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Biomedical subjects

A Członkowska

Publications and source records attributed to A Członkowska.

At least 19 recordsLinked to original sources
PubMed2006

Eligibility of stroke units in Poland for administration of intravenous thrombolysis.

Systemic thrombolysis treatment was approved in Poland in 2003 and should be performed in specialist stroke units (SU). We performed a survey to determine stroke service preparedness for thrombolysis treatment in Poland. We sent a questionnaire evaluating the neurological departments in Poland, where stroke patients are treated. We divided them into four categories: (i) class A SU (fulfilling criteria of the National Program for Stroke Prevention and Therapy and European Stroke Initiative guidelines), (ii) class B (conditionally fulfilling criteria), (iii) class C (not fulfilling criteria), and (iv) departments without SU. Only class A units are eligible for implementing thrombolysis. We obtained response from 194 of 222 (87.4%) departments; 90 (46.4%) declared having an SU. According to criteria, 20 class A, 56 class B, 14 class C. During one year, 71 208 patients were admitted to hospitals; 69,982 (98.2%) to neurological departments. A total of 10,959 (15.4%) were treated in class A SU, 23,650 (33.2%) in class B, 5153 (7.2%) in class C, whereas 30,220 (42.4%) in neurological departments without SU. Our survey showed that only 15.4% stroke patients in Poland are admitted to high-quality SU, where thrombolysis may potentially be administered. Improvement of SU quality in Poland is necessary for wide implementation of new methods of stroke therapy.

Disability Evaluation↗
PubMed2005

Wilson's disease-cause of mortality in 164 patients during 1992-2003 observation period.

We studied the cause of death in a consecutive series of 164 patients with Wilson's disease (WD) diagnosed over an 11 year period. A total of 20 [12% (95% CI 10.3-16.0)] died during the observation period. The relative survival rate of all patients in our group was statistically smaller than in Polish population. The main cause of death was the diagnosis in advanced stage of disease, but in six patients presenting with mild signs, we observed the progression of the disease despite treatment. There was no difference in mortality rate in patients treated with d-penicillamine or zinc sulphate as initial therapy. The prognosis for survival in the majority of WD patients is favourable, provided that therapy is introduced early.

Adult↗
PubMed2005

Immunization with myelin oligodendrocyte glycoprotein and complete Freund adjuvant partially protects dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced damage in mouse model of Parkinson's disease.

The concept of neuroprotective immunity identifies a new role of autoimmune cells in the CNS pathology. Specifically, immune cells infiltrating the CNS during an injury may help in a regeneration process and prevent the secondary degeneration of neurons. The objectives of our study were to determine the role of autoimmune and peripheral immune enhancement in neurodegeneration process, and to compare the results between young adult and aging animals. C57Bl mice were immunized with either myelin oligodendrocyte glycoprotein (MOG) 35-55 combined with complete Freund adjuvant (CFA), or CFA alone. Following 6 days, the animals were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to produce a damage of the nigrostriatal dopaminergic system. Although immunization with MOG 35-55 combined with CFA resulted in autoimmune encephalomyelosis, it substantially enhanced neuronal survival after the toxic insult. The immunization with CFA alone was also effective in preventing neuronal cell death, but the magnitude of the neuroprotective effect was smaller. Interestingly, the neuroprotective effect of MOG 35-55 and CFA was more pronounced in aging (i.e. 10-month-old) compared with young (i.e. 2-month-old) mice. Our results indicate that an increased immune activation may be beneficial for neurodegenerative processes following the CNS injury, but the mechanisms of such immune neuroprotection and of age differences need further investigation.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2005

Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson's disease.

Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism. The clinical phenotype of the disease is varied. It is proposed that this variation may be a result of differential functional disruption of ATPase7B (ATP7B) resulting from mutations in the gene ATP7B. We aimed to assess the relationship between specific mutational defects in ATP7B and divergence in the phenotypic expression of WD. One hundred and forty-two patients with clinically, biochemically and genetically diagnosed WD were included in the study. The phenotypic expression of WD was compared between patients with different types of mutations in ATP7B, detected by direct sequencing of exons 1-21 of the gene. Twenty-six mutations were identified in ATP7B; eleven of them were mutations predicted to result in the absence of a full-length normal protein [frameshift/nonsense mutations; classified as 'severe' mutations (SMs)], 14 were missense mutations (MMs) and one was a splice site mutation. Patients with one or two SMs on their alleles had lower serum copper and ceruloplasmin and were younger when the first symptoms of the disease appeared, compared with individuals with two MMs. The effect of SMs on the WD phenotype was dose-dependent. It is concluded that mutations within ATP7B are very heterogeneous. Frameshift and nonsense mutations are associated with a severe phenotype of WD.

Adenosine Triphosphatases↗
PubMed2002

Indomethacin protects against neurodegeneration caused by MPTP intoxication in mice.

The anti-inflammatory agents are postulated to be effective in treating neurodegenerative disorders. In this study, we showed that indomethacin (IND) in the dose of 1 mg/kg protected neurons against toxic damage caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice model of Parkinson's disease. IND also diminished microglial activation and lymphocytic infiltration in the injured areas. These observations suggest that anti-inflammatory properties of IND may play a role in the neuron's protection in this model. However, diminished inflammatory reaction may be secondary to less neuronal damage.

Animals↗
PubMed2001

Elevated levels of anti-heat shock protein antibodies in patients with cerebral ischemia.

One of the important mechanisms involved in the development of vascular lesions leading to ischemic stroke could be an immune response to heat shock proteins (hsp). For carotid atherosclerosis and myocardial infarction, an association with an increase in anti-hsp 65 antibodies has been demonstrated. The aim of our study was (1) to investigate whether ischemic stroke is associated with a humoral immune response to hsp; (2) to study the connection between anti-hsp antibodies and other stroke risk factors; (3) to estimate if the elevated levels of anti-hsp antibodies could be an independent risk factor for stroke. We examined 180 patients (in the first 48 h after stroke onset) and 64 age-matched healthy controls. The levels of IgG and IgM antibodies to hsp 65 and 70 were measured by ELISA. Ischemic stroke was connected with a significant elevation of anti-hsp 65 and anti-hsp 70 antibody levels (IgG and IgM) compared with controls (p < 0.0001). The multifactorial logistic regression analysis showed that increased levels of anti-hsp 65 and anti-hsp 70 IgG antibodies are independent risk factors for stroke. Our results suggest that humoral immunity to hsp is common in stroke patients and that elevated levels of anti-hsp antibodies could be triggering factors for stroke.

Aged↗
PubMed2001

Neuropathological analysis of pathological forms of astroglia in Wilson's disease.

A neuropathological study of Alzheimer type I (Alz I) and Alzheimer type II (Alz II) as well as Opalski (Opl) cells was performed serially on brain tissue from nine autopsied Wilson's disease (WD) cases. Conventional staining methods (Kluver-Barrera, HE, PAS) and immunocytochemical techniques (anti-GFAP and anti-Metallothionein-MT) were used. On conventional staining, each of the studied abnormal cell types retained common morphological characteristics of astroglia, and concurrently demonstrated its own distinctive features, specific only for a given cell type. Anti-GFAP staining revealed positive immunoreactivity of Alz I and Opl cells, and its absence in Alz II cells. On anti-MT staining both the cytoplasm and nucleus of Alz I and Opl cells showed positivity whereas in Alz II cells the cytoplasm was positive in contrast to the negative nucleus. The results of our study confirm the hypothesis of the astroglial origin of all three types of cells. The lack of immunoreactivity for GFAP and similar immunocytochemical staining patterns for MT in Alz II cells and protoplasmic astrocytes may suggest that Alz II cells originate from the protoplasmic type of astroglia. The fact that Alz I and Opl cells resemble fibrous astrocytes in their immunoreactive positivity for GFAP may lead to a supposition that they originate from the fibrous type of astroglia. MT-positive expression by the three abnormal cell types suggests that they may be involved in the process of copper detoxification in WD.

Adolescent↗
PubMed2001

[Treatment of neurodegenerative diseases: new perspectives].

The experimental models of neurodegeneration give a possibility to study the inflammatory reaction that starts in response to neuronal death. Inflammation consists of microglial and astroglial activation, expression of new molecules as cytokines, adhesion molecules and MHC antigens, and is potentially neurotoxic. This article is a summary of a few latest studies that investigate anti-inflammatory agents effect on neuron survival in MPTP mice model of Parkinson's disease. Murine model of Parkinson's disease uses a quite selective toxic effect of MPTP on nigrostriatal system. MPTP causes degeneration of dopaminergic cells bodies in the substantia nigra and of their endings in striatum. Our findings show that anti-inflammatory treatment protects neuronal death. It may indicate that the inflammation contributes to the dopaminergic neuron impairment following MPTP intoxication. However this hypothesis needs further investigation because recent studies suggest that inflammation may have also a protective effect in neurodegentration.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

Evaluation of cerebrospinal fluid for the presense of anticardiolipin antibodies (aCL) in NP-SLE patients.

Many neurological or psychiatric manifestations of SLE (NP-SLE) are related to the presence of anticardiolipin antibodies (aCL) in the patient's sera. The aim of this study was to evaluate the presence of aCL in cerebrospinal fluid (CSF) in SLE patients with NP features. Fifteen SLE patients were studied, all with NP features. CSF was evaluated for intrathecal IgG synthesis, oligoclonal IgG, and blood-brain barrier impairment. Sera and CSF were tested by ELISA for the presence of aCL-IgG and aCL-IgM with and without beta2 glycoprotein (beta2 GPI) cofactor. CSF and sera of 50 low back pain patients served as controls. Six patients were aCL(+) and nine aCL(-). In all patients the general CSF examination was normal. In all patients the value of indices of intrathecal IgG synthesis were normal but oligoclonal protein was present in the CSF of three patients. In none of the patients was the blood-brain barrier impaired. Neither aCL-IgG nor aCL-IgM was detected in the CSF of any NP-SLE patient. Mean levels of aCL in patients without cofactor beta2 GPI and with cofactor were as follows: for IgG class 0.005 and 0.057 OD (negative); for IgM class 0.004 and 0.024 OD (negative). We could not detect aCL in the CSF of patients with NP-SLE, even if sera were positive for aCL.

Adult↗
PubMed2000

Procreation ability in Wilson's disease.

OBJECTIVES: The clinical manifestations of Wilson's disease (WD) take the form of hepatic, neurological, renal as well as hormonal disturbances. Infertility and amenorrhea are reported in women and hypogonadism in men with WD. Our study was designed to analyse the procreation abilities of patients with WD. MATERIAL AND METHODS: We investigated by a questionnaire the course of pregnancy and delivery in 31 untreated women (mean age 22.5 years, 82 pregnancies) and 15 women (mean age 26.2, 25 pregnancies,) treated with D-penicillamine (D-p) or zinc sulphate (ZnS). We studied also procreation ability of 27 men (mean age 27.2 years). We analysed the congenital abnormalities and frequency of WD in children of our patients. RESULTS: One of 10 untreated women had difficulties with conception. The number and type of pathology (imminent abortions, gestosis, stillbirth, preterm births) were similar in treated and untreated patients. In both mentioned groups the most frequent pathology were spontaneous abortions, which were found in 26% of untreated and in 26.6% of treated women. This percentage is higher than in general population. Most of deliveries in patients with WD were spontaneous. Neither developmental malformations nor serious disorders were noticed in the offspring of our treated patients, 3 children of untreated patients were born with congenital heart disease. In 78 of the 110 children of our patients we examined the copper metabolism and we diagnosed WD in 5 cases (from 3 families). Among 27 investigated men only 1 was impotent. CONCLUSION: The risk of complications during pregnancy in asymptomatic and treated patients is higher than in general population, but it does not make the procreation impossible.

Adolescent↗
PubMed2000

[The relationship between immunological parameters with etiopathogenesis and clinical course of stroke].

We observed a lot of immune system disorders significantly influencing the development and clinical course of stroke. Depression of cell-mediated immune reactivity was observed in the early stage of stroke. It was manifested by the decrease of the number of T lymphocytes, depression in lymphocyte blastogenesis, diminished production of the migration inhibition factor and reduced delayed-type skin reactivity. Observed depression was probably caused by severe metabolic and endocrinological disorders often seen in the acute phase of the disease and related with increased patients' susceptibility to infections. Simultaneously we observed that the elevated total WBC was an independent stroke risk factor and predictor of 30-days stroke fatality. The activation of the adhesion molecules expression on granulocytes (CD18) and the increased cytokine production by leukocytes could favour leukocytes influence to the ischemic area and potentiate brain injury. The chronic inflammation could be also responsible for the development of vascular injuries leading to the ischemia. In our studies we demonstrated the high levels of antibodies to cardiolipins and heat shock proteins and the increased blood levels of immune complexes (i.c.). We observed the presence of Chlamydia pneumoniae and CMV antigens in isolated i.c. It suggests that different markers of chronic inflammation observed at very early stage of the disease are probably related with the chronic infection potentially leading to the development of atherosclerotic lesions and destabilization of atherosclerotic plaque.

Antibodies, Anticardiolipin↗
PubMed1999

The inflammatory reaction following 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine intoxication in mouse.

In degenerative disorders of the CNS an immune system involvement in the pathological process is postulated. The MPTP model of Parkinson's disease seem to be a good model for studying an inflammation following toxic neurodegeneration. In this model, microglial and astroglial reactions were previously found around impaired neurons. In the present work we showed an immune reaction, including lymphocytic infiltration of CD4+ and CD8+ T cells in the substantia nigra and striatum and elevated MHC class I and II antigens expression on microglia. Many activated lymphocytes were present, showing increased LFA-1 and CD44 antigen expression. We found also that ICAM-1 expression increased on the endothelium and appeared on microglia in the injured regions. Treatment with dexamethasone inhibited T-cell infiltration and MHC class II expression, lessened the glial reaction, and also diminished neuronal impairment. These findings suggest that an immune mechanism may contribute to the neuronal damage following MPTP administration.

Animals↗
PubMed1999

The influence of serotonin depletion on rat behavior in the Vogel test and brain 3H-zolpidem binding.

The influence of p-chlorophenylalanine (p-CPA) and 5,7-dihydroxytryptamine (5,7-DHT)-induced serotonin depletion on rat behavior as well as on zolpidem's the behavioral effects and binding to some brain areas of zolpidem, was examined with the help of Vogel's punished drinking test and autoradiography, respectively. Moreover, changes in the serotonin levels and turnover rate were studied in the forebrain and brainstem of rats pretreated with various ligands at the benzodiazepine (BDZ) receptors (midazolam, bretazenil, abecarnil, zolpidem). These drugs were given at doses shown previously to significantly disinhibit animal behavior suppressed by punishment in the Vogel test (Nazar et al., 1997). It was found that serotonin decrease in the frontal cortex and hippocampus after p-CPA significantly and inversely correlated with rat behavior controlled by fear in the VT. p-CPA produced an anticonflict activity in the absence of effect on spontaneous drinking, pain threshold and motility of animals. All applied benzodiazepine receptor ligands decreased the 5-HT turnover rate in the frontal cortex and hippocampus, whereas in the brainstem only abecarnil and zolpidem diminished 5-hydroxyindoleacetic acid levels. This part of the study replicated earlier data with neurotoxins and indicated that the anxiolytic-like effect of 5-HT depletion in some models of anxiety did not depend on changes in animal appetitive behavior or stimulus control. Moreover, the fact that all nonselective and selective (zolpidem) agonists of the type 1 benzodiazepine receptors seemed to produce the same anticonflict effect and decreasing 5-HT turnover indicates that this subtype of benzodiazepine receptor may be important for the interaction between brain 5-HT and GABA/BDZ systems. Accordingly, it was found that serotonin decrease enhanced the anticonflict effect of zolpidem in the Vogel test and increased 3H-zolpidem binding to the occipital cortex and substantia nigra. Altogether, the present study provides more arguments for the role of changes in the activity of brain 5-HT innervation in the control of emotional processes. Moreover, it points to the BDZ1 receptor subtype as a possible target of interaction between brain 5-HT and GABA(A)/BDZ systems.

5,7-Dihydroxytryptamine↗
PubMed1999

The role of the hippocampus and 5-HT/GABA interaction in the central effects of benzodiazepine receptor ligands.

The effects of an intrahippocampal administering of a nonselective full (midazolam), a partial benzodiazepine (BDZ) receptor agonist (bretazenil), and a BDZ1 selective (zolpidem) receptor ligand were examined in the open field test (OFT) of neophobia and Vogel's test (VT) of conflict behavior in rats. Moreover, the influence of local injections of a noncompetitive GABA(A) receptor antagonist, picrotoxin, on the anxiolytic-like effect of serotonin (5-HT) depletion (p-chlorophenylalanine, p-CPA) in the Vogel test was studied. It was found that in the OFT only midazolam (0.1 microg/site) given to the hippocampus (HP) disinhibited rat exploratory behavior, whereas all the examined compounds inhibited animal motor activity when injected locally at 10.0 microg/site, the highest dose used in the tests. In the VT, again, only midazolam disinhibited rat conflict behavior on a dose-dependent basis. Picrotoxin administered to the HP produced a tendency to increase locomotor activity in rats, and significantly attenuated the anti-conflict action of serotonin depletion without changing the pain threshold and spontaneous drinking of the animals. p-CPA induced potent, dose-dependent and selective 5-HT and 5-hydroxyindoleacetic acid decrease in the HP after administering the dose used in the behavioral experiment. Thus, the present data provide evidence for the lack of selective anxiolytic activity of a partial non-selective agonist and a full selective agonist at the BDZ1 receptor after their administration to the HP. The model of intra-HP drug injections appeared effective in discriminating the anxiolytic spectrum of activity of new psychotropic compounds. Moreover, the obtained results indicate that the dorsal HP is one of the central sites important for GABA/5-HT interaction that modulates rat emotional behavior.

Animals↗
PubMed1999

Phenotyping analysis of peripheral blood leukocytes in patients with multiple sclerosis.

Multiple sclerosis (MS) is a central nervous disease thought to be elicited by an autoimmune process. Many studies in recent years have concentrated on finding the alterations in the peripheral blood immune profile in MS patients that would reflect disease activity. In the present study, we investigated surface antigen expression on lymphocytes and granulocytes from MS patients and control subjects. We have studied 29 patients suffering from relapsing-remitting or relapsing-progressive forms of MS. The disease was diagnosed in all patients at least 12 months before inclusion into the study. All patients had no attack at the study entry date or within a previous month. The control group included 29 age-matched subjects. Phenotyping of peripheral blood leukocytes was carried out with different fluorescence-conjugated murine monoclonal antibodies. The analysis was performed with three-color flow cytometry. The following antigens were determined [cluster of definition (CD)]: leukocyte common antigen (LCA) (B220, T 200, Ly-5), CD45; LPS-R (lipopolysaccharide receptor), CD14; found on all T cells, CD3; LFA-2 (lymphocyte function associated antigen, T 11), CD2; coreceptor for MHC class II molecules, found on helper T cells, CD4; coreceptor for MHC class I molecules, found on suppressor/cytotoxic T cells, CD8; B4, found on all human B cells, CD19; NCAM (neural cell adhesion molecule), CD56; integrin beta2 subunit, associated with CD11a (CD11a/CD18, LFA-1, alphaLbeta2) and CD11b (CD11b/CD18, Mac-1,CR3, alphaMbeta2), CD18; alphaL, alpha subunit of integrin LFA-1 (alphaLbeta2, CD11a/CD18), CD11a; alphaM, alpha subunit of integrin Mac-1 (CR3, alphaMbeta2, CD11b/CD18), CD11b; ICAM-1 (intercellular adhesion molecule), CD54; H-CAM, Hermes antigen, Pgp-1, CD44; AIM (activation inducer molecule), early activation antigen, CD69; T-cell receptor gammadelta, TCR gammadelta. In the MS group, we have found a significant increased expression of CD54 and CD44 antigens on lymphocytes, and higher percentage CD54(+) and CD11a+CD54(+) lymphocytes out of all lymphocytes compared with the control group. We have also found a significant increased expression of CD11a, CD18 and CD54 antigens on granulocytes, and higher percentage CD11b+CD18(+) granulocytes out of all granulocytes in MS patients compared with control. Higher levels of expression of the adhesion molecules may reflect the activation state of leukocytes in MS patients.

Adult↗