bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of cytochrom c and Bad protein in post‐ischemic neuronal death – CsA protection
Authors: Dłużniewska J. , Zabłocka B. , Kozłowska H. , Sarnowska A. , Domańska‐Janik K. 
Published: May 2003

We have estimated cytosolic cytochrom c (cCyt c) as a measure of mitochondria permeability (MP) and its inhibition by CsA. In hippocampus of gerbils subjected to 5 min ischemia, cCyt c increased biphasically: transiently at 0.5 h and then steadily at ≥24 h. Involvement of proapoptotic protein Bad in the mechanism of MP after ischemia was studied too. Immediate interarterial infusion of CsA (10 mg/kg) totally inhibited early Cyt c translocation and protected CA1 neurons. This effect disappears with delayed application of the drug. Temporal ability of CsA to block apoptotic signaling and Cyt c translocation was verified on primary cortical neurons in vitro by confocal immuno‐imaging. The results confirm time‐limited effectiveness of CsA to inhibit mitochondrial cyclophilin D connected permeability to Cyt c and to protect hippocampus by relatively narrow ‘window of opportunity’ after ischemic insult.Acknowledgements:  Supported by PBZ‐KBN‐002/CD/P05/2000 and statutory theme 4.
Neonatal neurodegeneration after N‐acetyl‐aspartylglutamate (NAAG) administration in rat hippocampus
Authors: Bubeníková V. , Balcar V. J. , Druga R. , Pliss L. , Št'astný F. 
Published: May 2003

NAAG, an agonist at Group II metabotropic glutamate receptors and at the N‐methyl‐d‐aspartate (NMDA)‐type of ionotropic glutamate receptor, was infused at 250 nmoles in 0.25 μL of saline into each cerebral ventricle of 12‐day‐old rat pups. Proportion of pycnotic neurons was determined in 100 × 200 μm areas of medial and lateral blades of DG, and in areas CA1, CA3a, b of both dorsal and ventral hippocampus. In some sections we used Fluoro‐JADE‐B staining to visualize degenerating neuronal cell bodies. There was a marked neurodegeneration, particularly in the medial blade of DG, at 24 h after the administration of NAAG but it was lower at the 4‐day time point. No significant damage was observed in 50‐day‐old rat. The results indicate that early postnatal administration of NAAG can cause serious loss of neurons in rat hippocampus.Acknowledgement:  Supported by LNOOB122 MEYS CR.
Is quinolinic acid involved in etiopathogenesis of schizophrenia?
Authors: Št'astný F. , Tejkalova H. , Lisy V. , Buben´ıková V. , Balcar V. J. 
Published: May 2003

Retroviruses have been proposed as one of the infectious agents involved in the pathogenesis of schizophrenia. They can cause neuronal death by endogenous toxin(s), such as quinolinic acid (QUIN), released by virus‐activated brain macrophages/microglia. QUIN is an endogenous excitotoxin, with an affinity at specific NMDA‐R heteromers. We have administered QUIN to 12‐day‐old rat males by infusions of 250 nmol QUIN into each lateral ventricle. On day 50 the rats exhibited a tendency to higher basal acoustic startle responses (120 dB), but their prepulse inhibition (PPI) was deficient at 73, 75 and 80 dB. The deficit in PPI correlated with the neuronal losses and with the decreased receptor binding of [3H]glutamate in lesioned brains. The data provide further evidence that the toxin‐induced neuronal deficit and glutamate‐receptor loss in supra‐pontine brain regions may impair sensorimotor gating in the animal model of schizophrenia.Acknowledgement:  Supported by IGA MH CR No. NF6031‐3.
Differences in reversed plasmalemmal Na/Ca exchange activities among neuronal subtypes
Authors: Kiedrowski L. 
Published: May 2003

Under pathological conditions, when the Na+ and K+ concentration gradients collapse, plasmalemmal K‐dependent (NCKX) and K‐independent Na/Ca exchangers (NCX) may reverse and contribute to toxic Ca2+ accumulation. Vulnerability to ischemia or excitotoxicity greatly varies among neuronal subtypes and may be related, in part, to differences in reverse NCKX and/or NCX activities. Cultured cerebellar granule cells (CGCs) are more resistant to excitotoxicity than forebrain neurons (FNs). To examine whether NCKX or NCX activities in CGCs differ from those in FNs, cytosolic [Ca2+] transients mediated by reversed NCX and NCKX were monitored. NCKX and NCX reversal was triggered by gramicidin‐induced Na+ influx and K+ efflux. The NCX reversal was inhibited by 10 μm KB‐R7943, and that of NCKX by removal of external K+. In FNs, reversed NCX activity was much more robust than in CGCs, however, activity of reversed NCKX was similar. These data support the idea that vulnerability to excitotoxicity may be linked to reversal of plasmalemmal Na/Ca exchangers.Acknowledgement:  Supported by NS37390.
Total antioxidant capacity of human blood plasma from healthy adults
Authors: Lipińska S. , Gorąca A. , Nowak D. 
Published: May 2003

Reactive oxygen species are produced as a consequence of normal aerobic metabolism and could be important causative agents of a number of human diseases. Human serum contains many different antioxidants that may have importance of maintenance of antioxidant screen. Blood samples were obtained from healthy volunteers, at young (20–35 years) and old (36–60 years) age. Plasma was prepared and assayed within 3 h from blood collection and analyzed for the antioxidant capacity. At a low pH a ferric tripyridyltriazine (Fe3+‐TPTZ) complex is reduced to the ferrous (Fe2+) form that causes changes of sample absorbance at 593 nm. The plasma antioxidant capacity of young and old group corresponded to 22.69 ± 0.86 and 17.59 ± 1.17 μmol of Trolox (a water‐soluble analog of vitamin E). Young group had significantly higher ferric reducing/antioxidant power value than old subjects. These suggest that plasma antioxidant capacity declines with volunteers age.Acknowledgement:  The study was financed by a 502‐11‐809 Med. Univ. grant.
Macrophage migration inhibitor factor (MIF) can induce oxidative injury and apoptotic cell death of spinal cord neurons
Authors: Toborek M. , Chalimoniuk M. 
Published: May 2003

MIF is a cytokine produced by a variety of cells and tissues including the CNS. It can exert a variety of biological functions, such as induction of inflammatory responses and counterregulation of glucocorticoid effects. However, the role of MIF in the pathogenesis of spinal cord trauma is not fully understood. Therefore, the aim of the present study was to evaluate the cellular effects of MIF in cultured spinal cord neurons. A 3‐h exposure to MIF significantly enhanced intracellular calcium levels; an effect which was prevented by TMB‐8, an antagonist of the IP3 receptor. In addition, MIF treatment increased oxidative stress, decreased viability of spinal cord neurons, increased LDH release and stimulated apoptosis. These results suggest that MIF may play an important role in secondary spinal cord injury.Acknowledgements:  Supported by grants from KSCHIRT and Philip Morris External Research Program.
Assessment of total antioxidant capacity (TAC) of human blood plasma
Authors: Gorąca A. , Lipińska S. , Nowak D. 
Published: May 2003

Oxidative stress, initiated by reactive oxygen species is recognized as a pathogenic factor in a variety of organs, e.g. brain, heart, gastric, duodenum, lung. The aim of this study was to estimate plasma TAC of healthy volunteers aged 35–60 years and patients with chronic obstructive pulmonary disease (POCHP). The ferric reducing/antioxidant power (FRAP) assay was used to measure the TAC of human blood plasma. At a low pH a ferric tripyridyltiazine (Fe3+‐TPTZ) complex is reduced to the ferrous (Fe2+) form that causes changes at 593 nm. The antioxidant capacity of the control plasma corresponded to 17.59 ± 1.17 μmol of Trolox activity (a water‐soluble analog of vitamin E). The antioxidant capacity of the plasma obtained from patients with POCHP corresponded to 23.82 ± 1.82 μmol of Trolox activity and was higher (P < 0.02) than from healthy volunteers. This may represent the adaptive response to oxidative stress related to chronic inflammation.Acknowledgement:  This study was financed by a 502‐11‐809 grant.
Supraspinal and spinal melanocortin receptors influence morphine nociception
Authors: Starowicz K. , Bilecki W. , Przewłocka B. 
Published: May 2003

Melanocortin peptides have been reported to influence opiate tolerance, but the neuronal basis underlying these actions is unknown. We studied the contribution of melanocortin (MC4R) receptors to morphine effects. The MC4R mRNA level in the amygdala was decreased after acute morphine treatment and increased in rats tolerant to morphine as evidenced by quantitative real‐time PCR method. Moreover, the intra‐amygdalar microinjection of antagonist of MC4R attenuated morphine tolerance. Expression of the spinal MC4R after sciatic nerve injury was decreased in the early phase of neuropathy and slightly decreased 2–3 weeks after injury. These findings suggest that the altered melanocortin receptor function may contribute to the development of morphine‐induced effects. Thus, the melanocortin receptors may be a target for development of better and more effective drugs for the therapy of chronic pain.Acknowledgement:  Supported by KBN grant for the statutory activity.
Peripheral effects of opioids and nociceptin in neuropathic pain
Authors: Obara I. , Starowicz K. , Bilecki W. , Przewłocki R. , Przewłocka B. 
Published: May 2003

Recent studies have pointed to the role of peripheral receptors in chronic pain process. They are located on nerve fibers, which project to dorsal root ganglion (DRG). We demonstrated using RT PCR method that peripheral nerve injury caused a reduction in a number of mu‐opioid receptors in DRG. We also checked the peripheral effects of opioid (morphine, DAMGO, EM‐1, EM‐2) and ORL‐1 (nociceptin) receptor agonists. Our findings show that intraplantarly administered agonists were effective in antagonizing allodynia. Peripheral mu‐opioid and ORL1 receptors mediate the observed effects as was evidenced by treatment with naloxone methiodide, which is only peripherally active. The present results demonstrated that opioids after peripheral treatment, in spite of decreased expression of mu‐opioid receptor mRNA in DRG, are effective and their peripheral use may eliminate central unwanted side‐effects.Acknowledgement:   Supported by EU grant (No. QLRT‐2001‐02919).
Differential activation of C1 complement components in rat spinal cord after sciatic nerve injury
Authors: Mika J. , Przewłocka B. , Stover C. , Schwaeble W. J. , Weihe E. , Schäfer M. K.‐H. 
Published: May 2003

Neuroimmune interactions are discussed to drive neuropathic pain. We used the Bennett model to correlate pain and cellular expression profiles of the complement factors C1q and C1q‐associated serine proteases C1r/C1s in lumbar spinal cord. At 2 days C1q mRNA levels increased ipsilateral to the lesion, and peaked at 8 days when allodynia and severe walking problems were present. During regeneration walking problems disappeared together with C1q mRNA levels. C1q biosynthesis was restricted to microglia. Surprisingly, C1s/C1r biosynthesis was not increased after injury suggesting a role for C1q different from classical complement activation. Sustained C1q expression in spinal microglia after lesion in conjunction with pain behavior indicates that microglial C1q may be causally involved in the development and maintenance of neuropathic pain.Acknowledgements:  Supported by BMBF01GG9818, SFB297, DFGWE910/8‐3, KBN3P05C00623.
Characterization of nociceptin binding sites by novel peptide analogs and radioprobes
Authors: Benyhe S. , Gündüz Ö. , Farkas J. , Kocsis L. , Sipos F. , Ligeti M. , Magyar A. , Orosz G. , Tóth G. , Borsodi A. 
Published: May 2003

A number of new synthetic nociceptin ligands were studied in receptor binding and functional tests in rat brain membranes and in cloned systems. Ligand binding experiments were performed with three different radioprobes developed in our lab. The nociceptin derivatives exhibited high affinity in competition experiments. Receptor‐mediated G‐protein activation was determined in [35S]GTPgS binding assays. Among the new structures examined, Ac‐RYYRIK‐ol was found to be only a weak stimulator by itself, whereas this compound inhibited receptor‐mediated G‐protein activation. These data suggest that Ac‐RYYRIK‐ol is a high affinity peptide antagonist for the nociceptin receptor.Acknowledgements:  Supported by the Hungarian Scientific Research Fund OTKA T‐035211, T‐033078, T‐030841, and the Ministry of Education, NKFP 1/027 Hungary.
The influence of Id1 protein on human stem cells differentiation into neuronal pathway
Authors: Jurga M. , Bużańska L. 
Published: May 2003

Id1 protein is responsible for inhibition of bHLH transcription factors. It lacks basic region necessary for DNA binding and after dimerization with other bHLH proteins, competitively blocks their function. Relatively high expression of Id1 in cancer cells suggests its role in promoting cell division. To study the influence of Id1 protein on human neural stem/progenitor cells differentiation Dev and HUCB‐NS/P (human umbilical cord blood derived neural stem/progenitor) cell lines were applied. Id1 gene in sense and antisense orientation was introduced into cells with pEGFP‐N1 vector by electroporation. Overexpression of Id1 results in de‐differentiation of the cells in both experimental models. In contrast, transfection with antisense Id1 results in promotion of neuronal differentiation but only in HUCB‐NS/P cells. These results show the influence of Id1 on neural stem cells differentiation and its unique selectivity referred to neurogenesis inhibition.Acknowledgements:  Funded by Polish State Committee for Scientific Research (grant no. 76P05A.04920).
Estrogen‐mediated protection against methamphetamine‐induced inflammatory pathways in human brain endothelial cells
Authors: Lee Y. W. , Małecki A. , Toborek M. 
Published: May 2003

Recent evidence has demonstrated the potential role of estrogens as therapeutic agents in the prevention or treatment of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease or stroke. The present study focused on the protective mechanisms of estrogens in the methamphetamine (METH)‐mediated inflammatory reactions in human brain microvascular endothelial cells (HBMEC). Pretreatment with estrogens markedly blocked the activation of redox‐responsive transcription factors, such as AP‐1, NF‐kappaB and CREB, in HBMEC exposed to METH. In addition, estrogens inhibited METH‐induced expression of inflammatory genes in HBMEC. These results suggest that estrogens may attenuate the METH‐induced inflammatory cerebrovascular environments via blocking the transcription factor‐mediated molecular signaling pathways in human brain endothelial cells.Acknowledgements:  Supported by NIH; NS39254, MH63022, and AA013843.
NO participate in the communication between the first‐ and second‐order neurons in the trigeminal sensory tract in the dog
Authors: Maršala J. , Lukáčová N. , Pavel J. , Silvášiová M. , Kuchárová K. , Maršala M. 
Published: May 2003

Histochemical, immunocytochemical and radioassay study was performed to detect the occurrence of NOS‐immunoreactive primary trigeminal sensory somata in the trigeminal ganglion, including their fiber components. Spinal trigeminal tract and sensory trigeminal nuclei were studied using the same methods. It was found that more than 30% of all somata in the trigeminal ganglion are NOS immunoreactive. Corresponding fibers were detected in the spinal trigeminal tract. NOS immunoreactive fibers of three different categories could be followed to terminate in the sensory trigeminal nuclei. Data presented here confirm that trigeminal sensory system is richly endowed with NOS and that NO is used to communicate between the first and second‐order trigeminal sensory neurons.Acknowledgements:   Supported by VEGA Grant no. 2/3217/23PS9, STAA Grant no. 51‐013002 and by NIH grants NS 32794 and NS 40386 to M.M.
The effect of cauda equina constriction on nitric oxide synthase activity
Authors: Lukáčová N. , Kafka J. , Cižková D. , Maršala M. , Maršala J. 
Published: May 2003

The effect of cauda equina constriction (CEC) on nitric oxide synthase (NOS) activity has been studied in spinal cord of the dog. CEC lasting for 2 days caused significant increase in NOS activity in white matter of lumbar segments. The enzyme activity decreased to basal levels 5 days after injury. An extreme reduction of NO formation has been seen in sacral segments at 2 day of postsurgery. At 5 day, the enzyme activity greatly increased and in gray matter significantly exceeded baseline. Quantitative measurement of NOS activity produced a rise in gray matter of thoracic segments and indicated a decrease in gray matter of upper lumbar segments. The results indicate a time‐dependent formation of nitric oxide after CEC in spinal cord segments and regions.Acknowledgements:  Supported by VEGA Grants no. 2/2079/22 and 2/3217/23PS9, STAA Grant no. 51‐013002 and by NIH grants NS 32794 and NS 40386 to M.M.
Endocannabinoids, their effect on GABA uptake in globus pallidus and relevance to Parkinson's disease
Authors: Venderova K. , Brotchie J. , Brown T. , Ruzicka E. , Visnovsky P. 
Published: May 2003

Within the globus pallidus, CB1 cannabinoid receptors are localized presynaptically on GABAergic neurons. We focused on effect of endocannabinoids on GABA uptake in rat globus pallidus slices. Following incubation with 2‐arachidonyl glycerol (2‐AG) (1 and 3 μm), there was a 40%, and 30% increase, respectively, in [3H]‐GABA uptake (P < 0.05). When incubated with noladin ether (1 μm), an increase of 57% was observed (P < 0001). The effects of 2‐AG were reversed by the CB1 receptor antagonist AM 251 (1 μm), showing this mechanism is likely to be CB1 receptor‐mediated (P < 0.05). Neither anandamide (0.1–10 μm) nor synthetic cannabinoid WIN 55,212–2 (1–100 μm) had any effect. We suggest increased level of endocannabinoids, found in a Parkinson's disease model, might thus represent a compensatory mechanism.Acknowledgement:  Supported by CEZ:J13/98:11600004.
Transient forebrain ischemia modulates focal adhesion kinase (FAK)‐mediated signal transduction in gerbil hippocampus
Authors: Ziemka‐Nałęcz M. , Sarnowska A. , Zalewska T. 
Published: May 2003

Focal adhesion kinase (FAK) is thought to play a major role in conveying survival signals from extracellular matrix (ECM). Phosphorylated FAK may interact with other nonreceptor kinases such as Src, and adaptor molecule Cas, perhaps providing a pathway by which ECM may regulate cell viability. In the present study the expression and tyrosine phosphorylation of FAK, Src and Cas after 5 min of global ischemia were investigated. The primary activation/phosphorylation of FAK, observed during first 6 h after ischemic injury, was followed by its profound down‐regulation. At 72 h of reperfusion the level of phosphorylated FAK decrease to about 50% of the control. The decrease of FAK phosphorylation coincides with its proteolytic degradation. Cleavage of FAK coincided temporally with the loss of Src and Cas. Ischemia‐induced proteolytic processing of the investigated proteins may lead to the interruption of ECM‐derived signals and compromise neuronal survival.Acknowledgements:  Sponsored by SCSR 4P05A 08619 and Med. Res. Ctr.
Interaction of potassium channel openers with glioma cells mitochondria
Authors: Dębska G. , Kicińska A. , Skalska J. , Szewczyk A. 
Published: May 2003

Benzimidazolones such as NS1619 and NS004 have been reported to activate plasma membrane large conductance Ca2+ activated potassium channel (BK‐type K(Ca)). In the present study we have examined the effect of NS1619 and NS004 plasma membrane BK‐ channel openers on mitochondria in glioma cells. We described the effect of BK‐channel openers on mitochondrial membrane potential (ΔΨm), on mitochondrial respiration and membrane bilayer conductance. We have shown that BK channel openers caused significant decrease in ΔΨm with an EC50 value of 3.6 ± 0.4 μm for NS1619 and 5.4 ± 0.8 μm for NS004. This membrane depolarization was produced by inhibition of mitochondrial respiratory chain, probably complex I. Both BK‐channel openers had no effect on membrane bilayer current or conductance.Acknowledgement:  This work was supported by State Committee for Scientific Research grant 6P04A01219.
Peroxynitrite as a novel neuroprotective intercellular signal
Authors: Bolaños J. P. 
Published: May 2003

Peroxynitrite is thought to be a nitric oxide‐derived neurotoxic effector molecule involved in the disruption of key energy‐related metabolic and structural targets. Recent work from our laboratory has reported that (1) l‐arginine released from astrocytes in response to peroxynitrite is efficiently taken up by neighboring neurons, a fact that seems to be focussed to facilitate nitric oxide biosynthesis; and (2) peroxynitrite rapidly and strongly activates the pentose‐phosphate pathway in neurons and in astrocytes, a phenomenon that appears to be associated with glutathione regeneration and neuronal protection against apoptotic death. According to these lines of evidence we suggest that, whereas exerting delayed neurotoxicity, peroxynitrite may initially serve as a neuron/astrocyte intercellular signaling molecule that triggers key metabolic changes aimed at preventing the propagation of neurodegeneration.Acknowledgements:  Funded by MCYT Grant SAF2001‐1961 and JCYL Grant SA065/01.
Predicting Acute Renal Failure after Cardiac Surgery: Validation and Re‐definition of a Risk‐Stratification Algorithm
Authors: Thakar Charuhas V. , Liangos Orfeas , Yared Jean‐Pierre , Nelson David A. , Hariachar Srinivas , Paganini Emil P. 
Published: May 2003

Background:  Acute renal failure (ARF) after cardiac surgery is associated with significant morbidity and mortality, irrespective of the need for dialysis. Previous studies have attempted to identify predictors of ARF and develop risk stratification algorithms. This study aims to validate the algorithm in an independent cohort of patients that includes a significant proportion of female and black patients and compares two different definitions of renal outcome.Methods:  A large single center cardiac surgery database was examined (n, 24,660; 1993–2000) which included 29.9% females and 3.7% black patients. Post‐operative ARF was defined as: a) ARF requiring dialysis, b) > 50% reduction in creatinine clearance relative to baseline or requiring dialysis. Clinical variables related to baseline renal function and cardiovascular disease were used in recursive partitioning analysis for both outcome definitions. Chi‐square goodness of fit analysis was performed to validate the algorithm.Results:  The frequency of post‐operative ARF requiring dialysis ranged between 0.5 and 15.5% based on the risk categories with the area under the receiver operating characteristic (ROC) curve of 0.78. Using the more inclusive definition of ARF, the frequency was significantly higher ranging from 2.6 to 25%(P < 0.001) with an area under ROC curve of 0.65.Conclusions:  The renal risk stratification algorithm is valid in predicting post‐operative ARF in an independent cohort of patients, well represented by differences in gender and race. Since the need for dialysis remains subjective, a more objective and inclusive definition of ARF may help in identifying a larger number of patients ‘at‐risk’.