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Biomedical subjects

M Zilmer

Publications and source records attributed to M Zilmer.

At least 37 records · Page 2Linked to original sources
PubMed1998

Preconditioning with hydrogen peroxide (H2O2) or ischemia in H2O2-induced cardiac dysfunction.

The possible cardioprotective effects of preconditioning by ischaemia (IPC) or a low dose of H2O2 (HPC) prior to a high dose of H2O2 was investigated. Langendorff-perfused rat hearts (n = 10 in each group) were subjected to 10 min of 140 micromol/L H2O2 and 30 min recovery after either (1) control perfusion, (2) 20 micromol/L H2O2 for 10 min, recovery 10 min, or (3) 2 x 2 min global ischaemia and 5 min reperfusion. 140 micromol/L H2O2 increased left ventricular end-diastolic pressure from 0 to 68+/-8 mmHg in controls (mean+/-SEM), which was attenuated by IPC (46+/-9 mmHg, p<0.001) and HPC (18+/-4 mmHg, p < 0.001 compared to controls, p < 0.01 compared to IPC). HPC, but not IPC, improved coronary flow (p < 0.02) and left ventricular developed pressure (p < 0.001) during recovery. Troponin T release was similar in all groups. Tissue thiobarbituric acid reactive substances, antioxidant capacity, catalase, and glutathione peroxidase were not influenced by 140 micromol/L H2O2. H2O2 decreased the level of tissue glutathione. This reduction was augmented by HPC (p <0.02) and attenuated by IPC (p < 0.02). H2O2 increased superoxide dismutase (p < 0.04). The increase was attenuated by IPC (p < 0.05), but not influenced by HPC. HPC efficiently protected cardiac function in H2O2-induced cardiac injury, while IPC had only a small protective effect. The functional protection cannot be explained by reduction of irreversible injury, attenuation of lipid peroxidation, or modification of tissue antioxidant parameters.

Animals↗
PubMed1998

Comparison of the antioxidant activity of melatonin and pinoline in vitro.

Several recent experiments have shown that melatonin is an efficient antioxidant and free radical scavenger. In the present study the antioxidative effect of melatonin was compared with that of pinoline. Pinoline (6-methoxy-tetrahydro-beta-carboline) can be formed in the mammalian body under physiological conditions from 5-hydroxytryptamine or as a tricyclic metabolite of melatonin. Both melatonin and pinoline inhibited lipid peroxidation and showed comparable activity in a total antioxidant status test. Melatonin and pinoline concentration-dependently scavenged hydroxyl radicals with IC50 11.4+/-1.0 microM for melatonin and 62.3+/-3.8 microM for pinoline. These results support the importance of the indolic part of the molecule and the 5-methoxy group common to both compounds in terms of the ability of these molecules to quench the hydroxyl radicals. As pinoline has been shown to exert an antidepressant-like effect in behavioral experiments and has been reported to have a low toxicity, this compound should be further studied as a potential antidepressant with pronounced antioxidative effects. These results further support the importance of pineal gland in antioxidative protection.

Antioxidants↗
PubMed1998

Could long-term alimentary iron overload have an impact on the parameters of oxidative stress? A study on the basis of a village in southern Estonia.

The effects of long-term alimentary (drinking water) iron overload on the parameters of oxidative stress were evaluated. The study group (n = 35) from a village in southern Estonia was 37.1 +/- 13.3 years old, and the mean period of drinking water iron overload was 20.6 +/- 9.3 years. The serum iron content was significantly higher than normal. The total iron-binding capacity of serum tended to be lowered. There was no change in the transferrin content. The parameters of lipid peroxidation like conjugated dienes and thiobarbituric acid reactive substances showed also significant differences. In addition, the red blood cell glutathione content was also decreased. The total antioxidant capacity of serum was not changed. It can be concluded from our results that a long-term alimentary iron overload results in a positive serum iron balance, which, in turn, yields an increased oxidative stress.

Adult↗
PubMed1998

Use of nonbreakpoint DNA probes to detect the t(X;18) in interphase cells from synovial sarcoma: implications for detection of diagnostic tumor translocations.

Fluorescence in situ hybridization studies using non-breakpoint DNA probes were performed to detect the X;18 translocation on 4-microm sections of synovial sarcoma from paraffin blocks. This was done by using commercially available, large target unique sequence DNA probes for regions of the X chromosome short-arm and the 18 chromosome long-arm together with centromere probes for the alternate chromosomes. We determined that such probe combinations could detect the presence of the diagnostic X;18 translocation in interphase cells. Spatial association of dual color signals from the X centromere and the 18 unique sequence probe, as well as between an 18 centromere and the X unique sequence probe, was seen in a significantly higher percentage of synovial sarcoma cells (81.1% +/- 7.7%, confidence interval 95%) than in control nonsynovial soft tissue sarcomas (14.7% +/- 8.3%) and control peripheral blood lymphocytes (5.6% +/- 0.6%). The observed spatial association supports the use of this strategy to detect the X;18 translocation in synovial sarcoma and suggests that this technique could be applied in the diagnosis of other types of tumors with characteristic translocations when histopathological findings are inconclusive. This study is the first report describing the use of nonbreakpoint unique sequence probes for detecting translocations in tumors on paraffin-embedded slides.

Chromosomes, Human, Pair 18↗
PubMed1997

The evidence of oxidative stress in cardiac surgery and septic patients: a comparative study.

In present study, lipid peroxidation products (thiobarbituric acid reactive substances (TBARS) and diene conjugates (DC)) and markers of blood antioxidant status (serum antioxidative capacity (AOC) and red blood cells glutathione (RBC-GSH)) were measured to compare the extent of oxidative stress in 12 cardiac surgery and 10 septic general surgery patients. In heart surgery, arterial TBARS were significantly increased 15 min after the start and 15 min after cessation of cardiopulmonary bypass, while AOC at these times was decreased. Eighteen hours after surgery all parameters, except antioxidative capacity, had returned to preoperative levels. In septic patients, the preoperative level of lipid peroxidation was significantly higher and antioxidative capacity lower than in heart surgery patients. Surgery had no influence on oxidative stress markers in this group of patients. Increase in lipid peroxidation and reduction in blood antioxidant capacity, induced either by sepsis or cardiopulmonary bypass, were of comparable extent.

Adult↗
PubMed1997

Attempt to solubilize Na+/K+-exchanging ATPase with amphiphilic peptide PD1.

The effect of the 24-amino-acid-long peptide, PD(1), on rat cerebral cortical Na+/K+ -exchanging ATPase (EC 3.6.1.37) has been studied. Incubation of the enzyme preparation (25 degrees C for 10-25 min) with the peptide (10(-7) - 10(-4) M) did not appreciably affect the activity of the enzyme, only 5-8% activation being registered. On the other hand, PD(1) completely eliminated the cooperative nature of Na+ -binding to Na+/K+ -exchanging ATPase (n(H) decreased from 1.4 to 0.9) and slightly (1.2-fold) decreased the affinity for Na+. ATP, a substrate of activity for Na+/K+ -exchanging ATPase, blocked the PD(1)-promoted effect on the cooperativity for Na+. Incubation of cerebral cortical membranes with 5 x 10(-4) M PD(1) revealed a shift (from 19.5 degrees C to 21.4 degrees C) of the typical break on the Arrhenius plot (15-37 degrees C). Prolonged incubation of enzyme preparation (25 degrees C for 1-2 h) with PD(1) (4.5 x 10(-4) - 0.7 x 10(-2) M) followed by centrifugation of the mixture at 53,000 g for 90 min, resulted in loss of the activity both in the supernatant and the sediment, while the protein content in the supernatant and the sediment remained unchanged. After a short incubation (25 degrees for 10 min) with PD(1) (1 x 10(-6) M), followed by centrifugation, the full activity of Na+/K+ -exchanging ATPase in the sediment was restored. These data suggest that peptitergent PD(1) does not solubilize the transmembrane protein Na+/K+ -exchanging ATPase, although it abolishes the cooperative effect of Na+.

Animals↗
PubMed1996

A galanin-mastoparan chimeric peptide activates the Na+,K(+)-ATPase and reverses its inhibition by ouabain.

The effect of the neuropeptide galanin, the wasp venom toxin amphiphilic peptide toxin mastoparan and the chimeric peptide, galparan, consisting of N-terminal 13 amino acids of neuropeptide galanin linked at C-terminus to mastoparan amide (and its inactive analog Mas17) on the activity of Na+,K(+)-ATPase has been studied. Mastoparan inhibits the activity of the Na+,K(+)-ATPase with IC50 = 7.5 microM and also reduces the cooperativity for Na+ and K+, respectively, while galanin has no effect on the Na+,K(+)-ATPase activity. The chimeric peptide, galanin(1-13)-mastoparan amide (galparan), exhibits biphasic interaction with Na+,K(+)-ATPase, it activates the enzyme at maximal stimulating concentration of 4 microM followed by inhibition of the enzyme with IC50 of 100 microM. At maximum stimulating concentration (4 microM), galparan partly reduces the cooperativity only for Na+ and it also counteracts the inhibitory effect of oubain on Na+,K(+)-ATPase. Galparan's stimulatory effect was influenced by ATP. The chimeric peptide [19Lys,26Leu]-galparan, containing the inactive analog of mastoparan (Mas17), has no effects on rat brain Na+,K(+)-ATPase activity. Both chimeric peptides galparan and [19Lys,26Leu]-galparan are high-affinity galanin receptor ligands with IC50 of 6.4 nM and 0.71 nM, respectively, while galanin (1-13) and mastoparan alone have significantly lower affinity for the galanin receptor, IC50 of 125 nM and 1 microM, respectively. The ability of chimeric peptides to bind to galanin receptors does not correlate with their effects on the Na+,K(+)-ATPase.

Amino Acid Sequence↗
PubMed1996

Oxidative stress and hyperinsulinaemia in essential hypertension: different facets of increased risk.

OBJECTIVE: To evaluate oxidative stress markers in normo- and hyperinsulinaemic essential hypertension patients, and to relate these parameters to plasma glucose and insulin levels. METHODS: Diene conjugates, thiobarbituric acid reactive substances, iron-stimulated thiobarbituric acid reactive substances and anti-oxidative capacity of serum were detected in 32 untreated essential hypertension patients with normal glucose tolerance, divided into hyperinsulinaemic (n = 12, fasting plasma insulin level > 13.5 mU/l, means 2 SD of controls) and normo-insulinaemic (n = 20) subgroups, compared with 26 age- and body mass index-matched controls. Plasma glucose and insulin levels were measured during an oral glucose tolerance test. RESULTS: Levels of lipid peroxidation products (diene conjugates, thiobarbituric acid reactive substances and iron-stimulated thiobarbituric acid reactive substances) were elevated and serum anti-oxidative capacity decreased both in hyper- and in normo-insulinaemic patients compared with those in controls, with no significant differences between the hypertensive subgroups. No independent correlations were detected between oxidative stress markers and fasting or stimulated plasma insulin and glucose levels. The essential hypertension patients were characterized by a lower fasting glucose: insulin ratio and enhanced plasma insulin response to oral glucose test compared with controls. CONCLUSIONS: The results suggest that oxidative stress occurs, in addition to disturbances in glucose metabolism, in essential hypertension patients, thus potentially exposing them to increased risk of developing complications. Factors other than plasma insulin level are likely to contribute to oxidative stress in hypertensive patients with normal glucose tolerance.

Adult↗
PubMed1996

Markers of oxidative stress before and after exchange transfusion for neonatal sepsis.

Oxidative status before and after ET was assessed in eight septic newborns who received exchange transfusion (ET). Short-term elevations of conjugated dienes (CDs) and thiobarbituric acid reactive substances (TBARSs) (p < 0.05) and increased serum antioxidant capacity (AOC) (p = 0.06) were noted. Chromatographic migration of the red blood cells (CM RBCs), a measure of RBC deformability, also improved after ET. ET for neonatal sepsis does not cause significant oxidative stress; rather, it may help to restore the antioxidant depots and improve RBC deformability and microcirculation.

Antioxidants↗
PubMed1996

Evidence for oxidative stress in essential hypertension: perspective for antioxidant therapy.

BACKGROUND: Despite therapy, arterial hypertension continues to be a risk factor of coronary artery disease (CAD). The role of oxidative stress, an important source of vascular injury, in the genesis of this increased risk also needs to be defined, because several antihypertensive drugs have demonstrated antioxidant effects. This study tested the existence of oxidative stress in young (< 40 years) untreated patients with uncomplicated essential hypertension (EH). METHODS: Lipid peroxidation (LP) products (diene conjugates, basal and Fe-stimulated levels of thiobarbituric acid reactive substances) were detected spectrophotometrically in serum together with markers of antioxidant status (serum antioxidative capacity (AOC), red blood cell (RBC) glutathione) in 32 patients with mild-to-moderate EH and in 26 matched normotensive controls. RESULTS: All LP products were elevated (P < 0.01), while serum AOC was decreased (P < 0.001) and RBC glutathione increased (P < 0.05) in EH patients compared with controls. The presence of hypercholesterolaemia was not found to influence the differences in the measured parameters between hypertensive patients and controls significantly. CONCLUSIONS: The results indicate that oxidative stress occurs in young patients with uncomplicated EH. Therefore antihypertensive treatment; especially in patients whose vascular disease is still reversible, should provide antioxidant protection.

Adult↗
PubMed1995

Differential regulation of adenylate cyclase activity in rat ventral and dorsal hippocampus by rat galanin.

Rat galanin inhibits basal as well as forskolin-stimulated adenylate cyclase activity in rat ventral and dorsal hippocampus. The inhibition of adenylate cyclase activity, both basal and forskolin-stimulated, is characterised by IC50 values being 250-fold lower in ventral hippocampus (IC50 = 1.1 nM) compared to the dorsal hippocampus (IC50 = 270 nM). The maximal inhibition of basal and forskolin-stimulated adenylate cyclase activity in both ventral and dorsal hippocampus in the presence of 10 microM rat galanin is 34-45%. The analysis of the binding data obtained with 125I-labelled Tyr26-porcine galanin as a tracer reveals similar binding constants for rat galanin in both ventral and dorsal hippocampus with 4.8-fold higher concentration of galanin receptors in the ventral hippocampus. Putative galanin receptor subtype differences between the ventral and dorsal hippocampus have been noted by Hedlund et al. (Eur. J. Pharmacol., 224 (1992) 203-205). This study yields further confirmation for the existence of different galanin receptor subtypes or for differential coupling of galanin receptors to the adenylate cyclase in the dorsal versus ventral hippohampus.

Adenylyl Cyclase Inhibitors↗
PubMed1995

Time course of oxidative stress during open-heart surgery.

Oxidative stress and subsequent lipid peroxidation have been suggested as pathogenetically important for postischaemic reperfusion injury. We studied the time-course of oxidative stress in 14 adults undergoing cardiac surgery, evaluating serum levels of lipid peroxidation products--diene conjugates (DC) and basal and Fe-stimulated thiobarbituric acid reactive substances (TBARS, FeTEBARS)--as well as markers of blood antioxidant status--serum antioxidative capacity (AOC) and red blood cell glutathione (RBC-GSH) at 6 perioperative time-points. Arterial TBARS were significantly increased 15 minutes after start of cardiopulmonary bypass, 5 minutes after release of aortic cross-clamp and 15 minutes after cessation of bypass, compared with the preoperative levels (respective means 20.8, 38.5, 34.8 vs 7.5 nmol/g protein, p < 0.05). AOC had decreased at these times (means 21.3, 18.1, 23.2 vs 34.9%, p < 0.05). The TBARS changes correlated with AOC decrease (r = 0.30, p < 0.001). Changes in serum DC and RBC-GSH were not statistically significant. All lipid peroxidation parameters had returned to preoperative levels on the following morning, while antioxidative capacity remained suppressed (28.1%, p < 0.05). These data demonstrate a definite time-course of oxidative stress markers in arterial blood during open-heart surgery.

Adult↗
PubMed1994

Activation of Na,K-ATPase by an endogenous peptide, PEC-60.

Several peptidic and non-peptidic factors can modulate Na,K-ATPase activity, among them mainly inhibitors of this enzyme, ouabain being the most effective. In a very few cases only, activation of Na,K-ATPase by endogenous factors has been recorded. We have investigated the effect on Na,K-ATPase of a novel regulatory peptide, PEC-60, recently isolated from porcine intestine. Various biological effects have been described for PEC-60 in different tissues, including brain. We have found that PEC-60 caused a dose-dependent activation of Na,K-ATPase from rat brain frontal cortex, whereas the carboxymethylated form of PEC-60 or other hormonal peptides had no effect. The maximal value of activity reaches up to 125% at close to micromolar concentrations of PEC-60 and the dependence can be described with a bell-shaped curve, indicating a complex mechanism for the interaction. The activation of the enzyme by PEC-60 is apparently related to Na(+)-dependent steps of the Na,K-ATPase system. The kinetic parameters for K(+)-phosphatase were unaffected. Moreover, the activating effect was enhanced by preincubation at low concentrations of ATP that transform the enzyme into the Na(+)-form. Due to the crucial physiological role of Na,K-ATPase, its activity has to be finely controlled and thus PEC-60 may be one of the endogenous factors that regulate this enzyme.

Animals↗
PubMed1992

Lipid-protein interactions in neurotropic Na-pump regulation.

The role of lipid-protein interaction in the regulation of the brain Na-pump by different neurotropic agents (prostaglandin E2, middle molecules from blood plasma of uremic patients, neuropeptide galanin, the oligopeptide fraction from brain) was investigated. We established a definite correlation between the lipid status (the peroxidativity of the lipids, the phospholipids and cholesterol content) of the Na,K-ATPase enzyme preparation (plasma membrane fragments) and the influence of the neurotropic agents. Besides, after the treatment with delipidative agents (phospholipase A2, SDS) the inhibitory effects of these neurotropic agents, were diminished significantly. These facts do not contradict our previous suggestion that the lipid-protein interactions underlay the regulative action mechanism of the natural bioactive ligands.

Animals↗
PubMed1987

Gastrin, ACTH and STH after pylorus ligation and vagotomy in rats.

Plasma levels of gastrin, adrenocorticotropin (ACTH) and somatotropin (STH) were determined 24 hours after pylorus ligation and after pylorus ligation and vagotomy by radioimmunoassay. Pylorus ligation increases the serum levels of these hormones, while vagotomy inhibits the production of these ones. We conclude that the antiulcerogenetic effect of surgical vagotomy is closely related with the changes in the level of these hormones.

Adrenocorticotropic Hormone↗