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Biomedical subjects

I Németh

Publications and source records attributed to I Németh.

At least 19 recordsLinked to original sources
PubMed2001

Blood glutathione redox status in gestational hypertension.

Gestational hypertension during the third trimester reflects an exaggerated maternal inflammatory response to pregnancy. We hypothesized that oxidative stress present even in normal pregnancy becomes uncompensated in hypertensive patients. A glucose-6-phosphate dehydrogenase (G6PD) activity sufficient to meet the increased reductive equivalent need of the cells is indispensable for defense against oxidative stress. The erythrocyte glutathione redox system was studied, where G6PD is the only NADPH source. The glutathione (GSH) redox status was measured both in vivo and after an in vitro oxidative challenge in pregnant women with gestational hypertension (n = 19) vs. normotensive pregnant subjects (n = 18) and controls (n = 20). An erythrocyte GSH depletion with an increase in the oxidized form (GSSG) resulted in an elevated ratio GSSG/GSH (0.305 +/- 0.057; mean +/- SD) in hypertensive pregnant women vs. normotensive pregnant or control subjects (0.154 +/- 0.025; 0.168 +/- 0.073; p <.001). In hypertensive pregnant patients, a "GSH stability" decrease after an in vitro oxidative challenge suggested a reduced GSH recycling capacity resulting from an insufficient NADPH supply. The erythrocyte GSSG/GSH ratio may serve as an early and sensitive parameter of the oxidative imbalance and a relevant target for future clinical trials to control the effects of antioxidant treatment in women at increased risk of the pre-eclampsia syndrome.

Adult↗
PubMed2001

Xanthine oxidase activity and blood glutathione redox ratio in infants and children with septic shock syndrome.

OBJECTIVES: The possible role of xanthine oxidase (XO) activation in the signal transduction process during the septic shock syndrome was examined. The XO activity index after caffeine intake was assessed simultaneously with the blood glutathione redox ratio, a known parameter of oxidative stress. DESIGN AND SETTING: An investigational clinical study in a nine-bed pediatric intensive care unit. PATIENTS: Critically ill infants and children (n = 34) with systemic inflammatory response syndrome following infection, trauma or major surgery. Biochemical investigations (n = 54) were performed at various stages of the shock syndrome, characterized by pediatric risk of mortality and organ dysmetabolic scores. Controls consisted of 30 healthy children. MEASUREMENTS AND RESULTS: The in vivo XO activity index was measured as the urinary ratio of two metabolites of caffeine: 1-methyluric acid and 1-methylxanthine. The blood concentrations of oxidized (GSSG) and reduced glutathione (GSH) were determined. The XO activity index and redox ratio GSSG/GSH were highly increased in patients in shock dominated by the clinical symptoms of a proinflammatory response. A significantly lower XO activity index was found with an increased GSSG/ GSH in patients whose stage of shock was characteristic of an excessive anti-inflammatory response. The XO activity index and GSSG/ GSH were correlated closely with each other (r = 0.624, n = 54; p < 0.001), and were also related to the daily severity scores. CONCLUSION: Potent and simultaneous activation of the two redox systems strongly indicates a definite role of free radicals from XO in the overspill of the acute proinflammatory reaction of the shock syndrome, followed by a significant downregulation.

Biomarkers↗
PubMed2001

Inhibitory effects of methylxanthines on the pre-eclamptic-like symptoms in ewes.

OBJECTIVE: Our objective was to determine whether two methylxanthines, pentoxifylline (PTX) and allopurinol, would have beneficial effects on experimental pregnancy-induced pre-eclampsia- like disease in ewes. STUDY DESIGN: 20 animals at the gestational age of 130-135 days were divided into four groups (control; fasting; fasting, pentoxifylline-treated; and fasting, allopurinol-treated). The illness was provoked with a 4-day fasting period. Electrolytes, glucose, conventional parameters, plasma haem content, indirect bilirubin concentration and free thiol levels were measured. RESULTS: Unlike in the fasting group, conventional signs of the disease, such as hypertension, kidney and liver injury and platelet count decrease, were all mitigated in the fasting, drug-treated animals. In the treated animals plasma haem content increased by a less significant level, while indirect bilirubin concentration showed a more rapid rise. CONCLUSIONS: Both methylxanthines partly inhibited the pre-eclamptic-like symptoms in ewes. We speculate that the better induction of haem oxygenase might play an important role in this inhibitory effect on this particular animal model.

Albumins↗
PubMed2001

Impaired early neurologic outcome in newborn piglets reoxygenated with 100% oxygen compared with room air after pneumothorax-induced asphyxia.

Birth asphyxia is a serious problem worldwide, resulting in 1 million deaths and an equal number of neurologic sequelae annually. It is therefore important to develop new and better ways to treat asphyxia. In the present study we tested the effects of reoxygenation with room air or with 100% oxygen (O2) after experimental pneumothorax-induced asphyxia on the blood oxidative stress indicators, early neurologic outcome, and cerebral histopathology of newborn piglets. Twenty-six animals were studied in three experimental groups: 1) sham-operated animals (SHAM, n = 6), 2) animals reoxygenated with room air after pneumothorax (R21, n = 10), and 3) animals reoxygenated with 100% O2 after pneumothorax (R100, n = 10). In groups R21 and R100, asphyxia was induced under anesthesia with bilateral intrapleural room air insufflation. Gasping, bradyarrhythmia, arterial hypotension, hypoxemia, hypercarbia, and combined acidosis occurred 62 +/- 6 min (R21) or 65 +/- 7 min (R100; mean +/- SD) after the start of the experiments; then pneumothorax was relieved, and a 10-min reoxygenation period was started with mechanical ventilation with room air (R21) or with 100% O2 (R100). The newborn piglets then breathed room air spontaneously during the next 3 h. Blood oxidative stress indicators (oxidized and reduced glutathione, plasma Hb, and malondialdehyde concentrations) were measured at different stages of the experiments. Early neurologic outcome examinations (neurologic score of 20 indicates normal, 5 indicates brain-dead) were performed at the end of the study. The brains were next fixed, and various regions were stained for cerebral histopathology. In the SHAM group, the blood gas and acid-base status differed significantly from those measured in groups R21 and R100. In group R100, arterial PO2 was significantly higher after 5 (13.8 +/- 5.6 kPa) and 10 min (13.2 +/- 6.3 kPa) of reoxygenation than in group R21 (8.7 +/- 2.8 kPa and 9.2 +/- 3.1 kPa). The levels of all oxidative stress indicators remained unchanged in the study groups (SHAM, R21, and R100). The neurologic examination score in the SHAM group was 18 +/- 0, in group R21 it was 13.5 +/- 3.1, and in group R100 it was 9.5 +/- 4.1 (significant differences between SHAM and R21 or R100, and between R21 and R100). Cerebral histopathology revealed marked damage of similar severity in both asphyxiated groups. We conclude that the blood oxidative stress indicators and cerebral histopathology did not differ significantly after a 10-min period of reoxygenation with room air or with 100% O2 after pneumothorax-induced asphyxia, but reoxygenation with 100% O2 might impair the early neurologic outcome of newborn piglets.

Acid-Base Equilibrium↗
PubMed2000

[Reoxigenation after neonatal asphyxia with 21% or 100% oxygen in piglets].

Birth asphyxia represents a serious problem worldwide, resulting in 1 million deaths and an equal number of neurologic sequelae annually. It is therefore important to develop new and better ways to treat asphyxia. In the present study we tested the effect of reoxygenation with room air or 100% oxygen following experimental pneumothorax induced asphyxia on blood oxidative stress indicators, early neurologic outcome and cerebral histopathology of newborn piglets. 26 animals were studied in three experimental groups: sham-operated (SHAM, n = 6), reoxygenation with room air after pneumothorax (RORA, n = 10) and reoxygenation with 100% oxygen after pneumothorax (RO100, n = 10). In RORA and RO100 asphyxia was induced under anesthesia with bilateral intrapleural room air insufflation. Gasping, bradyarrhythmia, arterial hypotension, hypoxemia, hypercarbia and severe combined acidosis occurred 62 +/- 6 (RORA) and 65 +/- 7 min (RO100) after the start of the experiments, when the pneumothorax was relieved and ten min of reoxygenation period was started with mechanical ventilation with room air (RORA) or 100% oxygen (RO100). Then the spontaneously breathing animals were followed on room air during the next three hours. Blood oxidative stress indicators--as oxidized and reduced glutathione, plasma hemoglobin and malondialdehyde concentrations--were also measured at different stages of the experiments and early neurologic examinations (neurological score: 20 = normal, 5 = brain dead) were performed at the end of the study. Then the brains were fixed and stained. In SHAM blood gases and acid/base status differed significantly from values measured in RORA and RO100. In RO100 PaO2 was significantly higher at 5 (13.8 +/- 1.8 kPa) and 10 min (13.2 +/- 2.0 kPa) than in RORA (8.7 +/- 0.9, 9.2 +/- 1.0 kPa), respectively. All the measures of oxidative stress indicators remained unchanged in the study groups (SHAM, RORA, RO100). Neurologic examination scores from SHAM were 18 +/- 0, from RORA 13.5 +/- 1.0 and from RO100 9.5 +/- 1.3 (significant differences between SHAM and RORA and RO100, significant difference between RORA and RO100). Cerebral histopathology showed marked damage with similar severity in both asphyxiated groups. We conclude that blood oxidative stress indicators and cerebral histopathology did not differ significantly after 10 min reoxygenation either with room air or with 100% oxygen following pneumothorax induced asphyxia, but reoxygenation with 100% oxygen might impair the early neurologic outcome of newborn pigs.

Animals↗
PubMed2000

Diminished blood levels of reduced glutathione and alpha-tocopherol in two triosephosphate isomerase-deficient brothers.

The glutathione redox system and alpha-tocopherol, both of which are essential for maintaining the normal structure of biological membranes, some other lipid-soluble antioxidants (lycopene, beta-carotene, retinol), and lipid peroxidation, were investigated in the blood from two triosephosphate isomerase (TPI)-deficient brothers. Both of the genetically identical compound heterozygote brothers have congenital hemolytic anemia, but only one of them has a neurological defect, the second cardinal symptom of TPI deficiency. Whole blood reduced glutathione levels were markedly decreased in both brothers. The glutathione reductase activities as well as the NADPH contents of their erythrocytes were in the normal range or slightly enhanced. Increased ratio of oxidized/reduced glutathione, elevated glutathione S-transferase activity, and increased d-lactate level, a metabolite of the glyoxalase pathway, were detected only in the neurologically affected propositus. The plasma carotenoids (lycopene + beta-carotene), alpha-tocopherol/cholesterol + triglyceride ratios, and the erythrocyte alpha-tocopherol levels were significantly decreased in both patients. It seems conceivable that membrane alterations due to the low level of these reducing agents may contribute to the shortened life span of erythrocytes. The imbalance of the prooxidant/antioxidant homeostasis as well as the increased rate of methylglyoxal formation may also have been involved in the development of the neurological manifestations in the propositus.

Adult↗
PubMed2000

Vitamin E alleviates the oxidative stress of erythropoietin in uremic children on hemodialysis.

The efficacy of combined therapy with recombinant human erythropoietin (rhEPO) and vitamin E versus rhEPO alone in the treatment of anemia was examined in children (n = 10, aged 15.2 +/- 3.2 years) on chronic hemodialysis at the restart of rhEPO therapy after a 4-week interval. The results confirmed that rhEPO induced oxidative stress of the red blood cells as observed during the first rhEPO therapy. Vitamin E (15 mg/kg per day per os) was introduced after 2 weeks of rhEPO monotherapy, when the signs of acute oxidative stress appeared. The level of oxidized glutathione (GSSG) increased from 8.9 +/- 3.1 to 26.7 +/- 5.7 nmol/g hemoglobin (Hb) by that time. After 2 weeks of simultaneous vitamin E treatment, there was a significant difference in GSSG values compared with rhEPO monotherapy (10.1 +/- 3.9 vs. 56.7 +/- 15.8 nmol/g Hb, P < 0.001). A considerable decrease was observed in the previously high ratio of GSSG/reduced glutathione (GSH), an indicator of oxidative stress, and the level of carboxyhemoglobin, indicating hemolysis. A significant increase in Hb and hematocrit (P < 0.01) was achieved within 2 weeks of starting the combined therapy, while similar results occurred only at the 8th and 5th weeks without vitamin E. Antioxidant vitamin E supplementation improved the therapeutic effect of rhEPO in patients with chronic renal failure on hemodialysis.

Adolescent↗
PubMed2000

The roles of platelet function, thromboxane, blood lipids and nitric oxide in hypertension of children and adolescents.

The roles of platelet function, plasma lipids and nitric oxide (NO) were studied in adolescent patients with essential hypertension (JEHT group), with chronic renal failure (CRF) associated with hypertension (CRFH group), and CRF patients with normal blood pressure (CRF group), as compared with normal controls (cont. group). Platelet aggregation and the thromboxane B(2)(TxB(2)) level were significantly higher in the JEHT and CRFH groups as compared with the cont. group, whereas they were significantly lower in the CRF group. On the other hand, the platelet cAMP level was significantly lower in the JEHT and CRFH groups than in the cont. group. The plasma NO level was significantly higher only in the JEHT as compared with the cont. group (120 +/- 39 and 89 +/- 21 microM, respectively). The plasma total cholesterol, triglyceride and LDL cholesterol concentrations were normal in the JEHT group, but high in the CRF and CRFH group, the HDL cholesterol level was lower in the CRF and CRFH groups as compared with the cont. and JEHT groups. There was a positive correlation between the platelet aggregation and the TxB(2)level and between the BP and the platelet aggregation. In conclusion, hyperlipidaemia is commonly present in uraemia with haemodialysis, but is not specific for hypertension in children, while an increased platelet function is frequently associated with hypertension. The increased NO level might play a compensatory role in JEHT.

Adolescent↗
PubMed1999

Nonenzymatic antioxidants of blood in multiple sclerosis.

Free radical action has been suggested as a causal factor in multiple sclerosis. We investigated the plasma level of lipid peroxides expressed in terms of malone dialdehyde and changes in blood nonenzymatic antioxidants (glutathione, alpha-tocopherol, retinol, plasma sulfhydryl groups, and uric acid) in multiple sclerosis patients with exacerbation or in remission, including a group treated with beta-interferon. The malone dialdehyde level was increased by 38% (n.s.) during exacerbations. The blood concentration of oxidized glutathione was likewise elevated (P<0.05), while the ratio of plasma alpha-tocopherol to cholesterol plus triglyceride was decreased (P<0.001). These changes suggest increased free radical production and consumption of the scavenger molecules during the active phase of the disease. Blood reduced glutathione level was increased (P<0.01) during exacerbation and remission as well. The rise in this thiol is likely to be a compensatory mechanism defending the cells from further oxidant injuries. Beta-interferon increased plasma alpha-tocopherol levels (P<0.001) but not the lipid corrected alpha-tocopherol value. Other parameters were not influenced by the drug.

Adult↗
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

The caffeine metabolic ratio as an index of xanthine oxidase activity in clinically active and silent celiac patients.

BACKGROUND: The xanthine oxidoreductase system has been identified as one of the main sources of free radicals responsible for various forms of tissue injury. Because the intestinal villi are an important location of this enzyme, it was of interest to study the role of xanthine oxidase in gluten-sensitive celiac enteropathy, associated with characteristic villous atrophy. Measured by a noninvasive method, the ratio of caffeine metabolites excreted in the urine after a caffeine challenge had previously been shown to be indicative of the total xanthine oxidase activity of the patient. METHODS: The study involved 22 children with gluten-challenged celiac disease, exhibiting subtotal villous atrophy in specimens from the third intestinal biopsy in accordance with ESPGHAN criteria. Ten of the patients displayed overt clinical symptoms (active form), whereas 12 had no symptoms (silent form). Urinary caffeine metabolites were determined by high-pressure liquid chromatography. The total in vivo xanthine oxidase activity was expressed as the caffeine metabolite index. RESULTS: In patients with active celiac disease the xanthine oxidase activity index was considerably higher, whereas in those with silent disease it was significantly lower than the control value. A significant negative correlation was shown between the index indicative of xanthine oxidase activity and the serum iron level of the patients. CONCLUSIONS: Activation of xanthine oxidase may play a role in the pathogenesis of active celiac disease with definite malabsorption, gastrointestinal symptoms, and anemia. The caffeine test reflects the difference in the pathogenetic mechanism leading to the mucosal lesion and clinical symptoms of active and silent forms of celiac disease.

Caffeine↗
PubMed1998

Coeliac disease: always something to discover.

The authors present more than 20 years' experience with coeliac disease, with a summary of their published studies. Hair shaft characteristics were determined by scanning electron microscopy. Hair diameter was significantly lower and cuticular erosion scores higher in those who were not on gluten-free diets as compared to controls, showing a tendency towards normal values following start of gluten-free diets. Proton-induced X-ray emission showed significantly lower zinc content of the hair shaft in the group with acute coeliac disease and after a short-term diet, which approached the normal range only after a year-long diet. The serum prolactin levels in healthy controls and in coeliac patients on the diet were within normal limits, whereas in children with coeliac disease taking gluten in their meals, a significant hyperprolactinaemia was found. The erythrocyte glutathione content of coeliac children was elevated, and the glutathione disulfide level was significantly decreased, as compared to values in normal controls. The erythrocyte glutathione disulfide level and glutathione disulfide/erythrocyte glutathione ratio in coeliac children also differed from those in children with iron deficiency. With genotyping, the DQB1*0201/2 (p < 0.00001) and DR3 (p < 0.00001), DR7 (p < 0.01) alleles showed significant positive association with the disease.

Anemia, Iron-Deficiency↗
PubMed1998

Surface tension, glutathione content and redox ratio of the tracheal aspirate fluid of premature infants with IRDS.

OBJECTIVE: Determination of the surface tension (ST), the total glutathione (GL) content and the ratio of oxidized glutathione (GSSG) to reduced glutathione (GSH) in the tracheal aspirate (TA) of newborn infants with IRDS. METHODS: The ST of the TA was determined by monitoring the fluid level pulsated in a capillary glass tube by means of a digitalized videocomputerized picture analysis program, a technique developed in our laboratory. The concentrations of GSSG and total GL in the TA were determined enzymatically with glutathione reductase. All results of laboratory tests were referred to the total phospholipid (PL) concentration. Patients, Experimental Material: TA samples were collected from 32 intubated premature and newborn infants admitted to the NICU with IRDS during the first 2 weeks of their lives. Control samples were obtained from 11 children prior to elective surgery. RESULTS: The ST relative to the PL content (surface tension index, STI) was significantly lower in the newborns with IRDS than in the control group, and the concentration of GSH in the TA was also markedly decreased in all IRDS infants studied. The concentration of GSSG and the ratio of GSSG to GSH were significantly higher in the severe cases and in those with an unfavourable prognosis. Surfactant treatment had a protective effect against oxidative stress, it induced a decrease in both the GSSG concentration and in the GL redox ratio (GSSG/GSH) in the TA. There was a close correlation between the GSH content and the STI value of the samples studied. CONCLUSION: Oxidation and consequent depletion of GSH in the TA may be an aggravating factor in the development of the insufficient surface activity in intubated newborns with IRDS.

Body Fluids↗
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

[Prospective biochemical study of the antioxidant defense capacity in retinopathy of prematurity].

The study was carried out on 60 oxygen-treated premature infants weighed less than 2000 g (1529 +/- 302 g, x mean +/- S. D.) and on their mothers. Both the Retinopathy of Prematurity screening and the biochemical tests were started at the age of 6 weeks. According to our results, the signs of an acute oxidative stress could be seen in all 60 oxygen-treated prematures erythrocyte's glutathione redox system, independently of the presence of the retinopathy compared to prematures (n = 20) with the same gestational age but without oxygen therapy (1720 +/- 305 g, mean +/- S.D.). The concentrations of free sulfhydril groups in the plasma, and the blood selenium levels were significantly lower in the prematures suffering from moderate retinopathy (n = 5) than in the other oxygen-treated premature without retinopathy (n = 27) and with "any retinopathy" (n = 28) patients groups. The same tendency was seen in the mothers. Vitamin E treatment of "any retinopathy" infants seemed to have a positive effect against the development of Retinopathy of Prematurity. The close correlation found between the antioxidant capacity of the mothers and babies suggest that the supplementation of feeding with sulfur-containing amino acids (methionine, cysteine) during pregnancy would improve the antioxidant capacity of prematures. An antioxidant cocktail (selenium + vitamin E) given to the high-risk mothers (advanced age, smoking, pregnancy-induced hypertension) before delivery as suggested in literature might be useful in prevention of Retinopathy of Prematurity.

Antioxidants↗