Dietary and blood antioxidants in patients with chronic heart failure. Insights into the potential importance of selenium in heart failure.

BACKGROUND: Chronic heart failure (CHF) seems to be associated with increased oxidative stress. However, the hypothesis that antioxidant nutrients may contribute to the clinical severity of the disease has never been investigated. AIMS: To examine whether antioxidant nutrients influence the exercise capacity and left ventricular function in patients with CHF. METHODS: Dietary intake and blood levels of major antioxidant nutrients were evaluated in 21 consecutive CHF patients and in healthy age- and sex-matched controls. Two indexes of the severity of CHF, peak exercise oxygen consumption (peak VO2) and left ventricular ejection fraction (LVEF), were measured and their relations with antioxidants were analysed. RESULTS: Whereas plasma alpha-tocopherol and retinol were in the normal range, vitamin C (P=0.005) and beta-carotene (P=0.01) were lower in CHF. However, there was no significant association between vitamins and either peak VO2 or LVEF. Dietary intake (P<0.05) and blood levels of selenium (P<0.0005) were lower in CHF. Peak VO2 (but not LVEF) was strongly correlated with blood selenium: r=0.76 by univariate analysis (polynomial regression) and r=0.87 (P<0.0005) after adjustment for age, sex and LVEF. CONCLUSIONS: Antioxidant defences are altered in patients with CHF. Selenium may play a role in the clinical severity of the disease, rather than in the degree of left ventricular dysfunction. Further studies are warranted to confirm the data in a large sample size and to investigate the mechanisms by which selenium and other antioxidant nutrients are involved in CHF.

Arsenic speciation in human organs following fatal arsenic trioxide poisoning--a case report.

The aim of this investigation was to study the distribution of arsenic species in human organs following fatal acute intoxication by arsenic trioxide. The collected autopsy samples of most organs were ground and dried, and the total arsenic was measured by electrothermal atomic absorption spectrometry (ETAAS). The arsenic species--inorganic arsenic, in the form of arsenite [As(III)] and arsenate [As(V)], and its metabolites [monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)]--were quantified by ETAAS after extraction with methanol/water (1:1, by volume) and separation by HPLC. The results indicate that after acute intoxication, the liver and kidneys show the highest concentrations of total arsenic and that the total concentration in blood is 7- to 350-fold less concentrated than in organs. In all organs, As(III) is the predominant species, and MMA is more concentrated than DMA. MMA and DMA are more prevalent in lipidic organs (49% of total arsenic) compared with other organs (25% of total arsenic). As(V) was found in small quantities in the liver, kidneys, and blood.

Contribution to chromium and nickel enrichment during cooking of foods in stainless steel utensils.

Nickel ingestion can cause exacerbation of dermatitis in patients who are already nickel-sensitive; Chromium (Cr VI) is the 2nd allergen, after nickel. However, stainless steel is widely used in home cookware. In this study, we determined nickel and chromium levels by atomic absorption spectrometry in 11 habitual menus cooked in different grades of stainless steel utensils. We noted a great difference in nickel and chromium intake depending on the menu, and a significant difference between the glass and stainless steel saucepans, but this was very low compared with the levels of nickel and chromium contained in the menus; mean intakes of these elements were under the tolerable daily intake (TDI) recommended by the World Health Organization. Hence, there is no advantage for nickel-sensitive patients in switching to materials other than stainless steel, provided that this is of good quality.

Effect of selenium and vitamin E supplements on tissue lipids, peroxides, and fatty acid distribution in experimental diabetes.

The protective role of selenium (Se), given as a Se-rich yeast, selenomethionine or selenomethionine + vitamin E supplement, toward changes in lipid, peroxide, and fatty acid distribution in tissues of streptozotocin-induced diabetic rats, was investigated, after 24 wk of disease. Diabetes increased liver thiobarbituric acid-reactive substances and conjugated dienes; Se supplement completely corrected these changes. In kidney, as in heart, the peroxide levels were not significantly changed by diabetes. In diabetic rat liver, a significant drop in triglycerides and phospholipids (P < 0.05) was observed; this was modulated by Se + vitamin E supplementation. Se + vitamin E supplementation also inhibited the decrease in 18:2n-6 and the increase in 22:6n-3 observed in liver of diabetic rats, changes which reflect altered glycemic control. In kidney, heart, and aorta, diabetes produced some changes in lipid content and fatty acid distribution, especially an increase in heart triglycerides which was also corrected by the Se supplement. Se supplementation to diabetic rats also increased 18:0 ether-linked alcohol, 20:4 n-6, and 22:5 n-3 in cardiac lipids. In aorta, Se + vitamin E significantly increased 20:5 n-3. These polyunsaturated fatty acids are precursors, in situ, of prostaglandin I2 (PGI2) and PGI3 which may protect against cardiovascular dysfunction. In kidney, conversely, Se decreased 20:4 n-6, the precursor of thromboxane A2 implicated in diabetic glomerular injury. Thus Se, and more efficiently Se + Vitamin E supplementation, in experimental diabetes could play a role in controlling oxidative status and altered lipid metabolism in liver, thereby maintaining favorable fatty acid distribution in the major tissues affected by diabetic complications.

Effect of selenium and vitamin E supplementation on lipid abnormalities in plasma, aorta, and adipose tissue of Zucker rats.

Twenty-nine obese female Zucker rats (fa/fa) were fed with a laboratory chow supplemented or not with a selenium-rich yeast (Selenion), or Selenion + vitamin E, or vitamin E alone. Twelve lean female Zucker rats (Fa/Fa) of the same littermates fed with the same diet were used as control. After 32 wk of diet, obesity induced a large increase in plasma insulin and lipid levels. A significant decrease in the plasma vitamin E/triglycerides ratio (p<0.005) and an increase in plasma thiobarbituric reactive substances (TBARS) (p<0.005) were also observed. Plasma selenium and vitamin E increased in all supplemented rats. The plasma insulin level was decreased by selenion supplementation and the vitamin E/triglycerides ratio was completely corrected by double supplementation with Selenion + vitamin E. TBARS were also efficiently decreased in two obese groups receiving vitamin E. In plasma, adipose tissue and aorta, obesity induced an increase in palmitic acid (C16:0), a very large increase in monounsaturated fatty acids (palmitoleic acid C16:1, stearic acid C18:1) associated with a decrease in polyunsaturated n-6 fatty acids (linoleic acid C18:2 n-6, arachidonic C20:4 n-6). These alterations in fatty acid distribution were only partly modulated by Se and vitamin E supplements. However, in the aorta, antioxidant treatment in obese rats significantly reduced the increase in C16:0 and C16:1 (p<0.05 and p<0.01, respectively) and the decrease in arachidonic acid (p<0.05). These changes could be beneficial in the reduction of insulin resistance and help to protect the vascular endothelium.

Validated determination of total arsenic species of toxicological interest (arsenite, arsenate and their metabolites) by atomic absorption spectrometry after separation from dietary arsenic by liquid extraction: toxicological applications.

A validated method for the selective extraction of total As species of toxicological interest (arsenite, arsenate and mono- and dimethylated arsenic species) from urine, followed by atomic absorption spectrometric determination, is described. The mechanisms involved in extraction were studied and the extraction method was optimized. The urine sample was acidified with concentrated HCl and KI and sodium hypophosphite were added. Under these conditions, As species were reduced to their corresponding iodide arsines, extracted with toluene and back-extracted with 1 mmol l-1 NaOH solution. Only inorganic arsenic and its metabolites in humans (monomethylarsonic and dimethylarsinic acid) were extracted. Arsenobetaine of dietary origin was not extracted. This method can detect if any As increase in urine originates from inorganic As intoxication or only from dietary non-toxic As species such as arsenobetaine.

[Effect of ion exchange resins on the composition of milk]. / Effets des résines échangeuses d'ions sur la composition des laits.

Pretreatment of milk with either sodium or calcium polystyrene sulfonate resins is useful in limiting potassium dietary intake in children with renal failure. We therefore studied the in vitro effects of Kayexalate and Calcium Sorbisterit on potassium, sodium and calcium concentrations in 3 standard formulas and in human milk. It is concluded that wide variations in the final potassium, sodium and calcium concentrations can be observed according to the resin but also to the formula.

In vitro and in vivo effects of selenium and selenium with vitamin E on platelet functions in diabetic rats relationship to platelet sorbitol and fatty acid distribution.

In vitro 30 min of incubation with selenomethionine (Sm) + vitamin E multiplied by about five platelet selenium (Se) decreased significantly platelet thrombin and ADP-induced aggregation decrease. Four groups of streptozotocin-induced diabetic rats were fed with a supplemented purified diet with an Se-rich yeast (Selenion): DSel, Sm: DSm, Sm alpha-tocopherol: DSmE or unsupplemented diet: D. After 24 wk of supplementation, only a decrease in thrombin-induced aggregation in group DSel compared to DSm and DSmE and D was observed. However, after 24 wk of diet compared to 14 wk, in group D and DSm, a significant increase in thrombin-induced aggregation occurred (p < 0.0001), whereas a significant decrease in groups DSel and DSmE (p < 0.0001, p < 0.03) was noted. After 21 wk of diet, in DSmE, platelet adhesion to fibronectin was significantly decreased compared to group D (p < 0.05). These changes in DSmE were associated with a significant decrease in platelet sorbitol (p < 0.02) and a very significant increase in platelet Se (p < 0.0005). Sm associated with vitamin E would appear more efficient to prevent oxidative damage of diabetic platelet membrane and thus to modulate its hyperactivity.

A selenium supplement associated or not with vitamin E delays early renal lesions in experimental diabetes in rats.

Seventy rats were separated into five groups: one group of 12 was used as a control and received a purified diet, and four groups of streptozotocin-induced diabetic rats, totalling 58, were fed the same diet without or with selenium (Se) supplementation. Of the noncontrol rats, 14 were without supplementation (Group D), 14 were fed a Se-rich yeast diet (i.e., selenion) (Group DSel), 14 received selenomethionine (Group DSm), and 16 received selenomethionine + tocopherol acetate (Group DSmE). Supplementation with Se in all groups was 0.99 micromole/100g of diet and with tocopherol acetate was 0.145 micromole/100 g. All diabetic rats were mildly balanced by insulin. After 24 weeks of diet, plasma glucose tended to decrease in diabetic Se-supplemented groups DSmE > DSm > DSel versus Group D. In DSm and DSmE groups, plasma lipid peroxides also decreased compared with Group D, but this decrease reached significance only for DSmE (P < 0.01 for both TBARS and conjugated dienes). Plasma triglycerides also decreased in DSm and DSmE groups versus Group D (P < 0.01; P < 0.05, respectively). At the same time, Se increased significantly in kidneys of Groups DSel and DSm versus D and more weakly in Group DSmE, but in this case was associated with a large increase of vitamin E. These beneficial effects of selenium supplement and more so of selenium combined with vitamin E were associated with a protection of kidneys in diabetic rats which found expression in a significant correction of renal hyperfiltration (P < 0.05) and in a diminution of the number and severity of glomerular lesions (P < 0.0005).

[Selenium, glutathione peroxidase, peroxides and platelet functions]. / Sélénium, glutathion peroxydase, peroxydes et fonctions plaquettaires.

In the last five years, there has been a renewal of interest in the protective role of selenium in vascular disorders, inspired by experimental evidence that this trace element could modulate leukotriene and prostaglandin synthesis in both endothelial cells and platelets. In people living in low-selenium areas, a relationship has been established between a decrease in plasma selenium and an increase in the risk of coronary disease, atherosclerosis, platelet hyperaggregability and synthesis of proaggregant and proinflammatory compounds like thromboxane A2 and leukotrienes. Selenium, as an essential part of glutathione peroxidase, takes part in the reduction of hydrogen peroxides and lipid peroxides. The concentration of these peroxides, in turn, regulates the activities of cyclooxygenase and lipooxygenase pathways, ultimately influencing the production of eicosanoids and modulating the balance between a proaggregatory and antiaggregatory state. Recent evidence shows that selenium, via its action on glutathione peroxidase activity, may be primarily responsible for the regulation of the endogenous hydroperoxide level. In human platelets, the activity of glutathione peroxidase is particularly high and is very sensitive to the requirement of selenium. This sensitivity could explain why platelets of selenium-deficient subjects show increased aggregation, thromboxane B2 production and synthesis of the lipoxygenase-derived compounds. In these deficient subjects, selenium administration increases platelet glutathione peroxidase activity and inhibits platelet hyperaggregation and leukotriene synthesis. These results support the hypothesis that selenium supplementation has a positive effect on platelet aggregation in selenium-deficient subjects. In France, more than 10% of the population is selenium-deficient and long-term supplementation with low doses of selenium could have a beneficial effect on the prevention of both thrombosis and coronary heart disease in these subjects.

[Treatment of Wilson's disease with zinc. 5 cases]. / Traitement de la maladie de Wilson par le zinc. Cinq cas.

Zinc treatment of Wilson's disease was introduced by Schouwink en 1961 and is still uncommon in France. We evaluated the effectiveness and safety of zinc in 5 patients with Wilson's disease aged from 19 to 40 years. There were three neurological, one hepatic and one asymptomatic cases. Zinc was administered in doses of 120 to 272 mg/day, alone in 3 cases and combined with D-penicillamine in 2 cases. After 1 to 7 years of zinc therapy, our experience is consistent with data from recent literature and provides further evidence of zinc effectiveness. Zinc may be prescribed as first treatment in most patients, including asymptomatic cases. The only exception concerns patients with severe symptoms in whom it is recommended to combine zinc with D-penicillamine during the early phase of treatment for more rapid effectiveness. Because of its safety, zinc is particularly indicated in cases of intolerance to D-penicillamine and trien.

Effects of diabetes type and treatment on zinc status in diabetes mellitus.

Zinc status was assessed in 53 diabetic patients: 18 insulin-dependent diabetic patients (IDDM), 22 noninsulin-dependent diabetic patients (NIDDM) treated with oral antidiabetic agents, and 13 insulin-treated, noninsulin-dependent diabetic patients (IRDM). Plasma zinc concentrations were in the usual range for healthy subjects in these three groups (15.3 +/- 0.9 mumol/L). Urinary zinc excretions were elevated in the IDDM group (18.3 +/- 4.1 mumol/24 h; p less than 0.01 vs normal) and in the NIDDM group (17.5 +/- 3.5 mumol/24 h; p less than 0.01 vs normal), but normal in the IRDM group (11.3 +/- 2.4 mumol/24 h). In 14 NIDDM patients treated with transient continuous sc insulin injections, urinary zinc decreased from 16.5 +/- 2.2 mumol/24 h before insulin treatment to 11.5 +/- 0.3 mumol/24 h after insulin treatment without any modification in plasma zinc concentrations.

Aluminium bone deposits in normal renal function patients after long-term treatment by plasma exchange.

The accumulation of aluminium (Al) can cause Al bone deposits, osteomalacia and encephalopathy. As albumin solutions used as replacement fluid in plasma exchange (PE) are contaminated with Al, we studied Al overload in two symptomless patients with normal renal function, treated by long-term plasma exchange (PE). Total Al loading was calculated at 1750 mumol in patient 1 (178 PE sessions) and 2100 mumol in patient 2 (153 PE sessions). Bone biopsy showed Al deposits and low bone formation without osteomalacia in patient 1 and only osteoporosis in patient 2. Plasma Al levels were useless in detecting early Al overload, because the remained in the normal range, even after PE in both patients. Bone biopsy was the best means of recognizing Al intoxication, but cannot be recommended for frequent evaluations. However, the desferrioxamine mobilization test can be proposed as a repetitive non-invasive investigation method.

Determination of zinc in blood serum by electrothermal atomic absorption spectrometry with matrix modification.

Zinc determination in serum microsamples can be treated by graphite furnace atomic absorption spectrometry. To reduce the contamination risks and to obtain results as right as possible, the serum has been twenty fold diluted instead of 100-fold diluted (rate frequently obtained). In these conditions, the use as diluent of a 1% Triton X 100 solution or of a 33.7 mmol/l magnesium nitrate did not allow to obtain exact results. Yet, with an 37.8 mmol/l ammonium phosphate solution, the results given by the direct calibration on an aqueous calibration curve were in good accordance with those found with a recommended flame atomic absorption spectrometry method. The within-run RSD of our method was 2.6%.

[Desferrioxamine treatment of osteomalacia caused by aluminum poisoning]. / Traitement par la desferrioxamine de l'ostéomalacie par intoxication á l'aluminium.

Three haemodialyzed chronic renal failure patients with histologically proven osteomalacia due to aluminium toxicity were treated with repeated injections of desferrioxamine, a potent chelator of aluminium. The drug, in doses of 3 or 6 g, was administered intravenously once a week for 5 to 11 months, at the end of a dialysis session. Treatment was well tolerated. Dramatic clinical improvement was observed, with rapid regression of pain and functional impairment. There was a 65% increase in alkaline phosphatase and a rise of immunoreactive parathyroid hormone (terminal C fragment). Healing of fractures was confirmed by radiology, and a second bone biopsy in the 3 patients after double tetracycline labelling showed regression of morphological and dynamic signs of osteomalacia, considerable reduction in stainable aluminium deposits and strong increase in bone remodelling compatible with the development of hyperparathyroidism. It is concluded that a moderate dose of desferrioxamine administered once a week is effective against osteomalacia due to aluminium toxicity.

Serum aluminium concentration and aluminium deposits in bone in patients receiving haemodialysis.

Serum aluminium concentrations and biopsy specimens of bone were examined in 56 patients with end stage chronic renal failure receiving maintenance haemodialysis. Deposits of aluminium in bone specimens were often associated with low bone formation with or without osteomalacia. Serum aluminium concentrations of greater than 3.7 mumol/l (10 micrograms/100 ml) indicated a high probability of deposits of aluminium in bone specimens, although high serum concentrations did not predict the type of renal bone disease. Biopsy of the bone is the best method of detecting aluminium intoxication of bone. A serum aluminium concentration of 3.7 mumol/l should be the threshold beyond which bone biopsy should be performed to confirm an overload of aluminium and identify histological bone changes induced by aluminium.