Diagnosis rates, therapeutic characteristics, lifestyle, and cancer screening habits of patients with diabetes mellitus in a highly deprived region in Hungary: a cross-sectional analysis.

Introduction: Low socioeconomic status affects not only diagnosis rates and therapy of patients with diabetes mellitus but also their health behavior. Our primary goal was to examine diagnosis rates and therapy of individuals with diabetes living in Ormánság, one of the most deprived areas in Hungary and Europe. Our secondary goal was to examine the differences in lifestyle factors and cancer screening participation of patients with diagnosed and undiagnosed diabetes compared to healthy participants. Methods: Our study is a cross-sectional analysis using data from the "Ormánság Health Program". The "Ormánság Health Program" was launched to improve the health of individuals in a deprived region of Hungary. Participants in the program were coded as diagnosed diabetes based on diagnosis by a physician as a part of the program, self-reported diabetes status, and self-reported prescription of antidiabetic medication. Undiagnosed diabetes was defined as elevated blood glucose levels without self-reported diabetes and antidiabetic prescription. Diagnosis and therapeutic characteristics were presented descriptively. To examine lifestyle factors and screening participation, patients with diagnosed and undiagnosed diabetes were compared to healthy participants using linear regression or multinomial logistic regression models adjusted for sex and age. Results: Our study population consisted of 246 individuals, and 17.9% had either diagnosed (n=33) or undiagnosed (n=11) diabetes. Metformin was prescribed in 75.8% (n=25) of diagnosed cases and sodium-glucose cotransporter-2 inhibitors (SGLT-2) in 12.1% (n=4) of diagnosed patients. After adjustment, participants with diagnosed diabetes had more comorbidities (adjusted [aOR]: 3.50, 95% confidence interval [95% CI]: 1.34-9.18, p<0.05), consumed vegetables more often (aOR: 2.49, 95% CI: 1.07-5.78, p<0.05), but desserts less often (aOR: 0.33, 95% CI: 0.15-0.75, p<0.01) than healthy individuals. Patients with undiagnosed diabetes were not different in this regard from healthy participants. No significant differences were observed for cancer screening participation between groups. Conclusions: To increase recognition of diabetes, targeted screening tests should be implemented in deprived regions, even among individuals without any comorbidities. Our study also indicates that diagnosis of diabetes is not only important for the timely initiation of therapy, but it can also motivate individuals in deprived areas to lead a healthier lifestyle.

Epidemiology of Peripheral Artery Disease: Narrative Review.

Past decades have witnessed a major epidemiologic transition with a considerable increase in the disease burden associated with atherosclerotic cardiovascular diseases (CVDs), with low-income and middle-income countries (LMICs) experiencing substantial increase in CVDs. As the global population is aging and peripheral artery disease (PAD) is strongly age-related, it is estimated to become increasingly prevalent in the future. PAD shares risk factors with coronary and cerebrovascular risk factors, particularly diabetes mellitus and smoking, and is associated with significant CVD morbidity and mortality. Despite advances in therapeutic modalities, 236 million people were estimated to be suffering from PAD worldwide in 2015, and numbers have been rising since. The prevalence of asymptomatic PAD has remained high; PAD prevalence seems higher among women and is related to ethnicity. Although several epidemiological studies have been published on PAD during the past decades, data from LMICs are scarce. Besides providing up-to-date epidemiological data retrieved from the literature and the Global Burden of Disease (GBD) study database, this narrative review also intends to draw attention to the substantial disease burden of PAD manifesting in more Years of Life Lost (YLL), age-adjusted mortality and amputation rates, with a special focus on some European countries and especially Hungary, i.e., the country with the highest amputation rate in Europe.

Prevalence and Risk Factors of Problematic Internet Use among Hungarian Adult Recreational Esports Players.

Background: Esports are highly prevalent in modern culture, particularly among young people, and are a healthy hobby for the majority of users. However, there is a possible link between video gaming (including esports) and problematic internet use (so-called internet addiction, IA), mostly involving adolescents. Methods: Here we present an online survey focusing on the prevalence and risk factors of internet addiction among adult esports players. Demographics included age, gender, family type, type of work, working years and daily internet use. Medical conditions associated with IA such as smoking, alcohol and drug intake, hypertension, diabetes, ischemic heart disease, musculoskeletal pain and history of depression were also recorded. Results: Overall, 2313 players including 176 females (7.6%) and 2137 males (92.4%) participated in our online survey. Age distribution was the following: 18−25 years 90.3% (2088/2313), 26−35 years 7.95% (184/2313), 36−45 years 0.86% (20/2313), 46−55 years 0.82% (19/2313), 56−62 years 0.04% (1/2313) and 62 years or older 0.04% (1/2313). Internet addiction was detected in 19.9% of players (461/2313) based on the Problematic Internet Use Questionnaire. In a multivariate analysis internet addiction was significantly associated with age between 18 and 25 (OR: 1.675, p = 0.002), being single (OR = 1.505, p = 0.014), internet use > 6 h daily (OR = 4.338, p < 0.001), having < 3 children (OR: 2.037, p = 0.023) and having secondary employment (OR = 1.789, p = 0.037). Regular alcohol intake (OR = 18.357, p < 0.001) and history of depression (OR= 5.361, p = 0.032) were also strongly correlated with IA. Conclusion: This is the first study from Hungary investigating the prevalence and risk factors of internet addiction among adult esports players. One out of five adult gamers suffered from IA. Our study also draws attention to increased risk within this group and risk factors such as younger age, family status and type of employment.

Hemorheological Parameters in Diabetic Patients: Role of Glucose Lowering Therapies.

Diabetes mellitus influences several important hemorheological parameters including blood viscosity, erythrocyte aggregation and deformability. In the present study, 159 type-2 diabetic patients and 25 healthy controls were involved. Patient's age, body weight, body mass index (BMI), smoking habits, physical activity, history of cardiovascular diseases, current antidiabetic therapy and concomitant medication were recorded. Patients were grouped according to their antidiabetic treatment with insulin, or with one or more of the following antidiabetic drugs: metformin, sulfonylureas, acarbose, or no antidiabetic therapy. Hemorheological measurements (hematocrit, erythrocyte aggregation, plasma fibrinogen, whole blood and plasma viscosity), von Willebrand factor activity, and platelet aggregation measurements were performed. Platelet aggregation was investigated with the method of Born. Plasma viscosity and red blood cell aggregation were significatly higher in diabetes. No significant difference was found in hemorheological parameters between different antidiabetic regimens. Whole blood and plasma viscosity and red blood cell aggregation correlated with glucose levels but not with HbA1C levels. In conclusion, plasma and whole blood viscosity, as well as red blood cell aggregation appear to be associated with concurrent hyperglycemia, but not with the quality of glycemic control or the applied antidiabetic treatment. Platelet aggregation induced by ADP or epinephrine does not seem to be associated with diabetes even at subthreshold doses.

Framingham Risk Stratification of Middle-Aged Migraineurs.

Introduction. Migraine is a common primary headache disorder involving about 10-15% of the whole population. Several epidemiological and prospective studies showed a link between migraine (especially migraine with aura) and cardio- and cerebrovascular events. OBJECTIVES: We prospectively analyzed the data of vascular event-free middle-aged patients with migraine who were referred to our Headache Clinic between 01/2014 and 01/2018. Framingham 10-year risk were calculated; covariates included in the analysis were age, total cholesterol, HDL cholesterol, systolic blood pressure, antihypertensive medication use, current smoking, and diabetes status. RESULTS: Total of 1037 patients were screened and 221 were selected, 161 were women (mean age 55.5 ± 5.2 years) and 60 were men (mean age 56 ± 6 years). 25 patients (11.3%) were labelled as having low risk, 162 patients (73.3%) had moderate risk, and 34 patients (15.4%) had high or very high risk. Blood pressure and lipid targets were reached in 73% and in 49% in the moderate risk and in 53% and 12% in the high risk/very high risk groups, respectively. Migraine with aura (MA) was associated significantly higher cardiovascular risk profile compared with migraine without aura (MO). About one-third of our nondiabetic patients had fasting blood glucose above the normal levels. 24 patients (mean age 60 ± 4.9 years) were diabetic. Mean blood pressure was 149/85 Hgmm, mean choleterol was 5.11 mmol/l, and mean LDL was 2.93 mmol/l in this subgroup, respectively, which do not fall within the recommended targets. CONCLUSION: Our article draws attention to the higher cardiovascular risk profile of middle-aged migraineurs and highlights the deficiency of primary prevention. Pain physicians must be aware of the cardiovascular aspects of migraine and holistic approach is required instead of focusing only on pain and pain relief.

Characteristics of Patients Referred To A Specialized Headache Clinic.

Headache is a common problem with great effect both on the individual and on the society. Recent studies raised the possibility of increasing rate of specialty referrals, inappropiate treatment and advanced imaging for simple headache. The aim of our study was to analyze the characteritics of patients (including duration of symptoms, headache type, brain imaging, treatment) referred to our specialized headache clinic between 01/01/2014 and 01/01/2015 by their general practitioners and primary care neurologists due to chronic/treatment-resistant headache syndromes. 202 patients (mean age 53.6 ± 17.6 years) were evaluated in our clinic (102 females, mean age 50.14 ± 16.11 years and 100 males, mean age 57 ± 18.1 years). Migraine (84/202) and tension-type (76/202) were the most common syndromes. 202 plain brain CT, 60 contrast-enhanced CT and 128 MRI were carried out by their general practitioners or other healthcare professioners including neurologists before referral to our headache centre. Despite of extensive brain imaging appropiate treatment was started less than 1/3 of all patients and significant proportion received benzodiazepines or opioid therapy. Furthermore, more than 10% of referred patients presented with secondary headache including one meningitis. The management of headache is still a challenge for primary care physicians leading to medical overuse. Vast majority of our patients should not be referred to our specialized headache clinic as they had uncomplicated headache or other underlying conditions than pain.

Early Dynamics of P-selectin and Interleukin 6 Predicts Outcomes in Ischemic Stroke.

BACKGROUND: Thromboinflammatory molecules connect the prothrombotic state, endothelial dysfunction, and systemic/local inflammation in the acute phase of ischemic stroke. METHODS: We prospectively investigated (1) serial changes in the levels of thromboinflammatory biomarkers in 76 patients with acute ischemic stroke (6, 24, and 72 hours after onset); (2) compared with 44 patients with asymptomatic severe (≥70%) carotid stenosis and 66 patients with Parkinson disease; and (3) we applied multiple regression methods, relating biological biomarkers combined with demographic data and comorbidities to poststroke infection, death, and functional outcome, and assessed the ability of the models to predict each outcome. RESULTS: Interleukin 6 (IL-6) levels and change of IL-6 concentrations by 72 hours correlated with the size of tissue damage indicated by S100B titers. Levels of IL-6 and P-selectin at 72 hours were higher in patients with large-artery versus lacunar stroke. High concentration of IL-6, monocyte chemotactic protein 1, and S100B at 6 hours were associated with poststroke infections; high concentration of IL-6, S100B, and high-sensitivity C-reactive protein (hsCRP) correlated with death. Change of P-selectin from 6 to 72 hours by 1 unit increased the incidence of poststroke infections with an odds ratio of 22.7; each 100 units of IL-6 at baseline increased the odds of death by 9‰, and at 72 hours, the odds of poststroke infections by 4‰. Each unit of baseline hsCRP elevated the odds of death by 7%. CONCLUSIONS: In regression models, in which biological, demographic, and comorbid factors were combined, those biological biomarkers predicted poor outcome with high accuracy, which were characterized by an increasing concentration by 72 hours. Two particular biomarkers emerged to predict outcomes besides hsCRP: early dynamic changes in the systemic levels of P-selectin and IL-6.

Diabetic neuropathies: diagnosis and management.

INTRODUCTION: Changes in human behaviour and lifestyle over the last century have resulted in a dramatic increase in the incidence of diabetes worldwide. Neuropathy is a common and costly complication of both type 1 and type 2 diabetes. The prevalence of neuropathy is estimated to be about 8% in newly diagnosed patients and greater than 50% in patients with long-standing disease. There are two main types of diabetic neuropathies, named as sensorimotor and autonomic neuropathies. Sensorimotor neuropathy is marked by pain, paraesthesia and sensory loss, and autonomic neuropathy may contribute to myocardial infarction, malignant arrhythmia and sudden death. METHODS: In this article we reviewed the pathogenesis, clinical manifestations diagnosis and treatment of diabetic neuropathies. CONCLUSION: Sensorimotor and autonomic neuropathies (cardiovascular, gastrointestinal and genitourinary autonomic neuropathies) are common in diabetic patients. Apart from strict glycaemic control, no further therapeutic approach exists in the prevention of this phenomenon. Intensive diabetes therapy, intensive multifactorial cardiovascular risk reduction and lifestyle intervention are recommended in patients with cardiovascular autonomic neuropathy. Gastroparesis is the most debilitating complication of gastrointestinal autonomic neuropathy and genitourinary autonomic neuropathy can cause sexual dysfunction and neurogenic bladder; these conditions are hard to manage. The symptomatic treatment of sensory symptoms includes tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, gabapentin, pregabalin and opioids. Other treatment strategies are not so effective.

[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.

Association between XRCC1 polymorphisms and head and neck cancer in a Hungarian population.

BACKGROUND: Head and neck cancer is a significant current health problem in Hungary because the mortality of this cancer has increased by 387% in the last thirty-two years. Because of the important role of the XRCC1 gene in DNA repair, we wanted to test the effects of the Arg194Trp and Arg399Gln polymorphisms of XRCC1 on the clinical outcome of head and neck cancer. PATIENTS AND METHODS: A polymerase chain reaction-restriction fragment lenght polmorphism (PCR-RFLP) method was used. A total of 108 samples were taken from intraoperatively removed formalin-fixed, and paraffin-embedded blocks of tissue. An age- and sex-matched cancer-free control group was used to compare the frequency of polymorph variants. RESULTS: No significant difference was found between patients and controls in repect of the investigated polymorphisms. A significant difference was found between the patients with different XRCC1 194 polymorph status in clinical stage SIII. The survival proportion of patients with the Arg194Arg genotype was significantly lower than of those with the Arg194Trp genotype. CONCLUSION: The complex analysis of these factors may provide the basis for personal risk assessment and an opportunity for individualised therapy.

GSTM, GSTT and p53 polymorphisms as modifiers of clinical outcome in colorectal cancer.

BACKGROUND: Cancer of the colorectal region is the second most frequent cause of death among malignant diseases. The influence of two allelic polymorphisms of GSTM1 and GSTT1, and that of p53 gene codon 72 on colon cancer was investigated. PATIENTS AND METHODS: Intraoperatively removed tissue samples were processed from colorectal cancer patients. Cancer-free human samples were used as matched controls. Samples were digested with proteinase-K. DNA solution was used for PCR amplification. RESULTS: No significant difference was found between tumor patients and controls in the investigated polymorphisms. A significant association was found in Dukes' B stage patients between the GSTM1 and p53 gene variants and survival. In patients with GSTM1 null genotype and p53 Arg/Pro heterozygotes or Pro/Pro homozygotes the chance of survival is significantly lower than in the case of GSTM1+ and p53 Arg/Arg variants (p=0.009 and p=0.008, respectively). CONCLUSION: The significance of the investigated polymorphisms in prognosis is dependent on the tumor stage. These parameters might be used in certain cases as prognostic biomarkers in clinical diagnostics and in the planning of individual therapy.

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.

[The role of vinpocetine in the treatment of cerebrovascular diseases based in human studies]. / A vinpocetin szerepe az agyérbetegségek kezelésében az eddigi humán vizsgálatok alapján.

INTRODUCTION: It shows the importance of cerebrovascular diseases that they are the third main cause of death exceeded only by coronary artery diseases and cancer. Cerebral ischemia leads to irreversible brain damage, thereby it is important to rescue the hypoperfused areas. Patients without stroke but with chronic cerebral hypoperfusion can also benefit from the increasing of the cerebral blood flow. METHODS: The aim of this review was to summarize the indications and the potential effects of vinpocetine in acute and chronic cerebrovascular diseases based on clinical studies. RESULTS: There is no evidence that vinpocetine treatment is applicable in acute ischemic stroke, only few study with low patient number showed a slight but significant improvement in the patients conditions. In chronic cerebrovascular patients after single dose and long-term vinpocetine therapy, PET, TCD, SPECT and NIRS examinations showed increasing perfusion and elevated glucose and O 2 consumption of the examined areas, furthermore significant improvement of the rheologic factors was detected. A meta-analysis of international clinical studies showed a significant improvement in cognitive achievement in chronic stroke patients after oral therapy. CONCLUSION: The cited studies showed the potential multi-pharmacological effects of vinpocetine and its beneficial hemorheological potential. The drug also improves the blood flow and the metabolism of the affected brain areas. There is increasing evidence that vinpocetine improves the quality of life in chronic cerebrovascular patients.

Does glycoprotein IIIa gene (Pl(A)) polymorphism influence clopidogrel resistance? : a study in older patients.

BACKGROUND: Clopidogrel is a potent antiplatelet drug used for secondary prevention after ischaemic cardiovascular or cerebrovascular events. In patients with aspirin (acetylsalicylic acid) intolerance or resistance, it is used as monotherapy. Recent data report that Pl(A) polymorphism of the glycoprotein IIIa gene may account for differences in aspirin-induced antiplatelet effects. An increased degree of platelet reactivity was also reported in Pl(A2) carriers compared with Pl(A1/A1) patients after administration of a clopidogrel 300mg loading dose. OBJECTIVES: The aim of this study was to assess the modulatory effect of the Pl(A2) allele on platelet aggregation in patients taking long-term clopidogrel. M ETHODS: The prevalence of the Pl(A2) allele was assessed in 38 (21 males, 17 females; mean age 63 +/- 13 years) clopidogrel-resistant and 59 (26 males, 33 females; mean age 63 +/- 11 years) clopidogrel-responsive patients. The polymerase chain reaction-restriction fragment length polymorphism method was utilised to evaluate Pl(A) polymorphism. A Carat TX4 optical platelet aggregometer (Carat Diagnostics Ltd, Budapest, Hungary) was used to measure 5 and 10 micromol/L adenosine diphosphate-induced platelet aggregation. RESULTS: Significantly more patients were taking combination antiplatelet therapy in the clopidogrel-resistant group than in the clopidogrel-responsive group (50% vs 30%, respectively). The prevalence of the Pl(A2) allele did not differ significantly between the two groups (0.09 vs 0.13), even after adjustment for combination therapy and various risk factors. CONCLUSIONS: Our results show that carriers of the Pl(A2) allele do not have an increased risk of clopidogrel resistance. These findings and data from our previous studies suggest that patients with a Pl(A2) allele homozygosity may benefit from antiplatelet therapy based on clopidogrel rather than aspirin.

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.

Glycoprotein IIIA gene (PlA) polymorphism and aspirin resistance: is there any correlation?

BACKGROUND: Platelet glycoprotein (GP) IIb/IIIa receptors play an inevitable role in platelet aggregation. The GP IIIa gene is polymorphic (PlA1/PlA2) and the presence of a PlA2 allele might be associated with an increased risk for acute coronary syndrome (ACS). OBJECTIVE: To examine the prevalence of the PlA2 allele in patients with ACS and in subjects with or without aspirin resistance. METHODS: The prevalence of the PlA2 allele was assessed in 158 patients with ACS and PlA2 compared with its prevalence in 199 healthy volunteers. The antiplatelet efficacy of aspirin was examined in all patients with ACS, as well as in 69 individuals who had suffered ischemic stroke and in 58 high-risk subjects without any known ischemic vascular events. RESULTS: PlA2 prevalence was significantly higher in patients with ACS (59/158) than in the control group (51/199; p < 0.05). Carriers of the PlA2 allele had a significantly higher risk of developing ACS, even after an adjustment to the risk factors (OR 5.74; 95% CI 1.75 to 18.8; p = 0.004). The occurrence of the PlA2 allele was significantly higher among patients with aspirin resistance than in subjects who demonstrated an appropriate response to the drug (allele frequencies, 0.21 vs 0.14; p < 0.05). All patients homozygous for the PlA2 allele had an inadequate platelet response to aspirin. CONCLUSIONS: Our results support the hypothesis that carriers of the PlA2 allele might have an increased risk for ACS. PlA2 homozygosity was associated with an inadequate response to aspirin therapy. Our data further suggest that patients with PlA2 allele homozygosity might benefit from antiplatelet therapy based on adenosine diphosphate antagonists throughout secondary treatment for prevention of ACS.

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.