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Biomedical subjects

K Winnefeld

Publications and source records attributed to K Winnefeld.

At least 19 recordsLinked to original sources

[Selenium, antioxidant status and radical/reactive oxygen species in medicine].

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.

Antioxidants

[Selenium substitution in acute myocardial infarct].

BACKGROUND: Previous examinations have demonstrated decreased selenium levels in serum and full blood in patients with myocardial infarction. PATIENTS AND METHOD: 28 patients received a selenium treatment additional to the usual treatment of myocardial infarction. 19 patients with myocardial infarction with no supplementary selenium treatment served as a control group. Selenium levels in serum, full blood and urine were measured and the complications of the myocardial infarction documanted. RESULTS: There was a significant increase of serum and full blood selenium and glutathione peroxidase levels under i.v. selenium therapy in the acute phase of myocardial infarction (first to third day). Left heart failure more rarely occurred in the selenium group (20%) than in control patients (57%). Acute tachycardial cardiac rhythm disturbances such as ventricular extrasystoles and couplets diminished in both groups; ventricular extrasystoles decreased in the selenium group. CONCLUSIONS: Selen should be substituted in patients with acute myocardial infarction and decreased selen levels. It would be useful to carry out a prospective double-blind study.

Administration, Oral

[Selenium in phenylketonuria patients. Effects of sodium selenite administration].

PATIENTS AND METHOD: 17 patients (8 female, 9 male; age 8.2 +/- 3.7 years) with phenylketonuria under phenylalanin restricted diet were investigated prior to and after 3 months of selenium substitution (sodium selenite, 115 micrograms Se/m2 BSA/d). Different parameters in blood were determined: selenium, glutathione peroxidase (Gpx) activity, thyroid hormones, blood cell count, lymphocytic antigen expression, muscle function and -enzymes, cardiac ultrasound. RESULTS: The main significant results of selenium substitution are: increased plasma-selenium, blood cell selenium, plasma-Gpx activity and left ventricular cardiac index as well as decreased plasma thyroxin, free thyroxin, reverse triiodthyronin, total cholesterol, mean erythrocyte and thrombocyte volume and lymphocytic CD2 expression. CONCLUSION: The data indicate metabolic and functional signs of selenium deficiency in patients with phenylketonuria without selenium substitution. We conclude that, despite of lacking clinical symptoms, a selenium supply in phenylketonuria patients under diet is necessary and should be performed with usefull peroral sodium selenite (115 micrograms Se/m2 BSA/d) initially, followed by a dosage between 30 and 60 micrograms Se/m2 BSA/d).

Antioxidants

[Sex hormones and antioxidant status].

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.

Adult

[Behavior of thiobarbituric acid reactive substances, alpha-tocopherol, glutathione and selenium during hypertension in pregnancy].

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.

Female

[Levels of antioxidants after cesarean section and administration of Multibionta N, Inzolen and 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.

Antioxidants

[Blood selenium content after conditioning and during the course of bone marrow transplantation in children with malignant diseases].

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.

Adolescent

Protective effects of vitamin E and C on cisplatin nephrotoxicity in developing rats.

The kinetics of vitamin E was followed in serum, liver and kidney of 10- and 55-day-old rats after the administration of a single i.m. dose of 100 mg alpha-tocopherol acetate/100 g body wt. The basal levels without vitamin E administration were significantly higher in serum and liver of 10- than 55-day-old rats. The effect of vitamin E on cisplatin (CP; 0.6 mg/100 g body wt., i.p.) nephrotoxicity was investigated by determining urinary volume and protein excretion, as well as the concentration of blood urea nitrogen (BUN) and lipid peroxides in renal tissue (LPO). Previously described age differences in CP nephrotoxicity were confirmed. The administration of vitamin E, 12 h prior to CP, diminished the toxic effect of CP in young and adult rats. This effect could not be enhanced by a second administration of vitamin E. The simultaneous administration of vitamin E and C 12 h prior to CP intensified the protective effect of a single administration of vitamin E in 10- and 55-day-old rats without influencing the concentration of platinum in renal tissue.

Aging

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.

Age Factors

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.

Animals

[The value of selenotherapy in patients with mucoviscidosis].

In cystic fibrosis (CF) patients the antioxidative-oxidative balance is chronically disturbed. Free radicals were generated by bronchial-pulmonal infection and additional exist a deficiency of antioxidative substances by enteral malabsorption especially vitamin E and selenium. Because selenium is an essential content of glutathione peroxidase, which is acting in cytosol and cell membranes, for the present we tested a selenium therapy (peroral sodium selenite 155 micrograms (Se/m2 BSA/d i. e. 4 micrograms Se/kg/d; 4 fold of recommended supply) in 32 CF patients. After three months of this therapy we have seen positive metabolic (normalized content of plasma-selenium, -glutathione peroxidase), endocrine (enhanced efficacy of thyroid hormones, mild increased IgF-I reduced LDL-chol) and clinical consequences (enhanced left ventricular cardiac output), but in three patients side effects (anorexia, nausea, mild hair loss) were observed. Longtime sodium selenite therapy only with 60 micrograms Se/m2 BSA/d over 1 year, stabilized the favourable influences without side effects. For CF patients therefore we recommend a sodium selenite substitution therapy, the best in combination with vitamin E.

Administration, Oral

[Selenium level in patients with acute myocardial infarct and in patients with severe angina pectoris without myocardial infarct].

Selenium in serum and whole blood was determined in patients (n = 88) with acute cardiac infarction, in patients (n = 62) with severe clinical symptoms and signs of angina pectoris excluding cardiac infarction, and a control group (n = 62). The average selenium concentration of the 62 patients in the control group was 1.00 +/- 0.17 mumol/l in the blood. The serum selenium concentration of the patients with cardiac infarction was significantly decreased as compared with the control group both on the first and tenth day (alpha = 1%) as well as after three months (alpha = 5%). On the twentieth day as well as six and twelve months after cardiac infarction no significant difference could be established. At all times after cardiac infarction, the blood showed a clearly decreased selenium concentration as compared with the control group. The difference was highly significant (alpha = 0.1%) on the first, tenth and twentieth day as well as after three and six months, and it was significant (alpha = 1%) after twelve months. On the first day, the average selenium concentration in the serum of the 62 patients with a severe attack of angina pectoris excluding acute cardiac infarction was 0.88 +/- 0.18 mumol/l and thus highly significantly below the values for the control group (alpha = 0.1%). The decrease on the tenth day (0.93 +/- 0.19 mumol/l) turned out not to be significant. The blood selenium concentration was highly significantly decreased on the first and tenth day (alpha = 0.1%). It was measured to be 1.12 +/- 0.19 mumol/l and 1.10 +/- 0.20 mumol/l respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris

[Selenium and antioxidant status in various diseases].

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.

Acute Kidney Injury

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.

Aged

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.

Adult

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.

Adolescent

The ambiguous effect of ascorbic acid on chromate induced proteinuria in rats.

The influence of ascorbic acid (AA, 5 g/kg body weight) on chromate (Cr, 10 mg/kg) induced proteinuria, which is a sensitive parameter of its nephrotoxicity, was investigated in adult female Wistar rats. The concentrations of Cr and ascorbic acid (AA) were determined in renal tissue. Cr nephrotoxicity is related to its intracellular reduction from Cr(VI) to Cr(III). Proteinuria was completely prevented by enhancement of extracellular reduction of Cr(VI) to Cr(III) followed by rapid renal excretion when Cr and AA were given concomitantly. With an interval up to 1 h between Cr and AA, proteinuria was decreased probably by the radical scavenging function of AA. At an interval of 3 h AA enhanced Cr toxicity by increased intracellular Cr reduction. If the interval was increased to 5 h or if Cr was given 24 h after AA, no influence of AA could be detected. Our results confirm that AA is a very effective reductant of Cr which can influence Cr nephrotoxicity in very high concentrations. It depends on the interval between Cr and AA administration whether or not there is a beneficial effect of AA in Cr nephrotoxicity.

Animals