Tremor in neurodegenerative ataxias, Huntington disease and tic disorder.

INTRODUCTION: Tremor is the most prevalent movement disorder, defined as rhythmic oscillations of a body part, caused by alternating or synchronic contractions of agonistic or antagonistic muscles. The aim of the study was to assess prevalence and to characterize parameters of tremor accompanying de-generative ataxias, Huntington disease (HD) and tic disorders in comparison with a control group. MATERIAL AND METHODS: Forty-three patients with degenerative ataxias, 28 with HD and 26 with tic disorders together with 51 healthy controls were included in the study. For each participant, clinical and instrumental assessment (accelerometer, electromyography [EMG], graphic tablet) of hand tremor was performed. Frequency and severity of tremor were assessed in three positions: at rest (rest tremor), with hands extended (postural tremor), during the 'finger-to-nose' test and during Archimedes spiral drawing (kinetic tremor). Based on the mass load test, the type of tremor was determined as essential tremor type or enhanced physiological tremor type. RESULTS: The incidence of tremor in the accelerometry in patients with degenerative ataxia (50%) significantly differs from controls (10%) (p = 0.001). The dominant tremor was postural, low-intense, with 7-Hz frequency, essential tremor (23%) or other tremor type (23%), while enhanced physiological tremor was the least frequent (2%). Tremor in patients with HD and tic disorders was found in 10% and 20% of patients, respectively, similarly to the control group. Tremor was mild, postural and of essential tremor type, less frequently of enhanced physiological tremor type. No correlation between severity of tremor and severity of disease was found. CONCLUSIONS: The prevalence of tremor is considerably higher among patients with degenerative ataxias compared with HD, tic disorder and the control group. The most common type of tremor accompanying ataxias, HD and tic disorders is essential tremor type.

Tremor associated with focal and segmental dystonia.

BACKGROUND AND PURPOSE: Tremor occurs in 10-85% of patients with focal dystonia as so-called dystonic tremor or tremor associated with dystonia. The aim of this study was to assess the incidence and to characterize parameters of tremor accompanying focal and segmental dystonia. MATERIAL AND METHODS: One hundred and twenty-three patients with diagnosis of focal and segmental dystonia together with 51 healthy controls were included in the study. For each participant, clinical examination and objective assessment (accelerometer, electromyography, graphic tablet) of hand tremor was performed. Frequency and severity of tremor were assessed in three positions: at rest (rest tremor); with hands extended (postural tremor); during 'finger-to-nose' test and during Archimedes spiral drawing (kinetic tremor). Based on the mass load test, type of tremor was determined as essential tremor type or enhanced physiological type. RESULTS: The incidence of tremor was significantly higher in dystonic patients as compared to controls (p = 0.0001). In clinical examination, tremor was found in 50% of dystonic patients, and in instrumental assessment in an additional 10-20%. The most frequent type of tremor was postural and kinetic tremor with 7 Hz frequency and featured essential tremor type. In the control group, tremor was detected in about 10% of subjects as 9-Hz postural tremor of enhanced physiological tremor type. No differences were found between patients with different types of dystonia with respect to the tremor incidence, type and parameters (frequency and severity). No correlations between tremor severity and dystonia severity were found either.

Causes and consequences of falls in Parkinson disease patients in a prospective study.

BACKGROUND AND PURPOSE: Falls are common events in Parkinson disease (PD) but only a few prospective studies have focused on causes and consequences of falls in PD patients. The aim of the study was prospective analysis of direct causes and consequences of falls in PD patients in comparison to the control group. MATERIAL AND METHODS: One hundred PD patients and 55 age-matched controls were enrolled in the study. The diagnostic workup in all patients included neurological examination, Unified Parkinson's Disease Rating Scale, magnetic resonance imaging, electroencephalography, ultrasonography, otolaryngological, ophthalmological and autonomic function examination. During 12 months of follow-up, falls were registered in both groups, direct causes were classified according to the St. Louis and Olanow classification, and consequences were established. RESULTS: Falls occurred in 54% of PD patients and in 18% of control subjects. Analysis of direct causes of falls revealed that sudden falls were the most common (31%), followed by episodes of freezing and festination (19.6%), neurological and sensory disturbances (mostly vertigo) (12%), environmental factors (12%), postural instability (11%), orthostatic hypotension (4%), and severe dyskinesia (3.6%); 6.19% of falls were unclassified; 22% of patients had the same etiology of subsequent falls. In PD patients, intrinsic factors were dominant, whereas in the control group intrinsic and extrinsic factors occurred with the same frequency. Every third fall intensified fear of walking. 34% of falls caused injuries; among them bruises of body parts other than the head were most frequent. CONCLUSIONS: Intrinsic factors are the most common causes of falls in PD. Every third fall intensifies fear of walking and causes injuries.

The incidence and risk factors of falls in Parkinson disease: prospective study.

BACKGROUND AND PURPOSE: Although Parkinson disease (PD) patients suffer falls more frequently than other old people, only a few studies have focused on identifying the specific risk factors for falls in PD patients. The aim of this study was to assess the incidence and risk factors of falls in a prospective study in comparison to a control group. MATERIAL AND METHODS: One hundred patients with PD were recruited to the study along with 55 gender- and age-matched healthy controls. Both groups were examined twice; the second examination took place one year after the first one. Examination of the PD group included: medical history including falls, neurological examination, assessment of the severity of parkinsonism [Unified Parkinson's Disease Rating Scale (UPDRS), Schwab and England scale (S and E), Hoehn and Yahr scale (H and Y), Mini-Mental State Examination (MMSE)], Hamilton scale and quality of life scales (SF-36, EQ-5D) and Freezing of Gait Questionnaire (FOG-Q). In both groups falls were recorded over the 12 months. Frequent fallers are defined as having more than 3 falls a year. RESULTS: Over the year falls occurred in 54% of PD patients and 18% of controls. In a prospective study 28% of PD patients fell more frequently than in retrospective analysis. Frequent fallers were found in 20% of patients and in 7% of controls. Fallers showed higher scores in UPDRS, H and Y, S and E, MMSE, and Hamilton scale than non-fallers. Independent risk factors for falls were: age, previously reported falls and higher score in the FOG-Q. CONCLUSIONS: Falls in PD patients occurred three times more frequently than in controls. Independent risk factors for falls were: high score in FOG-Q, older age and presence of falls in medical history.

Interleukin 6-174G>C polymorphism and risk of aneurysmal subarachnoid hemorrhage: case-control study and meta-analysis.

OBJECTIVES: Vascular inflammation contributes to the pathogenesis of aneurysmal subarachnoid hemorrhage (aSAH). Interleukin 6 (IL6) is a proinflammatory cytokine involved in many vascular pathologies. Two studies analyzing an association of the functional IL6 gene -174G>C promoter polymorphism with aSAH provided inconsistent results. The aim of this study was to investigate whether this IL6 polymorphism is associated with aSAH in a Polish population. MATERIAL AND METHODS: We genotyped 276 aSAH patients and 581 unrelated control subjects. All were of Caucasian origin. In addition, a meta-analysis combining results of the current and previously published studies was conducted. RESULTS: The distribution of IL6 genotypes and alleles did not differ significantly between aSAH (GG - 29.7%, GC - 50.0%, CC - 20.2%, G - 54.7%) and control subjects (GG - 32.0%, GC - 47.3%, CC - 20.7%, G - 44.3%). In the meta-analysis, the IL6-174G>C polymorphism was not associated with aSAH risk either. CONCLUSIONS: We failed to find an association between the IL6 -174G>C polymorphism and aSAH in analyzed European populations.

Patient-reported quality of life in multiple sclerosis differs between cultures and countries: a cross-sectional Austrian-German-Polish study.

BACKGROUND: Patient-reported quality of life (QOL) is an outcome measure in clinical trials in multiple sclerosis (MS), but translated QOL instruments may affect the actual comparability of data. OBJECTIVES: We aimed to investigate possible differences in QOL in MS between cultures and countries. We employed the Functional Assessment of Multiple Sclerosis (FAMS) Version 4 questionnaire, which is a state-of-the-art QOL instrument. METHODS: Some 484 MS patients from Austria (145), Germany (144), and Poland (195) aged 20-60 years, and stratified for sex and disease severity as measured by the Expanded Disability Status Scale (EDSS) score completed the respective FAMS translation and a socio-demographic questionnaire. RESULTS: Analysis of variance and post-hoc Scheffé-test showed that 64% of the FAMS items were answered significantly differently (p < 0.001) between the three countries. A multivariate regression analysis including all the available disease-related and socio-demographic variables revealed the factors age, EDSS score, employment, social contacts, MS course, and country to be significant predictors of both the total FAMS score and the score for items answered differently between the three countries. CONCLUSIONS: Differences exist in the QOL of MS patients from Austria, Germany, and Poland which seem to lie beyond the impact of disease severity. They appear to be related to culture or other country-specific factors, as country was an independent predictor of differently answered items of the FAMS and thus also of the whole FAMS. QOL instruments should consider this aspect to faithfully reflect subjective information such as patient-reported benefit of treatment in multinational clinical trials.

Paraoxonase 1 gene polymorphisms do not influence the response to treatment in Alzheimer's disease.

BACKGROUND: Acetylcholinesterase inhibitors (AChEIs) are the treatment of choice for patients with Alzheimer's disease (AD). However, their efficacy is moderate and differs from patient to patient. Recent studies suggest that the Q192R variant of the paraoxonase 1 gene (PON1) might affect individual susceptibility to these drugs. METHODS: We investigated the influence of 3 single nucleotide polymorphisms (SNPs) in PON1 (rs 662, rs 854560, rs 705381) and the APOE common polymorphism in 101 Polish patients with late-onset AD in response to treatment with AChEIs. RESULTS: No significant differences were observed between carriers and non-carriers of the PON1 SNPs or the APOE common polymorphism in terms of treatment response. These results did not change after stratification of APOE status. CONCLUSION: Our results suggest that both the investigated PON1 and APOE common SNPs do not influence treatment response to AChEIs in patients with AD.

Paraoxonase gene polymorphism and the risk for Alzheimer's disease in the polish population.

BACKGROUND: The relationship between different paraoxonase (PON) gene polymorphisms and the risk of Alzheimer's disease (AD) was studied several times and the results were controversial. METHODS: We investigated the association of 4 single-nucleotide polymorphisms (SNPs) of the PON1 (M55L; Q192R; -161C/T) and the PON2 (C311S) genes that were shown to affect the risk of sporadic AD. We studied 360 Caucasian cases with late-onset AD and 354 nondemented controls. RESULTS: No significant differences were observed between the studied PON SNPs and AD risk. The results did not change after stratification of the apolipoprotein E status. Meta-analyses of studies in Caucasians assessing the associations between the PON1 M55L, -161C/T and Q192R SNPs and the risk of AD were performed, and no associations were found. CONCLUSION: Our results suggest that the studied PON1 and PON2 polymorphisms are not associated with late-onset AD.

Association between hyperglycemia, heart failure and mortality in stroke patients.

BACKGROUND: Acute hyperglycemia predicts increased mortality after stroke. The aim of our study was to determine if acute stroke patients with hyperglycemia suffer from increased rate of in-hospital adverse events which could influence survival such as pneumonia, heart failure and myocardial infarction. METHODS: In a retrospective study with prospective follow-up, 689 patients with first-ever ischaemic stroke and high frequency of cardiovascular diseases were eligible. Follow-up period was 1-7 years (14 308 person-months). RESULTS: The frequency of in-hospital heart failure and nosocomial pneumonia was the highest in patients without pre-hospital diagnosis of diabetes mellitus and with fasting glucose >or=7 mmol/l (50% and 20.2%, respectively) and the lowest in patients without pre-hospital diagnosis of diabetes and fasting glucose

Interleukin-1 gene -511 CT polymorphism and the risk of Alzheimer's disease in a Polish population.

Interleukin-1 is a potent proinflammatory cytokine involved in the pathophysiology of Alzheimer's disease (AD). We genotyped IL-1beta (-511 C/T) and the apolipoprotein E (APOE) common polymorphisms in a large case-controlled study in a Polish population. We included 332 patients with late-onset AD and 220 controls without any neurological deficit, cognitive complaints and history of neurological diseases, aged > or = 65 years. The distribution of the IL-1beta (-511 C/T) genotypes was similar to that in the controls (AD: C/C = 45.8%, C/T = 44.6%, T/T = 9.6% vs. controls: C/C = 53.9%, C/T = 38.3%, T/T = 7.3%, p > 0.05). Our study confirms previous reports that APOE epsilon4 is strongly related to the risk of AD (odds ratio = 6.60, 95% confidence interval 4.19-10.41). APOE status did not affect the distribution of the studied IL-1beta polymorphism. The IL-1beta (-511 C/T) polymorphism is not a risk factor for late-onset AD in a Polish population.

A-G-4G haplotype of PAI-1 gene polymorphisms -844 G/A, HindIII G/C, and -675 4G/5G is associated with increased risk of ischemic stroke caused by small vessel disease.

BACKGROUND: Plasminogen activator inhibitor type 1 (PAI-1) is the major inhibitor of fibrinolysis. It was reported that PAI-1 gene polymorphisms affected PAI-1 level and might therefore influence the risk of vascular diseases, including stroke. We studied the association of three common polymorphisms in PAI-1 gene (-844 G/A, -675 4G/5G, and HindIII G/C) with the odds of different causes of ischemic stroke. METHODS: We studied 390 patients with ischemic stroke due to large vessel disease (n = 117), small vessel disease (n = 121), and cardioembolism (n = 152) as well as 291 controls. The etiology of ischemic stroke was established using TOAST criteria. PAI-1 polymorphisms were genotyped with restriction fragment length polymorphism and single strand conformation polymorphism method. RESULTS: A-G-4G haplotype of PAI-1 gene was found more frequently in stroke patients with small vessel disease than in control subjects (44.9% vs 35.7%; P = 0.02). No association was found between investigated genotype or allele frequencies and distinct causes of ischemic stroke. CONCLUSIONS: Our results demonstrate that A-G-4G PAI-1 gene haplotype is associated with increased risk of small vessel disease stroke, but this study does not support an association of -844 G/A, -675 4G/5G, and HindIII G/C PAI-1 gene polymorphisms with particular etiology of ischemic stroke.

Prefrontal N-acetylaspartate and poststroke recovery: a longitudinal proton spectroscopy study.

BACKGROUND AND PURPOSE: Functional imaging studies suggest that poststroke recovery is related to the reorganization in both contralesional and ipsilesional prefrontal cortex. Little is known, however, about how longitudinal metabolic changes in prefrontal regions relate to the improvement after stroke. We sought to determine whether poststroke recovery is associated with changes in N-acetylaspartate/creatine (NAA/Cr) ratio within contralesional prefrontal regions. MATERIALS AND METHODS: Twenty-seven patients with a first ischemic stroke located outside the frontal lobes were included. Proton MR spectroscopy ((1)H-MRS) was performed on a 1.5T scanner. Point-resolved spectroscopy sequence (PRESS) was used. NAA/Cr was measured both in ipsilesional and contralesional prefrontal regions in early (14 +/- 6 days after stroke) and chronic phases of the disease (110 +/- 30 days after). Patients' neurologic status was assessed using Scandinavian Stroke Scale (SSS) at discharge from the stroke unit and during second (1)H-MRS examination. RESULTS: Subjects showing increased contralesional NAA/Cr from first to follow-up examination improved significantly more on the SSS than patients not showing this increase. Analysis was performed while correcting for change in NAA/Cr levels in the ipsilesional hemisphere. For the whole group, the change in contralesional NAA/Cr was significantly correlated to the change in SSS scores (r = 0.40, P = .03). Change in the ipsilesional NAA/Cr measures did not correlate with the change in SSS scores. CONCLUSION: Poststroke recovery was related to the increase in contralesional prefrontal NAA/Cr. This association may reflect recovery mechanisms involving the nonaffected hemisphere. Further assessment of these regions may provide information about mechanisms contributing to neurologic improvement.

Hypoalbuminemia in acute ischemic stroke patients: frequency and correlates.

OBJECTIVE: Hypoalbuminemia in acute stroke patients is associated with increased mortality and morbidity. The aim of our study was to determine the frequency and correlates of hypoalbuminemia in unselected cohort of patients with acute cerebral infarction. DESIGN: Prospective study. SETTING: University hospital. SUBJECTS: Seven hundred and five consecutive ischemic stroke patients. METHODS: Albumin and other serum protein fractions were measured within 36 h after stroke using electrophoresis. RESULTS: Hypoalbuminemia defined as serum albumin level <35 g/l was found in 45.5% of patients. Serum albumin level correlates significantly with age (r=-0.13, P<0.01), Scandinavian Stroke Scale score (r=0.14, P<0.01), body temperature on admission (r=0.14, P<0.01), leukocyte count (r=-0.17, P<0.01), fasting glucose (r=-0.16, P<0.01), total cholesterol (r=0.14, P<0.01), alpha1-globulin (r=-0.48, P<0.01), alpha2-globulin (r=-0.49, P<0.01), beta-globulin (r=-0.26, P<0.01) and gamma-globulin (r=-0.35, P<0.01). CONCLUSIONS: Hypoalbuminemia is a frequent finding in acute stroke patients and it is associated with more severe stroke and pro-inflammatory pattern of serum protein electrophoresis.

Increase in salsolinol level in the cerebrospinal fluid of parkinsonian patients is related to dementia: advantage of a new high-performance liquid chromatography methodology.

The study was carried out on the lumbar cerebrospinal fluid (CSF) samples taken from nonparkinsonian, early parkinsonian, and advanced parkinsonian patients. Some patients showed dementia, and some were treated with L-dopa. In the samples, salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) was assayed with a newly developed sensitive high-performance liquid chromatography (HPLC) method; 3-O-methyldopa (3-O-MD) and homovanillic acid (HVA) were also assayed by HPLC. CSF salsolinol concentrations were significantly enhanced in patients with signs of dementia, regardless of the degree of parkinsonism, and were not affected by L-dopa treatment; HVA and, particularly, 3-O-MD levels were elevated in patients receiving L-dopa. The strong association of CSF salsolinol level with dementia, but not with L-dopa treatment suggests that salsolinol does not originate from L-dopa metabolism, and that its elevation is an indicator of neurodegenerative processes resulting in damage to brain areas mediating cognitive functions. We found no correlation between the advancement of parkinsonism and the concentrations of 3-O-MD and HVA.

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.

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.

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.

Determination of nitrite/nitrate in human biological material by the simple Griess reaction.

Since a number of pathological processes such as septic shock, inflammation, graft rejection, diabetes, etc. are associated with a release of nitric oxide (NO), rapid and accurate methods of monitoring of NO concentration are of interest. Various methods for measurement of nitrite and nitrate (NO2-, NO3- ) -- the stable metabolites of NO -- are commonly used for this purpose. In this paper we have shown that the proper Griess procedure for nitrite determination significantly increases the sensitivity of this method. This procedure, supplemented with deproteinization and reduction of nitrates to nitrites in the presence of NADPH-sensitive reductase, can be successfully applied for measurement of NOx levels in human body fluids (serum, urine and CSF). Deproteinization of samples with methanol/diethylether is required and does not influence the sensitivity of detection of NO metabolites. The recovery of the method is 88%+/-6% (n = 30). The NOx concentrations measured by this procedure ranged from 25.0 to 39.0 micromol/l in blood, 4.6 to 14.6 micromol/l in CSF and 0.37 to 2.52 mmol/l (adjusted to creatinine concentration) in urine. The coefficient of variation for this method was between 1.3-2.2%. This method can also be recommended for measurement of NOx produced by cells in tissue cell culture.

The effect of insulin and sulodexide (Vessel Due F) on diabetic foot syndrome: pilot study in elderly patients.

OBJECTIVE: To assess the efficacy of insulin plus sulodexide (a mixture of 80% heparin-like substances and 20% dermatan sulphate) on diabetic ulcers, and its influence on foot skin microcirculation and diabetic neuropathy. RESEARCH DESIGN AND METHODS: Two groups of diabetic patients, suffering from severe neuropathy and ulceration, were randomly assigned to insulin (I) plus sulodexide (S) (n=12) or insulin plus placebo (P) (n=6) therapy, for 10 weeks. Laser Doppler assessment of foot skin flow (LDF), at rest and 30 or 60 s after arterial occlusion, and nerve conduction tests (sensorial evoked and motoric conduction potentials) have been evaluated in both groups. RESULTS: Postischaemic flow was 2.5 times shorter in ulcerated vs. non-ulcerated feet in diabetic patients. A significant increase in flows after 30 and 60 s ischaemia was detected in both groups at the end of therapy (IS group, ulcerated foot, LDF=60 s: from 99.1+/-14.3 to 218.6+/-28.6 PU, P<.001. IP group=from 110.5+/-13.0 to 164.8+/-15.4 PU, P<.05). The length of reactive hyperaemia was higher in IS vs. IP group (IS: from 30.3+/-2.9 to 43.9+/-2.2 s, P<.001; IP: from 28.7+/-3.0 to 33.3+/-3.3 s, ns). Ninety-two percent of ulcers heals in a mean time of 46.4 days (IS group) vs. 83% and 63.0 days, respectively, in IP group. Nerve conduction studies have not demonstrated within- and between-group differences. CONCLUSIONS: Sulodexide and insulin improve the postischaemic skin flow in ulcerated feet, without affecting nerve conduction tests. The effect of sulodexide results additive to insulin; it is clinically relevant, in the view of the possibility of reducing the time needed to completely heal ulcers. The ultimate validation of these preliminary results requires extensive trials.

Labile products of vascular endothelium as mediators and modulators of the functions of the central nervous system.

A rapid development of the knowledge about vascular endothelial cell function as an "endocrine gland" releasing the labile, highly biologically active products, caused a major reapprisal of our concepts concerning the pathophysiology of our body. The publication summarizes the present understanding of the involvement of nitric oxide (NO), endothelins (ETs) and arachidonic acid products in the mechanisms underlying the regulation of the tonus of vessels supplying blood to the CNS, their known modulatory and mediatory role in CNS functions such as a development and memory, peripheral nonadrenergic noncholinergic, or sensory neurotransmission. The regulation intracellular Ca+ +ion levels as a proposed mechanism for the neuroprotective, as well as the neurotoxic effect of the described endothelial products is presented. The supposed therapeutical usefullness of compounds which can modulate their biosynthesis, substitute their activity, or modify its degradation are also summarized.