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G Khoschsorur

Publications and source records attributed to G Khoschsorur.

17 recordsLinked to original sources
PubMed1999

Low density lipoprotein immunoapheresis does not increase plasma lipid peroxidation products in vivo.

Extracorporeal elimination of low density lipoprotein (LDL) is frequently used in drug-resistant hypercholesterolemia. LDL-immunoapheresis selectively removes LDL and lipoprotein(a) [Lp(a)] from plasma. Lipid peroxidation is one unwanted side effect, that occurs during extracorporeal plasma treatment. The purpose of this study was to investigate the effect of LDL immunoapheresis on lipid peroxidation. Before and after a single LDL-immunoapheresis treatment, plasma concentrations of lipid hydroperoxides, determined with two different spectophotometric assays, thiobarbituric acid-reacting substances (TBARS), determined spectrophotometrically and malondialdehyde (MDA), determined by an MDA-TBA/HPLC method, were measured in 13 hypercholesterolemic patients. In addition MDA was also determined in the eluate of the apheresis column. Before treatment, plasma cholesterol and LDL cholesterol concentrations were significantly higher in patients than in healthy control subjects, as were the lipid peroxidation products. LDL-immunoapheresis treatment of the patients led to significant decreases in total cholesterol (69+/-8%), LDL-cholesterol (79+/-7%), HDL-cholesterol (35+/-17%), triglycerides (38+/-21%), apolipoprotein-B (77+/-6%), apolipoprotein-A1 (25+/-5%) and Lp(a) concentrations (76+/-10%). Changes in plasma lipid peroxide concentrations (17+/-8 nmol/l before vs. 14+/-5 nmol/l after treatment) were not significant, neither were those in TBARS (3. 0+/-2.6 micromol/l vs. 2.3+/-1.3 micromol/l) or MDA concentrations (1.03+/-0.17 micromol/l vs. 1.0+/-0.20 micromol/l). Patients with high baseline values showed a decrease, whereas others did not. MDA was present (0.57+/-0.13 micromol/l) in the eluate of the apheresis column, suggesting that, along with LDL, lipid peroxidation products are also removed. From these results we conclude that a single LDL-immunoapheresis treatment effectively reduces LDL and Lp(a) in the absence of increases in plasma lipid peroxidation products.

Adult↗
PubMed1999

Normothermic liver ischemia and antioxidant treatment during hepatic resections.

The purpose of our study was to evaluate the clinical impact of reperfusion injury after normothermic ischemia during major liver resections and the effect of an intraoperative antioxidant infusion. This prospective randomized study comprised 50 patients; half of them (treatment group) were given an antioxidant infusion containing tocopherol and ascorbate immediately prior to reperfusion onset. Venous blood samples for the determination of MDA-TBARS (malondialdehyde-thiobarbituric acid reactive substances) by a HPLC-based test as a marker of lipid peroxidation were taken prior to ischemia, 30 min after reperfusion onset and at the end of the operation. In the control group there was a significant increase of MDA-TBARS (p = 0.001) at 30 min after reperfusion onset. At the end of the operation the values had returned to the initial level. The treatment group showed only a marginal increase (p-value for the difference between the two groups: 0.007). After exclusion of the patients with histologically proven advanced cirrhosis the increase in the control group (p < 0.001) and the difference between the increase in the two groups (p = 0.001) became more significant. Prothrombin time was also significantly better in the treatment group (p = 0.003). Postoperative complications such as prolonged liver failure, bleeding disorders and infections were seen more often in the control group. In our study MDA-TBARS was increased after liver ischemia, but in patients with advanced cirrhosis the effect was smaller or even absent. This increase and possible clinical consequences of reperfusion injury could be reduced by intraoperative administration of an antioxidant infusion.

Antioxidants↗
PubMed1998

The determination of metabolite M17 and its meaning for immunosuppressive cyclosporin therapy.

Cyclosporin A (CyA) is intensively metabolized by the hepatic cytochrome p450 III monooxygenase A system in the human liver, the most important metabolites being M1, M17, and M21. Because CyA and its metabolites have nephrotoxic, hepatotoxic, and neurotoxic side effects, CyA dosage must be calculated to avoid the risk of organ rejection through underdosage and toxic organ damage through overdosage or accumulation of metabolites. In this study, we determined the whole-blood concentrations of cyclosporin and metabolite M17 by high-pressure liquid chromatography (HPLC) and by monoclonal specific and polyclonal nonspecific fluorescence polarization immunoassay (Abbott) in patients after immunosuppressive treatment. Patients with different resorption and metabolization rates showed high individual variations. CyA concentrations in patients with good liver function and low concentrations of CyA metabolites showed a good correlation between the HPLC and the FPIA (TDx-monoclonal assay) methods in ranges between 25 and 180 ng/mL. TDx-monoclonal was not always as precise as HPLC. In cases of metabolic disorders, we found false high CyA concentrations assayed with the immunologic method, caused by a crossreaction of the elevated metabolite concentration. We found that HPLC rendered more information about the extent of immunosuppressive activity and the metabolization rate and showed a good correlation with the concentration of metabolite M17 and total metabolites measured with the Abbott CyA polyclonal kit.

Antibodies↗
PubMed1997

Rapid, sensitive high-performance liquid chromatographic method for the determination of cyclosporin A and its metabolites M1, M17 and M21.

Cyclosporin A (CyA) and its metabolites seem to have nephro-, hepato- and neurotoxic side effects. Immunosuppressive therapy is a narrow path between the risk of rejection by underimmunosuppression and toxic organ damage by overdosage. Thus CyA dosage must be calculated to avoid the risks of organ rejection through underdosage and toxic organ damage through overdosage or accumulation of metabolites. In routine monitoring of CyA therapy, it can be important to measure not only the parent drug but also the metabolites. We describe a rapid and isocratic high-performance liquid chromatographic method for measurement of CyA and its metabolites M1, M17 and M21 in whole blood. CyA was detected by ultraviolet absorption at 212 nm with a CN analytical column maintained at 50 degrees C and recycling of hexane-isopropanol as mobile phase for improved long-term column stability and efficiency. The minimum detectable concentration of CyA and the three metabolites was 10 ng/ml blood. Our modified HPLC method for the determination of CyA and its metabolites is a simple (isocratic), rapid (the retention times were 7.1 min for CYD, internal standard, 8.9 min for CyA, 11.0 min for M21, 12.9 min for M17 and 16.3 min for M1) and economical method suitable for measuring the concentration of the major metabolite, M17, and for routine monitoring of CyA-treated patients.

Chromatography, High Pressure Liquid↗
PubMed1997

Plasma vitamin C concentrations in patients with cystic fibrosis: evidence of associations with lung inflammation.

Vitamin C status and possible associations with the disease process in cystic fibrosis (CF) patients were investigated. Plasma vitamin C concentrations in patients from two different mid-European populations (Swiss, n = 62; Austrian, n = 60) taking no or low-dose vitamin C from multivitamin supplements did not differ from each other or from control subjects (n = 34). Vitamin C concentrations decreased with age (5.05 mumol.L-1, y-1). When followed up for 12 mo, patients had the highest plasma vitamin C concentrations in February and the lowest in May and August (P < 0.01); the decrease in vitamin C was accompanied by increases in plasma malondialdehyde (P < 0.001) and tumor necrosis factor alpha concentrations (P < 0.01). During supplementation with vitamin E for 2 mo or beta-carotene for 12 mo vitamin C concentrations did not change. They correlated inversely with white blood cell count (r = -0.36, P = 0.008), bands (r = -0.36, P = 0.02), alpha 1-acid glycoprotein (r = -0.45, P = 0.002), interleukin 6 (r = -0.46, P = 0.0006), and neutrophil elastase/alpha 1-proteinase inhibitor complexes (r = -0.34, P = 0.02). In patients with vitamin C concentrations < 40 mumol/L, all indexes of inflammation were relatively high, whereas those with concentrations > 80 mumol/L (upper quartile of control subjects) showed clearly lower values. These results are consistent with the hypothesis that by scavenging oxygen free radicals vitamin C interacts with an inflammation-amplifying cycle of activation of alveolar macrophages and neutrophils, release of proinflammatory cytokines and oxygen free radicals, and inactivation of antiproteases.

Adolescent↗
PubMed1996

Neutrophil elastase/alpha 1-proteinase inhibitor complex levels decrease in plasma of cystic fibrosis patients during long-term oral beta-carotene supplementation.

Lung inflammation in cystic fibrosis (CF) is associated with an increased release from activated neutrophils of oxidants and proteinases. Free radical generation is not efficiently neutralized, and the major anti-proteinase, alpha 1-proteinase inhibitor (alpha 1-PI) is thought to be oxidatively inactivated. We hypothesized that enhanced antioxidant protection could represent an additional long-term strategy to attentuate the host inflammatory response. The effect on plasma neutrophil elastase/alpha 1-PI (NE/alpha 1-PI) complex levels (as a marker of lung inflammation) and plasma malondialdehyde concentrations (as a marker of lipid peroxidation) of additional oral beta-carotene supplementation was studied in 33 CF patients who had already received long-term vitamin E supplementation. In the presence of a more than 10-fold increase in plasma beta-carotene concentrations (mean +/- SEM) (0.09 +/- 0.01 to 1.07 +/- 0.19 mumol/L; p < 0.0001), a small increase in plasma alpha-tocopherol concentrations (23.8 +/- 1.31 to 28.4 +/- 1.81 mumol/L; p = 0.02), and a more than 50% decrease in plasma malondialdehyde concentrations (1.00 +/- 0.07 to 0.46 +/- 0.03 mumol/L; p < 0.0001), plasma NE/alpha 1-PI complex levels decreased from 102.2 +/- 16.0 to 83.0 +/- 10.4 micrograms/L; (p = 0.02). Plasma retinol concentrations increased (1.05 +/- 0.06 to 1.23 +/- 0.07 mumol/L; p = 0.0001) due to conversion of beta-carotene to retinol, which could have contributed to the decrease in NE/alpha 1-PI complex levels. Based on these results, we speculate that efficient antioxidant supplementation could attenuate lung inflammation in CF.

Administration, Oral↗
PubMed1995

Enhanced resistance to oxidation of low density lipoproteins and decreased lipid peroxide formation during beta-carotene supplementation in cystic fibrosis.

We investigated the effect of correcting beta-carotene deficiency in cystic fibrosis (CF) patients on two parameters of lipid peroxidation. The resistance to oxidation of low density lipoprotein (LDL) was measured by the lag time preceding the onset of conjugated diene formation during exposure to copper(II) ions, and lipid peroxide formation was quantitated by malondialdehyde concentrations in plasma (TBA/HPLC method). Simultaneously, alpha-tocopherol and beta-carotene concentrations were determined in LDL and in plasma. Thirty-four CF patients were investigated before and after 3 months of oral beta-carotene supplementation. Beta-carotene concentrations increased (p < 0.0001) in plasma (mean +/- SD) (0.09 +/- 0.06 vs. 1.07 +/- 0.86 mumol/l) and in LDL (0.02 +/- 0.02 vs. 0.31 +/- 0.28 mol/mol), without significant changes in alpha-tocopherol, either in plasma (24.7 +/- 5.9 vs. 25.4 +/- 7.6) or in LDL (8.47 +/- 2.95 vs. 9.05 +/- 4.13). Lag times, being shorter (p < 0.05) in patients than in controls, increased from 48.5 +/- 21.3 to 69.1 +/- 27.9 min (p < 0.001) and plasma MDA concentrations, being greater (p < 0.0001) in patients than in controls, decreased from 0.95 +/- 0.32 to 0.61 +/- 0.15 mumol/l (p < 0.0001). At 3 months, lag times and MDA concentrations did not any longer differ between patients and controls. These data suggest that excess lipid peroxidation occurring in beta-carotene deficiency can be limited and normalized during efficient beta-carotene supplementation in CF patients.

Carotenoids↗
PubMed1993

A multivitamin infusion prevents lipid peroxidation and improves transplantation performance.

The objective of this study was to test the hypothesis that ischemia reperfusion damage in kidney transplantation is associated with lipid peroxidation and that inhibition of lipid peroxidation by antioxidants improves the function of the transplanted kidney. Lipid peroxidation was assessed by measuring the plasma malonaldehyde content (as thiobarbituric acid reaction product) with high-performance liquid chromatography. Kidney function was assessed by plasma creatinine and creatinine clearance. Thirty patients of an ongoing series were randomly selected into two groups, with 14 controls and 16 patients in the antioxidant therapy group. Therapy consisted of two ampoules of Omnibionta (which contains vitamins C, E, A and B complex) diluted in 500 ml physiological sodium chloride, which was infused intravenously prior to reperfusion onset. No significant differences existed for the age of the patients in the control (43.00 +/- 9.86 years) and the therapy group (41.56 +/- 14.14 years) nor in the kidney preservation time, which was 24.12 +/- 8.73 and 18.43 +/- 9.97 hours in the control and therapy group, respectively. The controls showed a transient increase of plasma lipid peroxides as measured by malonaldehyde with a peak one hour after onset of reperfusion. Compared to the baseline value of 0.74 +/- 0.26 (mean +/- SD) the one hour malonaldehyde value increased to 1.46 +/- 0.22 nmol/ml (P < 0.001). In the therapy group the plasma malonaldehyde level did not increase, but slightly decreased by about 20% compared to the baseline value. The difference of plasma malonaldehyde between the two groups one hour after reperfusion onset was highly significant (P > 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Human plasma lipid peroxide levels show a strong transient increase after successful revascularization operations.

This study was performed to evaluate the hypothesis that oxygen radicals/lipid peroxidation are involved in reperfusion injury in humans. The study included 37 patients, who underwent surgical revascularization operations for kidney transplantation (9 subjects) or limb salvage (28 subjects). Peripheral venous blood samples were taken 30 min before starting reperfusion (baseline) and 1, 2, 3, 4, and occasionally 6 to 18 h after revascularization. The amount of plasma malonaldehyde formed in the reaction with thiobarbituric acid (MDA-TBA) was determined by high-performance liquid chromatography (HPLC). The baseline MDA-TBA values of the patients were very close to the value determined for 20 age-matched healthy subjects (i.e. mean +/- SD 0.689 +/- 0.294 nmol/mL plasma [range 0.2 to 1.37] vs. 0.700 +/- 0.209 nmol/mL plasma [range 0.385 to 1.29]). All patients responded to successful revascularization with significant increase of the plasma MDA-TBA within about 1 h after onset of reperfusion. Thereafter the values decreased nearly to the preoperative state. The mean increase of MDA-TBA was 107% in kidney transplantation and 54% in limb revascularization. In a few patients with severe arteriosclerosis, revascularization was not optimal and no increase in the MDA-TBA value occurred. The results of this study indicate that therapeutic intervention to prevent lipid-peroxidation-mediated reperfusion injury is confined to a rather narrow time window and must be undertaken either prior to or immediately after revascularization.

Aged↗
PubMed1982

[Correlation between protein thiols and the doubling time of various rat hepatomas].

The SH content of the soluble proteins (nanomol./mg protein) from five transplantable rat hepatomas and from the DENA-hepatoma were determined with dithionitrobenzoate (Ellman reagent). Both the total number of thiols as well as the number of SH groups that can be blocked by hydroxypentenal (HPE) increase with increasing growth rate of the tumors. In comparison with the protein thiol content of the slowest growing DENA-hepatoma (doubling time 100 days), the total protein thiols of the fastest growing Yoshida hepatoma (doubling time 2,5 days) increase by 100% and the HPE-sensitive protein thiols by 350%. The total protein thiols are significantly correlated with the growth rate (probability of error 5%), the HPE-sensitive thiols are correlated with high significance (probability of error less than 1%). These results are in accordance with the "Molecular Correlation Concept" of G. Weber and might possibly be understood as a consequence of reprogramming of gene expressions.

Animals↗
PubMed1981

Quantitative cytospectrophotometrical determination of the total protein thiols with "mercurochrom": optimization and calibration of the histochemical reaction.

Mercurochrom (2,7-dibromo-4-(hydroxymercuri)-fluoresceine-disodium salt) reacts histochemically not only with protein-SH-groups, but is also bound unspecifically to cellular proteins. The amount of the unspecifically staining approximately equals the specific SH-staining. Two methods are described to remove the unspecifically bound Mercurochrom, without influencing the specific reaction with the protein thiols. The first applies 0,1 m thioglycolate pH 4.0 (MT4-method), the other a special tris-cyanide-buffer pH 7.4 (MCN)-method). Aliquots from preparations of rat hepatocytes, Yoshida ascites tumor cells, Ehrlich ascites tumor cells, isolated nuclei of Ehrlich-cells and chicken thymocytes were investigated as well for the protein thiol content of the cells macroscopically with DTNB as microspectrophotometrically for the extinctions of the cells after staining with MT4- or MCN-method. A strong correlation was found between the macroscopically determined total-protein-SH-contents and the microphotometrically determined mean-total-extinctions of the cells. Additionally the molar absorptivities determined macroscopically by Schauenstein and Scheuringer (1980) coincide excellently with the values found microspectrometrically on MT4- and MCN-stained cells.

Animals↗
PubMed1981

Quantitative microspectrometrical determination of the total protein and total protein-SH content of the nuclei of Ehrlich ascites tumor cells without prior isolation.

The total protein and total protein-SH content of both the cytoplasmic fraction and the nuclei of Ehrlich ascites tumor cells (EATC) were determined macroscopically and microspectrometrically. The separation into cytoplasmic and nuclear fraction was performed by a modification of the method of Mamaril et al. [4]. The macroscopical determination of the total protein and the total protein-SH content were performed with the Folin method of Lowry et al. [2] and the DTNB method of Ellman [1], respectively. The quantitative microspectrometrical determinations of total protein content and of total protein-SH content were performed using the tetrazonium staining method of Nöhammer [5] and Nöhammer et al. [6] and the mercurochromcyanide (MCN) method of Nöhammer et al. [7], respectively. Within the intact cells, fixed and stained histochemically, the total protein and the total protein-SH content of the nuclei were determined microspectrometrically. The so called "nuclear extinctions", measured as the sum of the extinctions of the nucleus and of the parts of the cytoplasm above and below the nucleus, were calculated into the true nuclear extinctions, which then show a good correspondence to the values measured both microspectrometrically and macroscopically on isolated nuclei. The calculation for the true nuclear extinctions is based on a special preparation of spherically shaped cells and nuclei.

Animals↗
PubMedDate not supplied

Antioxidative vitamin treatment: effect on lipid peroxidation and limb swelling after revascularization operations.

The objective of this study was to evaluate the antioxidative properties of the multivitamin cocktail Omnibionta (alpha-tocopherol, ascorbic acid, retinol, vitamin B complex) in terms of diminishing lipid peroxidation with improvement of leg edema performance after limb revascularization operations in humans. Fifty-one subjects were selected; the control group contained 27 patients and the treatment group 24 patients, who received the vitamin cocktail intravenously before the start of reperfusion. All patients suffered from acute or chronic arterial occlusive disease, except two subjects with arterial trauma. MDA-TBARS in plasma, quantified by HPLC, taken as a measure of lipid peroxidation was significantly increased (p < 0.001) in the control group 1 hour after reperfusion onset and decreased to its baseline value within the following 2 hours (0.73 +/- 0.26, 1.21 +/- 0.48, 0.99 +/- 0.48, 0.73 +/- 0.33 nmol/ml). In contrast, in the treatment group MDA-TBARS did not exceed the baseline value during the reperfusion period (0.93 +/- 0.30, 0.70 +/- 0.29, 0.65 +/- 0.23, 0.70 +/- 0.37 nmol/ml). Leg edema, expressed by extremity circumference, was significantly (p < 0.008) elevated in the control group (30.7 +/- 4.04 cm versus 35.35 +/- 4.12 cm) compared to a lack of increase in the treatment group (29.25 +/- 5.13 cm versus 29.76 +/- 5.70 cm). These results suggest that antioxidative vitamin treatment might be valuable in preventing lipid peroxidation and decreasing extremity edema.

Adult↗
PubMedDate not supplied

[Intracellular effect of hydroxyalkenals on animal tumors (author's transl)].

When incubated for 30 min in vitro, 4-hydroxyalkenals in a 5 x 10-3 M solution react with SH-groups of soluble cytoplasmic and nuclear proteins (ProtL-SH) of Morris hepatomas 9618 A and 5123 tc, and of Ehrlich ascites tumor (EAT) cells. The extent of the reaction strongly increases with decreasing doubling time of the respective tumors. Former experiments with EAT cells have shown that the reaction with cytoplasmic ProtL-SH causes inhibition of respiration, glycolysis, and probably of other SH-controlled processes associated with cell division. The intranuclear reaction leads to an inhibition of DNA- and RNA-synthesis. In a 2 x 10-4 M solution of hydroxyalkenals, however, the reaction with cytoplasmic ProtL-SH diminishes almost completely so that no measurable inhibition of respiration and only 3% inhibition of glycolysis are observed, while 20 to 30 percent of the nuclear ProtL-SH are still blocked. This corresponds well with a previous observation that a 2 x 10-4 M solution of hydroxypentenal inhibits DNA-synthesis by 90 percent.

Aldehydes↗