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Biomedical subjects

E Karg

Publications and source records attributed to E Karg.

At least 37 records · Page 2Linked to original sources
PubMed1999

Glutathione status in retinopathy of prematurity.

This study examines the glutathione status of red blood cells in patients with retinopathy of prematurity (ROP) both in vivo and after an in vitro oxidative challenge. Fifty ROP patients of different ages (between 6 weeks and 6 years), born prematurely (gestational age: 28.7 +/- 1.3 weeks; birth weight: 1210 +/- 313 g; mean +/- SD) suffering either from active ROP (<3 months old; n = 12) or from a visual handicap due to preceding ROP (3 months-6 years; n = 38) as well as control patients of similar age and maturity (n = 56) were included. Infants with active disease have the lowest levels of reduced glutathione (GSH), the highest levels of oxidized form (GSSG), the highest GSSG/GSH ratios and the greatest fall in GSH after an in vitro oxidative challenge. After an in vitro oxidative stress, defective glutathione recycling was found in patients with preceding ROP and was suggested as a factor predisposing to oxidative hemolysis. The glutathione redox ratio was warranted as a biochemical screen for active ROP in premature infants.

Child↗
PubMed1999

Health effects of sulfur-related environmental air pollution. I. Executive summary.

The motivation of simulating real-world environmental exposure in a number of long-term studies with dogs was to address the question of whether or not perpetual inhalation of air pollutants can initiate diseases in healthy lungs and can thus contribute to the increasing prevalence of respiratory diseases in industrialized countries. The major conclusion of this article is that this question has to be answered in the negative for the simultaneous inhalation of the major constituents of combustion-related air pollution, particle-associated sulfur(IV), and particle-associated hydrogen ions. Over 13 mo, 8 healthy beagle dogs were exposed in 2 whole-body chambers daily for 16.5 h to 1 microm neutral sulfite [sulfur(IV)] particles at a mass concentration of 1.5 mg m-3 and for 6 h to 1.1 microm acidic sulfate particles carrying 15 micromol m-3 hydrogen ions into the canine lungs. This longitudinal study was characterized by repeated observations of individual respiratory response patterns. To establish baseline data the dogs were repeatedly examined preexposure while the chambers were ventilated over 16 mo with clean air. Each individual served thus as its own control. Another eight dogs served as additional controls. They were housed in 2 chambers ventilated with clean air over the entire study period of 29 mo. To assess response patterns, respiratory lung function tests were performed pre- and postexposure, segmental lung lavages were repeatedly performed to obtain epithelial lining fluid from the lungs for analysis of cell content, cell function, and biochemical indicators of lung injury, and radiolabeled test particles were used to study pathways of intrapulmonary particle elimination. At the end of the study, the lungs of all animals were morphologically and morphometrically examined. Functional and structural responses were finally compared to those observed previously as a result of a sole exposure of canine lungs to neutral sulfite particles over 10 mo (Heyder et al., 1992). Interactions between responses induced by neutral sulfite and acidic sulfate particles occurred, but antagonism rather than synergism was observed. The responses induced by sulfur(IV) were less pronounced, not detectable, or even reversed when hydrogen ions were also delivered to the lungs. On the other hand, responses not induced by the sole exposure to sulfur(IV) were observed: The activity of alkaline phosphatase was elevated and type II pneumocytes proliferated. It can, however, be concluded that long-term exposure of healthy lungs to particle-associated neutral sulfur(IV) and hydrogen ions at concentration close to ambient levels causes subtle respiratory responses but does not initiate pathological processes in the lungs. In other words, the perpetual inhalation of sulfur(IV) and hydrogen ions from the atmospheric environment presents no health risk to the healthy lungs. It is thus also very unlikely that respiratory diseases can be initiated by the inhalation of these pollutants.

Air Pollutants, Occupational↗
PubMed1999

Health effects of sulfur-related environmental air pollution. II. Cellular and molecular parameters of injury.

Recently, concern has been raised about effects related to environmental sulfur and/or acidic aerosols. To assess long-term effects on nonrespiratory lung function, 8 beagle dogs were exposed over a period of 13 mo for 16.5 h/day to a neutral sulfite aerosol at a sulfur(IV) concentration of 0.32 mg m(-3) and for 6 h/day to an acidic sulfate aerosol providing a hydrogen concentration of 15.2 micromol m(-3) for inhalation. Prior to exposure the dogs were kept under clean air conditions for 16 mo to establish physiological baseline values for each animal. A second group of eight dogs (control) was kept for the entire study under clean air conditions. No clinical symptoms were identified that could be related to the combined exposure. Biochemical and cellular parameters were analyzed in sequential bronchoalveolar lavage (BAL) fluids. The permeability of the alveolo-capillary membrane and diethylenetriaminepentaacetic acid (DTPA) clearance was not affected. Similarly, oxidant burden of the epithelial lining fluid evaluated by levels of oxidation products in the BAL fluid protein fraction remained unchanged. Both the lysosomal enzyme beta-N-acetylglucosaminidase and the alpha-1-AT were increased (p <.05). In contrast, the cytoplasmic marker lactate dehydrogenase remained unchanged, indicating the absence of severe damages to epithelial cells or phagocytes. Various surfactant functions were not altered during exposure. Three animals showed elevated levels of the type II cell-associated alkaline phosphatase (AP), indicating a nonuniform response of type II cells. Significant correlations were found between AP and total BAL protein, but not between AP and lactate dehydrogenase, suggesting proliferation of alveolar type II cells. Absolute and relative cell counts in the BAL fluid were not influenced by exposure. Alveolar macrophages showed no alterations with regard to their respiratory burst upon stimulation with opsonized zymosan. The percentage of alveolar macrophages capable of phagocytozing latex particles was significantly decreased (p<.05), while the phagocytosis index was not altered. In view of the results of this and previous studies, we conclude that there is no synergism of effects of these two air pollutants on nonrespiratory lung functions. It is hypothesized that antagonistic effects of these air pollutants on phospholipase A2-dependent pathways account for compensatory physiological mechanisms. The results emphasize the complexity of health effects on lung functions in response to the complex mixture of air pollutants and disclose the precariousness in the risk assessment of air pollutants for humans.

Aerosols↗
PubMed1999

Health effects of sulfur-related environmental air pollution. IV. Respiratory lung function.

Recently concern has been raised about health effects related to environmental sulfur and/or acidic aerosols. To assess long-term effects on respiratory lung function, 8 beagle dogs were exposed over a period of 13 mo for 16.5 h/day to 1-microm neutral sulfite aerosol with a particle-associated sulfur(IV) concentration of 0.32 mg m(-3) and for 6 h/day to 1.1-microm acidic sulfate aerosol providing an hydrogen ion concentration of 15.2 micromol m(-3) for inhalation. Prior to exposure the dogs were kept under clean air conditions for 16 mo to establish physiological baseline values for each dog. A second group of eight dogs (control) was kept for the entire study under clean air conditions. Before and at the end of exposure, respiratory lung function was evaluated in both groups in anesthetized and mechanically ventilated animals. Lung volumes as well as static and dynamic lung compliances were measured. Series dead-space volumes and slopes of the alveolar plateau for respiratory (O2, CO2) and inert test gases (He, SF6) were determined from single-breath washout tracings. Monodisperse 0.9-microm DEHS droplets were used to assess convective mixing in the lungs and to evaluate airway dimensions in vivo. Gas exchange across the alveolar-capillary layer was characterized by membrane diffusing capacity for carbon monoxide and alveolar-arterial pressure differences for respiratory gases. A bronchial challenge with carbachol was used to assess airway responsiveness. In comparison to the control group, dogs exposed to sulfur(IV) and acidic aerosol exhibited no significant changes in any respiratory lung function parameter. Also the responsiveness of the bronchial airways to carbachol was not affected. In view of the results obtained in this and previous studies, we conclude that anticipated synergistic effects of the two air pollutants on pulmonary lung function were not observed. It is hypothesized that antagonistic effects of the air pollutants on the activity of phospholipase A2 play an important role and account for counteracting physiological compensatory mechanisms. The results emphasize the complexity of health effects on lung function in response to the complex mixtures of ambient air pollutants and witness the precariousness in the risk assessment of air pollutants for humans.

Aerosols↗
PubMed1999

Health effects of sulfur-related environmental air pollution. V. Lung structure.

The lungs of 8 male beagle dogs were examined morphologically and morphometrically after exposure for 13 mo to a respirable sulfur(IV) aerosol at a mass concentration of 1.53 mg m(-3) (16.5 h/day), and to an acidic sulfate aerosol carrying 15.2 micromol m(-3) hydrogen ions into the lungs (6 h/day). An additional eight dogs served as unexposed controls. Standard morphometric analyses of both the surface epithelia of the conducting airways and the alveolar region were performed. These analyses showed no difference between the exposure group and control group. However, there was a tendency to an increase in the volume density of bronchial glands in the exposure group. Five of eight exposed animals showed thickened ridges (knob-like structures) at the entrance to alveoli in the alveolar duct and alveolar sac. Transmission electron microscopy revealed that the thickening was mainly due to type II cell proliferation. As the previous experiment using sulfite aerosol only showed no alterations in the proximal alveolar regions, the changes observed may be considered as effects of acidic sulfate aerosol alone or in combination with sulfite. These findings suggest that sulfur aerosols have the potential to induce epithelial alterations in the proximal alveolar region, which is a primary target for air pollutants.

Aerosols↗
PubMed1998

[Glycolytic enzyme defects and neurodegeneration].

This study was devoted to the continued search for an explanation of the neurodegeneration found in a severely TPI deficient Hungarian patient whose brother with genomically completely identical TPI defect was completely free of neurological disorders. The changes found in the molecular species composition of the major PL subclasses and the decrease in PE plasmalogens explain the earlier round increase in membrane fluidity interfering thereby with the physiological function of membrane enzymes, receptors, signal transduction, protein-protein interactions and vesicle fusion. Plasmalogens have also the capacity to protect against oxidative stress, that is deemed to contribute to neurodegenerative processes. The presence of chronic oxidative stress was well reflected in the decreased levels of GSH and alpha-tocopherol in the affected brothers. Decrease in plasmalogens have been described recently in Zellweger's syndrome, in other peroxisomal neurodegenerative disorders, in demyelinating processes and in Alzheimer's disease. The brain in normal individuals is highly enriched in plasmalogens. The pathological decrease found in TPI deficient lymphocytes will presumably be more pronounced in excitatory tissues. The recently described role of expanding nucleotide triplets in the development of neurodegeneration is suggested to result through the selective binding via their polyglutamine repeats to GAPDH. The role of GAPDH in TPI deficiency may be of crucial help in the elucidation of the development of neurodegeneration, since the enzymatic defect of TPI can be partially bypassed by means of the HMP shunt which generates GAP via GAPDH without the participation of TPI. Considering the results found in TPI deficiency in comparison to the new literary findings in different neurodegenerative diseases the following pathomechanism may be proposed. The protein products of the defective genes due to their abnormal steric structure bind GAPDH in a different manner or in differing quantity than their normal counterparts. The PL composition and the resulting differences in the biophysical properties of the cell membranes have crucial impact on these protein-protein interactions and on the activity of enzymes and membrane transport functions. The plasmalogen decrease impairs the protection against oxidative stress with consecutive worsening of the neurodegenerative process. The final common pathway to neuronal death leads through destabilization of intracellular Ca2+ homeostasis via elevation of intracellular Ca2+ to apoptosis. The most important conclusion is that lipids are not an inert environment of membrane proteins. Unravelling of the pathogenesis of neurodegeneration needs more concerted investigation of the interactions between genetic changes with biophysical and biochemical cell membrane lipid alterations.

Erythrocytes↗
PubMed1997

Oxidative stress induced by bloodless limb surgery on humans.

Measure of oxidative stress were studied in blood samples from 10 patients undergoing bloodless lower limb surgery. Ischaemia induced a significant increase in plasma hypoxanthine concentration and xanthine oxidase activity both in the operated leg and in the systemic circulation. Five minutes after reperfusion, ratio of xanthine oxidase/total xanthine oxidase and dehydrogenase activities rose moderately, whereas at 20 min xanthine oxidase accounted for all xanthine oxidoreductase activity in the systemic circulation. A significant increase in blood glutathione redox ratio, enhanced oxidation of haemoglobin to methaemoglobin and rise in plasma haemoglobin concentration were present only in the operated limb. Thus, although the level of the potential free radical generators rose significantly both locally and in the systemic circulation, oxidative stress, as indicated by blood glutathione and erythrocyte injuries, remained limited to the reperfused leg.

Aged↗
PubMed1994

Morphologic effects of a sulfur(IV) aerosol on the nasal cavity of beagle dogs.

Morphologic changes were observed in nasal cavities of beagle dogs after long-term exposure to a respirable sulfur(IV) aerosol at a concentration equivalent to a sulfur dioxide (SO2) concentration of 0.6 mg/m3. The changes were characterized by a thickened epithelial layer resulting from epithelial proliferation, by a loss of secretory material, and by moderate mononuclear cell infiltration.

Administration, Inhalation↗
PubMed1993

Hydrogen peroxide as an inducer of elevated tyrosinase level in melanoma cells.

The effects of systems generating active oxygen species (superoxide anion, hydrogen peroxide, hydroxyl radical) on tyrosinase have been studied in cultured human melanoma cells. Tyrosinase activity was determined by measuring the quantity of 5-S-L-cysteinyl-L-dopa (5-S-CD) formed in the presence of D,L-dopa and L-cysteine. In some experiments, the enzyme protein was determined by radio immunoassay [RIA]. Exposure of cells to xanthine/xanthine oxidase or glucose/glucose oxidase resulted in a dose-related elevation of tyrosinase. Catalase, but not superoxide dismutase, prevented this increase indicating that hydrogen peroxide may be the agent responsible for the action, whereas superoxide anion is not involved. Hydroxyl radicals formed by the Haber-Weiss or Fenton type reactions were not found to produce elevation of tyrosinase. Catalase determinations showed no enzyme in the medium but a high concentration in the cells. Inhibition of intracellular catalase by 3-amino-1,2,4-triazole caused an increase in the tyrosinase level. The effects of dopac, xanthine/xanthine oxidase, and glucose/glucose oxidase all producing hydrogen peroxide, and increasing tyrosinase, were enhanced by the inhibition of catalase. It is concluded that hydrogen peroxide, formed by the systems, accounts for the elevation of tyrosinase level. When tyrosinase activities determined by 5-S-CD formation were compared to enzyme amounts found by RIA, the ratios of these values were always constant. This fact indicates that the increase in the tyrosinase activities was not due to an activation of the enzyme, but mirrored the quantities of enzyme protein present in the samples. On the basis of our findings, it is assumed that hydrogen peroxide is a regulator of tyrosinase in normal melanocytes and melanoma cells.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Hydrogen peroxide as a mediator of dopac-induced effects on melanoma cells.

Dopac increases tyrosinase activity and exerts cytotoxic effects in cultures of human melanoma cells. The possible role of hydrogen peroxide in these actions was examined. Catalase (100 micrograms/ml) completely reversed the cytotoxic action of 0.3 mM dopac and reduced its tyrosinase-stimulating effect by approximately one half. The results show that extracellular hydrogen peroxide is a mediator of both the tyrosinase-stimulating and cytotoxic actions of dopac. Analysis of the degradation products of melanin from dopac-treated melanoma cells after hydriodic acid (HI) hydrolysis revealed the presence of aminohydroxy-phenylacetic acid (AHPAc). This substance is obtained by HI hydrolysis of melanin formed by oxidation of cysteinyl-dopac. Thus, the presence of AHPAc indicates that dopac is transported into the melanocytes where it serves as a substrate for tyrosinase.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Glutathione in human melanoma cells. Effects of cysteine, cysteine esters and glutathione isopropyl ester.

Thiols are of great importance for the regulation of many cellular functions including metabolism, transport and cell protection. In this study the usefulness of L-cysteine methyl and octyl esters, of N,S-diacetyl-L-cysteine methyl ester and glutathione isopropyl ester as cellular cysteine and GSH delivery systems was investigated in the human IGR 1 melanoma cell line. The L-cysteine methyl and octyl esters proved to be highly toxic to the cells. Treatment of the cultures with 1 mM N,S-diacetyl-L-cysteine methyl ester or 3 mM glutathione isopropyl ester for 24 h resulted in marked elevation of the cellular glutathione level without apparent or with slight cell loss, respectively. Thus the administration of the latter two compounds seems to be suitable for inducing GSH elevation in the cultured melanoma cells.

Acetylcysteine↗
PubMed1990

Enzyme release from cultured human melanoma cells.

The lysosomal enzyme beta-hexosaminidase and the melanocyte specific enzyme tyrosinase were examined in human melanoma cell cultures. The beta-hexosaminidase activity of the medium was approximately 40% of the total cellular activity after 24 h, while after 48 h the activity in the medium was twice that of the cells. The tyrosinase activity in the medium was 5% and 19% of the total cellular activity after the 24 h and 48 h incubation, respectively. The low level of lactate dehydrogenase activity in the medium after 24 as well as 48 h of incubation indicated that the release of beta-hexosaminidase and tyrosinase was not due to membrane injury. The data suggest, that 1) beta-hexosaminidase may be a candidate for tumor markers in malignant melanoma, and 2) the tyrosinase activity found in sera of melanoma patients may be due, at least partly, to enzyme release by living cancer cells.

Cell Line↗
PubMed1989

Modulation of glutathione level in cultured human melanoma cells.

The effects of buthionine sulphoximine (BSO) treatment on cellular glutathione (GSH) content and on the cytotoxic action of menadione were investigated in cultured IGRI human melanoma cells. Addition of BSO (10(-8)-0.5 X 10(-3) M) to the cultures resulted in a dose- and time-dependent depletion of cellular GSH. BSO (10(-5) and 10(-6) M) did not influence cell multiplication up to 48 h, as determined by trypan blue staining. Menadione (3 X 10(-5) M) treatment decreased the cellular GSH concentration and also reduced cell number after a 24 h exposure. Its cytotoxicity was increased by BSO (10(-5), 10(-6) M), though the potentiating effect was moderate.

Antimetabolites↗
PubMed1989

Adenylate cyclase activity in homogenates of human melanoma cells. Effect of alpha-MSH and isoprenaline.

The effects of the alpha-melanocyte-stimulating hormone (alpha-MSH) (10(-7)-10(-5) M) and the beta-adrenoceptor agonist isoprenaline (10(-9)-10(-4) M) on adenylate cyclase (AC) activity were investigated in homogenates of the human IGR 1 melanoma cells with or without additional GTP. Basal AC activity was increased by the administration of 10 microM GTP. Alpha-MSH had no effect on cyclic AMP (cAMP) accumulation, while isoprenaline stimulated AC activity in a dose-dependent manner.

Adenylyl Cyclases↗
PubMed1989

Stimulation of tyrosinase by dihydroxy phenyl derivatives.

Isoprenaline (0.3 mM) moderately increased the tyrosinase activity of cultured human melanoma cells, while another beta-adrenoceptor agonist, terbutaline (1-3 mM) and a catechol compound, dopac (0.1-0.3 mM) induced a several fold increase in the enzyme activity. Isoprenaline (0.3-1 mM) and dopac (0.3-1 mM) also exerted pronounced toxic effects on the cells. The data suggest: 1) a possible role for beta-adrenoceptors in the regulation of human melanogenesis; 2) two different ways of action for isoprenaline in inducing tyrosinase elevation; 3) the possible usefulness of dopac as a chemotherapeutic agent.

3,4-Dihydroxyphenylacetic Acid↗