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Biomedical subjects

A Szczudlik

Publications and source records attributed to A Szczudlik.

At least 19 recordsLinked to original sources

Paraoxonase gene polymorphisms and sporadic ALS.

BACKGROUND: The human paraoxonase (PON) gene family consists of three members, PON1, PON2, and PON3, located adjacent to each other on chromosome 7. PON catalytic activity may be influenced by frequent amino acid variants. Chronic exposure to certain chemicals or to environmental factors causing enhanced lipid peroxidation metabolized by paraoxonases may be a risk factor for sporadic ALS (sALS). OBJECTIVE: The aim of this study was to examine the association between PON1 Q192R, PON1 L55M, and PON2 C311S functional polymorphisms and the risk of sALS in a Polish population. METHODS: The authors included 185 patients with a definite or probable diagnosis of sALS (El Escorial Criteria) and 437 healthy controls of similar age and gender. The paraoxonase polymorphisms were studied by PCR and restriction enzyme digestion. RESULTS: Using logistic regression analyses, the C allele of the C311S polymorphism was associated with sALS in dominant and additive models, whereas the R allele of the Q192R polymorphism was associated with sALS in recessive, additive, and dominant models. The authors compared the distribution of haplotypes between cases and controls. The R-C haplotype was overrepresented among cases (odds ratio 3.44, 95% CI: 1.55 to 7.62, p = 0.002). CONCLUSIONS: Frequent amino acid variants in the paraoxonase 1 and paraoxonase 2 genes are associated with sporadic ALS in a Polish population.

Adult↗

Implementation of X-ray fluorescence microscopy for investigation of elemental abnormalities in amyotrophic lateral sclerosis.

The abnormalities of metallochemical reactions may contribute to the pathogenesis of Amyotrophic Lateral Sclerosis (ALS). In the present work, an investigation of the elemental composition of the gray matter, nerve cells and white matter from spinal cord tissues representing three ALS cases and five non-ALS controls was performed. This was done with the use of the synchrotron microbeam X-ray fluorescence technique (micro-SRXRF). The following elements were detected in the tissue sections: P, S, Cl, K, Ca, Fe, Cu, Zn and Br. A higher accumulation of Cl, K, Ca, Zn and Br was observed in the nerve cell bodies than in the surrounding tissue. Contrary to all other elements, Zn accumulation was lower in the white matter areas than in the gray matter ones. The results of quantitative analysis showed that there were no general abnormalities in the elemental accumulation between the ALS and the control group. However, for individual ALS cases such abnormalities were observed for the nerve cells. We also demonstrated differences in the elemental accumulation between the analyzed ALS cases.

Amyotrophic Lateral Sclerosis↗

Serum albumin level and nosocomial pneumonia in stroke patients.

Hypoalbuminemia is associated with increased risk of infections. The aim of this study was to determine if serum albumin level is an independent predictor of nosocomial pneumonia in stroke patients. Data of 705 consecutive ischemic stroke patients admitted within 24 h after stroke onset were analyzed retrospectively. Serum albumin level was measured within 36 h after stroke onset. Nosocomial pneumonia was found in 10.5% of stroke patients. Patients with pneumonia had significantly lower serum albumin level than those without pneumonia (31.9 +/- 7.5 g/l vs. 35.5 +/- 6.9 g/l) and serum albumin level was associated with risk of pneumonia on multivariate analysis (OR: 0.95, 95% CI: 0.91-0.98). Our results show that serum albumin level is an independent predictor of nosocomial pneumonia in stroke patients.

Aged↗

ACE I/D polymorphism in different etiologies of ischemic stroke.

OBJECTIVES: Data concerning an association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and ischemic stroke (IS) remain inconsistent. Results of some studies suggest that DD genotype may be a risk factor for small vessel disease (SVD) stroke. Here, we investigated whether this polymorphism is associated with IS of different etiologies in a Polish population. SUBJECTS AND METHODS: Ischemic stroke etiology was established according to the TOAST criteria. We studied 92 stroke patients with large vessel disease and their 184 matched controls; 96 stroke patients with SVD and 192 controls; 180 patients with cardioembolic stroke (CE) and 180 controls. ACE I/D polymorphism was determined using the polymerase chain reaction method. RESULTS: The distribution of ACE genotypes and alleles was essentially the same in all analyzed IS subtypes and their matched controls. CONCLUSIONS: We failed to find an association between ACE polymorphism and etiological subtypes of IS in a Polish population.

Aged↗

Improvement of motor function in early Parkinson disease by safinamide.

A median safinamide (SAF) dose of 70 mg/day (range 40 to 90 mg/day) increased the percentage of parkinsonian patients improving their motor scores by > or =30% from baseline (responders) after 3 months from 21.4% (placebo) to 37.5% (p < 0.05, calculated by logistic regression analysis). In a subgroup of 101 patients under stable treatment with a single dopamine agonist, addition of SAF magnified the response (47.1% responders, mean 4.7-point motor score decrease; p > or = 0.05). These results suggest that doses of SAF exerting ion channel block and glutamate release inhibition add to its symptomatic effect and warrant exploration of higher doses.

Adult↗

DD genotype of ACE gene is a risk factor for intracerebral hemorrhage.

Genetic factors may play a role in susceptibility to stroke. The angiotensin converting enzyme (ACE) gene is a candidate gene for two phenotypically different types of stroke affecting small perforating arteries: spontaneous intracerebral hemorrhage (SIH) and ischemic stroke due to small vessel disease (SVD). The authors report evidence that ACE gene DD homozygosity of the I/D polymorphism in intron 16 is an independent risk factor for SIH, and not for SVD stroke, in a Polish population.

Adult↗

Serum interleukin-6 predicts cortisol release in acute stroke patients.

Altered hypothalamo-pituitary-adrenal axis was reported in stroke patients; however, mechanisms responsible for this phenomenon are barely understood. Acute cerebral ischemia triggers interleukin-6 (IL-6) release into blood. Circulating IL-6 can stimulate hypothalamo-pituitary-adrenal axis. The goal of our study was to assess a relationship between serum IL-6 and cortisol in acute ischemic stroke. Twenty two patients with ischemic stroke and 17 controls were included. Serum samples were collected on the 2nd day of stroke at 6:00, 10:00 18:00, 22:00 h and at the same time points in control group. Cytokines and cortisol levels were measured using ELISA method. Serum IL-6 and cortisol levels were higher in stroke patients than in controls. Cortisol displayed diurnal variations in both stroke patients and controls. In contrast with control subjects, serum IL-6 levels did not display diurnal variations in stroke patients. In stroke patients, but not in controls, IL-6 level correlated significantly with cortisol level and morning serum IL-6 level independently predicted evening/night cortisol level. In conclusion, brain ischemia could stimulate IL-6 release in blood and in this way modulate hypothalamo-pituitary-adrenal axis.

Acute Disease↗

Microalbuminuria and hyperthermia independently predict long-term mortality in acute ischemic stroke patients.

OBJECTIVES: To investigate the association between microalbuminuria (MA) and hyperthermia in acute ischemic stroke and to evaluate their significance as the predictors of long-term mortality after stroke. MATERIAL AND METHODS: We assessed neurologic deficit, urinary albumin excretion and body temperature in 60 patients admitted within 24 h after the onset of their first ischemic stroke. Outcome was assessed by 90-day and 1-year mortality. RESULTS: MA was found in 46.7% of patients. Hyperthermia was found in 18.3% patients on Day 1 and in 25% patients on Day 2. The correlation between albuminuria on Day 2 and the body temperature on Days 1 and 2 was found (r = 0.45, and r = 0.30, respectively; both P < 0.05). The mortality was significantly higher in the group of patients with both MA and hyperthermia on Day 2 (73% vs 10% after 90 days; P < 0.0001 and 73% vs 18% after 1 year, P < 0.005). In the logistic regression analysis, albuminuria (P = 0.017), hyperthermia on Day 1 (P = 0.028) and neurologic deficit on admission (P = 0.044) independently predicted 1-year mortality after ischemic stroke. CONCLUSION: Daily urinary albumin excretion correlates with the body temperature in acute stroke patients, but the predictive power of both these variables is independent of that association.

Acute Disease↗

Transient hyperglycemia in ischemic stroke patients.

The aim of the study was to investigate glucose derangement and its short- and long-term prognostic significance in nondiabetic ischemic stroke patients. The study involved 262 consecutive patients, mean age: 70.1+/-12.4 years, with a supratentorial ischemic stroke. The following data were collected: patients characteristics, risk factors, comorbidities, and stroke severity assessed by the Scandinavian Stroke Scale (SSS). Serum glucose levels were measured on admission, on the next, 2nd, 3rd, 5th, 7th and 14th day after stroke onset. The outcome measures on day 30 were mortality and capacity to perform daily activities: the Barthel Index and Rankin Scale. The 1-year survival was estimated by the Kaplan-Meier method. Cox proportional hazards regression was used to assess predictors of 1-year mortality in nondiabetics. Diabetes mellitus was found in 24.8% of patients and transient hyperglycemia in 36.3% of patients. Patients with transient hyperglycemia scored lower on SSS in the subsequent days of assessment than patients with either diabetes mellitus or normoglycemia. They had larger ischemic lesions on computer tomography (CT) than diabetics and had higher 30-day mortality than normoglycemics (p<0.05). One-year mortality was similar in transient hyperglycemics and diabetics, and both were significantly higher than in normoglycemics (p<0.05). A proportional hazards model analysis showed that transient hyperglycemia is not an independent predictor of death within a year after stroke.

Adult↗

[Mechanisms determining the occurrence of microalbuminuria in patients with acute ischemic stroke].

Microalbuminuria is more prevalent in patients with risk factors for cardiovascular diseases and reflects the widespread vascular damage predisposing to atherosclerosis. It is also found in acute clinical conditions, e.g. myocardial infarction, pancreatitis and stroke, and predicts poor outcome. The mechanism leading to increased albuminuria in these conditions is unknown, therefore we designed the study to investigate the relationship between increased urinary albumin excretion in acute stroke and biochemical markers of stress and inflammatory reaction as well as markers of endothelial damage. Sixty patients with first-time ischemic stroke, admitted within 24 hours to the stroke unit took part in the study. We excluded patients with diabetes, infection, nephropathy and abnormal urinalysis. Neurological deficit was assessed on admission and after 24 hours by Scandinavian Stroke Scale. Daily urinary albumin excretion on Day 2 was measured using the immunonephelometric method. The serum cortisol concentration was measured on Day 1 at 6.00 AM, 10.00 AM, 6.00 PM and 10.00 PM. Daily urinary excretion of epinephrine and norepinephrine was measured on Day 1 and on Day 3. We assessed also hematocrit, ESR, serum glucose and fibrinogen, leukocytosis, thrombocytosis and von Willebrand factor activity. Microalbuminuria was found in 46.7% of patients. There was no difference between patients with micro-albuminuria and those without it regarding sex, age and the prevalence of risk factors for stroke. Patients with micro-albuminuria had greater urinary excretion of epinephrine on Day 1. We did not find any differences regarding von Willebrand factor activity, serum cortisol concentration or other assessed variables. In logistic regression analysis the urinary excretion of epinephrine on Day 1 was the only independent variable predicting the occurrence of microalbuminuria in patients with acute ischemic stroke.

Aged↗

[The diagnosis of subclinical hepatic encephalopathy].

Subclinical hepatic encephalopathy, has been recognized in patients with cirrhosis, irrespectively of its etiology. Patients exhibit different cognitive deficits (in visual-spatial perception, attention, concentration, constructional ability, etc.), which are not detectable during standard neurological examination, but adversely affect daily functioning. The prevalence of this disorder among patients with cirrhosis is estimated to vary from 30 to 84% according to various studies. We presented the pathogenesis of subclinical hepatic encephalopathy. We discussed psychometric tests, which were the most important and sensitive diagnostic tools in this disorder. The significance of the abnormalities in the electrophysiological examination (EEG, visual evoked potentials, P300 wave, event-related potentials) and in computed tomography, magnetic resonance imaging, single photon emission computed tomography and proton-magnetic resonance spectroscopy were presented.

Electroencephalography↗

Activation of MAP kinase (ERK-1/ERK-2), tyrosine kinase and VEGF in the human brain following acute ischaemic stroke.

We examined expression of vascular endothelial growth factor (VEGF), phosphorylation of mitogen activated protein kinase (MAP) kinase (ERK1 and ERK2) and tyrosine phosphorylation in 19 patients (aged 58-90 years; mean 75) who died 1-44 days after acute ischaemic stroke. In the grey matter penumbra, 13 of 19 patients showed an increase in MAP kinase tyrosine phosphorylation (ERK1; 2.0- to 8-fold, ERK2; 2.2- to 11-fold) compared with normal contralateral tissue. In almost all cases, ERK-2 phosphorylation was higher than ERK1. Of these 13 patients, 11 also showed a general increase in tyrosine kinase phosphorylation, and eight expressed increased levels of VEGF protein (2.5- to 5-fold). In tissue examined directly from the infarct core, activation of the above proteins was not observed in the, majority of patients. In the white matter, seven of 19 patients (penumbra), and nine of 19 patients (stroke) had an increase in MAP kinase tyrosine phosphorylation (ERK1; 2.0- to 4.6-fold and ERK-2; 2.3- to 5.4-fold respectively) compared with normal contralateral tissue. There was no relationship between activation of MAP kinase and expression of VEGF. Examination of phosphorylated MAP kinase by immunohistochemistry revealed an increase in immunoreactivity in neurones, astroglial cells, reactive microglia and endothelial cells in areas surrounding infarcts, especially in areas with the highest density of microvessels. In conclusion, chronic activation of tyrosine phosphorylated events, in particular redistribution and phosphorylation of MAP kinase (ERK1/ERK2) occurs consistently in the grey matter penumbra of brain tissue following ischaemic stroke, and may be associated with increase in expression of VEGF. These signal transduction events could be important determinants of the extent of neuronal survival and/or angiogenic activity in the recovering brain tissue.

Acute Disease↗

Neurochemical changes induced by acute and chronic administration of 1,2,3,4-tetrahydroisoquinoline and salsolinol in dopaminergic structures of rat brain.

The finding that endogenous tetrahydroisoquinolines may be involved in the etiology of Parkinson's disease suggests that their administration may cause changes resembling those observed in parkinsonian brain. We tested, using a high-performance liquid chromatography method, how single and chronic administration of 1,2, 3,4-tetrahydroisoquinoline and salsolinol affects dopamine and serotonin metabolism in the neurons of extrapyramidal and mesolimbic dopaminergic systems. We report that chronic administration of tetrahydroisoquinoline and salsolinol causes a decrease in a dopamine metabolism: the effect of tetrahydroisoquinoline was limited to the striatum, while salsolinol caused also a dramatic decline of dopamine level in the substantia nigra. The effect of both compounds on serotonin metabolism was small or absent. The tetrahydroisoquinolines produced no changes in the nucleus accumbens. The results indicate that tetrahydroisoquinoline and salsolinol specifically affect the nigrostriatal dopamine system, but only when administered chronically, and thus are compatible with the view that endogenous tetrahydroisoquinolines may participate in pathogenesis of Parkinson's disease.

Animals↗

Serial measurement of vascular endothelial growth factor and transforming growth factor-beta1 in serum of patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Both vascular endothelial growth factor (VEGF) and transforming growth factor-beta1 (TGF-beta1) are expressed in higher than normal concentrations in the penumbra of patients after ischemic stroke. Because both cytokines are central to the processes of angiogenesis, tissue inflammation, and fibrosis, we performed serial measurements of these cytokines in patients with cerebral infarction and determined their relationship to stroke etiology and volume. METHODS: We serially (at days 0, 1, 3, 7, and 14) measured the serum levels of VEGF and active TGF-beta1 in 29 patients with acute ischemic stroke. Age-matched healthy subjects (n=26) were used as controls. RESULTS: Expression of VEGF was significantly increased in the majority of patients after acute stroke at each of the time points compared with normal controls. Highest expression occurred at day 7 (588+/-121 pg/mL; P=0.005), and it remained significantly elevated at 14 days after stroke. Expression of VEGF correlated with infarct volume, clinical disability (Scandinavian Stroke Scale), and peripheral leukocytosis and was significantly higher in patients with atherothrombotic large-vessel disease and ischemic heart disease (P<0.05 in all cases). In contrast, expression of active TGF-beta1 was not significantly different from control patients at any of the measured time points. When the mean concentration of TGF-beta1 from each patient (pooled time points) was compared with the control mean, a significant increase was found in only 2 patients, whereas levels decreased in 12 patients (P<0.05). There was no correlation between circulating active TGF-beta1 and VEGF expression, leukocytosis, stroke subtype, or patient disability as assessed by Scandinavian Stroke Scale score. CONCLUSIONS: VEGF but not TGF-beta1 showed a dramatic increase in serum of stroke patients. Correlation between stroke severity and VEGF concentration suggests it could be involved in the subsequent repair processes resulting in partial recovery after stroke. Correlation between VEGF expression and peripheral leukocytosis suggests that these changes may also reflect the immunologic status of the patient. VEGF may play an important role in the pathophysiology of acute ischemic stroke and could be of value in future treatment strategies.

Acute Disease↗

Progressive multifocal leukoencephalopathy (PML) in a patient with silicosis treated previously with steroids. A report of a case with JC virus infection confirmed immunohistochemically and by electron microscopy.

We present a case of progressive multifocal leukoencephalopathy (PML) diagnosed at autopsy, in which JC virus infection of the central nervous system was confirmed by means of electron microscopy and immunohistochemistry. The patient had been receiving steroid hormones due to suspected sarcoidosis or pneumoconiosis. Diffuse silicosis in lungs and in hilar and mediastinal lymph nodes was diagnosed at autopsy. Intranuclear inclusions, ultrastructurally typical of JC virus were found in some oligodendrocytes in the white matter. However the strongest immunopositive viral deposits were found in the cerebellar cortex, also within Purkinje cells. Numerous apparently apoptotic cells seen in white matter suggest that this mechanism of cell elimination plays an important role in PML pathogenesis and hence anti-apoptotic treatment may alleviate the symptoms and prolong survival.

Adult↗