Search PubMed⌕ Search

Biomedical subjects

B Kuklinski

Publications and source records attributed to B Kuklinski.

At least 19 recordsLinked to original sources

Body nitrosation potential measured by a novel 15N breath test.

Oxygenated nitrogen species, for example, the protonated form of nitrous acid (H2ONO+), dinitrogentrioxide (N2O3), dinitrogentetroxide (N2O4), or peroxynitrite (ONOO-), can react with amines to form molecular nitrogen. These reactions can occur spontaneously with primary aliphatic amines or via cytochrome P450 catalysed reactions with secondary amines. In principle measurements of the excretion of the molecular nitrogen generated by these reactions could be used as an index of the levels of oxygenated nitrogen compounds acting as nitrosating agents. To test this idea, [15N2]urea (3 mmol) was administered orally to five patients infected with Helicobacter pylori (as diagnosed by the [13C]urea breath test) and to four healthy volunteers. All participants ingested 3-mmol sodium nitrate as a precursor for NA 5 min before the ingestion of the nitrogen tracer. During the test the participants breathed 100% oxygen to increase the sensitivity of detection of endogenous molecular nitrogen. After the administration of [15N2]urea, the patients with H. pylori showed significantly increased 15N enrichments of exhaled N2, expressed as delta value (per 1000), compared with healthy volunteers (patients: 3.5 +/- 0.9 vs. volunteers: 1.3 +/- 0.4; p < .05). We speculate that the endogenous production of molecular nitrogen is a protective process controlling the body NO and nitrite levels. The 15N breath technique allows the noninvasive estimation of the body nitrosation and could indicate the health risk, possibly the oxidative stress status, caused by highly reactive oxygenated nitrogen species and carbenium ion intermediates.

Adult↗

Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: results of a placebo-controlled, double-blind study.

One hundred twenty-six patients with cirrhosis, hyperammonemia (>50 micromol/L), and chronic (persistent) hepatic encephalopathy (HE), which developed spontaneously without the existence of known precipitating factors, were enrolled in a randomized, double-blind, placebo-controlled clinical trial of intravenously administered L-ornithine-L-aspartate (OA). Patients with subclinical (grade 0, West-Haven criteria) hepatic encephalopathy (SHE), characterized by a prolonged number connection test A (NCT-A) time, and manifest HE (grades I and II, West-Haven criteria) were included in the investigation. The trial was planned as a confirmatory clinical trial OA administered in a dose of 20 g/d, as well as placebo, were dissolved in 250 mL of 5% fructose and infused intravenously for a period of 4 hours during 7 consecutive days with a superimposed protein load at the end of the daily treatment period. Primary variables were postprandial venous ammonia and NCT-A performance time measured following OA or placebo infusions to evaluate the net effect of the treatment on the prevention of the protein-induced hyperammonemia, and on parameters such as NCT-A influenced by hyperammonemia. Mental state gradation, portal systemic encephalopathy index (PSEI), and fasting ammonia levels were estimated as additional efficacy parameters. The data presented are based on the total study sample (intent-to-treat analysis), which included 63 patients in the placebo group and 63 patients in the OA group. Of the 126 patients, 114 met all the criteria for inclusion and completed the trial and treatment as outlined in the protocol (treated-per-protocol analysis). During baseline, the placebo and treatment groups were homogeneous with regard to mental states, NCT-A performance time, fasting venous blood ammonia levels, and Child-Pugh criteria. Although a slight improvement occurred in the placebo group, NCT-A performance times (P < .001) and postprandial venous ammonia concentrations in the OA-treated group showed improvements in comparison with placebo. In addition, venous fasting blood ammonia concentration (P < .01), mental state gradation (P < .001), and PSEI (P < .01), which includes the mental state gradation, NCT-A time, and postprandial venous ammonia in this trial, improved to a much higher degree in the OA group than in the placebo group. In subgroups retrospectively classified according to their initial mental state gradation, OA showed differential but uniformly significant efficacies in patients with manifest HE with respect to ammonia-lowering, improvement in NCT times, and mental state gradation. In patients with initial SHE, OA revealed differences between the medications in the psychometric test used. Adverse events consisting of mild gastrointestinal disturbances were observed in 3 of the OA-treated patients (5%). OA infusion appears to be a safe, effective treatment of chronic (persistent) manifest HE in cirrhotic patients. Additional investigations are required to assess the efficacy of OA in patients with SHE, as well as in patients with more severe grades of HE.

Adult↗

[Results of an open study for evaluating the effectiveness and tolerance of adjuvant administration of the ISF nutrient program in HIV positive patients].

HIV positive patients usually show a gradual deterioration of their general condition and the laboratory key values which are accompanied by the resulting negative effects on their subjective condition. This study showed a very good stabilization of HIV positive patients by using the complex ISF nutrient program over a period of ten or 15 months. Only a very low proportion of antiviral and antibiotic supply had been given. The ratio did not change over the entire testing period of 15 months. The mortality rates observed here were a fraction of the AIDS mortality rates that are otherwise published. The data of this study also show a very good benefit/risk relationship for the patients, which can be derived from the overall favorable statements on the tolerance.

Adolescent↗

[Decreasing mortality in acute pancreatitis with sodium selenite. Clinical results of 4 years antioxidant therapy].

UNLABELLED: Results obtained from pancreatitis research prove the genesis if free radicals in acute pancreatitis. Xenobiotics, ethanol as well as biliary diseases will induce a deficiency in antioxidants. In antioxidative treatment sodium selenite as a water soluble redox substance represented an alternative. In the middle of the year 1990 the therapy regime was introduced in Rostock, a short time later in Dresden too. The diagnosis was made by CT enhanced by a contrast medium as well as by clinical and paraclinical parameters. CT was repeated after a week. Up to May 31, 1994 there were 245 patients treated in Rostock and 85 patients in Dresden (n = 330). Immediately after making the diagnosis 200 micrograms were given as a bolus, 800 micrograms in the following 24 hours. From the second day on 500 micrograms of selenite were administered daily. In addition, infusions of carbohydrates, electrolytes (no calcium), fluid and analgetics were given. Lavation of the intestine was made three times daily. With a well-timed selenium therapy the rates of letality, complications and operation dropped drastically. In spite of a constant number of patients no patient has died in Rostock since 1993, in Dresden 8 of 85 patients came ad exitum. Complications occurred if the therapy began too late (if patients were administered too late) and in biliary forms. CONCLUSION: An improvement in the prognosis of acute pancreatitis can be achieved if antioxidative selenium therapy with sodium selenite is introduced in time. In rare cases total necroses and complications in organs only occurred in those patients who were admitted to this therapy too late.

Acute Disease↗

Coenzyme Q10 and antioxidants in acute myocardial infarction.

Sixty-one patients admitted with acute myocardial infarction, and a symptom's duration of less than 6 hr were randomized into two groups. Immediately after hospitalisation, members of the verum group (n = 32) received 500 mcg of selenium (as sodium selenite). Thereafter they received a daily dosage of 100 mg coenzyme Q10 (Bio-Quinone) and 100 mcg selenium (Bio-Selenium in the form of 1-seleno-methionine) for a period of one year. The control group (n = 29) were given matching placebo preparations. The groups were comparable as with respect to age, sex and medical treatment. Biochemical parameters showed a reduced concentration of CPK- and ASAT-level in the verum group during the acute phase (although not statistically significant). None of the patients in the verum group (i.e. on antioxidative treatment) showed prolongation of the frequency corrected QT-interval. In the control group, 40% revealed a prolongation of the QT-interval by more than 440 msec (p < 0.001). There were no significant differences, with respect to early complications. During the one-year follow-up period after myocardial infarction, six patients (20%) from the control group died from re-infarction whereas one patient from the verum group suffered a non-cardiac death.

Antioxidants↗

[The effect of low and high molecular weight dextrans on selected lipid parameters in serum. Part 3].

After a ten-day treatment of 21 patients with low molecular weight dextran (MW = 40,000), a decrease in the plasma concentrations of total cholesterol of 25%, LDL-cholesterol of 32% and apoprotein B of 22% was observed. The HDL fraction only showed a reduction of 10%. These dextran effects were dose-dependent. During the post-treatment period of 20 days a continuous increase in the lipid parameters to the preinfusion values was demonstrated. Dextran caused stronger lipid changes in HLP patients than in normolipaemics.

Apolipoprotein A-I↗

[Alcohol-induced toxic hepatitis--a "free radical" associated disease. Lowering fatality by adjuvant antioxidant therapy].

Toxic liver diseases coincide with oxidative stress correlating positively with the seriousness of the course of disease. For the purpose of elucidating the pathogenic significance of an increased radical generation. 56 patients suffering from acute alcohol-toxic hepatitis of the clinical grade of seriousness B and C according to Child/Pugh were classified randomly into antioxidant subgroups (n = 31) and control groups (= 25). The basis therapy being identical, the patients of the antioxidant group received additionally 600 mg of D-alpha tocopherol per day, 200 micrograms of selenium and 12 mg of zinc. Due to the supplementation of antioxidants there were quicker significant changes in the concentration of bilirubin, malondialdehyde and of ammonia in the serum. In comparison with the control group the length of stay in hospital could be reduced by 6 days. In the control group the mortality rates amounted to 40% (10 of 25), in the antioxidant group to 6.5% (2 of 31). The results confirm the pathogenic significance of oxidative stress in alcohol-toxic liver disease because a distinct improvement of prognosis could be achieved by using a low-cost adjuvant antioxidant supplementation.

Adult↗

[Diabetes mellitus--a free radical-associated disease. Results of adjuvant antioxidant supplementation].

Our investigations carried out in patients with diabetes mellitus revealed oxidative stress loads. The study presented here was to clarify whether a therapy with antioxidants can contribute to an improvement of prognosis. 80 patients affected with a long term diabetic late syndrome were randomised and arranged to 4 groups of n = 20 each. In contrast to a control group these patients received 600 mg of alpha lipoic acid or 100 micrograms of selenium (sodium selenite) daily or 1200 IE of D-alpha-tocopherol respectively for a time of 3 months. In comparison with the control group all groups treated in an antioxidative way showed significantly diminished serum concentrations of thiobarbituric acid reactive substances and of urinary albumin excretion rates. The symptoms of distal symmetric neuropathy measured according to the thermo- and vibration sensitivity also improved in a highly significant manner. The results prove that oxidative stress plays a promoting role in developing of long term diabetic late complications and that a therapy with adjuvant antioxidants may lead to a regression of diabetic late complications.

Adult↗

[Effect of low and high molecular weight dextrans on selected serum lipid parameters. 1].

Three male patients with hyperlipidaemia were given daily infusions of dextran over a period of 10 days. Plasma levels of total cholesterol, LDL and HDL cholesterol, apolipoprotein B and AI and triglycerides were analysed after the infusion of dextrans different in dose and molecular size. Dextrans caused alterations of some plasma lipids and lipoproteins exceeding the haemodilution effect. The degree of lipid lowering depends on the volume and molecular size of the administered dextran.

Adult↗

[The effect of low and high molecular weight dextrans on selected serum lipid parameters. 2].

The effect of dextran infusions on plasma levels of total cholesterol, LDL and HDL cholesterol, apolipoprotein B and AI and triglycerides is investigated within a patient group. Some plasma lipids and lipoproteins still remain significantly lowered after the end of the 10 days treatment period. Comparing the normolipidaemic with the hyperlipidaemic patients of type IIa and IIb the degree of alterations is different between these 3 groups.

Aged↗

[Protection from uv-light-induced oxidative stress by nutritional radical scavengers].

Two series of examinations were carried out in two voluntary test groups for the purpose of elucidating the correlation between ultraviolet light load and oxidative stress as well as the way it is influenced by nutritive radical scavengers. After a 6 to 7-hour impact of sunshine on the whole body (sunbathing beach) at n = 8 a continuous progredient increase of thiobarbituric acid reactive substances could be identified in the serum (from 5.56 +/- 0.98 to 8.91 +/- 0.99 mumol/l, p < 0.001), which after new exposure to sunshine reached 11.3 +/- 2.4 mumol/l. Likewise, a 15-minute exposure to ultraviolet light at n = 24 induced increases of TBRS concentrations lasting from 1-2 days. After 14-day supplementation with beta-carotene (n = 6), D-alpha-tocopherol (n = 6), selenium (n = 6), and ginkgo biloba extract (n = 6) the extent of the oxidative stress could be inhibited during a second exposure to ultraviolet light up to the following efficiency: Se > Ginkgo > beta-carotene > vitamin E. The clastogenous effect of sunshine and ultraviolet light must be regarded as a factor for initiating and promoting cancerogenesis in the total organism. Concerning the aetiopathogenesis of malignant melanoma the paramagnetic properties of free radicals with their nonenergetic effects of the magnetic field have to be considered more carefully in scientific examinations.

Adult↗

[Superoxide dismutase activity of Ginkgo biloba extract].

The Ginkgo biloba extract is obtained from green leaves of the Ginkgo biloba tree. Preparations with this active substance are among others used for the treatment of disturbances of the cerebral function and arteriosclerotic diseases. In in-vitro and in-vivo studies antagonistic effects of radical scavenger and PAF (platelet activating factor) were described. In this study a concentration-depending superoxide dismutase activity of the Ginkgo biloba extract rökan liquid could be made evident.

Diterpenes↗

[Anti-oxidative therapy of pancreatitis--an 18-month interim evaluation].

99 patients affected with acute pancreatitis of different genesis were treated in hospital (necrotizing n = 38, mild form n = 61) from May 1990 to November 1991. Nearly 80% of these illnesses were ethanol-induced, 12% were of biliary origin. 90 patients were submitted to an adjuvant antioxidant therapy with selenium and D-alpha-tocopherol (necrotizing form n = 29, mild form n = 61). The average lethality rate of 34% (1982-1989) fell to 1.1% (1 female patient with biliarily induced pancreatitis). No lethal courses were observed in alcohol-induced, idiopathic, post-traumatic, and post-operative forms. Clinical courses proceeded more easily under adjuvant antioxidant therapy, surgical treatment was not necessary. A treatment at reasonable costs can be made in all general internal wards.

Acute Disease↗

[Acute pancreatitis--a free radical disease. Decrease in fatality with sodium selenite (Na2SeO3) therapy].

Malonic dialdehyde as an indirect marker of the lipid peroxidation was found increased in the acute pancreatitis compared with persons of the same age and sex. Its concentrations inversely correlated to those of the serum calcium during the course of the disease and additionally they proved to be indicator of the prognosis. Postulating that the acute pancreatitis must be a "free radical disease", in a randomized clinical study the adjuvant therapy of the acute necrotizing pancreatitis (n = 8) with sodium selenite was carried out in a daily dose of 500 micrograms. The lethality of the control group was 89% (8 out of altogether 9 patients), no patient died in the therapy group. By the selenium therapy within 24 hours a normalization of the serum calcium and a decrease of the increased MDA-values could be achieved. It was concluded that by selenium increased activities of the phospholipid-hydroperoxide-glutathione peroxidase were induced, by means of which a peroxidation protection of membrane fatty acids, an inhibition of the activity of phospholipase A2 and an interruption of the arachidonic acid cascade must have been reached.

Acute Disease↗

[Tangier disease--a "free radical"-associated disease. Results of HDL and anti-oxidant therapy with selenium and D-alpha tocopherol].

In a 26-year-old patient there have been benign enlargements of the lymphatic nodes and a splenomegaly since the end of the adolescence. In the 21st year of age the diagnosis of a Tangier disease was made. Allogenic HDL-rich serum fraction (COHN IV/1-fraction, prepared according to the modified method 6) infused under therapeutic aspect led to a prolonged increase of the serum total cholesterol and of the thrombocytes. The results pled for an activation of the reverse cholesterol transport. Excessively high malonic dialdehyde concentrations in the serum were relating to a "free radical"-associated metabolic defect, which was caused by the hypocholesterolaemia, the reduced transport capacity of vitamin E in the plasma and the nutrition poor in selenium and cholesterol, respectively. Under a nutritive antioxidant supplementation with sodium selenite and D-alpha-tocopherol a slight increase of the total cholesterol, of the thrombocytes as well as a normalization of the MDA values could be reached. The chronic oxidative stress appeared in the patient in a distinct lipofuscinosis of the skin and formations of naevus-cell naevi as an expression of massive denaturations of protein-lipids. In the Tangier disease we must reckon with an increased mutagenic effect of free radicals with an additional DNS repair capacity as well as an increased sensitivity to radical-generating cancerogenic xenobiotics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Latent antioxidant deficiency in the East German population--causes and clinical significance. II].

The hitherto yielded results of the research groups for arteriosclerosis and trace elements of the Medical Clinic of Leipzig University were summarized and valuated. The most important results were than in 800 healthy persons of three counties of the GDR who were examined depending on sex and age a serum selenium deficiency with regional differences was stated and this deficiency could be increased by an antiatherogenic mode of nutrition (n = 94, p less than 0.001). A consecutive depletion of vitamin E out of normal values was to be explained as a reference of an insufficient status of antioxidants. Analyses on nearly 1,000 foodstuffs and sorts of coffee, tea, tobacco, alcohol, etc. showed as cause a high-degree depletion of vegetable foodstuffs in selenium. The established daily minimum uptake of selenium of 12 to 15 micrograms by cooked foods was covered by above all cholesterol-rich animal foodstuffs and was further lowered by their withdrawal. In a double blind study first results of a supplementation of sodium selenite referred to a favourable influence on the immune status. After explanation of the reasons which may lead to an additional insufficiency of antioxidants was postulated that the protection from activated oxygen species is indicated both for the primary prevention of autoimmunigenic, atherogenic and cancerogenic diseases and for the curative medicine by a supplementation of selenium.

Adult↗