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Biomedical subjects

K Rejdak

Publications and source records attributed to K Rejdak.

At least 19 recordsLinked to original sources
PubMed2006

Increased urinary excretion of nitric oxide metabolites in longitudinally monitored migraine patients.

This study evaluated a relationship between nitric oxide (NO) and migraine attacks in order to gain insight into migraine pathomechanism. The study groups consisted of 12 migraineurs and eight controls. All subjects collected morning urine samples for 40 consecutive days. Urinary NO metabolites, nitrite/nitrate (NO(x)) levels were measured with the vanadium-based assay, whilst creatinine (Cr) and neopterin were determined with high-performance liquid chromatography. The mean urinary NO(x)/Cr ratio and number of NO(x) peaks was significantly greater in the migraine group compared with controls (P = 0.01 and P = 0.007, respectively). In the second approach, high NO(x) values were re-assessed in relation to raised neopterin, a marker of systemic infection or inflammation, and were excluded. The excretion of NO(x) persisted being pulsatile, and migraineurs had more peaks compared with controls (P = 0.01). In seven patients, NO(x) peaks coincided with headache days. This was more frequent than expected by random association in four patients (Monte-Carlo simulation; odds ratios: 2.16-7.77; no overlap of 95% CI). In four patients, NO(x) peaks preceded or followed headache days. Although there is a difference in the pattern of urinary NO(x) excretion between control and migraine populations, the variable temporal association of NO(x) peaks and headaches suggests a complex role of NO in this condition.

Biomarkers↗
PubMed2005

Axonal pathology in subarachnoid and intracerebral hemorrhage.

Electrically active axons degenerate in the presence of nitric oxide (NO) in vitro. High CSF NO concentrations have been observed in patients with hemorrhagic brain injury such as subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH). This study investigated the evidence for axonal injury in SAH and ICH and related this to CSF NO levels. In this study, neurofilament phosphoforms (NfH(SMI34), NfH(SMI35), NfH(SMI38), NfH(SMI310)), surrogate markers for axonal injury, and NO metabolites (nitrate, nitrite = NOx) were measured by ELISA in cerebrospinal fluid (CSF) from patients with SAH and ICH and from a group of controls. Injury severity was classified using the Glasgow Coma Scale, and survival was used as the outcome measure. Compared to the control group, a higher proportion of patients with SAH and ICH had elevated NfH(SMI34) levels from day 0 to day 6 (p < 0.001), elevated NfH(SMI35) levels from day 1 to 6 (p < 0.001), and elevated NfH(SMI310) levels at day 0, 1, 4, and 6 (p < 0.001). The NOx levels were higher in the SAH and ICH patients than in the controls (p < 0.05) and distinguished the non-survivors from the survivors (p < 0.05). No direct correlation was found for NOx with any of the NfH phosphoforms. This study provides evidence for primary and secondary axonal injury in patients with SAH and ICH, with non-survivors also having higher NOx levels. CSF NfH phosphoforms might emerge as a putative surrogate marker for monitoring the development for secondary axonal degeneration in neurocritical care and guiding targeted neuroprotective strategies.

Adult↗
PubMed2004

CSF nitric oxide metabolites are associated with activity and progression of multiple sclerosis.

OBJECTIVE: To investigate the relationship of CSF and the serum nitric oxide metabolites nitrite and nitrate (NOx) to disease activity and progression in patients with multiple sclerosis (MS). METHODS: The study was divided into cross-sectional and follow-up. In the cross-sectional study, 20 patients with relapsing-remitting (RR), 21 with secondary progressive (SP), and 10 with primary progressive (PP) MS and 14 control subjects were included. Patients were assessed on clinical (Expanded Disability Status Scale [EDSS], Ambulation Index [AI], 9-Hole Peg Test [9-HPT]) and MRI measurements. In the follow-up study, 34 MS patients from the cross-sectional study agreed to be assessed again after an average of 3.0 +/- 0.5 years. NOx was measured using a vanadium-based assay. RESULTS: In the cross-sectional study, CSF NOx was raised in patients with RR-MS (p = 0.001) and PP-MS (p = 0.02) vs controls. Higher CSF NOx levels were found in patients with mild disability (AI < or = 6.0; EDSS < or = 4.0; Multiple Sclerosis Severity Score [MSSS] < or = 4.8) vs patients with advanced disease (AI > 6.0 [p = 0.002]; EDSS > 4.0 [p = 0.02]; MSSS > 4.8 [p = 0.01]). In the subgroup of patients having Gd-enhancing MRI lesions (n = 11), correlation between the volume of enhancement and CSF NOx was found (r = 0.74, p = 0.01). In the follow-up study, patients with disability progression had higher baseline CSF NOx levels than those who were stable on EDSS (p = 0.02) or AI (p = 0.03). A positive correlation was found between baseline CSF NOx and the change in MR T2-weighted lesion load (r = 0.4, p = 0.03). CONCLUSIONS: CSF nitrite and nitrate levels were increased in mildly disabled patients with MS and found to correlate with the volume of Gd-enhanced lesions on MRI. Raised baseline CSF NOx was associated with clinical and MRI progression in MS patients over 3-year follow-up.

Adult↗
PubMed2004

Axonal degeneration and inflammation in acute optic neuritis.

AIMS: To investigate whether plasma biomarkers for axonal injury and inflammation are related to loss and recovery of visual function in acute optic neuritis (ON). METHODS: Eighteen patients with ON and 14 controls were investigated in a longitudinal, prospective study. Plasma phosphorylated neurofilament heavy chain (NfHSMI35; a surrogate marker of axonal injury), nitric oxide metabolites (NOx), and citrulline (surrogate markers of inflammation) were measured. RESULTS: Patients with ON had higher median plasma NfHSMI35 values than controls (0.17 versus 0.005 ng/ml; p < 0.05) and higher NOx values (49 versus 35.5 microM; p < 0.001). Plasma NfHSMI35 values correlated inversely with visual acuity at presentation (R = -0.67; p = 0.01). NfHSMI35 was higher in patients with poor recovery of visual acuity than in those with good recovery (0.25 ng/ml versus 0.09 ng/ml; p < 0.05). Three of four patients with high NfHSMI35 and high NOx values experienced a poor recovery as opposed to only one of five with high NOx but normal NfH(SMI35) values. CONCLUSIONS: NfHSMI35, a surrogate marker for axonal damage, is a prognostic indicator and should be considered in the design of neuroprotective treatment strategies.

Acute Disease↗
PubMed2004

Treatment response in relation to inflammatory and axonal surrogate marker in multiple sclerosis.

BACKGROUND: This study aimed to investigate if treatment response could retrospectively be related to inflammatory or axonal pathology as measured by plasma surrogate markers. METHODS: In this 1-year observational study 30 multiple sclerosis (MS) patients with relapsing-remitting disease were treated with intramuscular IFNbeta-1a or subcutaneous IFNbeta-1b. Responders and nonresponders were defined according to clinical and magnetic resonance imaging criteria. The control group consisted of 14 healthy subjects. Plasma levels of surrogate markers for inflammation (nitric oxide metabolites (NOx)), astrocytic activation (S100B) and axonal damage (NfH(SM135)) were measured using standard assays. RESULTS: There were 11 nonresponders and 19 responders to IFNbeta treatment. Median S100B levels were elevated in a higher proportion of treatment responders (63%, 42.9 pg/mL) compared to nonresponders (18%, 11.7 pg/mL, P < 0.05, Fisher's exact test) and controls (0%, 2 pg/mL, P < 0.001). Levels of NOx were found to be more frequently elevated in nonresponders (72%, 39 microM) compared to healthy controls (0%, 37 microM, P < 0.05). Levels of NfH(SM135) were more frequently elevated in responders (58%, 300 pg/mL, P < 0.001) and nonresponders (72%, 500 pg/mL, P < 0.001) compared to controls (0%, 4.5 pg/mL). CONCLUSION: Patients with relapsing-remitting MS who had surrogate marker supported evidence for astrocytic activation responded more frequently to treatment with IFNbeta.

Adjuvants, Immunologic↗
PubMed2003

Serum and urine nitrate and nitrite are not reliable indicators of intrathecal nitric oxide production in acute brain injury.

This study examined the correlation between nitric oxide (NO) metabolites in the three major body fluid compartments and assessed performance of newly described vanadium-based assay for simultaneous detection of nitrite and nitrate (NO(x)) in human samples. Vanadium reduces nitrate to nitrite, which can be measured after a colorimetric reaction with Griess reagents. Cisternal cerebro spinal fluid (CSF), serum and urine samples from 10 patients with acute brain injury (ABI) were compared to control subjects. Significantly higher CSF NO(x) levels were found in brain injury patients compared to control patients (19.7+/-13.7 vs. 6.5+/-2.3 microM; p=0.01), which persisted for 10-day period of observation. The serum and urine levels of NO(x) on admission were not statistically different (42.8+/-28.2 microM; 584.1+/-337.8 micromol/g Cr, respectively) from controls (36.8+/-14.8 microM; 819.7+/-356.0 micromol/g Cr), but tended to decrease during the disease course reaching the lowest level on day 6 (serum: 19.3+/-8.4 microM, urine: 300.4+/-111.9 micromol/g Cr). CSF levels of NO(x) correlated moderately with those in serum (p=0.001, R=0.5). Serum NO(x) concentrations correlated weakly with urine levels (p=0.04, R=0.3). There was no significant correlation between CSF NO(x) and urine NO(x) levels. In conclusion, patients suffering brain injury had increased NO(x) concentrations in CSF, which remained independent from other body fluid compartments. Serum and urinary NO(x) levels cannot be used as a reliable index to assess intrathecal NO production.

Adult↗
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↗
PubMed2001

Postgraduate education in neurology in Central and Eastern Europe.

The policy of the European co-operation in the new atmosphere of an international solidarity became one of the priorities of the European Federation of Neurological Societies (EFNS). It could be hardly pursued more efficiently in any other field of neurological performance as in education. To review several aspects of neurological practice and education the 'First European Co-operation Neurology Workshop' was held in the castle of Trest', Czech Republic, 13-20 April 2000. Participants from 15 countries (Albania, Belarus, Bulgaria, Croatia, Czech Republic, Estonia, Georgia, Hungary, Moldova, Poland, Romania, Russia, Slovak Republic and Slovenia), covering a region of 316 million inhabitants and 25 000 neurologists, presented their national postgraduate education systems (besides other topics). We refer data on density of medical doctors and that of neurologists, pre-board certification phase, board examination, continuing medical education (CME), and qualification rewards. Illustrative data were put in the comparative tables. This first meeting has founded the basis for a dynamic future collaboration in order to continue the integration process and an exchange of current information regarding CME amongst central and eastern countries as well as western Europe.

Certification↗
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

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

Head trauma and neuroprotection.

Traumatic brain injury is a serious clinical problem connected with high mortality rate and long-term neurobehavioral and socioeconomic consequences. Pathomechanism of such insult is complex and not clear in all aspects as yet. Thus, a primary mechanistic insult to the brain initiates metabolic and inflammatory processes which exacerbate the primary traumatic injury to neurons, leading to secondary brain damage. In this paper we present the main components of destructive cascade with relevant theoretical strategy for neuroprotection. It should be emphasized that pathological processes involved in secondary brain damage are complex and interrelated. It makes blockade of a single mechanism unlikely to prevent either early or delayed cellular death.

Apoptosis↗
PubMedDate not supplied

Interleukin-6 concentration in serum and cerebrospinal fluid in multiple sclerosis patients.

INTRODUCTION: The aim of the investigation was to determine pleiotropic cytokine IL-6 concentrations in serum and CSF of MS patients, with regard to clinical circumstances. MATERIAL AND METHODS: The study covered 27 MS patients: 23-51 years old; in the 2-7 clinical stage according to Kurtzke's Scale; mean 3.6 +/- 1.8; disease duration time ranged between 2-22 years. Serum and CSF interleukin-6 were determined by the use of commercial ELISA kits. RESULTS: Increase of Il-6 in serum of MS patients was found (12.1 +/- 1.8 pg/ml) in comparison to the control group (6.6 +/- 4.5 pg/ml) (p = 0.03). Concentration of IL-6 in CSF of MS patients was 13.4 +/- 1.77 pg/ml and in the majority of patients it was higher than in the serum. The highest mean of IL-6 concentrations in serum and CSF have been found in patients at the longer disease duration time, although there were not statistically significant. We have found some degree of dependence between serum IL-6 concentration and the level of disability in Kurtzke's scale. CONCLUSIONS: IL-6 participation in the basic MS immune processes is confirmed by its elevated concentration in serum and CSF, its relation to disease severity with the more expressed rise in cerebrospinal fluid.

Adult↗
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↗