Selenium and zinc in patients with acute and chronic uveitis.

Patients with chronic inflammation often show decreased serum levels of trace elements. This study aimed to investigate serum levels of selenium and zinc in patients with uveitis. Twenty-four patients (13 female, 11 male) with a mean age of 40.6 +/- 15.5 yr were included in this study. According to their underlying disease, they were divided into acute (n = 13) or chronic (n = 11) uveitis. Selenium and zinc determination was performed by atomic absorption spectroscopy in EDTA blood samples. Patients with acute or first-time uveitis showed selenium and zinc concentrations within the normal range. In contrast to this, patients with chronic recurrent uveitis tend to result in decreased selenium and zinc levels. Especially selenium showed a remarkable reduction in serum concentration below the normal range. Furthermore, there was a tendency to decreased trace element concentrations with increasing age. A sex dependency could not been found. Especially patients with chronic, recurring uveitis show remarkable decreased selenium concentration in the EDTA-blood. Further studies should investigate possible positive effects of therapeutic selenium and zinc supplementation in patients with chronic, recurrent uveitis.

Functional and morphological aspects of thallium-induced nephrotoxicity in rats.

Until now the effect of thallium (Tl) on renal function has not been investigated systematically. Therefore, the dose (5, 10, 15, 20 mg Tl2SO4/kg body wt., intraperitoneally) and time-dependence of renal damage was investigated in diuresis experiments on conscious rats. Morphology was evaluated after perfusion fixation in situ. Morphologic changes were localized in the thick ascending limb of the loop of Henle, mostly expressed at the 2nd day after Tl administration, which were completely normalized again at the 10th day. Other parameters such as Tl concentration, changes in water content and the activity of Na+/K(+)-ATPase as well as the diuretic effect of furosemide confirmed the Tl effect to be localized in the renal medulla. One single Tl administration is followed by a decrease in glomerular filtration rate (GFR) and urine volume and an increase of proteinuria. Electrolyte excretion was only slightly changed. All changes were reversible within the 10-day investigation period.

Kinetics of chromium(V) formation and reduction in fronds of the duckweed Spirodela polyrhiza--a low frequency EPR study.

The uptake of chromate by the duckweed Spirodela polyrhiza was investigated with atomic absorption spectroscopy and the reduction of Cr(VI) to Cr(V) was measured using low frequency EPR spectroscopy. The biphasic kinetics of the uptake was fitted to parameters of a proposed kinetic model. Another model was developed to simulate chromate reduction. The first step of chromate reduction was found to be much faster than the uptake of Cr(VI) from the free space. Most probably, this step occurs already in the cell wall or on the cell membrane surface. Further reduction of Cr(V) to Cr(III) was estimated to be slower. The disappearance of the Cr(V) signal, following transfer of the plants into a Cr-free solution, lasted several tens of hours; the kinetics was mono- or biexponential depending on the length of Cr loading. The rate constants for Cr reduction in living plants were determined for the first time.

Riboflavin can decrease the nephrotoxic effect of chromate in young and adult rats.

The influence of 5 mg vitamin B2/100 g b.wt. (B2, riboflavin) on the nephrotoxic effect of 1 or 2 mg Na2Cr2O7/100 g b.wt. (Cr) was investigated in 55- and 10-day-old rats, respectively. Nephrotoxic effect was evaluated by the determination of urinary volume and protein excretion as well as the concentration of blood urea nitrogen (BUN). The concomitant administration of Cr and B2 only in 55-day-old rats increased the nephrotoxicity shown by enhanced proteinuria and BUN. B2, administered 3 h after Cr, was able to diminish Cr nephrotoxicity significantly in 55- and 10-day-old rats. The effect of B2 on Cr nephrotoxicity could be interpreted not by the stimulatory effect of B2 on GSSG reductase, which was abolished by Cr; but by its antioxidant effect.

LLU-alpha, an endogenous metabolite of gamma-tocopherol, is more effective against metal nephrotoxicity in rats than gamma-tocopherol.

Antioxidants of the vitamin E family have protective effects against metal toxicity. We examined the protective effect of racemic LLU-alpha [2,7,8-trimethyl-2-(carboxyethyl)-6-hydroxychroman] a metabolite of gamma-tocopherol, in comparison to the effect of alpha- and gamma-tocopherol in rats treated with sodium dichromate (Cr) or thallium sulfate (Tl). We measured metal nephrotoxicity based on urinary protein excretion and discussed it with respect to the metal concentration in renal tissue. The ranking of antioxidant activity (iron stimulated lipid peroxidation, luminol and lucigenin amplified chemiluminescence) was determined in the following order: alpha-tocopherol

Zinc concentration in serum and leucocytes in chronic inflammatory diseases.

In connection with inflammatory diseases of various origins an increasing amount of research has been directed towards trace elements, in particular zinc. However, proving changes in the zinc concentration of organisms or single cells still encounters major methodological difficulties. This is also probably the reason why many of the research findings to be found in current publications still significantly differ from one another. The present study utilizes a novel leucocyte-preparation method, which proved to be very reliable as regards the constancy of measured values. Thus, results obtained in 1989 which show a significant decrease in leucocyte zinc concentrations of patients with Crohn's disease were confirmed (1) as well as extended to the clinical pictures of Colitis ulcerosa and chronic pancreatitis of ethylic origin by studying a group of patients. Significant changes in serum zinc levels could not be proved. There was also no correlation between the leucocyte zinc concentrations and the serum zinc concentrations, on the one hand and the clinical parameters C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), body weight, humeral muscle area as well as activity of the disease, on the other.

Determination of iron, copper, zinc, magnesium and selenium in plasma and erythrocytes in neurosurgical patients.

A direct method for determination of Fe, Cu, Zn, Mg and Se in erythrocytes was developed. The aim of the present study was to establish a method for examining perioperative levels of the above mentioned elements simultaneously in erythrocytes and plasma by atomic absorption spectrophotometry in 11 patients undergoing neurosurgery for acute spinal nerve compressions because of intervertebral disk prolapses. Reference values for erythrocytes were 11.49 +/- 3.48 mmol/mmol Hb; 0.82 +/- 0.087 mmol/mmol Hb; 9.01 +/- 2.20 mmol/mmol Hb; 0.104 +/- 0.032 mmol/mmol Hb; 0.07 +/- 0.050 mmol/mmol Hb for iron, copper, zinc, magnesium, and selenium, respectively. Postoperative erythrocyte concentrations did not differ significantly compared to those obtained preoperatively and remained within the reference ranges perioperatively. For plasma the following reference values were used: 19.0 +/- 8.0 mmol/l (Fe); 20.1 +/- 8.2 mmol/l (Cu); 15.4 +/- 4.6 mmol/l (Zn); 0.9 +/- 0.15 mmol/l (Mg); 1.02 +/- 0.3 mmol/l (Se). There was a significant decrease in the concentration of copper in plasma (13.41 +/- 3.46 mmol/l, p < 0.1) and zinc (10.73 +/- 2.73 mmol/l, p < 0.1) immediately postoperative, iron (10.56 +/- 3.91 mmol/l, p < 0.1) and zinc on day 1 (11.28 +/- 1.88 mmol/l, p < 0.10), and a significant postoperative increase of copper on day 5 (18.81 +/- 3.97 mmol/l, p < 0.1), postoperatively. The mean plasma concentrations of iron, copper, zinc magnesium and selenium remained within the reference ranges during the entire period.

Vitamin E and C in the prevention of metal nephrotoxicity in developing rats.

The protective effect of vitamin E and C on sodium chromate (Cr) and thallium (Tl) induced nephrotoxicity was tested in 10- and 55-day-old rats. The concentrations of Cr and Tl were determined in renal cortex and medulla by atomic absorption spectrometry. Urinary volume and protein excretion as well as blood urea nitrogen (BUN) concentration were determined as parameters of nephrotoxicity. Cr and Tl induced nephrotoxicity was significantly more expressed in adult than in young rats. In Cr and Tl nephrotoxicity the protective effect of vitamin E was evident in both age groups. Vitamin E decreased Tl concentration in renal tissue. Therefore its protective effect is not to be attributed to its known antioxidant effect but to lower Tl concentration in renal tissue. Vitamin C was protective in Cr and Tl induced nephrotoxicity in adult rats without influence on metal concentrations in renal tissue. The dose necessary for protection against toxic Cr action in adult rats was not tolerated by young rats. The combined administration of both vitamins abolished the protective effect against Cr nephrotoxicity of the administration of each vitamin alone in adult rats. When vitamin E and C were administered in Tl treated adult and young rats the protective effect was the same as after the administration of each vitamin alone. Possible mechanisms are discussed.

Increased content of zinc and iron in human cataractous lenses.

The purpose of the study was to examine the zinc and iron content of human lenses in different types of cataract and to investigate the possible influence of diabetes on the zinc and iron content of the lens. Iron and zinc of 57 human lenses (28 corticonuclear cataracts and 29 mature cataracts with a mean age of 70.6 +/- 16.1 and 74.7 +/- 11.1 yr, 41 nondiabetics and 16 diabetics) were determined by atomic absorption spectroscopy. The zinc content of human lenses was significantly increased in mature cataracts compared to corticonuclear cataracts (0.51 +/- 0.33 vs 0.32 +/- 0.20 micromol/g dry mass, p=0.012). The iron content of mature cataracts was also higher than in corticonuclear cataracts (0.11 +/- 0.09 vs 0.07 +/- 0.05 micromol/g dry mass, p=0.071). Furthermore, a significant increase of the lens zinc content could be observed with increasing lens coloration (light brown 0.33 +/- 0.17 vs dark brown 0.52 +/- 0.35 micromol/g dry mass, p=0.032). Diabetic patients seem to have both increased zinc and iron contents in the lens compared to nondiabetic subjects (zinc: 0.45 +/- 0.42 vs 0.40 +/- 0.22 micromol/g dry mass; iron: 0.12 +/- 0.10 vs 0.08 +/- 0.05 micromol/g dry mass). These data suggest a possible influence of the lens zinc and iron content on the development of lens opacification. Especially advanced forms of cataract and dark brown colored lenses show significantly increased zinc and iron content.

Sodium selenite therapy and thyroid-hormone status in cystic fibrosis and congenital hypothyroidism.

The effectiveness of a peroral sodium selenite therapy (115 micrograms Se/m2 BSA/d) administered to cystic fibrosis patients (n = 32) could after three months be identified in a significant serum selenium increase (0.69-->0.96 mumol/L), a significant malondialdehyde decrease (2.72-->1.64 mumol/L), as well as in a significant serum vitamin E increase (4.31-->5.72 micrograms/mL). Parallel to that, a serum T3 increase as well as a highly significant decrease in the serum T4/T3-ratio were found, too, which point to improved peripheral T4-->T3 conversion during selenium medication. Type-I-iodothyronine-5'-deiodinase has recently been identified as a specific selenoenzyme. In the case of congenital hypothyroidism (n = 37) application of sodium selenite in the above specified dosage yielded a mean serum selenium increase (0.87-->1.12 mumol/L), a not significant T3 increase (2.57-->2.61 nmol/L) as well as a not significant TSH decrease (5.34-->4.49 mIU/L) without an expected T4 decrease. With the serum lipids, however, a lowering of total cholesterol (4.85-->4.53 mmol/L) simultaneous with a mean increase in HDL-cholesterol (1.52-->1.66 mmol/L) as well as a decrease in LDL-cholesterol (2.93-->2.52) could be observed. We view the reduction of the atherogenic serum lipid constellation in the course of selenium medication as an expression of increased thyroid-hormone efficacy. Apart from an improvement of the antioxidant status a stimulation of thyroid-hormone efficacy owing to increased T4--T3 conversion is also noteworthy in sodium selenite medication.

Selenium in serum and whole blood in patients with surgical interventions.

Selenium values of serum and whole blood were determined for two groups of patients undergoing large surgical interventions (e.g., gastrectomy) and receiving a total parenteral nutrition (TPN). All patients showed low selenium values at the beginning of TPN. The first group received a supplementation of selenium, and it was established that selenium levels normalized after 6-7 d. The balances of selenium turned out to be positive in all cases. The second group, which was not administered selenium supplementation, showed significantly lower values of selenium. It can, therefore, be concluded that a substitution of selenium prior to large surgical interventions following TPN clearly helps patients combat the increase in the oxidant stress reactions.

[Pharmacokinetics and nephrotoxicity of aluminum in rats of various ages]. / Pharmakokinetik und Nephrotoxizität von Aluminium bei Ratten unterschiedlichen Alters.

Experiments were done in 5-, 10-, 20-, 33-, 55-, and 105-d-old rats to clarify whether or not age-dependent differences in pharmacokinetics and nephrotoxicity of Al exist. Using kidney function tests distinct signs of alumina (Al) nephrotoxicity can be demonstrated following 1 or 2 mg Al/100 g b. wt. i.p.: polyruria, reduced concentration of sodium in urine, elevated blood urea nitrogen concentrations. There is the same degree of nephrotoxicity both in adult and in young rats with an immature kidney function. Following administration of 2 mg Al/100 g b. wt. i. p. the initial plasma concentration of Al is distinctly lower in young than in adult rats. A rapid phase of elimination of Al from plasma (alpha-slope) is absent in 5-d-old rats and fully expressed in 33- and 55-d-old rats. In young rats the relative volume of distribution of Al is smaller than in adults. Following the administered dose nephrotoxicity in ducing concentrations of Al were obviously reached also in kidney tissue of young rats.

Effect of intravenous magnesium on ventricular tachyarrhythmias associated with acute myocardial infarction.

Ventricular ectopy and left ventricular dysfunction are important predictive factors for an unfavourable outcome following an acute myocardial infarction (MI). Tachyarrhythmias are a major cause of death subsequent to MI. Magnesium was postulated to have an antiarrhythmic effect after MI. Therefore we have investigated the influence of intravenous and oral magnesium (Mg) therapy on ventricular tachyarrhythmias. 67 patients with myocardial infarction (MI) diagnosed according to the WHO criteria of anamnesis, infarct-specific electrocardiogram (ECG), and enzymatic status were included in a prospective study. 23 patients (group 1) received 2 g Mg per day (= 82 mmol Mg/24 h) intravenously for the first 3 days followed by oral magnesium adipate administration of 3 x 2 coated tablets of magnesium 50 Apogepha (= 300 mg Mg/24 h or 12.34 mmol Mg/24 h, respectively) for the full duration of the study. 26 patients (group 2) received only i.v. magnesium for the first 3 days after admission (2 g Mg/24 h). The results of this treatment were compared to those of a control group of 18 MI patients without magnesium administration. All groups were identical with regard to other forms of treatment. The magnesium levels in serum and erythrocytes of all patients were measured at the following time points: days 0 (admission time), 1, 2, the day of discharge (about day 20) and after 12 weeks. The tachyarrhythmias were monitored by 24-h-continuous-electrocardiography on days 0, 1 and on the day before discharge (about day 20). The serum magnesium levels rose significantly during i.v. Mg-administration (1 and 2 day) but decreased in group 2 subsequently until the time of discharge from hospital. In contrast group 1 patients receiving oral as well as intravenous magnesium did not show this drop. The uptake of magnesium into the erythrocytes was less obvious. The erythrocyte magnesium concentration of the control group remained significantly low in serum and red blood cells. Significantly less ventricular premature beats and runs (< 5 ventricular premature beats and > 5 ventricular premature beats) compared to admission day were observed in both treated groups. These data suggest that the frequency of ventricular tachyarrhythmias is reduced by administration of intravenous magnesium and support an early high dose administration of intravenous magnesium in the wake of myocardial infarction.

[Selenium, antioxidant status and radical/reactive oxygen species in medicine]. / Selen, Antioxidanzienstatus und Radikale/reaktive Sauerstoffspezies in der Medizin.

BACKGROUND: In all organisms with a metabolism of oxygen, radicals/reactive oxygen species appear. Normally a balance exists between formation and destruction of radicals. Many diseases show a disturbance of this balance with the destruction of biological structures. Results in patients with sepsis, terminal renal failure, bone marrow transplantation and cancer are given. CONCLUSION: To avoid a possible pro-oxidative effect (vitamins C and E) and intoxications (selenium), before substitution a monitoring is necessary.

[Behavior of thiobarbituric acid reactive substances, alpha-tocopherol, glutathione and selenium during hypertension in pregnancy]. / Verhalten von thiobarbitursäurereaktiven Substanzen (TBARS), alpha-Tocopherol, Glutathion und Selen während der hypertensiven Erkrankung in der Schwangerschaft.

PATIENTS AND METHOD: In a longitudinal study the changes of serum or plasma levels of TBARS, alpha-tocopherol, glutathione and selenium were investigated comparing 46 pregnant women with hypertensive syndrome and 18 women with normal pregnancies. RESULTS AND CONCLUSIONS: A significant increase in TBARS serum level was found in women suffering from hypertension. There was no correlation between the severity of hypertension and the extent of the TBARS rise. An absolute deficiency of the antioxidants alpha-tocopherol, glutathione and the elements selenium, calcium, magnesium, iron and zinc as a cause or a consequence of hypertension in pregnancy could be excluded. Low serum levels of copper and selenium could decrease the activity of glutathione peroxidase (Gpx) resulting in higher levels of TBARS and glutathione during the last trimester of pregnancy and delivery. Increased concentrations of iron in women with hypertensive syndrome may affect the formation of lipid peroxides. The outcome of children was unaffected by increased lipid peroxide levels when an antihypertensive therapy was consequently performed.

[Effect of administration of selenium and vitamin E on heart failure and ventricular arrhythmias in patients with acute myocardial infarct]. / Einfluss der Substitution von Selen und Vitamin E auf Herzinsuffizienz und ventrikuläre Herzrhythmusstörungen bei Patienten mit akutem Myokardinfarkt.

PATIENTS AND METHOD: Patients with acute myocardial infarction were treated with selenium and vitamin E as antioxidants in addition to the standard therapy. They were compared to a reference group which received no additional therapy. It was to be investigated whether selenium and vitamin E are able to positively influence the course of the infarction, measured by way of the insufficiency symptoms, ventricular cardiac arrhythmia in long-term ECG and the ejection fraction determined by echocardiography. The concentrations of selenium, malonic dialdehyde (TBARS), glutathione peroxidase and vitamin E were measured at various points in time. RESULTS: During the course of the in-patient treatment, significant percentage increases in selenium, glutathione peroxidase and vitamin E were detected. Group differences were similarly significant. It was not possible to detect differences in the clinical parameters. Possible explanations to be discussed are the duration of the treatment, the times of the examinations and the different proportions of patients treated thrombolytically in the 2 groups.

[Selenium and antioxidant status in various diseases]. / Der Selen- und Antioxidanzienstatus bei verschiedenen Krankheitsbildern.

All healthy mammalian organisms are characterized by an equilibrium between the occurrence of highly reactive oxygen species and their destruction by anti-oxidants. Numerous diseases go hand in hand with a disturbance of the homoeostatis. In order to avoid or minimize the destructive effect of the oxidant stress on biological structures, therapies utilizing drugs with anti-oxidant effects are increasingly being applied. Preconditions for these therapies are a characterisation and a follow-up of the anti-oxidant status in the diseased organism. In the course of the present study selenium, glutathione peroxidase and malondialdehyde were determined in patients with various clinical pictures (terminal renal insufficiency, septic shock, high-risk gravidieties, arterioscleroisis, pulmonary carcinoma, acute myocardial infarction, test patients taking the contraceptive pill). Patients with terminal renal insufficiency and those suffering from septic shock syndromes clearly show a selenium decrease in serum and whole blood as well as a drop in the GSH-Px-activity, and increased malondialdehyde concentrations in the serum. Both are a reflection of an increased lipid peroxidation. First results of a selenium therapy are available for patients with therminal renal insufficiency and post-traumatically induced renal failure. The interpretation of the findings in the categories "high-risk gravidity" and "women on the contraceptive pill", which show a normal GSH-Px-activity and significantly increased malondialdehyde concentrations, seems problematic. The organism counteracts an increased lipid peroxidation with a normal plasma-GSH-Px-activity, clearly a sign of a still normal anti-oxidant potential.

[Levels of antioxidants after cesarean section and administration of Multibionta N, Inzolen and selenase]. / Das Verhalten von Antioxidanzien nach Schnittentbindung und Substitution von Multibionta N, Inzolen und selenase.

PATIENTS AND METHOD: In 29 women with the necessity to terminate pregnancy via Cesarean section, lipid peroxidation and antioxidative state were investigated before and 24 hours after the surgical intervention as well as after substitution of antioxidants and trace elements. RESULTS: The results indicate that administration of antioxidants protects at least partially from consequences of surgically induced oxidative burden.

[Sex hormones and antioxidant status]. / Sexualhormone und Antioxidanzienstatus.

Physiologically, an influence of sex steroids on the antioxidative capacity can be seen at least as a short-term effect. First of all the steroid effects are due to the estrogen component rather than the progestin component. The antioxidative potential of natural estrogens is several times higher than that of vitamin E. Long-term studies should be performed to verify this in perimenopausal hormone replacement.

[Blood selenium content after conditioning and during the course of bone marrow transplantation in children with malignant diseases]. / Blutselengehalte nach Konditionierung sowie im Verlauf der Knochenmarktransplantation bei Kindern mit malignen Erkrankungen.

PATIENTS AND RESULTS: Prior to bone marrow transplantation (BMT), at the end of the conditioning phase, we found in 42 investigated children with malignant diseases subnormal lowered plasma- and blood selenium levels. Parallel to the diminished selenium status the plasma glutathione peroxidase activity (Gpx) was not reduced as it is in selenium deficiency, but markedly elevated and probably reflecting cytolytic processes. In the group of combined conditioning (fractionated total body irradiation plus chemotherapy) we found significantly more elevated plasma Gpx values in comparison to the only-chemotherapy group. The renal selenium excretion was elevated during the whole observation and could be caused by disturbed tubular function. CONCLUSION: We conclude, that in the situation of BMT a selenium substitution in a dosage of at least 1 to 2 micrograms Se/kg/d is necessary. Patients' selenium status should be monitored by analyses of plasma- and blood selenium contents.