Jacek Kurzepa

Publications

• 2.41

  Impact points

  The decrease of serum MMP-2 activity corresponds to alcoholic cirrhosis stage.

  Agnieszka Madro, Grazyna Czechowska, Maria Slomka, Krzysztof Celinski, Stanislawa Szymonik-Lesiuk, Jacek Kurzepa

  Alcohol (Fayetteville, N.Y.). 09/2011; 46(2):155-7.

  Because of numerous limitations for liver biopsy, a noninvasive marker of liver cirrhosis is sought. Promising indicators seem to be matrix metalloproteinases (MMPs) that are responsible for degradation of extracellular matrix. The aim of the study was to evaluate the gelatinase activities (MMP-2 an... [more] Because of numerous limitations for liver biopsy, a noninvasive marker of liver cirrhosis is sought. Promising indicators seem to be matrix metalloproteinases (MMPs) that are responsible for degradation of extracellular matrix. The aim of the study was to evaluate the gelatinase activities (MMP-2 and MMP-9) in patients with different stages of alcoholic cirrhosis. Sixty-seven outpatients who presented various stages of alcoholic cirrhosis according to Child-Turcotte-Pugh criteria and 26 healthy control subjects were enrolled. Blood samples were collected for MMP-2 and MMP-9 activities. A significant decrease of serum MMP-2 activity was noted in stages B and C of cirrhosis in comparison with control. Serum MMP-9 activity did not depend on the stage of cirrhosis. The MMP-2 levels, but not those of MMP-9, may be of value in understanding the pathogenesis and progression of alcoholic cirrhosis.
• 2.35

  Impact points

  Simvastatin displays an antioxidative effect by inhibiting an increase in the serum 8-isoprostane level in patients with acute ischemic stroke: brief report.

  Anna Szczepańska-Szerej, Jacek Kurzepa, Joanna Wojczal, Zbigniew Stelmasiak

  Clinical neuropharmacology. 09/2011; 34(5):191-4.

  Oxidative stress plays an important role in ischemic stroke pathophysiology. Some drugs are known to have a substantial influence on oxidative stress. In this study, we examined the antioxidant effect of simvastatin through its influence on patients' serum 8-isoprostane levels. We measured serum... [more] Oxidative stress plays an important role in ischemic stroke pathophysiology. Some drugs are known to have a substantial influence on oxidative stress. In this study, we examined the antioxidant effect of simvastatin through its influence on patients' serum 8-isoprostane levels. We measured serum 8-isoprostane levels in 67 patients with acute ischemic stroke treated and not treated with simvastatin within 5 days after stroke onset, in comparison with 20 normal controls. Stroke patients from both groups had significantly higher initial serum 8-isoprostane levels than the controls. The median value of serum 8-isoprostane level was significantly lower in the simvastatin-treated group after 5 days of treatment. The results confirm the contribution of oxidative stress to brain ischemia and suggest antioxidative properties of statins in the acute phase of ischemic stroke patients.
• 2.32

  Impact points

  CT volume/density ratio as the marker of ischaemic brain injury.

  J Kurzepa, J Bielewicz, E Czekajska-Chehab, H Bartosik-Psujek, A Grabarska, Z Stelmasiak

  Acta neurologica Scandinavica. 05/2011; 123(5):310-5.

  We believe that the CT volume/density ratio (VDR) of infarcted area reflects the degree of brain tissue damage during ischaemic stroke (IS). Forty six patients with IS were prospectively enrolled into the study. CT scan was performed on days 1 and 10 of hospitalization. S100BB serum level, gelatinas... [more] We believe that the CT volume/density ratio (VDR) of infarcted area reflects the degree of brain tissue damage during ischaemic stroke (IS). Forty six patients with IS were prospectively enrolled into the study. CT scan was performed on days 1 and 10 of hospitalization. S100BB serum level, gelatinase activities (MMP-2 and MMP-9) and neurological examination (NIHSS) were performed on days 1, 5 and 10 of IS. After 3 months, 42 patients were examined by functional disability scales: Barthel index (BI) and modified Rankin scale (mRS). The VDR of ischaemic focus correlated well with the average S100BB serum level, MMP-9 serum activity and NIHSS score. The weak but statistically significant relationships were noticed between the VDR vs BI and mRS estimated 3 months after stroke. VDR reflects well the damage ratio of brain tissue during IS. In addition, the study underlines the relationship between VDR vs patients' neurological status and disability after IS.
• 2.72

  Impact points

  Does serum Tau protein predict the outcome of patients with ischemic stroke?

  Joanna Bielewicz, Jacek Kurzepa, Elżbieta Czekajska-Chehab, Zbigniew Stelmasiak, Halina Bartosik-Psujek

  Journal of molecular neuroscience : MN. 03/2011; 43(3):241-5.

  The prediction of outcome after ischemic stroke (IS) is currently based on indirect data from clinical and radiological evaluation. We evaluated the usefulness of serum Tau protein as possible prognostic markers for IS. Fifty-six patients with computed tomography-confirmed IS were enrolled. Blood sa... [more] The prediction of outcome after ischemic stroke (IS) is currently based on indirect data from clinical and radiological evaluation. We evaluated the usefulness of serum Tau protein as possible prognostic markers for IS. Fifty-six patients with computed tomography-confirmed IS were enrolled. Blood samples were obtained on days 1, 3, 5, and 10 after stroke onset. Tau and S100BB serum levels were measured by commercially available enzyme-linked immunosorbent assay. Neurological deficits were quantified by the National Institute of Health Stroke Scale on days 1, 3, 5, and 10 of stroke. Functional disability was rated with the Barthel Index and Rankin Scale on days 1, 3, 5, and 10 and additionally 3 months after the stroke. Computed tomography scan was performed to calculate infarct volume on admission to hospital and on day 10 from the diagnosis of IS onset. Tau protein was detected in the serum of 47.8% patients with IS. Patients in whom Tau protein was detected in serum, when compared with patients without Tau protein, developed more severe neurological deficits, had worse functional status measured in the early and late phase of IS, and were found to have larger volume of infarction. However, Tau protein concentrations measured within the early phase of IS did not correlate with degrees of neurological deficit and disability in the early phase and also after 3 months of IS. Detection of Tau protein in the serum of patients with IS but not its concentration can be considered as a bad prognostic factor for the clinical outcome in early and late phase of IS.

• [Processes of free radical lipid peroxidation with a particular regard to the role of paraoxonase-1 in the pathogenesis of multiple sclerosis].

  Jerzy Berbecki, Krystyna Mitosek-Szewczyk, Jacek Kurzepa, Marcin Nastaj, Katarzyna Łobejko, Zbigniew Stelmasiak

  Wiadomości lekarskie (Warsaw, Poland : 1960). 01/2011; 64(1):31-6.

  Oxidative stress is an imbalance between free radicals production and antioxidant defences. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) can attact and demage a variety of critical biological molecules, including lipids, essential cellular proteins and DNA and may be exert in pa... [more] Oxidative stress is an imbalance between free radicals production and antioxidant defences. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) can attact and demage a variety of critical biological molecules, including lipids, essential cellular proteins and DNA and may be exert in pathogenesis of many disorders. Products of lipid peroxidation can be easily reliably detected in biological fluids and tissues, yielding sensitive and specific signals of lipid peroxidation occurred in vivo. Those products are: isoprostanes (isoP) dimalonealdehyde (MDA), 4-hydroxynonenal (4-HNE). Paraoxonase-1 (PON-1) play a key role in defence of lipid peroxidation. PON-1 is an serum enzyme bound up with high density lipoproteins (HDL). The aim of this work is to discuss the role of oxidative stress in the pathogenesis of multiple sclerosis.

• Matrix metalloproteinases and atherosclerosis

  Fic Piotr, Zakrocka Izabela, Kurzepa Jacek, Stepulak Andrzej

  Postępy Higieny i Medycyny Doświadczalnej. 01/2011;

  Matrix metalloproteinases (MMPs), a family of proteolytic enzymes that degrade extracellular matrix (ECM), seem to have an important role in pathogenesis of atherosclerosis. Released by inflammatory cells and smooth muscle cells, MMPs regulate the vascular remodeling process. The expression and acti... [more] Matrix metalloproteinases (MMPs), a family of proteolytic enzymes that degrade extracellular matrix (ECM), seem to have an important role in pathogenesis of atherosclerosis. Released by inflammatory cells and smooth muscle cells, MMPs regulate the vascular remodeling process. The expression and activity of MMPs is regulated at the level of transcription by a variety of cytokines, proenzyme activation by several cellular and serum proteases, as well as by endogenous and exogenous inhibitors. Overproduction of MMPs could promote arteriosclerosis, leading to atherosclerotic plaque formation, and plaque rupture, resulting in clinical consequences such as myocardial infarction, or critical limb ischemia. Increased plasma levels of some MMPs are now regarded as potential biomarkers of atherosclerosis and cardiovascular risk. The potential significance of MMP inhibitors in atherosclerosis therapy is discussed.
• 1.17

  Impact points

  Matrix metalloproteinase-9 contributes to the increase of tau protein in serum during acute ischemic stroke.

  Jacek Kurzepa, Joanna Bielewicz, Aneta Grabarska, Zbigniew Stelmasiak, Marta Stryjecka-Zimmer, Halina Bartosik-Psujek

  Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 08/2010; 17(8):997-9.

  Previous studies indicate that tau protein, a marker of damage to neurons, is present in the serum of healthy patients at a concentration approximately 40 percent that of patients with ischemic stroke We assumed that increased serum activity of gelatinases (matrix metalloproteinase [MMP]-2 and MMP-9... [more] Previous studies indicate that tau protein, a marker of damage to neurons, is present in the serum of healthy patients at a concentration approximately 40 percent that of patients with ischemic stroke We assumed that increased serum activity of gelatinases (matrix metalloproteinase [MMP]-2 and MMP-9) can influence the level of tau protein in serum, probably due to disruption of the blood-brain barrier. We obtained blood sera from 31 patients admitted within the first 24 hours of ischemic stroke on days 1, 5 and 10, following the onset of stroke. Tau protein was detected in the serum of 12 patients (38.7 percent). The highest MMP-9 activity was recorded on day 5 (p < 0.05). Serum gelatinase activity did not differ between tau protein-positive or -negative individuals. However, a high degree of correlation between mean MMP-9 activity and the maximum tau protein level was observed for patients with detectable tau protein (r = 0.71, p = 0.009). Our study suggests that MMP-9 can increase the tau protein level in the sera of patients during acute ischemic stroke.

• [The novel views on the patomechanism of ischemic stroke].

  Joanna Bielewicz, Jacek Kurzepa, Monika Łagowska-Lenard, Halina Bartosik-Psujek

  Wiadomości lekarskie (Warsaw, Poland : 1960). 01/2010; 63(3):213-20.

  Stroke is the third cause of death and the first cause of handicap. Current knowledge about stroke allows to apply the effective methods of treatment or prophylaxis. Eighteen five percent of all strokes are ischemic (IS), 15% are haemmorrhagic (HS). Unequal oxygen supply and the changes occurring in... [more] Stroke is the third cause of death and the first cause of handicap. Current knowledge about stroke allows to apply the effective methods of treatment or prophylaxis. Eighteen five percent of all strokes are ischemic (IS), 15% are haemmorrhagic (HS). Unequal oxygen supply and the changes occurring in the macro and microcirculation results in the division of ischemic focus into the two areas; central core with an irreversible destruction of brain cells and penumbra, "semi-shadow area" around the core. The insufficient blood flow within the penumbra manifests the clinical symptoms of IS however the changes are reversible after the restoration of the correct circulation. We assumed five pathways leading to neurons' death: excitotoxicity and ionic imbalance, oxidative stress, inflamamation, peri-infract depolarization and apoptosis. This review briefly describes biochemical mechanism of IS development.
• 2.35

  Impact points

  Neurofilament ELISA validation.

  Axel Petzold, Ayse Altintas, Laura Andreoni, Ales Bartos, Achim Berthele, M A Blankenstein, Luc Buee, Massimiliano Castellazzi, Sabine Cepok, Manuel Comabella, [......], Vincent van Pesch, Hugo Vanderstichele, Christian Vedeler, Marcel M Verbeek, Luisa Maria Villar, Robbert Weissert, Brigitte Wildemann, Cui Yang, Karen Yao, Charlotte Teunissen

  Journal of immunological methods. 10/2009;

  BACKGROUND: Neurofilament proteins (Nf) are highly specific biomarkers for neuronal death and axonal degeneration. As these markers become more widely used, an inter-laboratory validation study is required to identify assay criteria for high quality performance. METHODS: The UmanDiagnostics NF-light... [more] BACKGROUND: Neurofilament proteins (Nf) are highly specific biomarkers for neuronal death and axonal degeneration. As these markers become more widely used, an inter-laboratory validation study is required to identify assay criteria for high quality performance. METHODS: The UmanDiagnostics NF-light (R)enzyme-linked immunoabsorbent assays (ELISA) for the neurofilament light chain (NfL, 68kDa) was used to test the intra-assay and inter-laboratory coefficient of variation (CV) between 35 laboratories worldwide on 15 cerebrospinal fluid (CSF) samples. Critical factors, such as sample transport and storage, analytical delays, reaction temperature and time, the laboratories' accuracy and preparation of standards were documented and used for the statistical analyses. RESULTS: The intra-laboratory CV averaged 3.3% and the inter-laboratory CV 59%. The results from the test laboratories correlated with those from the reference laboratory (R=0.60, p<0.0001). Correcting for critical factors improved the strength of the correlation. Differences in the accuracy of standard preparation were identified as the most critical factor. Correcting for the error introduced by variation in the protein standards improved the correlation to R=0.98, p<0.0001 with an averaged inter-laboratory CV of 14%. The corrected overall inter-rater agreement was subtantial (0.6) according to Fleiss' multi-rater kappa and Gwet's AC1 statistics. CONCLUSION: This multi-center validation study identified the lack of preparation of accurate and consistent protein standards as the main reason for a poor inter-laboratory CV. This issue is also relevant to other protein biomarkers based on this type of assay and will need to be solved in order to achieve an acceptable level of analytical accuracy. The raw data of this study is available online.
• 0.92

  Impact points

  The effects of hypo- and hyperthyroidism on nuclear, cytosolic, endoplasmic and mitochondrial fractions of sialoglycoproteins in rabbit hepatocytes.

  E Nowosadzka, S Szymonik-Lesiuk, J Kurzepa

  Folia biologica. 02/2009; 55(1):7-10.

  Enhanced sialylation of glycoproteins occurs during hypo- and hyperthyroidism. The role of sialic acid (SA) in cell membranes is well-standing, but its role in intracellular structures is still under analysis. We wanted to evaluate the influence of thyroid hormones on the sialylation ratio of intrac... [more] Enhanced sialylation of glycoproteins occurs during hypo- and hyperthyroidism. The role of sialic acid (SA) in cell membranes is well-standing, but its role in intracellular structures is still under analysis. We wanted to evaluate the influence of thyroid hormones on the sialylation ratio of intracellular proteins presented in cytosolic, mitochondrial, endoplasmic and nuclear fractions of rabbit hepatocytes. Twenty-one New Zealand male rabbits were divided into three groups. Hypothyroidism (N = 7) or hyperthyroidism (N = 7) was induced by adding propylthiouracyl (2 mg/l) or L-thyroxine (12 mg/l), respectively, to the drinking water for four weeks. Results were compared with healthy (euthyroid) control animals (N = 7). After isolation of intracellular fractions, standard SDS-PAGE electrophoresis and transfer onto nitrocellulose membrane were performed. Identification of SA residue was carried out with digoxigenin- labelled lectins: Sambucus nigra agglutinin (SNA) and Maackia amurensis agglutinin (MAA). We noticed significantly higher level of SNA than MAA linkage sialoglycoproteins in all evaluated fractions. The sialylation ratio was significantly lower (P < 0.05) in the nuclear fraction in case of hyperthyroidism (detected with both agglutinins). In contrast to the nuclear fraction the content of SNA-detected sialoglycoproteins was significantly reduced in mitochondrial fraction of hyperthyroid hepatocytes (P < 0.05). Non-significant augmentation of MAA-detected sialoglycoproteins was observed in the mitochondrial fractions in both hypo- and hyperthyroidism. The fluctuations of sialoglycoproteins in endoplasmic fraction were not significant. Our work showed that the subcellular structures are rich in SA residues. Differing effects of thyroid hormones on sialylation ratio suggest an important role for hypo- and hyperthyroidism in sialoglycoprotein metabolism.
• 0.86

  Impact points

  Serum bilirubin and uric acid levels as the bad prognostic factors in the ischemic stroke.

  Jacek Kurzepa, Joanna Bielewicz, Zbigniew Stelmasiak, Halina Bartosik-Psujek

  The International journal of neuroscience. 01/2009; 119(12):2243-9.

  Bilirubin (Bil) and uric acid (UA) are the endogenous antioxidant compounds possibly involved in the pathogenesis of ischemic stroke (IS). Our goal was to find the relationship between serum Bil and UA levels with clinical presentation and outcomes of patients suffering from IS. Forty-three patients... [more] Bilirubin (Bil) and uric acid (UA) are the endogenous antioxidant compounds possibly involved in the pathogenesis of ischemic stroke (IS). Our goal was to find the relationship between serum Bil and UA levels with clinical presentation and outcomes of patients suffering from IS. Forty-three patients (mean age: 71.9 years, +/- 12.1; women: 48.8%) with confirmed IS were enrolled. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) after 1, 3, 5, and 10 days and functional disability was assessed three months after stroke onset using the Barthel Index (BI). Serum Bil and UA levels were measured 1, 3, 5, and 10 days after stroke. The difference between NIHSS scores from days 1 and 10 (improvement ratio) inversely correlated with the average UA serum level (r = -0.48, p < .01) but not with the average Bil level. Negative correlations were observed between the BI measured three months after stroke compared to the average Bil serum level (r = -0.5, p < .01). However, no relationship between BI and UA level was observed. Our results indicated that Bil and UA levels are poor prognostic factors for ischemic stroke.

• Gelatinolytic activity of matrix metalloproteinases 2 and 9 in middle ear cholesteatoma.

  Danuta Suchozebrska-Jesionek, Marcin Szymański, Jacek Kurzepa, Wiesław Gołabek, Marta Stryjecka-Zimmer

  Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale. 11/2008; 37(5):628-32.

  BACKGROUND: Cholesteatoma of the middle ear or mastoid is a hyperproliferative disorder of keratinocytes characterized by a progressive bone erosion. Matrix metalloproteinase (MMP)-2 and MMP-9 gelatinases are endopeptidases targeting extracellular protein. Several studies examined the role of gelati... [more] BACKGROUND: Cholesteatoma of the middle ear or mastoid is a hyperproliferative disorder of keratinocytes characterized by a progressive bone erosion. Matrix metalloproteinase (MMP)-2 and MMP-9 gelatinases are endopeptidases targeting extracellular protein. Several studies examined the role of gelatinases in the pathogenesis of cholesteatoma, but the biologic mechanism by which cholesteatoma destroys the bone tissue remains unclear. OBJECTIVES: The aim of this study was to characterize the activity of MMP-2 and MMP-9 in human cholesteatoma and external auditory canal skin. METHODS: In the study, specimens of cholesteatoma and middle ear canal skin from 14 patients treated surgically at the Department of Otolaryngology were used. After two-step extraction of MMP-2 and MMP-9 from tissue samples, gelatinolytic activity was assessed with zymography. RESULTS: We noticed the augmentation of MMP-9 (p = .0001) and MMP-2 (p = .046) activity obtained from cholesteatoma in comparison with control skin. The MMP-9 active to latent ratio was significantly higher in cholesteatoma samples versus normal skin. CONCLUSION: The present study indicates that MMP-9 and, to a lesser degree, MMP-2 overexpression may be implicated in the molecular mechanisms of cholesteatoma invasion and bone destruction.
• 0.92

  Impact points

  The effect of interferon beta-1a on MMP-2 and MMP-9 proteolytic activity.

  J Kurzepa, M Stryjecka-Zimmer

  Folia biologica. 02/2007; 53(6):220-1.

  MMP-2 and MMP-9 play a significant role in the development of numerous diseases mainly with the inflammatory pathogenesis. One of the drugs exerting an effect on metalloproteinases is IFN-beta. Previous studies showed that IFN beta-1b can decrease MMP synthesis and moreover inhibit their proteolytic... [more] MMP-2 and MMP-9 play a significant role in the development of numerous diseases mainly with the inflammatory pathogenesis. One of the drugs exerting an effect on metalloproteinases is IFN-beta. Previous studies showed that IFN beta-1b can decrease MMP synthesis and moreover inhibit their proteolytic activity. The aim of our study was to analyse the influence of recombinant IFN beta-1a (identical with natural IFN-beta) on MMP-2 and MMP-9 activities. The gelatinolytic activity was evaluated with zymography in sera obtained from 10 healthy donors. After electrophoresis gels were incubated with or without IFN beta-1a (2000 U/ml) for 18 h. We noticed a significant decrease of MMP-2/72 kDa (P = 0.0283) and the augmentation of MMP-9/92 kDa (P = 0.0042) activities after incubation with interferon. The elevation of MMP-9/92 kDa activity suggests that IFN beta-1a can exhibit proinflammatory features besides well-known anti-inflammatory properties.
• 2.26

  Impact points

  Astrocytic activation in relation to inflammatory markers during clinical exacerbation of relapsing-remitting multiple sclerosis.

  K Rejdak, A Petzold, T Kocki, J Kurzepa, P Grieb, W A Turski, Z Stelmasiak

  Journal of neural transmission (Vienna, Austria : 1996). 01/2007; 114(8):1011-5.

  The study aimed to assay the cerebrospinal fluid (CSF) levels of protein S100B, a biomarker of astrocyte activation in relation to kynurenic acid (KYNA) and nitric oxide (NO) metabolites, nitrate/nitrite (NOx) concentrations in acute relapse multiple sclerosis (MS) patients. Twenty relapsing-remitti... [more] The study aimed to assay the cerebrospinal fluid (CSF) levels of protein S100B, a biomarker of astrocyte activation in relation to kynurenic acid (KYNA) and nitric oxide (NO) metabolites, nitrate/nitrite (NOx) concentrations in acute relapse multiple sclerosis (MS) patients. Twenty relapsing-remitting MS (RR-MS) patients and 10 controls were enrolled. RR-MS patients were assessed on the expanded disability status scale (EDSS) and underwent lumbar puncture. The CSF KYNA, NOx and S100B levels were significantly higher in RR-MS group compared to controls (p = 0.01, 0.001, 0.04, respectively). There was a significant correlation between CSF S100B and KYNA (p = 0.01) but not NOx (p > 0.05) in RR-MS. CSF KYNA, NOx or S100B concentrations did not correlate with disease characteristics of MS patients.Our study suggests the activation of the kynurenine pathway leading to the increase of neuroprotective KYNA in the CSF of MS patients during acute relapse what contrasts with chronic phases of the disease.
• 0.92

  Impact points

  Simvastatin could prevent increase of the serum MMP-9/TIMP-1 ratio in acute ischaemic stroke.

  J Kurzepa, A Szczepanska-Szerej, M Stryjecka-Zimmer, T Malecka-Massalska, Z Stelmasiak

  Folia biologica. 01/2006; 52(6):181-3.

  MMP-9 plays an important role in the pathogenesis of AIS and predicts haemorrhagic transformation of the ischaemic focus. The aim of our study was to analyse both serum MMP-9 and its most specific endogenous inhibitor (TIMP-1) levels in AIS and to check whether HMG-CoA reductase inhibitor (simvastat... [more] MMP-9 plays an important role in the pathogenesis of AIS and predicts haemorrhagic transformation of the ischaemic focus. The aim of our study was to analyse both serum MMP-9 and its most specific endogenous inhibitor (TIMP-1) levels in AIS and to check whether HMG-CoA reductase inhibitor (simvastatin) affects the MMP-9/TIMP-1 ratio value. Fifty patients with AIS were randomly divided into two groups: Group I (N = 25) treated with 40 mg/day with simvastatin within 24 hours after the onset of stroke and Group II (N = 25) non-treated with statin. To evaluate MMP-9 and TIMP-1 serum levels, the ELISA method was used. The serum MMP-9 level was significantly elevated on the 7th day of stroke in both groups (from 668 to 862 ng/ml and 670 to 855 ng/ml, respectively, in Group I and II). The serum TIMP-1 level was also elevated on the 7th day of stroke in both groups but the results were not significant. The MMP-9/TIMP-1 ratio was elevated on the 7th day of stroke in both groups, but the result was significant only in the Group II (P < 0.01). These findings indicate that simvastatin given during 24 hours after the onset of stroke could have an influence on the MMP-9/TIMP-1 ratio during AIS.

• Oligoclonal bands measured in unconcentrated cerebrospinal fluid and other biochemical parameters in multiple sclerosis.

  Jacek Kurzepa, Marcin Nastaj, Krystyna Mitosek-Szewczyk, Halina Bartosik-Psujek, Zbigniew Stelmasiak

  Annales Universitatis Mariae Curie-Skłodowska. Sectio D: Medicina. 02/2004; 59(2):392-6.

  Various biochemical parameters of cerebrospinal fluid (CSF) obtained from sixty-nine patients with RRMS (relapse-remitting MS) were compared in this study. Total protein level, white blood cells (WBC) count and presence of oligoclonal bands (OB) in CSF were examined. The presence of OB in unconcentr... [more] Various biochemical parameters of cerebrospinal fluid (CSF) obtained from sixty-nine patients with RRMS (relapse-remitting MS) were compared in this study. Total protein level, white blood cells (WBC) count and presence of oligoclonal bands (OB) in CSF were examined. The presence of OB in unconcentrated CSF using an isoelectrofocusing assay on agarose gels and silver staining were measured in 72 percent of patients. The average CSF total protein level measured by Lowry assay was 269 mg/l (range from 61 to 712 mg/l). The mean level of white blood cells (WBC) was higher than in general population and it was 12 cells/microl. We found an increased level of WBC count among patients with the presence of oligoclonal bands in CSF.

• Thymectomy as an effective treatment in myasthenia.

  Maria Pilarczyk, Marcin Nastaj, Andrzej Fidor, Jacek Jaworski, Jacek Porebiak, Jacek Kurzepa, Zbigniew Stelmasiak

  Annales Universitatis Mariae Curie-Skłodowska. Sectio D: Medicina. 02/2004; 59(2):369-70.

  The paper describes a patient case with early diagnosed myasthenia introduced, who after thymectomy and postsurgical pharmacology achieved a total remission of the disease within six years.... [more] The paper describes a patient case with early diagnosed myasthenia introduced, who after thymectomy and postsurgical pharmacology achieved a total remission of the disease within six years.

• Neurofilament ELISA validation

  Axel Petzold, Ayse Altintas, Laura Andreoni, Ales Bartos, Achim Berthele, Marinus A. Blankenstein, Luc Buee, Massimiliano Castellazzi, Sabine Cepok, Manuel Comabella, [......], Vincent Van Pesch, Hugo Vanderstichele, Christian Vedeler, Marcel M. Verbeek, Luisa Maria Villar, Robert Weissert, Brigitte Wildemann, Cui Yang, Karen Yao, Charlotte E. Teunissen

  Journal of Immunological Methods.

  BackgroundNeurofilament proteins (Nf) are highly specific biomarkers for neuronal death and axonal degeneration. As these markers become more widely used, an inter-laboratory validation study is required to identify assay criteria for high quality performance.MethodsThe UmanDiagnostics NF-light ®enz... [more] BackgroundNeurofilament proteins (Nf) are highly specific biomarkers for neuronal death and axonal degeneration. As these markers become more widely used, an inter-laboratory validation study is required to identify assay criteria for high quality performance.MethodsThe UmanDiagnostics NF-light ®enzyme-linked immunoabsorbent assays (ELISA) for the neurofilament light chain (NfL, 68 kDa) was used to test the intra-assay and inter-laboratory coefficient of variation (CV) between 35 laboratories worldwide on 15 cerebrospinal fluid (CSF) samples. Critical factors, such as sample transport and storage, analytical delays, reaction temperature and time, the laboratories' accuracy and preparation of standards were documented and used for the statistical analyses.ResultsThe intra-laboratory CV averaged 3.3% and the inter-laboratory CV 59%. The results from the test laboratories correlated with those from the reference laboratory (R = 0.60, p < 0.0001). Correcting for critical factors improved the strength of the correlation. Differences in the accuracy of standard preparation were identified as the most critical factor. Correcting for the error introduced by variation in the protein standards improved the correlation to R = 0.98, p < 0.0001 with an averaged inter-laboratory CV of 14%. The corrected overall inter-rater agreement was subtantial (0.6) according to Fleiss' multi-rater kappa and Gwet's AC1 statistics.ConclusionThis multi-center validation study identified the lack of preparation of accurate and consistent protein standards as the main reason for a poor inter-laboratory CV. This issue is also relevant to other protein biomarkers based on this type of assay and will need to be solved in order to achieve an acceptable level of analytical accuracy. The raw data of this study is available online.
• 2.09

  Impact points

  Simvastatin inhibits the increase in serum tau protein levels in the acute phase of ischemic stroke.

  Jacek Kurzepa, Joanna Bielewicz, Halina Bartosik-Psujek, Anna Szczepańska-Szerej, Zbigniew Stelmasiak

  Pharmacological reports : PR. 60(6):1014-8.

  Our goal was to analyze the effects of treatment with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (simvastatin, 40 mg/day) on serum S100BB and tau protein levels during the acute ischemic stroke (IS). Twenty four patients with IS were divided into two equal groups; treated ... [more] Our goal was to analyze the effects of treatment with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (simvastatin, 40 mg/day) on serum S100BB and tau protein levels during the acute ischemic stroke (IS). Twenty four patients with IS were divided into two equal groups; treated and untreated with simvastatin. Blood was obtained four times during acute IS. Tau protein was noticed in six patients from treated group and in five patients from untreated group. The serum tau protein levels significantly increased on the 10th day only in patients untreated with simvastatin (p < 0.05). Simvastatin did not exert an effect on serum S100BB protein levels.
• 0.45

  Impact points

  [Role of matrix metalloproteinases in the pathogenesis of multiple sclerosis]

  Jacek Kurzepa, Halina Bartosik-Psujek, Danuta Suchozebrska-Jesionek, Konrad Rejdak, Marta Stryjecka-Zimmer, Zbigniew Stelmasiak

  Neurologia i neurochirurgia polska. 39(1):63-7.

  Multiple sclerosis (MS) is an autoimmune disease whose features include a massive lymphocyte recruitment into the central nervous system and segmental demyelinization of the white matter. One of the MS development factors is an increase of matrix metalloproteinases (MMPs) activity with a coincidenta... [more] Multiple sclerosis (MS) is an autoimmune disease whose features include a massive lymphocyte recruitment into the central nervous system and segmental demyelinization of the white matter. One of the MS development factors is an increase of matrix metalloproteinases (MMPs) activity with a coincidental decrease of tissue inhibitors of MMPs (TIMPs) activity. Investigations of serum, cerebrospinal fluid and brain tissue of patients showed an increase of MMP-1, -2, -3, -7, -9 and MMP-12 activity. MMPs disrupt the blood-brain barrier (BBB), increase lymphocyte migration into the central nervous system and are involved in degradation of myelin proteins. MMPs induce the appearance of an active form of tumor necrosis factor alpha, a strong proinflammatory cytokine. The drugs used in MS treatment decrease MMPs expression. Multiple actions of MMPs prove their involvement in the pathogenesis and treatment of MS.