[Vinpocetin in neurological diseases]. / Vinpocetin alkalmazása neurológiai kórképekben.

INTRODUCTION: Stroke is the third leading cause of death worldwide (following cardiovascular and cancer mortality) and associated with serious disability for the vast majority of patients. There is no salvage therapy for irreversibly damaged brain areas, improving the circulation of the surrounding hypoperfused areas may be associated with beneficial clinical effects. Cerebral hypoperfusion may play a role in the pathogenesis of other kind of neurological diseases, improvement of global circulation may have a preventive effect on these conditions. AIMS: The aim of our study was to review the experimental and clinical articles focusing on the role of vinpocetin in different neurological conditions. RESULTS: Vinpocetin appears to have several different mechanisms of action that allow for its antiinflammatory, antioxidant, vasodilating, antiepileptic and neuroprotective activities in experimental conditions. On the other hand, several meta-analysis of the existing studies in acute stroke examining short and long term fatality rates with vinpocetin was unable to assess efficacy. In chronic cerebrovascular patients, vinpocetin improves impaired hemorheologic variables, has significant vasodilating properties, improves endothelial dysfunction, neuroimaging studies showed selective increase in cerebral blood flow and cerebral metabolic rate, all of which are potentially beneficial in cerebrovascular disease and may improve cognitive functions. SUMMARY: Based on the above mentioned results, vinpocetin plays an important role both in basic research and in clinical management of different neurological diseases.

Thrombosis preventive potential of chicory coffee consumption: a clinical study.

The protective effects of plant polyphenol intake on cardiovascular morbidity and mortality are widely acknowledged. Caffeine-free chicory coffee is a rich source of plant phenolics, including caffeic acid, which inhibits in vitro platelet aggregation, and also phenylpyruvate tautomerase enzymatic activity of the proinflammatory cytokine, macrophage migration inhibitory factor (MIF). To assess whether chicory coffee consumption might confer cardiovascular benefits a clinical intervention study was performed with 27 healthy volunteers, who consumed 300 mL chicory coffee every day for 1 week. The dietary intervention produced variable effects on platelet aggregation, depending on the inducer used for the aggregation test. Whole blood and plasma viscosity were both significantly decreased, along with serum MIF levels, after 1 week of chicory coffee consumption. Moreover, significant improvements were seen in red blood cell deformability. No changes in hematocrit, fibrinogen level or red blood cell counts were detected. The full spectrum of these effects is unlikely to be attributable to a single compound present in chicory coffee, nevertheless, the phenolics, including caffeic acid, are expected to play a substantial role. In conclusion, our study offers an encouraging starting-point to delineate the antithrombotic and antiinflammatory effects of phenolic compounds found in chicory coffee.

Relation of platelet aggregation and fibrinogen levels to advancing age in aspirin- and thienopyridine-treated patients.

In our present study we investigated the association between platelet aggregation in patients treated with the most widely used antiplatelet agents (100 and 300-325 mg acetylsalicylic acid (ASA), 75 mg clopidogrel, 500 mg ticlopidine and the combination of 100 mg aspirin and 75 mg clopidogrel), fibrinogen levels and aging. Between 2001 and 2005 we measured in vitro platelet aggregation in 5026 vascular patients according to the method of Born. Platelet aggregation was tested with 5 and 10 microM adenosine-diphosphate, 2 microg/ml collagen and 10 microM epinephrine stimulants. Fibrinogen level was simultaneously measured in a subgroup of 3243 patients. The subjects were divided by age into decades. Platelet aggregation increased significantly with advancing age in the case of 100 and 300-325 mg ASA-treated patients (p<0.001). In aspirin-treated patients also fibrinogen levels increased with aging (p<0.001). There was no association between platelet aggregation or fibrinogen levels and aging either in patients treated with 75 mg clopidogrel or with 500 mg ticlopidine. Thienopyridine-treated patients exhibited significantly lower fibrinogen levels than ASA-treated individuals (p<0.001). Our results suggest that advancing age is associated with elevated platelet aggregability in widely used antiplatelet regimens that might contribute to higher risk of cardiovascular events in the elderly.

Viscosity, hemostasis and inflammation in atherosclerotic heart diseases.

BACKGROUND: In atherosclerotic diseases vascular reserve is impaired and pressure gradient is decreased, therefore the reduced blood fluidity can lead to tissue ischemia more rapidly. In previous investigations we demonstrated the deterioration of plasma and whole blood viscosities in patients with acute ischemic coronary syndromes, chronic coronary artery disease, and percutaneous transluminal coronary angioplasty. METHODS: Hemorheological variables (plasma and whole blood viscosities, hematocrit, red blood cell aggregation), hemostaseological parameters (plasma fibrinogen and von Willebrand factor (vWf)), and platelet aggregation were detected in more recent studies in cardio- and cerebrovascular diseases, and diabetes mellitus. Common risk factors (lipid profile, smoking, glucose level, previous diseases) and medication were also recorded. RESULTS: High portion of vascular patients were demonstrated to have poor ex vivo platelet inhibition. Effective antiplatelet treatment detected by aggregometry was related to lower plasma fibrinogen concentration and red blood cell aggregation and was also associated with less recurrent vascular events during the follow-up (p < 0.001). Beside the impaired hemorheological characteristics, the diabetic patients showed elevated vWf activity, which turned to correlate with hemoglobin A1c concentration (p < 0.01) rather than the fasting glucose. SUMMARY: Our studies indicate the active role and interaction of hemorheological and hemostaseological factors in atherosclerotic heart diseases.

Hemorheological methods in drug research.

Development of new drugs is a sophisticated process that requires several, different methods. In our experiments we have applied two rheological models to study experimental and clinically used drugs. The antioxidant properties of several agents were estimated by erythrocyte filtration technique. The known antioxidant compound vitamin E was used to validate our measurements. An experimental cardioprotective agent, H-2545 provided significant protection against oxidative changes in red blood cell filterability (p<0.001). Although some of the examined, known cardiovascular drugs also showed significant antioxidant effect, they were less efficient than H-2545 and the scavenger effect of this novel agent exceeded the antioxidant properties of vitamin E. Modification of mexiletine with a pyrroline ring improved significantly its antioxidant capacity suggesting this molecular segment to be responsible for the antioxidant effect. In our second model the antiplatelet effect of experimental poly(ADP-ribose) polymerase (PARP) inhibitors was evaluated. Two widely used antiplatelet agents: acetyl salicylic acid and eptifibatide served as controls in the validation of the measurements. PARP inhibitors reduced ADP-induced platelet aggregation in a dose-dependent manner (p<0.05). However, their hindrance on platelet aggregation waned as the concentration of ADP rose. Regarding the platelets' role in the development of ischemic vascular diseases, the antiaggregating property of PARP inhibitors may exert additional beneficial effects on tissue blood supply under conditions of compromised vascular flow.

[Effects of cardiovascular risk factors on hemorheologic parameters in cerebrovascular patients]. / A kardiovaszkuláris rizikófaktorok hatása az agyérbetegek hemoreológiai viszonyaira.

INTRODUCTION: Hemorheological factors are of significance in the determination of flow characteristics of blood and play an important role in the pathogenesis of cerebrovascular diseases. AIMS AND METHODS: In this study the changes of rheological factors--hematocrit (Hct), plasma fibrinogen concentration (PFC), whole blood (WBV) and plasma viscosity (PV), red blood cell aggregation (AI) and deformability and the association between these parameters and cardiovascular risk factors were investigated in 297 patients (173 males, 124 females, mean age: 60 11 years) with chronic phase (3 months after onset) ischemic cerebrovascular diseases, and in 68 healthy volunteers (30 males, 38 females, mean age: 36 6 years). RESULTS: All investigated hemorheological factors were significantly (p < 0.05-0.0001) elevated in cerebrovascular patients compared to normal controls, the rise in Hct, WBV and PV are some of the most prominent findings. In the group of hypertensive, hyperlipidemic patients, smokers and alcoholics Hct, PFC, WBV, PV and AI were significantly (p < 0.05-0.0001) higher compared to healthy controls, the same factors except plasma fibrinogen concentration showed association with diabetic history. Comparing cerebrovascular patients with or without risk factors, the most severe hemorheological deficit was observed in patients with hyperlipidemia and smoking habits. CONCLUSIONS: In this study the authors proved in chronic ischemic cerebrovascular patients that hemorheological abnormalities persist in most cases for a long time after an acute stroke, significant correlation could be seen between blood rheology and cardiovascular risk factors. Examination of rheological parameters can support to choose the optimal medical treatment in the secondary prevention of stroke, correction of hemorheological disturbances can reduce the risk of recurrent stroke.