN OUTCOME MEASURES: Plasma cholecystokinin was measured using a sensitive bioassay before and after the ingestion of the liquid meal. RESULTS: Basal cholecystokinin levels were similar (0.9 to 1 pM equivalent CCK-8) in the three groups. Postprandial levels were significantly increased over basal (P less than 0.05). The maximal cholecystokinin value was lower in Group 1 (3.5 +/- 0.8 pM equivalent CCK-8) and Group 2 (3.3 +/- 0.77 pM equivalent CCK-8) than in Group 3 (8.3 +/- 2 pM equivalent CCK-8) (P less than 0.05). Integrated plasma cholecystokinin was also similar in Group 1 (171 +/- 38 pM.60 min), (P less than 0.05). CONCLUSION: The increase of postprandial maximal levels of cholecystokinin is more related to malnutrition than to aging.     

Mean cell haemoglobin concentration in subjects with haemoglobin C,D, E and S traits

Summary The Bayer H1 automated blood counter was used to assess the MCHC values of 40 non-anaemic patients with HbC trait, 21 with HbD trait, 23 with HbE trait and 69 with HbS trait. These were compared with values from controls with a normal Hb phenotype. Values were significantly higher in those with HbC, D and S traits and approached significance in those with HbE trait. In 45% of subjects with HbC trait the MCHC value was ≥35 g/dl. Such values may prove a useful marker for this abnormality. In a further 12 patients with HbC, D, E or S traits and coexisting iron deficiency anaemia, MCHC values were usually higher and the percentage of hypochromic cells (red cells with CHC < 28 g/dl, directly measured by the H1) usually lower than values derived from controls with a normal Hb phenotype and iron deficiency anaemia of similar degree. In individuals with HbC, D, E or S traits, the MCHC and proportion of hypochromic cells are less sensitive indicators of iron lack than in subjects with a normal Hb phenotype.     

Transdermal estrogens do not appear to modify the extent of lesional areas of aortic atherosclerosis in oophorectomized rabbits on a cholesterol-rich diet

Cardiovascular disease (CVD) is the leading cause of death in older women in industrialised countries. It has been suggested that it is the cessation of estrogen production by the ovaries that puts postmenopausal women at increased risk of CVD. Estrogen therapy has demonstrated a protective effect against CVD and several reports suggest that diverse mechanisms may be involved. Oral estrogen appears to be associated with a better lipid profile than the use of transdermal estrogens; however, it is assumed that estrogens, oral and non-oral, have direct actions on the blood vessels that may exert an important role in cardiovascular disease prevention. To investigate the effect of transdermal estrogen therapy on aorta atherogenesis, we studied 20 cholesterol-fed New Zealand White rabbits for 4 months. The rabbits were oophorectomized and randomly assigned to two groups. Ten rabbits underwent bilateral ovariectomy followed by treatment with transdermal 17-beta-estradiol (group E) and the other 10 received placebo after sterilization (Group C). After diet total levels of cholesterol increase in group C from 50. 0+/-12.5 to 820.9+/-186.0 mg/dl, and in group E from 52.6+/-9.4 to 811.4+/-213.0 mg/dl (no significant differences were observed between groups). Estrogen therapy increased twofold the total reactive antioxidant potential (TRAP group C: 22.5+/-16.7 mmol of Trolox/l vs. TRAP group E: 43.4+/-22.4 mmol of Trolox/l; P<0.04). At 4 months, the cholesterol-rich diet caused atherosclerotic lesions in both treated and untreated rabbits affecting 18.7+/-14.5 and 21. 6+/-9.7% of the aortic surface respectively. In summary, the principal result from this study was that although treatment with transdermal 17-beta-estradiol in cholesterol-fed ovariectomized rabbits increases the TRAP to pre-surgery values, it does not inhibit aortic cholesterol accumulation.     

Plasma kinetics of a cholesterol-rich microemulsion in subjects with heterozygous beta-thalassemia

Patients with beta-thalassemia trait have been reported to present lower plasma concentrations of low-density lipoprotein (LDL) and lower frequencies of acute myocardial infarction than normal subjects. In this study, the metabolism of LDL was tested in 12 patients with heterozygous beta-thalassemia trait (HBT) and 13 healthy subjects without the disease by determining the plasma kinetics of an artificially made cholesterol-rich microemulsion (LDE) that mimics the LDL metabolism and binds to LDL receptors. The emulsion was labeled with 14C-cholesterol ester and injected intravenously into the subjects. Blood samples were drawn at regular intervals over 24 hr to determine the plasma decay curve of the emulsion radioactive label and to estimate its plasma fractional clearance rate (FCR, in hr(-1)). FCR of the 14C-cholesterol ester was greater in HBT compared to controls (0.0631 +/- 0.0178 hr(-1) and 0.0501 +/- 0.0094 hr(-1), respectively; mean +/- SD, P = 0.022). No differences were found regarding LDL cholesterol plasma concentration between the two groups, but apolipoprotein B concentration was lower in HBT than in control subjects (80 +/- 44 and 96 +/- 14, respectively; mean +/- SD, P = 0.026). Our results show that LDE FCR is increased in HBT, indicating that LDL clearance is increased in patients with beta-thalassemia trait possibly due to the increased proliferation in the bone marrow of erythroid precursors.