Autonomic Nervous System Function in Newly Diagnosed Multiple Sclerosis: Association With Lipid Levels and Insulin Resistance.

Autonomic nervous system (ANS) disorders are common in multiple sclerosis (MS). Previous studies showed differences in insulin resistance (IR) and lipoprotein levels in MS subjects compared to controls. Lipolysis caused by increased sympathetic activity could be one of the possible linking mechanisms leading to dyslipidemia in MS. Our study aimed to evaluate ANS activity in the context of glucose and lipid metabolism in people with MS. We prospectively measured short-term heart rate variability (HRV), fasting lipoprotein concentrations, and calculated IR indices based on plasma glucose and insulin levels during oral glucose tolerance test (oGTT) in 32 patients with MS and 29 healthy controls matched for age, sex and body mass index in our study. There was no significant difference in HRV parameters and lipoprotein levels between MS and controls. A significant positive correlation was found between low/high-frequency power ratio (LF/HF) and triglycerides (r=0.413, p=0.021) in MS subjects but not in controls. A significantly lower whole-body insulin sensitivity index (ISIMat) was found in patients with MS compared to the control group (7.3±3.7 vs. 9.8±5.6, p=0.041). No significant correlations were found between LF/HF and IR parameters. In MS subjects, the positive correlation of LF/HF with triglycerides could reflect the effects of sympathetic activity on lipolysis. Positive correlations of sympathetic activity with increased lipoprotein levels could rather reflect processes associated with immune system activation/inflammation, than processes involved in glucose homeostasis maintenance.

Excessive daytime sleepiness in sleep apnea: any role of testosterone or vitamin D?

Recent studies reported association of sleep-disordered breathing (SDB) with testosterone and vitamin D deficiency. Low testosterone and vitamin D levels have been linked to fatigue and excessive daytime sleepiness (EDS). However, the impact of testosterone and vitamin D deficiency on EDS in subjects with SDB remains unknown. The aim of this study was to explore the predictors of EDS in habitual snorers. Role of testosterone, and vitamin D was studied in detail. We also looked for associations between testosterone, vitamin D, and sleep-related indices. We prospectively enrolled 291 consecutive male patients with habitual snoring. Baseline clinical characteristics were recorded on admission. Standard overnight polysomnography was performed to detect SDB, and Epworth Sleepiness Scale (ESS) was used to assess EDS. Blood samples were obtained in a fasting condition in the morning after polysomnography to determine levels of testosterone and vitamin D. Respiratory disturbance index (RDI) (95 % CI: 1.004-1.024, p=0.005) and the use of antihistamines (95 % CI: 1.083-11.901, p=0.037) were the only independent variables significantly associated with EDS in binary logistic regression analysis. In linear multiple regression analysis, body mass index (BMI) (Beta=-0.282, p<0.001) and oxygen desaturation index (Beta=-0.150, p=0.043) were the only independent variables significantly associated with testosterone levels, and BMI (Beta=-0.142, p=0.016) was the only independent variable significantly associated with vitamin D. We failed to find any independent association of testosterone and vitamin D with subjectively rated EDS among habitual snorers. Our results suggest an independent association between the magnitude of nocturnal desaturation and testosterone levels.

VLA4 Gene Polymorphism and Susceptibility to Multiple Sclerosis in Slovaks.

Multiple sclerosis (MS) is an inflammatory autoimmune disease occurring in genetically sensitive individuals. As migration of immune cells into the CNS is facilitated by the Very Late Antigen 4 (VLA-4) integrin molecule, the VLA4 gene may be considered as a plausible candidate genetic risk factor for susceptibility to MS. Therefore, the objective of our study was to investigate the association between two genetic polymorphisms located in the VLA4 gene and the risk of multiple sclerosis. One hundred seventeen MS patients and 165 control subjects from Slovakia were genotyped for VLA4 gene SNP polymorphisms at positions 269 (C/A) and 3061 (A/G). The same study cohorts were also genotyped for the rs3135388 polymorphism tagging the HLA-DRB1*15:01 allele, which is a known genetic factor associated with susceptibility to develop MS in many populations. Our findings show for the first time that the rs3135388 polymorphism is a strong risk factor for MS in the Slovak population. Investigation of the VLA4 gene polymorphisms revealed a significantly higher frequency of the 3061AG genotype in MS patients compared to the controls (P ≤ 0.05). We suggest that the 3061AG polymorphic variant is an independent genetic risk factor for MS development in our population as it was significantly associated with this disease. The association was also confirmed after applying multivariate logistic-regression analysis adjusted for gender, age and HLA-DRB1*15:01 positivity as possible influencing factors.

Eclampsia as a cause of secondary non-obstructive central sleep hypoventilation.

The central alveolar hypoventilation of Ondine's curse is a disorder characterized by absent or diminished ventilatory response to hypercapnia, hypoxia or both, with parallel decrease in saturation to 50%. The secondary form may begin mainly after insult that affects the brain stem. We present a case of a 24-years old primipara in the 41st gestational week with an uncomplicated course of pregnancy and with secondary non-obstructive sleeping hypoventilation which occurred after eclamptic seizure. This obstetric case provides evidence for the benefit of home BiPAP use for patients with secondary Ondine's curse.

Optical coherence tomography and its use in optical neuritis and multiple sclerosis.

Optical coherence tomography is a relatively new non-invasive imaging technique used for obtaining the images and quantifying the layers of the retina. It also provides information about optic nerve head topography, peripapillary retinal nerve fiber layer thickness, and macular volume which correlates with axonal loss. Until now, this method was used mainly in ophthalmology; now it has emerged as relevant in neurology as well. RNFL thickness is of particular interest in optic neuropathies and in multiple sclerosis. In sclerosis multiplex, axonal loss occurs as early as the first stages and the quantification of the RNFL thickness by OCT provides an indirect measure of axonal and neuronal loss in the anterior visual pathways. Because OCT is noninvasive, easy to obtain, and highly reproducible, it can be used as a marker of axonal loss and as an endpoint in clinical trials. This paper presents a comprehensive summary of the use of this new diagnostic method in multiple sclerosis patients (Fig. 1, Ref. 58).

Frequencies of polymorphisms in CYP2C9 and VKORC1 genes influencing warfarin metabolism in Slovak population: implication for clinical practice.

OBJECTIVES: The study was aimed at establishing an effective molecular-genetic method for detecting polymorphisms in genes CYP2C9 and VKORC1, which affect the pharmacogenetics of warfarin, and at determining their prevalence in Slovak population. BACKGROUND: Warfarin, derivative of coumarin, belongs to the most commonly prescribed oral anticoagulants with narrow therapeutic index. An insufficient dose of warfarin can result in failure to produce the antithrombotic effect, whereas an overdose increases the risk of bleeding. It was proven that genetic variability in two genes, CYP2C9 a VKORC1, has a significant influence on the individual's response to the dosage of warfarin. METHODS: In a control group of 112 randomly selected individuals, we tested the frequency of selected single nucleotide polymorphisms including CYP2C9*2 (430C>T), CYP2C9*3 (1075A>C), VKORC1*2 (1173C>T) by allele-specific Real-Time PCR and VKORC1*2 (-1639G>A) by using PCR-RFLP. RESULTS: Due to the combination of frequent alleles CYP2C9*2, CYP2C9*3 and VKORC1*2 in Slovak population we determine that 25% of population need a standard 5-mg daily dose of warfarin, while 44%, 23%, and 8% need 4 mg, 3 mg and 2 mg of warfarin per day. CONCLUSION: Slovak population is in Hardy-Weinberg equilibrium and frequencies of SNPs were in accordance with other published results in European populations (Tab. 5. Fig. 3, Ref. 51).

Clinical accuracy of the distinction between Alzheimer's disease and frontotemporal lobar degeneration.

Alzheimer's disease (AD) is the most common cause of dementia. Frontotemporal lobar degeneration (FTLD), although less prevalent overall, is almost as common as AD in patients under the age of 65. AD and FTLD are histopathologically distinct, with AD being characterised by extracellular amyloid plaques and intraneuronal neurofibrillary tangles, and FTLD by the presence of non-AD histological pathology, most commonly either tau-positive inclusions or ubiquitin-positive or TDP 43 positive inclusions. Clinically, AD and FTLD may occur with overlapping symptoms, especially in the early stages of the disease. In the case of Alzheimer's disease, it is represented by isolated decline of recent episodic memory; later on, by the impairment of time and space orientation, whereby the alteration of social behaviour and amnesic aphasia occur predominantly in the advanced phases of the disease. Frontotemporal lobar degeneration is demonstrated in three clinical subunits: 1) The behavioural-dysexecutive variant of FTLD (frontotemporal dementia, the frontal variant of FTLD, {fvFTLD}), 2) Progressive non-fluent aphasia, 3) Semantic dementia (SD) with the profound impairment of social conduct (fvFTLD) or with severe speech impairment (PNFA, SD). Considering the different clinical symptomatology with FTLD diagnostics, it is necessary to use different psychometric tests than in the case of Alzheimer's disease. Therapy and the degree of dependence of the affected person are also different. All three diseases within the FTLD category, mainly the behavioural-dysexecutive variant, require a higher level of nursing care on the part of other persons or institutions in comparison with Alzheimer's disease. The goal of our publication is to point to the differences in clinical manifestation and the findings of auxiliary examinations that are helpful in the clinical accuracy of the distinction between these two types of dementia (Tab. 1, Fig. 3, Ref. 18).

Association of non-diabetic hyperglycemia with autonomic shift in acute ischaemic stroke.

BACKGROUND AND PURPOSE: The etiology of hyperglycemia in acute stroke remains controversial. It is unclear whether hyperglycemia arises as an epiphenomenon of stroke or as a reflection of underlying diabetes. Autonomic shift to sympathetic overactivity has been repeatedly observed in acute stroke. We hypothesize that hyperglycemia in acute stroke relates to autonomic imbalance and that the respective deleterious effects on stroke outcome may be cross-linked. METHODS: A total of 75 non-diabetic patients with ischaemic stroke were included in a prospective study. Glucose levels at admission, fasting glucose, and glucose profiles were recorded. Autonomic function was quantified by the assessment of spontaneous baroreflex sensitivity (BRS) using a cross-correlation method. Demographic and clinical data including stroke volumes and admission National Institute of Heath Stroke Scale scores were included into the analysis. Functional outcome at 90 days was assessed using the modified Rankin Scale. RESULTS: Hyperglycemia was correlated with decreased BRS independent of stroke severity or volume (r = -0.46, P < 0.001). In two separate regression models, glucose levels and BRS independently predicted unfavorable outcome at 3 months (OR = 1.06, CI = 1.02-1.11, P = 0.004 and OR = 0.75, CI = 0.56-0.99, P = 0.04). However, combining the models, only glucose levels (OR = 1.06, CI = 1.02-1.11, P = 0.004) remained independent predictor of outcome at 3 months. CONCLUSIONS: We observed an association between hyperglycemia and decreased BRS in non-diabetic patients, suggesting that hyperglycemic reaction in acute stroke may reflect stroke-related autonomic changes. Moreover, outcome effects of autonomic changes and hyperglycemia seem to be interdependent, putatively having the sympatho-vagal imbalance as common underlying mechanism. The possible therapeutic relevance of this finding warrants further studies.

Real-life experiences in migraine therapy.

OBJECTIVE: To evaluate the effectiveness of eletriptan for acute migraine treatment and patient satisfaction with the drug in usual clinical practice settings. METHODS: Male and female patients of practicing neurologists, aged 18 to 65 years, were eligible for inclusion in the study if they met International Headache Society criteria for migraine. RESULTS: Of 637 patients enrolled, 611 completed the study. At 1 hour post-dose headache response was 59.5% (average from three attacks), pain-free 13%, absence of vomiting 86.3%, and improvement in functioning 55%. Headache recurrence occurred in 12%, second dose was used by 12.6% patients, and rescue medication by 6.4%. Patient preference for eletriptan versus any other triptan used in the past was 97%. CONCLUSION: In this real-life setting, eletriptan displayed high efficacy, consistency of response over three attacks and was preferred by 97% patients (Tab. 2, Fig. 5, Ref. 16). Full Text (Free, PDF) www.bmj.sk.

[The role of cholesterol in embryogenesis and the Smith-Lemli-Opitzov syndrom]. / Uloha cholesterolu v embryogenéze a Smith-Lemli-Opitzov syndróm.

The role of cholesterol in cell biology has been known for years. The sight of cholesteol biological function has changed after the discovery that the genetic disorder Smith-Lemli-Opitz syndrome is caused by a defect in cholesterol biosynthetic pathway. Cholesterol has an important role in regulation and modification of Hedgehog proteins, what links cholesterol to early embryonic development. Hedgehog proteins comprise a family of secreted signaling molecules that are essential for embryonic patterning and morphogenesis. The deficit of cholesterol during embryogenesis causes severe abnormalities in SLOS because of disrupt autoprocessing of hedgehog proteins. SLOS is an autosomal recessive disorder of sterol metabolism. The underlying pathogenetic basis for SLOS has been shown to be a deficiency of 7-dehydrocholesterol reductase, which catalyzes the last step in cholesterol biosynthesis. Reduced enzyme activity leads to a deficit of cholesterol and accumulation of precursor sterols. The human 7-dehydrocholesterol reductase gene (DHCR7) is localized on chromosome 11q 12-13.

Efficacy and tolerability of piroxicam-beta-cyclodextrin in the outpatient management of chronic back pain.

BACKGROUND: Piroxicam-beta-cyclodextrin (PBC) is the first nonsteroidal anti-inflammatory drug (NSAID), in which the active substance is complexed with the cyclic oligosaccharide cyclodextrin, which acts as an artificial receptor. This complex allows single molecules of the NSAID to be released adjacent to the gastrointestinal mucosa, instead of crystals. Since the piroxicam is immediately bioavailable in this formulation, the onset of action is similar to that of a parenteral drug. Since the time contact with gastric mucosa is reduced, the risk of direct-contact gastric irritation is also reduced. There is good evidence that PBC is beneficial in managing acute non-specific back pain (BP) but sufficient evidence on chronic BP is lacking. METHODS: Thirty-one eligible patients aged 18-85 years, resistant to previous therapy with different NSAIDs, were treated with PBC 20 mg once daily in a 40-day open-label noncomparative study. The patients experienced chronic BP defined as pain between the occipital region and gluteal fold, lasting for at least 6 weeks but not more than 6 months. Efficacy was assessed by changes in pain intensity, paravertebral tonus, functional impairment and morning stiffness using a 4-point numerical rating scale. Patients also self-assessed nocturnal and diurnal pain using the visual analogue scale. Tolerability was assessed by adverse events and routine laboratory evaluations. Global assessment of efficacy and tolerability by physician and patients was performed at the last visit. RESULTS: Using intention-to-treat analysis, all efficacy assessments demonstrated statistically significant improvements over baseline at each follow-up. 90.3% of the patients evaluated the efficacy of PBC as improved or greatly improved, and investigators rated the treatment as improved or greatly improved in 87.1% of patients. Remission was achieved in 19.3% of the patients. Tolerability was also rated highly, with 83.9% of the patients characterizing PBC treatment as good or very good, and the investigators rated the treatment as good or excellent in 87.1% of the patients. Drug related adverse events were reported in 9.7% of patients and prompted discontinuation of the study medication in 3.2% of patients. No serious adverse events were reported. CONCLUSION: These results suggest that the newly developed dosage form of piroxicam is effective and well tolerated in the treatment of patients with chronic BP. Thus, PBC, may be an important new treatment option in this condition. (Tab. 3, Fig. 3, Ref. 36.).

Effect of propentofylline on cerebral blood flow in a gerbil focal cerebral ischemia.

BACKGROUND AND PURPOSE: Neuroprotection and improvement of cerebral blood flow are two basic principles of pharmacological intervention in acute stroke. Propentofylline, an adenosine uptake and phosphodiesterase inhibitor, has been shown to be neuroprotective in various models of cerebral ischemia. However, its effect on cerebral circulation in ischemic conditions is not yet fully elucidated. Present experiments were designed to investigate the effect of propentofylline on regional cerebral blood flow (rCBF) in the gerbil permanent focal cerebral ischemia model. METHODS: Focal cerebral ischemia in gerbils was produced by clipping one common carotid artery and contralateral external carotid artery. rCBF was measured in both parietal cortices concurrently by the hydrogen clearance. RESULTS: Propentofylline at 10 mg/kg administered intraperitoneally 30 min after induction of cerebral ischemia significantly increased rCBF in ischemic regions (increase of 94.6%). Effects were dose dependent. Higher dosage (30 mg/kg) induced reductions of ischemic rCBF, which were associated with significant decreases of mean arterial blood pressure. Lower dosage (5 mg/kg) was without significant effect. CONCLUSIONS: Results suggest that propentofylline at suitable dosage improves rCBF in ischemic brain areas. Taking into account neuroprotective potentials of propentofylline, results offer additional rationale for clinical trials investigating efficacy of propentofylline in treatment of acute stroke.

[General principles of drug evaluation within the framework of drug policy]. / Vseobecné princípy hodnotenia liekov v rámci liekovej politiky.

This paper reviews the problems connected with drug evaluation in particular periods of its development. Requirements for drug registration, which represents the entrance of the drug on the market, are created by legislation. Drug application in the therapeutic process is determined by several factors and state regulations. The amount of evidence, reliability and validity of the facts should be the key factors of drug selection within the ambit of drug politics. Categorization of drugs means drug selection with regard to state reimbursement by means of health-insurance companies. Methods of drug categorization together with further regulations by means of positive letters, hospital blanks, should respect the criteria of professionality, transparency and sociopharmacology. Effective prognostication of drug use should ensure well-proportioned accessibility of effective safe drugs within the ambit of rational pharmacotherapy.

Effect of long-term administration of stobadine on exploratory behaviour and on striatal levels of dopamine and serotonin in rats and their offspring.

Stobadine (STB), a cardioprotective drug, was evaluated for its effect on the intensity and habituation of exploratory behaviour in open field testing and on the levels of striatal dopamine (DA), serotonin (5-HT) and their metabolites (3,4-dihydroxyphenylacetic acid, homovanillic acid, 5-hydroxyindole-3-acetic acid) in rats and their offspring. Dams were treated by oral gavage with STB (50 mg kg-1) for a total of 56 days from 14 days before mating to day 21 postpartum (pp). The first open field measurements of the dams were performed over 4 days at the beginning of the experiment, the second on days 21-24 pp and the third on days 49-52 pp (recovery period). Their offspring were tested on postnatal (pn) days 30-33 and 60-63. The biochemical analysis (HPLC with electrochemical detection) in the dams was performed at the same time schedule as given for the open field testing, but in their offspring only on pn day 60. Motor activity of the dams was decreased on days 21-24 pp. The increase of motor activity in female offspring was observed on pn days 30-33. Neurochemical analysis of the striatum of the dams revealed a significant increase of the levels of DA, 5-HT and 5-hydroxyindole-3-acetic acid. In male offspring the levels of DA were significantly decreased, whereas in females the levels were increased. These results suggest that maternal administration of STB resulted both in dams and their offspring in minor alterations in spontaneous behaviour components and changes in the dopaminergic and serotonergic system, but without inducing overtly detectable toxicity.

HPLC method for measurement of purine nucleotide degradation products in cerebrospinal fluid.

We describe a convenient method for the separation and quantification of xanthine, hypoxanthine, and uric acid in 20 microL of cerebrospinal fluid (CSF) with use of HPLC and ultraviolet detection. The analysis is performed on a Sepharon SGX C18 column and the elution system consists of potassium phosphate buffer, pH 5.1, with 20 mL/L methanol. The lower limit of detection was 4 pmol for hypoxanthine and xanthine and 6 pmol for uric acid. Analytical recoveries of purine metabolites ranged from 98.6% to 102.9%. The intra- and interassay CVs were <3%. The applicability of the method is illustrated with the determination of micromolar concentrations of xanthine, hypoxanthine, and uric acid in CSF samples obtained from 113 patients with various neurological disorders.

[The spinal canal, dural sac and spinal cord on cervical myelograms. Possibilities of quantification using a computer]. / Spinálny kanál, durálny vak a miecha na cervikálnych myelogramoch. Moznosti kvantifikácie pomocou pocítaca.

The objective of the presented work was to investigate anatomical structures of the cervial spine and their interrelations on cervical myelograms in a neutral position and in retroflexion. Cervical myelograms were made in 34 patients from a lateral approach between the first and second vertebra. In a neutral position and in retroflexion the relations of the dural sac and spinal canal were investigated in 26 subjects with a normal antero-posterior diameter of the spinal canal and in eight patients with congenital stenosis of the spinal canal. Quantification by means of a computer revealed that in retroflexion the antero-posterior diameters of the dural sac diminishes significantly in subjects with a normal antero-posterior diameter of the spinal canal as well as in subjects with congenital stenosis of the spinal canal. Moreover, the authors provided evidence that the area of the dural sac diminishes significantly in retroflexion, as compared with the neutral position in subjects with a normal spinal canal as well as in subjects with congenital stenosis of the spinal canal.

[Specific aspects of mobility and changes in the shape of the dural sac in functional lumbosacral myelography]. / Niektoré specifiká pohyblivosti a zmien tvaru durálneho vaku pri funkcnej lumbosakrálnej myelografii.

The purpose of the work was an analysis of lateral myelograms of the lumbosacral spine in the neutral position, in anteflexion and retroflexion from the aspect of the mobility of the dural sac and its relationship to the spinal canal. The group comprised 50 patients with clinically obvious discopathies and other vertebrogenic syndromes. The areas of the dural sac were measured planimetrically and evaluated by means of a computer. It was revealed: 1. The Soinal canal and dural sac are not static variables but dynamic ones. By movements of the lumbosacral spine the size of the dural sac changes and so does its shape. These phenomena can be evaluated not only qualitatively but also quantitatively. 2. The anteroposterior diameter of the dural sac on the myelograms in anteflexion and in retroflexion changes significantly, as compared with the neutral position, it increases during anteflexion and diminishes during retroflexion. 3. The area of the dural sac increases during anteflexion and diminishes in retroflexion, as compared with the neutral position. 4. Changes in the shape of the dorsal portion of the dural sac revealed in the segment of the discopathy are considered to be due to hypertrophy of the yellow ligaments.

[The new hemorheologic drug VULM 957 improves cerebral circulation]. / Nové hemoreologikum VULM 957 zlepsuje mozgovú cirkuláciu.

The authors investigated the effect of a newly synthetized haemorheological drug VULM 957 for basic haemorheological parameters in vitro and on the cerebral flow in vivo. It was revealed that substance VULM 957 inhibits in a dose-dependent and time-dependent way the platelet aggregation, reduces the viscosity of blood, increases the deformability of red blood cells and increases the cerebral blood flow. Analysis of possible mechanisms of action of VULM 957 indicates that the observed positive haemorheological effects are due to the influence on the fluidity of the platelet and red cell membrane. The increased cerebral blood flow after administration of VULM 957 depends obviously on the reduced viscosity of the blood and the inhibited formation of platelet microaggregates. The presented results justify the assumption that VULM is a perspective substance in the therapy of cerebrovascular diseases.

[Optimism or pessimism in the treatment of cerebral infarct]. / Optimizmus ci pesimizmus v liecbe mozgového infarktu.

The aim of the study was to analyse the effects of drug and rehabilitation treatment of cerebral stroke. Material consists of 2,500 patients with focal brain ischemia. About three-fourths (68.7%) of patients with cerebral stroke improved receiving complex drug treatment, rehabilitation and psychological care. 54.9% of the whole group of patients had a neurological deficit score below 150, i.e. more than one half of the whole group (n = 2,500) left the hospital practically in good health capable of carrying on in their original occupation. Only 11.9% of patients died, but 48.9%, i.e. practically one half of them showed an extracerebral cause of death. The results of treatment are dependent on age. In the higher age group, the number of deteriorated cases as well as the number of death increases. The results of treatment are dependent on an early initiation of treatment after the onset of brain ischemia. In the 2nd time-period, the results of treatment are better in comparison to the 1st period due to new strategies of treatment, i.e. due to drugs that improve heart failure, rheological properties of the blood and brain metabolism and due to intensive rehabilitation care. The results have shown the improvement not only in movement possibilities of the patients, but also the improvement in majority of the psychological parameters (IQ, emotionality, sociability scale etc.).

[Is the effect of naloxone on cerebral circulation mediated by blood platelets?]. / Je úcinok naloxonu na cerebrálnu cirkuláciu sprostredkovaný krvnými dostickami?

In an attempt to elucidate the mechanism of action of the opiate antagonist, naloxone, on the cerebral circulation the authors investigated changes of thrombocyte aggregation in whole blood (impedance aggregometry) and in the regional cerebral blood flow (hydrogen "wash-out" method) after a single dose of naloxone (1 mg/kg) to intact gerbils and gerbils with hemispheric cerebral ischemia. Under physiological conditions naloxone significantly reduced the cerebral blood flow and at the same time increased platelet aggregation. Under conditions of hemispheric cerebral ischemia naloxone increased the blood flow but did not affect the platelets activated by ischemia. The authors assume that naloxone induced hyperaggregation of platelets is at least partly responsible for the reduced cerebral blood flow after naloxone administration to intact animals. The favourable effect of naloxone on the ischemic cerebral circulation is, however, certainly not mediated by the effect on the platelet activity.