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Biomedical subjects

B B Mrsulja

Publications and source records attributed to B B Mrsulja.

At least 19 recordsLinked to original sources
PubMed1996

Alteration of erythrocyte membrane Na, K-ATPase in children with borderline or essential hypertension.

The aim of this study was to evaluate the substrate (ATP) kinetics of erythrocyte membrane Na, K-ATPase in children with borderline or essential hypertension. Although the activity of Na, K-ATPase in the presence of in vivo concentrations of ATP was not significantly altered, kinetic studies showed an obvious inhibition of enzyme activity in the erythrocyte membrane of children with borderline or essential hypertension. Hanes plot analysis revealed a decrease of V(max) from 7.19 in erythrocytes from control subjects to 4.93 and 3.33 in those from children with borderline or essential hypertension, respectively. A mean value of the K(m) decreased from 0.10 in the control to 0.08 and 0.02 in children with borderline or essential hypertension, respectively. The energy status of erythrocytes, estimated by ATP, ADP and AMP levels, ATP/ADP ratio, and adenylate energy charge (AEC) was not significantly changed in the cells from hypertensive children. The use of a free radical-generating system (FeSO4/ascorbate) in vitro significantly reduced enzyme activity in the control erythrocytes while in those from hypertensive children it was abolished completely. The level of lipid peroxides was considerably higher (+ 37 per cent) in the plasma, while that of reduced glutathione was significantly lower both in the erythrocytes and the plasma of children with essential hypertension than in healthy children. These results indicate significant alterations of the antioxidant status which could be the cause of the inhibited Na, K-ATPase activity in erythrocyte membranes from hypertensive children.

Adenosine Diphosphate↗
PubMed1994

The relationship between cerebral ischemic edema and monoamines: revisited.

The association of changes in the metabolic pathway of monoamines (dopamine and 5-hydroxytryptamine) with mitochondrial enzymatic systems which are involved in the production and removal of free radicals formed during dopamine metabolism and formation of edema was investigated in bilateral brain ischemia in gerbils. The results suggest that the involvement of DA-derived free radicals in brain edema is unlikely in early reflow, because disbalance between H2O2-producing reactions of DA-metabolism, and mitochondrial antioxidative capacity does not occur prior to 1 hour reflow after 15 min bilateral ischemia in gerbils. However, the findings of this study reinforce the participation of 5-HT in the formation of ischemic brain edema.

Animals↗
PubMed1994

'Therapeutic window's for multiple drug treatment of experimental cerebral ischemia in gerbils.

The effects of the following drugs: nimodipine (1 mg/kg b.w., i.p.), 2-amino-5-phosphonovaleric acid (4 mg/kg b.w., i.p.) and propentofylline (25 mg/kg b.w., i.p.), administered (alone or in combination) at the end of 15 min bilateral ischemia in gerbils were evaluated on mitochondrial superoxide dismutase (SOD), glutathione reductase (GR), glucose-6 phosphate dehydrogenase (G6PD), monoamine oxidase (MAO) activities, and thiobarbituric acid reactive material (TBARM), and brain water content at 1 hour of reperfusion. The combined treatment virtually abolished early postischemic brain edema (4.1% v.s. 0.6%) and efficiently counteracted ischemia-induced changes [decreased SOD (79% v.s. 98%), GR (52% v.s. 105%) and MAO (25% v.s. 79%), and increased TBARM (198% v.s. 108%)]. The same combination of drugs administered 15 min before ischemia had a similar effect (e.g., reduced brain swelling and lipid peroxidation) as when given at the end of ischemia, whereas a limited or absent impact was seen when the drugs were given 15 min or 1 hour after ischemia, respectively. The data suggest that (post)ischemic brain swelling and mitochondrial dysfunction can be reduced by drugs which synchronously prevent processes induced in the early stages of reperfusion.

2-Amino-5-phosphonovalerate↗
PubMed1994

Liposome-entrapped superoxide dismutase reduces ischemia/reperfusion 'oxidative stress' in gerbil brain.

Bilateral common carotid artery occlusion (15 min.) followed by two hours of recirculation reduced mitochondrial superoxide dismutase (SOD) and glutathione reductase (GR) activities, and increased susceptibility of mitochondrial membranes to in vitro lipid peroxidation in brain regions (i.e., cortex, striatum and hippocampus) of Mongolian gerbil. Intraperitoneal bolus injection (2 mg/kg b.w.) of liposome-entrapped CuZn superoxide dismutase (1-SOD) increased the endogenous SOD activity in normal brain tissue and, when given at the end of ischemia, counteracted both the ischemic reduction of endogenous SOD and the increased peroxidation of mitochondrial membranes. 1-SOD treatment was ineffective in reducing brain swelling, suggesting that superoxide radicals are not a main participant in the process of (post)ischemic brain edema formation.

Animals↗
PubMed1993

Dopamine metabolism and free-radical related mitochondrial injury during transient brain ischemia in gerbils.

Regional extracellular release of dopamine (DA) and its metabolites, 3,4-dihydroxy-phenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxytyramine (3-MT) was measured in gerbils (with or without pargyline pretreatment) subjected to bilateral carotid artery occlusion (15 min) and various periods of recirculation (up to 6 hr), utilizing intracerebral microdialysis and high-performance liquid chromatography (HPLC) with electrochemical detection. Mitochondrial monoamine oxidase (MAO) and superoxide dismutase (SOD) activities and in vitro stimulated lipid peroxidation (TBARM) were determined in separate experimental groups of animals. The ischemically induced DA release, decrease of MAO-derived DA metabolites DOPAC and HVA, and accumulation of 3-MT were potentiated and prolonged by pargyline pretreatment. Mitochondrial MAO and SOD activities were significantly reduced during ischemia alone and up to 1 hr of reperfusion, whereas TBARM was enhanced during reflow only. The data suggest that reduced activity of mitochondrial antioxidative enzyme(s) but not DA metabolism by MAO may contribute to free radical-mediated injury of (mitochondrial) membranes.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Excitatory amino acid receptors, oxido-reductive processes and brain oedema following transient ischaemia in gerbils.

A key mechanism of brain injury after cerebral ischaemia is supposed to be the iron-dependent formation of highly reactive oxygen free radicals initiated by the intracellular accumulation of calcium and promoted by the excess release of glutamate. Oxido-reductive processes (formation of superoxide radicals and lipid peroxidation) are mediated through NMDA-receptors, while non-NMDA receptors, associated with (or being a part of) Na,K-ATPase, are responsible for postischaemic brain swelling. The hypothesis was put forward for consideration that release of glutamate (and other related endogenous excitatory amino acids) due to depolarization in the early minutes of ischaemia and (non)-NMDA antagonists may have roles in the development and prevention of metabolic brain impairment and cytotoxic oedema, respectively, in the ischaemic state.

2-Amino-5-phosphonovalerate↗
PubMed1989

Cerebral ischemia: changes in monoamines are independent of energy metabolism.

The relationship of neurotransmitters and neuroeffectors to the energy state of the brain was examined in the gerbil model of ischemia after 5 and 15 min of bilateral common carotid artery occlusion only or with 1 hr of reperfusion. The gerbil brains were fixed by microwave irradiation and a total of 15 metabolites were measured from a single piece of tissue from either the hippocampus or the striatum. The rapid alterations in energy-related compounds and cyclic nucleotides appeared to be directly related both to the loss of oxygen and glucose during ischemia and the resupply of these nutrients during reflow. Significant reduction in the level of monoamines occurred principally during reflow, at a time when the energy-related metabolites were restored. It is proposed that the changes in monoamines were triggered by other ischemic-induced events unrelated to energy depletion.

Adenosine Triphosphate↗
PubMed1989

Ischemic modification of cerebrocortical membranes: 5-hydroxytryptamine receptors, fluidity, and inducible in vitro lipid peroxidation.

The effect of ischemia on the properties of 5-hydroxytryptamine1A + B (5-HT1A+B) and 5-hydroxytryptamine1B (5-HT1B) binding sites, physical-state "fluidity" of the membrane, and its susceptibility to peroxidation in vitro was investigated in the cerebral cortex of gerbils. Ischemia was induced by bilateral carotid artery occlusion for 15 min alone or with release for 1 h. Ischemia both with and without reflow decreased the number of 5-HT1A + B and 5-HT1B binding sites, whereas ischemia and reflow altered the affinity for 5-HT1B binding sites. Resistance to the temperature-dependent increase in "fluidity" of the membrane was detected (by fluorescence anisotropy using 1,6-diphenyl-1,3,5-hexatriene as a probe) after ischemia and reflow but not in ischemia alone. Susceptibility of the membranes to Fe2+- and ascorbic acid-stimulated lipid peroxidation in vitro was decreased following ischemia and recirculation only. These findings strongly suggest that the composition and the function of the membrane are markedly disturbed during recirculation after ischemia.

Animals↗
PubMed1988

Alterations in synaptosomal membrane Na,K-ATPase of the gerbil cortex and hippocampus following reversible brain ischemia.

The present experiments were designed to determine the kinetic pattern of Na,K-ATPase in the presence of varying concentrations of Na+ and K+ ions in controls and gerbils exposed to 1 and 5 min of ischemia, respectively, and 60 min and 4 days of recirculation following 5 min of transient ischemia. The pattern of Na,K-ATPase activity in the control cerebral cortex and hippocampus is different. The cortical Na,K-ATPase apparently is more resistant in keeping an optimal activity than the enzyme in the hippocampus. After ischemic insult of either 1 or 5 min in duration, the enzyme activity is inhibited in both brain structures. 4 days after 5 min of ischemia, indicating greater flexibility of the cortical enzyme or less damage than in the hippocampus. Furthermore, the data obtained show that only through the enzyme behavior and kinetic parameters is it possible to reach conclusions about the enzyme function or dysfunction under pathological conditions.

Animals↗
PubMed1988

Effect of ischemia on noradrenergic and energy-related metabolites in the cerebral cortex of young and adult gerbils.

Relationships between ischemic changes in the cerebral cortical content of energy and noradrenergic metabolites were evaluated in young and adult gerbils. Groups of 3-week- and 3-month-old gerbils were subjected to 5 or 15 min of bilateral carotid artery occlusion alone or with 1 hr of release. Ischemia of 5 and 15 min depleted energy-related metabolites but did not affect the content of either norepinephrine or homovanillic acid in young and adult gerbils. At 1 h of reflow, after 5 and 15 min of ischemia, the levels of norepinephrine significantly decreased, while those of homovanillic acid increased in the adult but not in the young gerbils. At this time a complete recovery of energy reserves was seen in both the young and the adult gerbils. These results indicate that the ischemic change in homeostasis of energy metabolism is not directly associated with that of the noradrenergic system in young and adult cerebral cortex.

Aging↗
PubMed1988

Delayed hypometabolism induced by bilateral ischemia in the gerbil: regional metabolic thresholds.

The common carotid arteries were occluded in gerbils for 5 min and the metabolic rate was estimated by measuring the loss of high-energy phosphate equivalents at 4 days of reperfusion in the cerebral cortex, hippocampus, and striatum. Metabolites values at 4 days of reperfusion were not different from those of controls with the exception of glycogen, which was significantly elevated in the hippocampus. The metabolic rate, as determined by the "closed-box" method at 4 days of reflow, was decreased by more than 50% in all three regions after 5 min of bilateral ischemia. The ischemic time necessary to elicit the hypometabolic response at 4 days of reflow was 2, 3 and 4 min for the striatum, hippocampus, and cortex, respectively. It is suggested that delayed postischemic hypometabolism may be a component of an adaptive process which counteracts, to varying degrees, the deleterious effects of ischemia depending on the region examined.

Adenosine Triphosphate↗
PubMed1988

Glutathione reductase during and after brain ischemia in gerbils.

The activity of glutathione reductase (GR) was measured in crude mitochondrial fraction isolated from cerebral cortex and basal ganglia of Mongolian gerbils subjected to bilateral carotid occlusion of various duration (1, 2, 3, 5, 10, and 15 min), or reflow (1, 24, and 96 hr) following ischemia (5 or 15 min). Ischemia up to 5 min does not induce changes in GR activity in either structure. Basal ganglia activity is halved at 10 min and cortical at 15 min of ischemia. In reflow, basal ganglia GR activity is diminished, while cortical GR is transiently reduced at day 1 of reflow. The persistent and profound decrease in GR activity in basal ganglia following ischemia is indicative of the lowered antioxidative capacity of these cells, being possibly related to their greater vulnerability toward ischemia.

Animals↗
PubMed1987

Depression and Parkinson's disease: possible role of serotonergic mechanisms.

Depression is frequently encountered in Parkinson's disease and was seen to occur in 14 of 26 patients studied. The levels of 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of serotonin (5-HT), in CSF samples of the patients were significantly lower than in those of controls. However, within the group of patients the levels of 5-HIAA in CSF samples were significantly lower in the depressive subgroup compared with the non-depressive patients. Moreover, no correlation was recorded between motor disability and depression. The results indicate that disturbed 5-HT metabolism may possibly play a role in Parkinson's disease as a predisposing factor in the development of depression.

Aged↗
PubMed1987

Cerebrocortical modulation of S2-receptors and turnover rate of 5-hydroxytryptamine in ischemia.

A possible relationship between the changes in the properties of S2-receptor binding sites and the turnover rate of 5-hydroxytryptamine (5-HT) has been investigated in cerebral ischemia associated with either little or marked edema. Bilateral common carotid artery occlusion for 5 or 15 min with 1 hour of reestablished blood flow in gerbils served as a model for the respective studies. An alteration in kinetic characteristics of S2-receptor binding sites labeled with [3H]ketanserin (the potent 5-HT antagonist for postsynaptic receptors) was detected in the synaptosomes separated from brains of gerbils subjected to 1 hour release after 15 but not following 5 min of bilateral ischemia. At the same time, an increased turnover rate of 5-HT was found in the cerebro-cortical homogenate. The duration of ischemic insult which leads to the changes in the properties of S2-binding sites and the increase in turnover rate of 5-HT has been identical with that needed for the marked accumulation of water in the gerbil brain reported previously. Thus, these findings are consistent with the implicated involvement of 5-HT in the formation of ischemic cerebral edema.

Animals↗
PubMed1987

Cyclic nucleotides in cerebrospinal fluid of drug-free Parkinson patients.

Concentrations of cyclic nucleotides--adenosine-3',5'-monophosphate (c-AMP) and guanosine-3',5'-monophosphate (c-GMP)--were measured in cerebrospinal fluid (CSF) of 17 drug-free Parkinson patients and 12 controls. No significant difference between the cyclic nucleotide contents (p greater than 0.05) in CSF of patients and controls was detected, nor was there a correlation between the content and the degree of neurological disability. Besides, no changes in the cyclic nucleotide contents were detected in the subgroups of patients according to the prominence of tremor or rigidity/akinesia as the main symptoms of the disease.

Cyclic AMP↗
PubMed1987

Effect of single and repeated scalding on adenine nucleotides concentration in rat liver.

Changes in ATP, ADP, AMP, and total adenine nucleotide (TAN) concentrations and in the adenylate energy charge (EC) were investigated in the livers of rats subjected to single and repeated scalding. Single scaldings were of two grades of severity: 20% (nonlethal) and 40% (lethal within 24 hr) of the total body surface area. A repeated scald (additional 20%) was inflicted on the intact skin of the opposite side of the body either 3 hr or 3 days after a nonlethal scald. The results suggest that the energy state of the liver is related to the severity of a single scald, that the EC at the moment of repeating the scald is important for survival, and that the changes in ATP, EC, and TAN following a repeated scald are qualitatively or quantitatively different from those after a single scald.

Adenine Nucleotides↗
PubMed1986

Modulation of glycogen metabolism in cerebromicrovascular smooth muscle and endothelial cultures.

The separately cultured smooth muscle and endothelial cells derived from dissociated cerebral microvessels are characterized by high content of glycogen. Norepinephrine induces glycogenolysis while 5-hydroxytryptamine stimulates glycogenesis in both cell types. The endogenous glucose of the endothelium but not that of the smooth muscle serves as a direct source for the 5-HT enhancement of glycogen formation. Indomethacin, the known inhibitor of cyclooxygenase modulates the glycogen content in the smooth muscle only. These findings strongly suggest that the carbohydrate metabolism of each cell has a distinct control mechanism compatible with the underlying integral microvascular function.

Adenosine Triphosphate↗