Evaluation of platelet reactivity during combined antiplatelet therapy in patients with stable coronary artery disease in relation to diabetes type 2 and the GPIIB/IIIA receptor gene polymorphism.

Antiplatelet therapy resistance against acetylsalicylic acid (ASA) and/or clopidogrel in coronary heart disease (CHD) is common with diabetes mellitus. One factor might involve platelet receptor ITGB3 gene polymorphism. We aimed to assess resistance together with platelet reactivity parameters, the polymorphism, plus diabetes type 2 coexistence. The study included 185 patients with CHD, including 58 diabetics, aged 62.3 ± 8.2 years. Patients were treated long-term with ASA, plus clopidogrel, both 75 mg/d. Platelet aggregation was measured with arachidonic acid (ASPI test; ASA-response assessment) or ADP (ADP test; clopidogrel-response assessment). Thromboxane B2 (TXB2) and fibrinogen concentrations were measured and ITGB3 PIA1>A2 variants identified. Increases in PLT, glucose and SBP were demonstrated with dual resistance or to clopidogrel. Regardless of response, diabetics (versus non-diabetics) had elevated platelet aggregation with the ADP test (P = 0.0198), higher TXB2 (P = 0.0501), BMI (P = 0.0003) and SBP (P = 0.0627). ITGB3 PIA1/A1 homozygotes had higher platelet aggregation with the ASPI test (P = 0.0513), and fibrinogen concentrations (P = 0.0133), relative to A2 allele carriers. Significant associations of diabetes with clopidogrel resistance (P = 0.0011) and PIA1/A1 homozygotes with ASA resistance (P = 0.0518) were found. Higher concentrations of TXB2 (P = 0.0223) and higher SBP (P = 0.0063) were found with diabetes (versus non-diabetic) in PIA1/A1 homozygotes. We concluded that diabetes with CHD weakens response to antiplatelet drugs, especially to clopidogrel; and hyperglycaemia, hypertension and obesity might also play an important role. Diabetics' resistance to ASA is associated with increased platelet reactivity, perhaps related to the more frequent ITGB3 PIA1 allele and increased TXB2 generation. The PIA1 allele may be a potential factor for aspirin resistance with elevated fibrinogen concentration.

Variable gender-dependent platelet responses to combined antiplatelet therapy in patients with stable coronary-artery disease.

Antiplatelet therapy is considered as a standard procedure against atherosclerotic cardiovscular disease but this therapy has limited effect if resistance to acetylsalicylic acid or clopidogrel is present. Important factors associated with resistance are gender; or inflammation possibly associated with membrane microparticles (MP). It was decided to challenge the hypothesis that differential responses to dual antiplatelet therapy are conditioned by gender and/or proinflammatory status. The study involved 160 patients with stable coronary heart disease (118 men, 42 women) aged 65.2 ± 7.8 years. Patients were treated long-term with acetylsalicylic acid (ASA); plus clopidogrel starting 6 days before percutaneous coronary intervention (both 75 mg/day). Response was evaluated using platelet aggregation with either arachidonic acid (the ASPI test; predominantly for ASA response) or adenosine diphosphate (the ADP test; predominantly for clopidogrel response). MP levels were measured as follows: total (MP-total); with TF expression (MP-TF); or platelet-derived microparticles (PDMP), as well as proinflammatory parameters: C-reactive protein (CRP), leukocytes (WBC) and platelet numbers (PLT). Analysis of platelet-aggregation levels with regard to gender revealed higher aggregation in women: with resistance to ASA (ASPI test: P = 0.0383, ADP test: P = 0.0027); resistance to clopidogrel (ASPI test: P = 0.0003; ADP test: P = 0.0566) and with sensitivity to both drugs with the ADP test (P = 0.0190). In women relative to men, regardless of response, significantly higher CRP (P = 0.0012), WBC (P = 0.0244) and PLT numbers (P = 0.0001) were found. In contrast, in men significantly higher concentrations of MP-TF (P = 0.0286) and triglycerides (P = 0.0296) were found in the clopidogrel-resistant group. We conclude that women have an inferior response to dual antiplatelet therapy relative to men, possibly associated with higher platelet reactivity (especially when measured with the ADP test), with a more accentuated proinflammatory status. In contrast, among the factors supporting the resistance in men can be an elevated concentration of MP-TF which, together with the coexistence of hypertriglyceridemia, may constitute an important mechanism of resistance to clopidogrel.

Gender differences in hemostatic and inflammatory factors in patients with acute coronary syndromes: a pilot study.

Many studies have shown gender differences in the progress of acute coronary syndromes (ACS). These differences include, amongst others, processes involved in hemostasis and inflammation, and in the present study we put forward the hypothesis that these are the primary cause of other differences. The study included 66 ACS patients (27 women and 39 men) aged 43 - 83 years, 23 with non-ST-elevation myocardial infarction (NSTEMI) and 43 with ST-elevation myocardial infarction (STEMI). Blood samples were taken on day 3 (NSTEMI) or day 5 (STEMI) after hospitalization, and fibrinogen, D-dimers, von Willebrand factor, C-reactive protein and interleukin-6 levels measured. Men, compared to women, had significantly higher levels of fibrinogen (STEMI: P = 0.028; NSTEMI: P = 0.008), C-reactive protein (STEMI: P <0.0001; NSTEMI: P = 0.004) and interleukin-6 with STEMI (P = 0.015), but a lower D-dimer concentration with NSTEMI (P = 0.042). In women fibrinogen concentration was significantly higher with STEMI compared to NSTEMI (P = 0.052). Significant correlations were found between hemostatic and proinflammatory factors, especially in men, regardless of ACS type. In addition, correlations between fibrinogen and D-dimers were found: negative for women (r = -0.67) ) and positive for men (r = +0.60), as was that between C-reactive protein and interleukin-6: women (r = -0.72); men (r = +0.56). Based on these findings, we conclude that acute coronary syndromes in men may be potentially related to inflammatory processes, as indicated by strong associations between elevated C-reactive protein, interleukin-6 and hyperfibrinogenemia, most clearly shown in STEMI. By contrast in women, factors possibly most important for the course of acute coronary syndrome are D-dimer concentrations and an increased turnover of fibrin with NSTEMI and hyperfibrinogenemia with STEMI.

Spatial differences of matrix metalloproteinase-2 and matrix metalloproteinase-9 within abdominal aortic aneurysm wall and intraluminal thrombus.

Formation of an abdominal aortic aneurysm is a complex process involving aortic wall degradation. The matrix metalloproteinases (MMPs) mainly involved in this process are MMP-2 and MMP-9. Most aneurysms contain an intraluminal thrombus. It is suggested that the thrombus' thickness correlates with the risk of aneurysm rupture and may be a new prognostic factor. The purpose of the present study was to investigate enzyme protein levels in thick (A1) and thin (B1) segments of the thrombus and aneurysm wall sections A (adjacent to A1) and B (adjacent to B1). Aneurysm samples from one aneurism sac were collected from 36 patients that underwent aneurysm repair. MMP-2, MMP-9 and a tissue inhibitor of metalloproteinases (TIMP-1) were measured using enzyme-linked-immunosorbent assay of protein extract. MMP-9 concentrations were significantly higher in B1 samples compared with A1 (113.4 ± 118.0 versus 63.0 ± 61.2, P = 0.004), A(113.4 ± 118.0 versus 31.7 ± 30.0, P < 0.001) or B (113.4 ± 118.0 versus 39.5 ± 41.5, P < 0.001). Likewise MMP-9/TIMP-1 ratio was elevated in B1 compared with A1 (18.9 ± 27.8 versus 9.1 ± 10.6, P = 0.017), A (18.9 ± 27.8 versus 2.5 ± 2.2, P < 0.001) or B (18.9 ± 27.8 versus 3.6 ± 4.5, P < 0.001). MMP-2 and TIMP-1 were higher in A compared with A1 (18.4 ± 8.5 versus 7.2 ± 7.6, P < 0.001; 14.3 ± 5.9 versus 8.5 ± 5.4, P < 0.001, respectively) and B1 (18.4 ± 8.5 versus 5.2 ± 2.9, P < 0.001; 14.3 ± 5.9 versus 8.9 ± 4.9, P < 0.001, respectively) as well as in B compared with A1 (15.9 ± 7.3 versus 7.2 ± 7.6, P < 0.001; 13.0 ± 5.0 versus 8.5 ± 5.4, P < 0.001, respectively) and B1 (15.9 ± 7.3 versus 5.2 ± 2.9, P < 0.001; 13.0 ± 5.0 versus 8.9 ± 4.9, P = 0.003, respectively). There were significant correlations between thin thrombus TIMP-1 and thrombus thickness (ß = -0.24, P = 0.021) and between thin thrombus MMP-9/TIMP-1 ratio and thrombus thickness (ß = 1.75, P = 0.003). Our study has revealed that the presence of thrombi with thin segments in the aneurysm sac, associated with higher proteolytic activity, could possibly be used as a potential indicator of a rupture site.

Kynuramines induce overexpression of heat shock proteins in pancreatic cancer cells via 5-hydroxytryptamine and MT1/MT2 receptors.

Kynuramines, metabolites of melatonin and L-tryptophan, are synthesized endogenously by oxygenases or in spontaneous reaction by an interaction with free radicals. We have reported previously that melatonin stimulates expression and phosphorylation of heat shock protein (HSP) 27, as well as production of HSP70 and HSP90αß in pancreatic carcinoma cells (PANC-1). Based on those results, we hypothesized that above processes could have been involved in the interruption of intrinsic proapoptotic pathway. Herein, we report that incubation of PANC-1 cells with N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK) or with L-kynurenine (L-KYN) lead to the overexpression of heat shock protein synthesis and these effects are partially reversed by 5-HT3 or MT1/MT2 receptor antagonists. PANC-1 cells in culture were treated with AFMK or L-KYN, with non selective MT1/MT2 receptor antagonist (luzindole), with 5-HT2 and 5-HT3 receptor antagonists (ketanserin and MDL72222), or combination of these substances. Both AFMK and L-KYN significantly decreased cytoplasmic HSP27 and this effect was presumably due to increased of its phosphorylation and consequent nuclear translocation, confirmed by immunoprecipitation of phosphorylated form of HSP27. These changes were accompanied by marked augmentation of HSP70 and HSP90αß in the cytosolic fraction. Pretreatment of cell cultures with luzindole or MDL72222 followed by the addition of AFMK or L-KYN reversed the stimulatory effects of these substances on HSP expression in PANC-1 cells, whereas ketanserin failed to influence mentioned above phenomenon. We conclude that activation of HSPs in pancreatic carcinoma cells seems to be dependent on an interaction of AFMK or L-KYN with MT1/MT2 or/and 5-HT3 receptors.

The dynamics of heat shock system activation in Monomac-6 cells upon Helicobacter pylori infection.

Immune system cells, particularly phagocytes, are exposed to direct contact with pathogens. Because of its nature - elimination of pathogenes - their cytoprotective systems supposed to be quick and forceful. Physiological consequence of phagocytosis for the phagocyte is the apoptotic death to prevent the eventual survival of bacteria as intracellular parasites. However, in some cases, defense systems used by the bacteria force the immune cells to prolong the contact with the pathogen for its effective elimination. Experiments were performed on Monomac-6 cells exposed to live CagA, VacA expressing Helicobacter pylori (H. pylori) over different period of time. Total cellular RNA, cytoplasmic and nuclear proteins were isolated for polymerase chain reaction, Western-blot and electrophoretic mobility shift assay, respectively. We found that Monomac-6 cells infection with H. pylori resulted in the translocation of the entire cellular content of the heat shock protein 70 (HSP70) into the cytoplasm, where its presence could protect cell against toxic products of engulfed bacteria and premature apoptosis. At the same time the nuclear translocation of heat shock factor 1 (HSF-1) and activation of HSP70 gene transcription was noticed. Action of HSP70 might to postpone monocyte apoptosis through protecting cytoplasmic and nuclear proteins from damaging effect of bacterial products, what could be the defending mechanism against the toxic stress caused by engulfed bacteria and provide the immune cell with the sufficient amount of time required for neutralization of the bacteria from phagosomes, even at the expense of temporary lack of the protection of nuclear proteins.

Haemostatic factors and intraluminal thrombus thickness in abdominal aortic aneurysm. Is secondary fibrinolysis relevant?

Many circulating haemostatic markers have been investigated in relation to the abdominal aortic aneurysm (AAA) size, growth as well as intraluminal thrombus (ILT) size. However, the results of these studies seem to be uncertain and inconsistent. The first aim of the present study was to compare the haemostatic parameters of fibrinolysis and some of thrombotic markers in patients with AAA and controls. We also examined the relationship between those parameters and both maximum aneurysm diameter and intraluminal thrombus thickness. Tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), fibrinogen (Fb), D-dimer, prothrombin fragments 1 and 2 (F1+2), thromboxane B2 (TXB2) and lipids profile were measured in 36 patients with AAA and 30 controls. The mean maximum aortic diameter in patients with the AAA was 59±12 mm (range 42-100). The mean ILT thickness was 32±10 mm (range 8-56). Among haemostatic factors, t-PA and D-dimer levels, but not PAI-1, were significantly higher in subjects with the AAA. There was a strong positive correlation between thickness of intraluminal thrombus and maximum aneurysm size (r=0.69, p<0.0001), and the negative relationship between t-PA and ILT thickness (r= -0.53, p=0.001) as well as aneurysm diameter (r= -0.38, p=0.023). Higher plasma concentrations of t-PA and D-dimer support the hypothesis that the secondary fibrinolysis plays an important role in the pathogenesis of the aortic abdominal aneurysm formation. In addition, the negative correlation between t-PA plasma level and ILT thickness suggests that thrombotic/fibrinolysis imbalance may favour accelerated formation of intraluminal thrombus and possibly aneurysm progression.

Indapamide enhances the protective action of carbamazepine, phenobarbital, and valproate against maximal electroshock-induced seizures in mice.

PURPOSE: To determine the influence of indapamide on the protective action of numerous conventional and second-generation antiepileptic drugs (carbamazepine, lamotrigine, oxcarbazepine, phenobarbital, topiramate and valproate) in the mouse maximal electroshock seizure model. MATERIAL AND METHODS: Electroconvulsions were evoked in Albino Swiss mice by a current (sine-wave, 0.2 s stimulus duration) delivered via auricular electrodes. Adverse-effect profiles with respect to motor performance, long-term memory and skeletal muscular strength were measured along with total brain antiepileptic drug concentrations. RESULTS: Indapamide (up to 3 mg/kg, i.p., 120 min before the test) neither altered the threshold for maximal electroconvulsions, nor protected the animals against maximal electroshock-induced seizures in mice. Moreover, indapamide (3 mg/kg, i.p.) significantly enhanced the anticonvulsant action of carbamazepine, phenobarbital and valproate, but not that of lamotrigine, oxcarbazepine or topiramate in the maximal electroshock seizure test in mice. Indapamide (1.5 mg/kg) had no impact on the anticonvulsant action of all studied antiepileptic drugs in the maximal electroshock seizure test in mice. Estimation of total brain antiepileptic drug concentrations revealed that the observed interaction between indapamide and phenobarbital was complicated by a significant pharmacokinetic increase in total brain concentrations of phenobarbital. In contrast, indapamide had no impact on the total brain concentrations of carbamazepine and valproate in mice. CONCLUSIONS: The selective potentiation of the anticonvulsant action of carbamazepine and valproate by indapamide and lack of any pharmacokinetic interactions between drugs, make the combinations of indapamide with carbamazepine or valproate of pivotal importance for epileptic patients taking these drugs together.

Smokers with airway obstruction are more likely to quit smoking.

BACKGROUND: Chronic obstructive pulmonary disease (COPD), usually caused by tobacco smoking, is one of the leading causes of morbidity and mortality. Smoking cessation at an early stage of the disease usually stops further progression. A study was undertaken to determine if diagnosis of airway obstruction was associated with subsequent success in smoking cessation, as advised by a physician. METHODS: 4494 current smokers (57.4% men) with a history of at least 10 pack-years of smoking were recruited from 100 000 subjects screened by spirometric testing for signs of airway obstruction. At the time of screening all received simple smoking cessation advice. 1177 (26.2%) subjects had airway obstruction and were told that they had COPD and that smoking cessation would halt rapid progression of their lung disease. No pharmacological treatment was proposed. After 1 year all subjects were invited for a follow up visit. Smoking status was assessed by history and validated by exhaled carbon monoxide level. RESULTS: Nearly 70% attended a follow up visit (n = 3077): 61% were men, mean (SD) age was 52 (10) years, mean (SD) tobacco exposure 30 (17) pack-years, and 33.3% had airway obstruction during the baseline examination. The validated smoking cessation rate in those with airway obstruction was 16.3% compared with 12.0% in those with normal spirometric parameters (p = 0.0003). After correction for age, sex, nicotine dependence, number of cigarettes smoked daily, and lung function, success in smoking cessation was predicted by lower lung function, lower nicotine dependence, and lower tobacco exposure. CONCLUSIONS: Simple smoking cessation advice combined with spirometric testing resulted in good 1 year cessation rates, especially in subjects with airway obstruction.

Tannic acid-stabilized pericardium tissue: IR spectroscopy, atomic force microscopy, and dielectric spectroscopy investigations.

Infrared (IR) spectroscopy, atomic force microscopy (AFM), and dielectric spectroscopy methods were employed to study structural and dynamic changes in the tannic acid (TA)-stabilized pericardium tissue. Chemically stabilized pericardium tissue is widely used in construction of the tissue derived bioprostheses. IR spectra recorded in the range 400-4000 cm-1 allowed us to recognize different types of TA-collagen interactions. Formation of hydrogen bonds between amine as well as amide NH groups from collagen and hydroxyl groups of TA was analyzed. The AFM imaging showed that the stabilization procedure with TA introduces considerable changes in both surface topography and thickness of collagen fibrils as well as in fibril arrangement on the tissue surface. It was found, that these structural changes have an impact on the dielectric behavior of the TA-stabilized tissue. The dielectric spectra for the native and TA-stabilized tissues were measured in the frequency and temperature ranges of 10(-1) -10(7) Hz and 120-270 K, respectively. The dielectric spectra revealed the relaxation process due to orientation of bound water supplemented by the fluctuation of collagen polar side groups. At the temperatures above approximately 210 K, the relaxation due to ion migration process was observed. It was found that both relaxation processes were influenced by the TA-collagen interaction.

Atomic force microscopy and FT-IR spectroscopy investigations of human heart valves.

Human aortic, mitral, tricuspid and pulmonary heart valves were investigated by the contact mode atomic force microscopy (AFM) in air, and using FT-IR spectroscopy in the frequency range 950-4000 cm(-1). Heart valves were collected post mortem from 65-78 years old patients who died from non-cardiac diseases. All of the examined valves showed considerable heterogeneity in the surface topography of collagen fibrils as well as in their organization on the tissue surface. The AFM images revealed areas with significantly different spatial organization of the collagen fibril bundles. We observed zones with multidirectional, stacked collagen fibrils as well as areas of thin fibrils packed regularly, densely and "in phase". The majority of the collagen fibrils reproduced the typical transverse D-banding pattern, with the band interval varying in rather wide range of 70-90 nm. Using AFM imaging, objects that correspond to some pathological states of heart valves at their early stages, i.e. some forms of mineral deposits, were observed. The FT-IR spectra allowed us to recognize main components, i.e. collagen and elastin, in di.erent layers (ventricularis, fibrosa) of the valve leaflets as well as they gave also support for the presence of mineral deposits on the valve surface. The presented results showed, that the AFM imaging and FT-IR spectroscopy can be applied as a complementary methods for structural characterization of heart valves at the molecular and supramolecular levels.

Structural changes in pericardium tissue modified with tannic acid.

INTRODUCTION: Structural modification of proteins, mainly collagen in connective tissues, is important in the manufacture of tissue-derived biomaterials. Natural compounds like genipin or tannic acid (TA) have been proposed instead of glutaraldehyde which shows cytotoxic effects on the processed tissue. Furthermore, calcification of glutaraldehyde-treated tissue limits the functional lifetime of bioprostheses. TA is known to form numerous hydrogen bonds with proteins. The purpose of our study was to investigate structural changes in porcine pericardium upon chemical modification with tannic acid. METHODS: Porcine pericardium tissue (PP) was soaked in 2% TA for 4, 24 or 48 hours. Changes in tissue structure were studied using electrophoresis (SDS-PAGE) and histological examination. Structural stability of PP tissue was evaluated by SDS/NaCl extraction method and enzymatic digestion with pancreatin. RESULTS: TA-modification of PP caused a time-dependent decrease in the number of peptides extracted from tissue. Microscopic studies revealed no significant morphological differences between native and TA-modified tissues, except for the native pancreatin-digested tissue where lack of both cells and low molecular peptides was observed. CONCLUSION: Modification of PP with TA causes the structural changes leading to an increase in the tissue resistance to SDS/NaCl extraction and enzymatic digestion, providing experimental evidence for the higher structural stability of TA-treated tissue.

Atomic force microscopy investigation of chemically stabilized pericardium tissue.

Native and chemically stabilized porcine pericardium tissue was imaged by the contact mode atomic force microscopy (AFM), in air. Chemically stabilized pericardium is used as a tissue-derived biomaterial in various fields of the reconstructive and replacement surgery. Collagen type I is the main component of the fibrous layer of the pericardium tissue. In this study, the surface topography of collagen fibrils in their native state in tissue and after chemical stabilization with different cross-linking reagents: glutaraldehyde (GA), dimethyl suberimidate (DMS) and tannic acid (TA) was investigated. It has been found that chemical stabilization causes considerable changes in the surface topography of collagen fibrils as well as in the spatial organization of the fibrils within the tissue. The observed changes in the D-spacing pattern of the collagen fibril correspond to the formation of intrafibrilar cross-links, whereas formation of interfibrilar cross-links is mainly responsible for the observed tangled spatial arrangement of fibrils and crimp structure of the tissue surface. The crimp structure was distinctly seen for the GA cross-linked tissue. Surface heterogeneity of the cross-linking process was observed for the DMS-stabilized tissue. SDS-PAGE electrophoresis was performed in order to evaluate the stabilization effect of the tissues treated with the cross-linking reagents. It has been found that stabilization with DMS, GA or TA enhances significantly the tissue resistance to SDS/NaCl extraction. The relation between the tissue stability and changes in the topography of the tissue surface was interpreted in terms of different nature of cross-links formed by DMS, GA and TA with collagen.

Ionic diffusion and space charge polarization in structural characterization of biological tissues.

In this study, a new approach to the analysis of the low-frequency (1-10(7) Hz) dielectric spectra of biological tissue, has been described. The experimental results are interpreted in terms of ionic diffusion and space charge polarization according to Sawada's theory. The new presentation of dielectric spectra, i.e. ([Formula: see text]) [Formula: see text] has been used. This method results in peaks which are narrower and better resolved than both the measured loss peaks and an alternative loss quantity [Formula: see text]. The presented method and Sawada's expression have been applied to the analysis of changes in the spatial molecular structure of a collagen fibril network in pericardium tissue exposed to glutaraldehyde (GA), with respect to the native tissue. The diffusion coefficient of ions was estimated on the basis of a dielectric dispersion measurement for an aqueous NaCl solution with a well-calibrated distance between the electrodes. The fitting procedure of a theoretical function to the experimental data allowed us to determine three diffusive relaxation regions with three structural distance parameters d(s), describing the spatial arrangement of collagen fibrils in pericardium tissue. It has been found that a significant decrease in the structural distance d(s) from 87 nm to 45 nm may correspond to a reduction in the interfibrillar distance within GA cross-linked tissue.

Von Willebrand factor, fibrinogen and other risk factors of thrombosis in patients with a history of cerebrovascular ischemic stroke and their children.

BACKGROUND AND AIM: Von Willebrand factor (vWF) and fibrinogen (Fb) have recently emerged as plausible familial determinants of atherothrombosis. We investigated whether the vWF and Fb levels in patients with ischemic cerebrovascular stroke (ICS) correlate with those in their children. METHODS AND RESULTS: The study group consisted of 28 families (56 parents and 34 children) with one parent who had suffered an ICS at least three months before the study. All of the ICS patients had hyperlipoproteinemia and most arterial hypertension. The control group consisted of 15 families (30 parents and 20 children). The age of the parents and children did not exceed 55 and 16 years. The ICS parents had significantly higher vWF, Fb and protein C (PC) levels than the controls (vWF--fathers: 121.0 +/- 42.5% vs 79.2 +/- 23.4%; vWF--mothers: 110.7 +/- 40.1% vs 82.4 +/- 20.9%; Fb--fathers: 4.12 +/- 0.74 g/L vs 3.01 +/- 0.54 g/L; Fb--mothers: 3.64 +/- 0.84 gL vs 2.98 +/- 0.35 g/L; PC--fathers: 116.0 +/- 12.3% vs 105.6 +/- 13.7%; PC--mothers: 114.4 +/- 15.8% vs 105.0 +/- 12.2%). The children of the ICS parents had significantly higher PC and body mass index (BMI) values than the controls (PC: 102.6 +/- 13.7% vs 92.7 +/- 10.7%; BMI: 20.6 +/- 3.8 vs 17.8 +/- 3.5 Kg/m2), as well as an atherogenic lipid profile, higher blood pressure (BP) and a tendency toward higher vWF levels. Correlations between the ICS parents and their children were found for vWF, factor VIIc, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and BP, which were closer in the case of fathers. CONCLUSION: Regardless of gender, the parents with a history of ICS had a procoagulant state, with high levels of vWF, Fb and PC. In terms of inheritance, the most adverse risk factor profile was found in the children of ICS fathers.

Photoconductivity of synthetic dopa-melanin polymer.

The photoconductivity effect in synthetic dopa-melanin polymer with relation to the charge hopping conduction has been investigated. Measurements of the rise and decay of photocurrents upon visible radiation (400-800 nm) and at temperatures of 293-326 K allowed the determination of the major trapping levels as follows: 56, 35 and 26 kJ/mol. Spectral response of the steady-state photocurrent in the range 367-1100 nm showed significant departures from the absorption spectrum of melanin. The high concentration of traps or recombination centers can explain the long time-constants calculated from the photocurrent rise and decay curves. The results obtained can support the postulated earlier polarons and hopping model of conductivity in synthetic dopa-melanin.

[Fibrinogen (Fb) concentrations in patients with ischaemic heart disease undergoing coronary angiography]. / Analiza stezenia fibrynogenu (Fb) u chorych z angiograficznie udokumentowana choroba niedokrwienna serca.

Increasing evidence suggests the role of hemostatic risk factors in the development of ischemic heart disease (IHD). A raised plasma fibrinogen has been related to increased risk of IHD. The aim of the study was to determine the relationship between plasma fibrinogen and the coronary vessels state based on the coronary angiogram. 119 patients undergoing coronary angiography were classified into 5 groups according the severity of IHD: Group 0 without significant atherosclerotic lesions (control group), Group 1 with single vessel disease, Groups 2, 3 with multivessel disease (two and three affected arteries, respectively) and Group 4 with positive history of myocardial infarction. A statistically nonsignificant rise in fibrinogen levels in Groups 1, 2, 3 (3.9 +/- 0.8 g/l, 4.0 +/- 0.9 g/l, 4.1 +/- 0.9 g/l, respectively) as compared to control Group 0 (3.7 +/- 0.7 g/l) was found. In Group 4 plasma fibrinogen was significantly lower (2.8 +/- 0.6 g/l) comparing to Group 0 (p < 0.05). In addition plasma fibrinogen was positively correlated with blood pressure. These results supports the role of raised plasma fibrinogen in the pathogenesis and development of IHD.

Lp(a), homocysteine and a family history of early ischemic cerebral stroke.

BACKGROUND AND AIM: High plasma lipoprotein(a) [Lp(a)] and homocysteine (HCY) levels are now considered to be independent risk factors for cerebro- and cardiovascular atherosclerotic occlusive disease, but little is known about the influence of Lp(a) and HCY on the early events of ischemic disease or their significance in subjects with a positive family history of ischemia. The aim of this study was to evaluate the relationship between HCY levels and the severity of ischemic cerebral stroke, and investigate whether there was a correlation between Lp(a) and HCY levels in the stroke patients and their children. METHODS: The study involved 35 patients with early ischemic cerebral stroke aged 46.1 +/- 6.6 years and their 50 children aged 17.2 +/- 5.5 years. The patients were grouped on the basis of the form of the stroke (transient, progressive or complete stroke), and their levels of Lp(a), HCY, uric acid (UA), fibrinogen (Fb) and factor VII (FVII) activity were measured. RESULTS: HCY and Lp(a) concentrations increased with the severity of the ischemia, being highest in the patients with complete stroke (15.1 +/- 2.9 mumol/L and 32.9 +/- 37.6 mg/dL respectively). A similar trend was found in the offspring, with the highest HCY and Lp(a) values in the children of complete stroke patients (12.6 +/- 4.4 mumol/L and 23.0 +/- 24.6 mg/dL). The control values were respectively 8.7 +/- 1.6 mumol/L and 5.35 +/- 7.05 mg/dL. The following correlations between the parents and children were noted: Lp(a) (r = 0.87 p < 0.0001), UA (r = 0.71 p < 0.001), HCY (r = 0.45 p < 0.05), FVII (r = 0.45 p < 0.05), and Fb (r = 0.42 p = 0.06). Correlations between Lp(a) and HCY (r = 0.47 p < 0.05) and Fb and FVII (r = 0.60 p < 0.01) were found in the children. Multiple regression analysis revealed that only Lp(a) and Fb significantly influenced HCY levels in the offspring with a positive family history. CONCLUSIONS: HCY levels correlate with the severity of ischemic cerebral stroke and, in families with a history of ischemic cerebral stroke, the levels of the risk factors in children are determined by the levels in their parents.

Effect of monoterpene derivative KP-19 on the pressor activity of catecholamines in rats.

The present study investigated the influence of KP-19, the propranolol analogue, bearing natural monoterpene moiety in its structure, on the blood pressure and respiration, the effect on the isolated heart rhythm disturbances induced by occlusion and reperfusion and on the pressor activity of catecholamines in normotensive rats.

Influence of new monoterpene homologues of GABA on the central nervous system activity in mice.

This behavioral study in mice showed that the monoterpene homologues of GABA (SL-1, SL-2 and SL-3), characterized by low toxicity, induced an increase in spontaneous locomotor activity (SL-2 and SL-3). Moreover, SL-3 shortened hexobarbital-induced sleeping time, and SL-1 showed anticonvulsant activity in pentetrazole-induced seizures.