Biomedical subjects

R Rejdak

Publications and source records attributed to R Rejdak.

14 recordsLinked to original sources

PubMed2006

Homocysteine levels in aqueous humor and plasma of patients with primary open-angle glaucoma.

We determined homocysteine (Hcy) levels in aqueous humor (AH) and plasma and their association with B-vitamin levels in patients with primary open-angle glaucoma (POAG) and controls. Both AH Hcy and plasma Hcy levels were significantly increased in POAG, and elevation of AH Hcy and plasma Hcy was a significant risk factor for POAG. In contrast to controls, neither plasma nor AH Hcy of POAG patients demonstrated a significant association with important non-genetic determinants of elevated Hcy such as low B-vitamin levels, increasing age and caffeine consumption. Considering that Hcy is a neurotoxin that induces apoptotic retinal ganglion cell death via stimulation of the N-methyl-D-asparate (NMDA) receptor, increased Hcy concentrations in AH and plasma might contribute to the optic nerve damage in POAG.

Aged↗

PubMed2006

Kynurenic acid synthesis in bovine retinal slices--effect of glutamate agonists.

The purpose of the present study was to investigate the effect of glutamate agonists upon kynurenic acid (KYNA) production in bovine retinal slices. Quantitative analysis of newly synthesized KYNA was carried out using an HPLC system and detected fluorimetrically. Glutamate at the concentration of 0.01, 0.1 and 1 mM reduced KYNA synthesis in the retinal slices to 70% (p < 0.05), 35% (p < 0.01) and 23% (p < 0.001), respectively. The concentration of glutamate reducing production of KYNA by 50% (IC(50)) was 0.035 mM (0.02-0.06). Aspartate at the concentration of 0.01, 0.1 and 1 mM lowered KYNA synthesis in the retinal slices to 80% (p < 0.01), 57% (p < 0.001) and 43% (p < 0.001), respectively. In contrast, kainic acid (up to 5 mM), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) (up to 1 mM) and 1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD) (up to 3 mM) turned out to be ineffective in diminishing KYNA synthesis. These data demonstrate that glutamate, aspartate and N-methyl-D-aspartate (NMDA) inhibit KYNA synthesis in bovine retinal slices with different potency.

Animals↗

PubMed2001

Presence of kynurenic acid and kynurenine aminotransferases in the inner retina.

Kynurenine aminotransferases (KATs I and II) are pivotal to the synthesis of kynurenic acid (KYNA), the only known endogenous glutamate receptor antagonist and neuroprotectant. This study is the first to identify KYNA in the rat retina and to examine immunohistochemically the distribution of KAT isoforms. As determined by HPLC, KYNA concentration in the retina was 99.9 +/- 24.6 pmol/g wet wt. Immunohisto- chemical experiments showed that both KATs were present in the retina. KAT I was preferentially localised on Müller cell endfeet while KAT II was expressed in cells within the ganglion cell layer. In conclusion, KYNA is present and synthesised in the inner retina. This may suggest a modulatory role in glutamate-mediated retinal neurotransmission.

Animals↗

PubMed2001

2-deoxyglucose enhances epileptic tolerance evoked by transient incomplete brain ischemia in mice.

The aim of the study was to assess the influence of chronic treatment with a non-metabolisable glucose analogue, 2-deoxyglucose (2-DG) at a 150 mg/kg dose on long-term epileptic tolerance (ET) evoked by 30 min bilateral carotid artery clamping (BCCA) in mice. The effects of protein synthesis inhibition with cycloheximide (CHX), given in three daily doses of 2.5 mg/kg starting either 1 day before (peri-insult regimen) or 1 day after the priming insult (post-insult regimen), on ET development was also studied. Seizures were induced 14 days after BCCA with 3.5 mg/kg of bicuculline; this dose (CD97) evokes convulsions in 97% of normal untreated mice. BCCA resulted in decreased mortality, prolonged latency to the onset of generalised convulsions and decreased overall seizure score. CHX given in the post-insult regimen did not influence, while the peri-insult regimen abolished, all signs of BCCA-evoked ET. 2-DG treatment of sham-operated animals resulted in a moderate but significant decrease in mortality rate and a tendency toward a lower seizure score. BCCA combined with 2-DG treatment resulted in a marked decrease in mortality rate, as well as reduction in all indicators of seizure susceptibility. CHX abolished the antiepileptic effects of BCCA alone, as well as BCCA combined with 2-DG, while it did not influence the 2-DG-related decrease in mortality. We conclude that the development of BCCA-induced epileptic tolerance, as well as unmasking antiepileptic effects of 2-DG by BCCA, is dependent on protein synthesis.

Animals↗

PubMed2001

The effects of citicoline and/or MK-801 on survival, neurological and behavioral outcome of mice exposed to transient hyperglycemia and oligemic hypoxia.

UNLABELLED: The effects of citicoline and/or low dose of MK-801 (sufficient to prevent the development of seizures) on survival, neurological and behavioral recovery following transient hyperglycemic-oligemic-hypoxic insult have been evaluated in mice. Neurological recovery was assessed semi-quantitatively on the third and the 10th day after the insult, and behavioral tests evaluating spontaneous locomotor activity, motor coordination and spontaneous alternation performance were performed on day 10. Neither drug given alone did influence survival rate, but the combination of MK-801 and higher citicoline dose decreased mortality on day 10. Behavioral performance was markedly compromised by the insult. Citicoline, but not MK-801, slightly but significantly improved behavioral outcome in all three tests. CONCLUSION: when brain ischemic insult is complicated with acute hyperglycemia, post-treatment with citicoline combined with MK-801 in low anti-convulsive dose improves survival and neurological recovery, and citicoline but not MK-801 enhances behavioral recovery.

Animals↗

PubMed2000

The influence of CGP-40116 on bicuculline evoked seizures in mice exposed to transient episode of brain oligemia.

To assess the role of NMDA receptors in the modulation of a brain tolerance after a transient cerebral mild ischemia, adult mice were exposed for 30 min to bilateral clamping of the common carotid arteries (BCCA) under pentobarbital anaesthesia. The competitive NMDA antagonist CGP-40116 was administered intraperitoneally (i.p.) in two experimental paradigms: a) acute treatment: twice, 4.0 mg/kg; 1.5 hour before the clamping of vessels and 6 hours after re-circulation and b) chronic treatment in a dose of 1.0 mg/kg; started 24 hours after re-circulation and continued once daily for 13 days with the last injection 24 hours before the induction of convulsions. Seizures were evoked with bicuculline (3.5 mg/kg, i.p.) 14 days after BCCA. Transient brain oligemia induced protection against bicuculline toxicity. The acute treatment with CGP-40116 only partially diminished the anticonvulsant phenomenon. In contrast, the chronic treatment with the drug markedly potentiated the effect. It can be concluded that NMDA receptors only partially participate in the induction of a protective effect against bicuculline toxicity after BCCA. The chronic treatment with low doses of the NMDA antagonist may enhance the brain tolerance, possibly due to the chemical preconditioning.

2-Amino-5-phosphonovalerate↗

PubMed2000

The influence of MK-801 on bicuculline evoked seizures in adult mice exposed to transient episode of brain ischemia.

The aim of the study was to examine the role of NMDA receptors in modulation of protective effect against bicuculline toxicity after transient brain ischemia in mice. Animals were exposed for 30 min to bilateral clamping of the common carotid arteries (BCCA) in anaesthesia. MK-801 was administered intraperitoneally in two paradigms: a) acute treatment: twice, 1.0 mg/kg; 1 hour before clamping and 6 hours after re-circulation and b) chronic treatment: 0.1 mg/kg; started 24 hours after re-circulation and continued once daily for 13 days, the last injection was administered 24 hours before seizure induction. 14 days after BCCA, the animals were injected with bicuculline (3.5 mg/kg s.c). A significant decrease in seizure susceptibility could be observed in BCCA treated mice compared with sham-operated controls. Acute treatment with MK-801 did not affect seizure activity both in sham and BCCA mice. Chronic treatment with the drug potentiated anticonvulsant effect of brain ischemia but had no influence on seizure activity in sham-operated mice. The analysis of GABA content in brain tissue performed 14 days after BCCA showed a moderate increase in vehicle-treated mice and significant elevation after chronic treatment with MK-801. It can be suggested that NMDA receptors are not involved in the induction of a protective effect against bicuculline toxicity after transient brain ischemia. The prolonged treatment with low doses of MK-801 may potentiate a developed process in a mechanism of chemical preconditioning.

Age Factors↗

PubMed2000

Synthesis and pharmacological properties of 1-(4-substituted)butyl derivatives of amides of 7-methyl-3-phenyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimi dine-5 -carboxylic acid.

The synthesis of 1-(4-substituted)butyl derivatives of amides of 7-methyl-3-phenyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimid ine-5- carboxylic acid and the results of the preliminary pharmacological screening are described in this paper. Some of them showed a weak analgesic action and caused suppression of the spontaneous locomotor activity of mice.

Analgesics, Non-Narcotic↗

PubMed2000

The effect of CGP-40116 on pilocarpine evoked seizures in mice exposed to transient episode of brain ischemia.

The objective of the study was to examine the role of N-methyl-D-aspartate (NMDA) receptors in the modulation of a brain tolerance after a transient cerebral ischemia. Adult mice were exposed for 30 min to bilateral clamping of common carotid arteries (BCCA) under anaesthesia. The competitive NMDA antagonist CGP-40116 was administered intraperitoneally (i.p.) in two experimental paradigms, (a) acute treatment: twice, 4.0 mg/kg; 1.5 h before the clamping of vessels and 6 h after re-circulation and (b) chronic treatment in a dose of 1.0 mg/kg; started 24 h after re-circulation and continued once daily for 13 days with the last injection 24 h before the induction of convulsions. Seizures were evoked with pilocarpine (400 mg/kg, i.p.) 14 days after BCCA. The preliminary study showed that BCCA induced protection against pilocarpine toxicity. The acute treatment with CGP-40116 partially diminished the anticonvulsant phenomenon. In contrast, the chronic treatment with the drug led to a marked potentiation of the effect. The whole brain gamma-aminobutyric acid (GABA) analysis performed 14 days after BCCA showed a moderate increase in vehicle-treated mice and a significant elevation after chronic treatment with CGP-40116. It can be concluded that NMDA antagonists may exert the opposite effects on the brain tolerance against pilocarpine toxicity after BCCA. The acute treatment with CGP-40116 diminished its induction while the chronic low-dose treatment enhanced a brain tolerance, possibly through the mechanism of chemical preconditioning.

2-Amino-5-phosphonovalerate↗

PubMed2000

Synthesis of some N-substituted 3,4-pyrroledicarboximides as potential CNS depressive agents.

As a continuation of our work on N-[4-aryl(heteroaryl)piperazin-1-ylalkyl]-3,4-pyrro ledicarboximides, which were characterized by strong analgesic activity and CNS depressive action, several novel N-substituted 3,4-pyrroledicarboximides were prepared and eleven representatives were examined in a series of in vivo CNS tests. A few of these compounds displayed a similar profile of biological selectivity to that of 3,4-pyrroledicarboximides described previously; their structure-activity relationships are discussed.

Amphetamine↗

PubMed2000

[The mechanisms of neuronal death and advances in the neural protection in epilepsy].

Epilepsias are chronic central nervous system diseases which manifest by recurrent seizures. They may be classified into channelopathies resulting from mutations of ionic channels or receptors for neurotransmitters, and epilepsias which are secondary to cortical damage and result from the reconstruction of cortical neural networks. Chronic or generalized seizures initiate processes called the "excititoxic cascade" the effector side of which, quite similar to that of the "ischemic cascade", may lead to neuronal death through either apoptosis or necrosis. Therefore, complementing pharmacological treatment of epilepsia with neuroprotective substances such as free radical scavenger or CDP-choline which blocks the activation of phospholipase A2 may be indicated.

Brain↗

PubMedDate not supplied

Evidence for intraocular synthesis of kynurenic acid, a putative endogenous neuroprotectant.

Kynurenic acid (KYNA), an excitatory amino acid antagonist preferentially active at glycine binding site of the NMDA receptor, has been previously identified in the brain. This study was designed to examine its presence in the rabbit vitreous humor. Mean (+/- SD) level of KYNA in the vitreous was 22.3 +/- 3.9 pmol/ml as determined by HPLC. Intravitreal administration of 10 mmol aminooxyacetic acid (AOAA), a KYNA synthesis inhibitor, diminished its production by 9.6% after 2 h, 47.8% after 24 h and 21.5% after 48 h. It can be concluded that AOAA decreases the intravitreal concentration of KYNA, providing evidence of its intraocular origin.

Aminooxyacetic Acid↗

PubMedDate not supplied

Effect of MK-801 on pilocarpine-evoked seizures in mice exposed to transient incomplete brain ischemia.

The aim of the study was to examine the role of NMDA receptors in the modulation of brain tolerance after transient cerebral ischemia. Adult mice were exposed for 30 min to bilateral clamping of common carotid arteries (BCCA) under anaesthesia. The non-competitive NMDA antagonist, MK-801 was administered intraperitoneally (ip) in two experimental paradigms: a) acute: twice at 1.0 mg/kg; 1 h before the clamping of the vessels and 6 h after re-circulation; b) chronic at a dose of 0.1 mg/kg, started 24 h after recirculation and continued once daily for 13 days with the last injection 24 h before the induction of convulsions. Seizures were evoked with pilocarpine (400 mg/kg, ip) 14 days after BCCA. It was found that transient incomplete brain ischemia induced protection against pilocarpine toxicity. The acute treatment with MK-801 did not diminish the anticonvulsant action of the procedure. In contrast, the chronic treatment with the drug led to a marked potentiation of the effect. In conclusion, it can be suggested that studied NMDA receptor antagonist used at relatively low dose may enhance the brain tolerance activated after a transient ischemic episode.

Animals↗

PubMedDate not supplied

Brain tolerance and preconditioning.

In this review article the authors describe a phenomenon of "brain tolerance" which represents transient resistance of brain tissue to a lethal insult established by preconditioning with a mild insult of short duration. Tolerance evoked by brief ischemia resembles transient ischemic attack(s) (TIA) often preceding full-blown ischemic stroke in a clinical setting. A series of recent studies have described another relevant phenomenon termed "chemical preconditioning". Several substances interfering with cellular energy metabolism applied in subtoxic doses may provide protection against lethal insults of a different type. For example, 3-nitropropionic acid (3-NP), antibiotics erythromycin and kanamycin, acetylsalicylic acid, and 2-deoxyglucose have been shown to evoke tolerance. Recently, we have reported that NMDA receptor antagonists and 2-deoxyglucose used at relatively low doses were potent agents to potentiate the protective anticonvulsant effect induced by transient brain mild ischemia. Further studies are expected to prove similar action of these drugs in other experimental models. Based on the accumulated experimental and clinical data the brain tolerance subsequently reinforced by pharmacological intervention might become a successful prophylactic strategy against serious brain insults in patients.

Brain↗