LITHIUM FLUORIDE CRYSTALS AS FLUORESCENT NUCLEAR TRACK DETECTORS.

Radiophotoluminescence signal of LiF crystals was found to be sufficiently strong to visualize tracks of a single charged particle. This was achieved with a wide-field fluorescent microscope equipped with a ×100 objective and LiF single crystals grown with the Czochralski method at IFJ PAN. The tracks of alpha particles, protons, as well as products of 6Li(n,α)3H reaction with thermal neutrons (moderated Pu/Be source), were observed. These encouraging results are the first steps towards practical use of LiF as fluorescent nuclear track detectors. The most promising dosimetric application seems to be neutron measurements.

Oenothera paradoxa defatted seeds extract containing pentagalloylglucose and procyanidins potentiates the cytotoxicity of vincristine.

The purpose of the study was a comparison of Oenothera paradoxa Hudziok defatted seeds extract (EPE) effect with the activity of individual constituents of the extract: pentagalloylglucose (PGG), gallic acid, (+)-catechin and the procyanidin fraction, as well as an assessment of the combined effect of EPE and vincristine (VCR) in the absence or presence of MRP1 (indomethacin) and P-glycoprotein (verapamil) inhibitors, on two human cancer cell lines, metastatic melanoma (HTB-140) and hepatoma (HepG2). The presence of EPE, PGG and procyanidins caused a marked reduction in viability (MTT assay) and rise in mortality (LDH release assay) of HTB-140 cells. The combined use of EPE (25 µg/mL) and VCR (1 µM) in HTB-140 and HepG2 cells produced an increased cytotoxicity as compared to vincristine alone - by more than 4 and 1.5 times, respectively. In HTB-140 cells, the level of intracellular ATP (measured by bioluminescence) was lowered over 7-fold as a result of exposure to the combination of EPE and VCR, while the addition of MRP-1 inhibitor did not cause an increased cytotoxicity or further lowering of the ATP level. Our results demonstrate that EPE, containing PGG and procyanidins, significantly increased the sensitivity of cancer cells, particularly the melanoma cells, to the action of vincristine.

Propionate reduces the cytokine-induced VCAM-1 and ICAM-1 expression by inhibiting nuclear factor-kappa B (NF-kappaB) activation.

Adhesion and migration of leukocytes into the surrounding tissue are crucial steps in inflammation, immunity and atherogenesis. Expression of cell adhesion molecules by endothelial cells plays a role in these processes. Propionate is a naturally occurring short chain fatty acid produced by bacterial fermentation of dietary fibre. High intake of dietary fibre has been associated with an improved bowel function and with a reduced risk of cardiovascular disease. However, the molecular mechanisms responsible for these effects remain unknown. In this study, the effects of propionate on the expression of endothelial leukocyte adhesion molecules by cytokine-stimulated human umbilical vein endothelial cells (HUVEC) were investigated. Pretreatment of HUVEC with propionate significantly inhibited the tumor necrosis factor alpha (TNF-alpha)-induced expression of vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) in a time- and dose-dependent manner. At 10 mM, propionate also inhibited the interleukin-1 (IL- 1)-mediated VCAM-1 and ICAM-1 expression, with the latter effect being more pronounced, as well as decreased the TNF-alpha-induced VCAM-1 and ICAM-1 mRNA expression in a similar manner. The decrease in VCAM-1 and ICAM-1 expression was associated with a reduction of adherence of monocytes and lymphocytes to the cytokine-stimulated HUVEC. In addition, propionate significantly inhibited the TNF-alpha-induced activation of nuclear factor-kappa B (NF-kappaB) and significantly increased the expression of peroxisome proliferator-activated receptor alpha (PPARalpha) in HUVEC. These results demonstrate that propionate may have antiinflammatory and possibly antiatherogenic properties. Our findings warrant further investigation into the therapeutic effects of propionate on a number of pathological events nvolving leukocyte recruitment.

Optimized RT-PCR method for assaying expression of monocyte chemotactic protein type 1 (MCP-1) in rabbit aorta.

The reverse transcription polymerase chain reaction (RT-PCR) is one of the most useful molecular biology methods in opening the way to understanding of the mechanisms of atherosclerosis on the gene structure and/or expression level. We optimized this technique for assaying expression of the monocyte chemotactic protein type 1 (MCP-1) gene in rabbit aorta with respect to the temperature profile, yield to cycle number, interference of genomic DNA with the RNA matrix, and repeatability. Variability of expression of the constitutive GAPDH gene was also examined. The study was done in 18 New Zealand rabbits allocated to two groups and fed a standard chow for 2 (S1) or 3 (S2) months. The experiment ended with removal of part of the ascending rabbit aorta, from which RNA was isolated. The optimal temperature for binding of specific primers to the MCP-1 and GAPDH genes was 63 degrees C, and the optimal number of cycles for PCR amplification was 22 for MCP-1 and 26 for GAPDH. The GAPDH amplicon size was 465 base pairs in the presence or absence of reverse transcriptase showing contamination of the RNA matrix with genomic DNA. Repeatability of the RT-PCR method was 8.7%, and variability of expression of the GAPDH gene was 7.7%. Thus, RT-PCR adjusted for contaminating genomic DNA provides a reliable way of assaying expression of the MCP-1 gene in rabbit aorta.

Effects of novel plant antioxidants on platelet superoxide production and aggregation in atherosclerosis.

Superoxide anion is produced in human platelets predominantly by Nox2-dependent NADPH oxidases. In vitro experiments have shown that it might play a role in modulating platelet functions. The relationship between platelet superoxide production and aggregation remains poorly defined. Accordingly, we aimed to study superoxide production and aggregation in platelets from subjects with significant cardiovascular risk factors (hypertension, hypercholesterolemia, smoking and diabetes mellitus) and from control individuals. Moreover, we studied the effects of novel polyphenol-rich extracts of Aronia melanocarpa (chokeberry) berries on platelet function in vitro. Superoxide production was significantly increased in patients with cardiovascular risk profile when compared to controls, while platelet aggregation in response to either collagen or thrombin were borderline higher, and did not reach statistical significance. Interestingly, no relationship was observed between platelet aggregation ex vivo and platelet superoxide production in either of studied groups. No correlation was found between endothelial function (measured by FMD) and platelet aggregation ex vivo either. Polyphenol-rich extracts of A. melanocarpa berries caused a significant concentration dependent decrease in superoxide production only in patients with cardiovascular risk factors, while no effect was observed in the control group. A. melanocarpa extracts abolished the difference in superoxide production between risk factor patients and controls. A. melanocarpa extracts exerted significant concentration dependent anti-aggregatory effects in both studied groups, which indicated that these effects may be independent of it's ability to modulate superoxide production. The anti-aggregatory effects of chokeberry extracts were similar irrespective of aggregation inducing agent (collagen or thrombin). Moreover, they appear to be independent of platelet NO release as NOS inhibition by L-NAME did not lead to their abrogation.

Potential parapharmaceuticals in the traditional Polish diet.

The basic parapharmaceuticals in the Polish diet include natural anti-oxidants - bioflavonoids found in berry fruit. They were proven to have the ability to regulate genetic transcription and increase the synthesis of nitric oxide which counteracts dysfunction of the vascular endothelium. They also display anti-oxidant action through the inhibiting effect on cyclooxygenase - COX-2, and increase the level of adiponectin. We have also more and more proof of the important biological role of short-chained fatty acids formed as a result of fermentation of fibre by probiotic bacteria. Through their effects on peroxisome proliferators activated receptors (PPAR), butyric and propionic acids may reduce the expression of adhesion molecules and exert anti-inflammatory action both in the gastrointestinal tract as well as systemically.

Trans fatty acids induce apoptosis in human endothelial cells.

The present study was designed to investigate the hypothesis that trans fatty acids can induce apoptosis of human umbilical vein endothelial cells (HUVEC). To test this hypothesis apoptosis was measured in HUVEC treated with 0.1, 1.0 or 5.0 mM trans elaidic acid (t-18:1) or linoelaidic acid (t,t-18:2) for 24 hours. For the detection of apoptosis, TdT-mediated dUTP nick end labelling assay (TUNEL), cell binding of annexin V and propidium iodide uptake were measured. Active Caspase-3 and cleaved PARP (poly-ADP-ribose polymerase) were also measured in the cell lysate. Moreover, cellular ability to produce ROS (reactive oxygen species) was measured by DCF fluorescence Both acids studied induce both early (annexin-positive cells) and late stages of apoptosis (cells stained by propidium iodide) in a dose-dependent manner. Also the appearance of TUNEL-positive cells was induced by both trans fatty acids tested, in a dose dependent manner. Both trans acids induce apoptosis through their effect on Caspase-3 activity and on intracellular ROS production. It is worth emphasising that linoelaidic acid proved to be a more potent inducer of apoptosis and ROS production in endothelial cells than elaidic acid. The present studies suggest that trans fatty acids may play a role in damaging and death of vascular endothelial cells in atherosclerosis.

Simvastatin modulates TNFalpha-induced adhesion molecules expression in human endothelial cells.

Adhesion and transendothelial migration of leukocytes into the vascular wall is a crucial step in atherogenesis. Expression of cell adhesion molecules by endothelial cells plays a leading role in this process. We investigated the effect of simvastatin, an inhibitor of HMG-CoA reductase administered to reduce plasma levels of LDL-cholesterol, on the expression of vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1) by human umbilical vein endothelial cells (HUVEC) stimulated with tumor necrosis factor alpha (TNFalpha). We found the expression to be significantly inhibited by the drug in a time and concentration-dependent manner and to a greater extent in the case of VCAM-1 as compared with ICAM-1. In TNFalpha-stimulated HUVEC, simvastatin decreased VCAM-1 and ICAM-1 mRNA levels, inhibited TNFalpha-induced activation of nuclear factor kappaB (NF-kappaB) and enhanced expression of peroxisome proliferator-activated receptor alpha (PPARalpha). These effects were associated with reduction of adherence of monocytes and lymphocytes to HUVEC. The present findings suggest that the benefits of statins in vascular disease may include the inhibition of expression of VCAM-1 and ICAM-1 through effects on NF-kappaB.

Effects of perindopril treatment on hemostatic function in patients with essential hypertension in relation to angiotensin converting enzyme (ACE) and plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms.

BACKGROUND AND AIM: An imbalance in the hemostatic system is a frequent finding in untreated essential hypertension (HT), and it has been shown that treatment with angiotensin converting entyme (ACE) inhibitors improves hemostatic function. In order to elucidate the role of genetic factors, we studied hemostasis in patients with untreated and treated HT and correlated the results with ACE I/D and plasminogen activator enhibitor-1 (PAI-1) 4G/5G gene polymorphisms. METHODS AND RESULTS: Forty-three males with HT (mean age 31.7 +/- 6.8 years) were compared with 34 age and gender-matched controls. All of the patients were treated with perindopril (4 mg/day) and, after one and six months of therapy, their levels of plasma fibrinogen (Fb), t-PA antigen, PAI-1 antigen, von Willebrand factor (vWF), ACE activity and blood pressure were measured. ACE and PAI-1 genotypes were identified by means of the polymerase chain reaction on DNA isolated from peripheral blood lymphocytes. Untreated patients had significantly higher levels of Fb, PAI-1 (p < 0.01) and t-PA (p < 0.05) regardless of their ACE or PAI-1 genotypes. Perindopril reduced blood pressure regardless of ACE or PAI-1 genotype (p < 0.001). ACE II homozygotes showed the greatest decrease in ACE activity (p < 0.01) and a significant reduction in Fb levels (p < 0.05) after just one month of treatment. Analysis of the group as a whole revealed an increase in t-PA antigen levels after six months of treatment, regardless of ACE or PAI-1 genotype (p < 0.01). CONCLUSIONS: Our results show that essential hypertension predisposes to the procoagulant state characterized by hyperfibrinogenemia and hypofibrinolysis. Perindopril reduced fibrinogen levels in ACE II homozygotes due to its more potent inhibitory action on the renin-angiotensin system in such patients. It improved fibrinolysis by increasing t-PA levels regardless of ACE and PAI-1 genotype.

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.

Rapid quantification of human ABCA1 mRNA in various cell types and tissues by real-time reverse transcription-PCR.

BACKGROUND: The ABCA1 gene encodes for a member of subfamily A of the ATP-binding cassette transporters that plays an important role in cellular export of cholesterol and phospholipids; therefore, quantification of the ABCA1 mRNA is critical in many studies related to its expression and regulation by metabolic factors, nutritional status, and new antiatherogenic drug candidates. We developed a rapid, sensitive, specific, and reproducible real-time reverse transcription-PCR (RT-PCR) method for detection and quantification of ABCA1 transcripts in total RNA isolated from cultured human cells and tissues. METHODS: To quantify ABCA1 mRNA, we generated a calibration curve from serial dilutions of in vitro-transcribed RNA corresponding to an amplified ABCA1 cDNA 205-bp fragment (homologous calibrator). Two pairs of fluorescent hybridization probes were used to detect the ABCA1 and porphobilinogen deaminase (PBGD) mRNAs; the latter served as an internal control. PCR was performed as real-time amplification of ABCA1 mRNA in 100 ng of total RNA isolated from various human tissues, and cultured cells were calculated from the calibration curve. In addition, normalized values of target (ABCA1/PBGD ratio) were calculated. RESULTS: Using this method, we quantified ABCA1 transcripts in various human tissue samples as well as in monocytes, THP-1 cells, fibroblasts, and adipocytes. We demonstrated ABCA1 mRNA up-regulation during human adipocyte and monocyte differentiation. In addition, we examined the effect of cholesterol loading and deloading on ABCA1 expression in monocytes, THP-1 cells, and fibroblasts. CONCLUSIONS: Our RT-PCR assay allows the specific and highly reproducible detection and quantification of minute amounts of human ABCA1 mRNA. This new method is more accurate, more informative, and less laborious than the classic RT-PCR methods and Northern blot; it therefore could simplify all studies on ABCA1 mRNA expression.

[Reduction of the plasma LDL-cholesterol level among young healthy men as a result of the change from butter to soft margarine in the unbalanced diet]. / Redukcja stezenia frakcji LDL-cholesterolu w surowicy mlodych zdrowych mezczyzn w wyniku zamiany masla na margaryne miekka w zwyczajowej diecie.

The aim of the study was to evaluate the level of lipid profile on 83 healthy males consuming soft type margarine instead of butter, in their unbalanced diet. For this purpose double blind, cross-over methodology was applied. After stabilization period of consuming the diet, the whole sample was randomly divided into two subgroups (A n--37; B n--46). First group was consuming 15 g of the butter twice a day (30 g in total) and the second identically packed soft type margarine (also twice a day 15 g; 30 g in total) containing high level (33.3 g/100 g) of polyunsaturated fatty acids. After four weeks, the diet of subgroups was mutually exchanged--group consuming margarine consumed butter and the opposite. The feeding pattern of both groups was monitored with the aid of FOOD 2 computer programme. The group under investigation consisted of healthy males at the age 23.3 +/- 2.5, BMI 24.4 +/- 3.9 kg/m2; WHR 0.82 + -0.06 and normal blood pressure. Exchange of butter into soft margarine caused the increase of P/S ratio from 0.30 to 0.78 in their diet. Both investigated groups shoved average decrease of 10.7% of blood cholesterol content (in group A 13.8%), LDL cholesterol of about 9.8% and triglycerides ca 12.7% (higher decrease in group B--16.7%). Both groups while on margarine diet shoved small decrease of HDL cholesterol (3.9%). It can not be the matter of serious concern due to average HDL content in both groups was ca 52 mg/dl (ca 1.4 mmol/l)--it means considerably excessive the limited risk (35 mg/dl; 0.90 mmol/l). Application of the margarine diet in group A caused the decrease the ratios of total cholesterol to HDL cholesterol from 3.84 into 3.52; whereas in group B from 4.15 into 3.75. It was also concluded, that the low trans isomer margarine show no effect on lipoprotein Lp(a). Back to the diet with butter after 4 weeks carry down the beneficial effects of diet with margarine on lipid profile. The results indicate that for lipid profile the consumption of soft margarine was more beneficial than butter, even for unbalanced diet.

A pleiotropic antiatherogenic action of ibuprofen.

Ibuprofen is a cyclooxygenase (COX-1 and COX-2) inhibitor known to reduce the production of prostaglandins that play prominent role in inflammation. Other properties of the drug, aside from its anti-inflammatory effects, have been recently studied. In this paper we shall discuss several properties of ibuprofen that making the drug interesting for treatment of conditions associated with atherosclerosis. Ibuprofen exerts pleiotropic effects such as inhibition of adhesion and transendothelial migration of leukocytes, suppressing intracellular production of reactive oxygen species and oxidative modification of LDL. Interestingly, ibuprofen increased HDL cholesterol levels and reduced the level of triglicerides. Ibuprofen can also modulate efficiency of fibrynolisis by inhibiting production of plasminogen activator inhibitor (PAI-1). This properties of ibuprofen may be due to changing the activity of transcription factors. Ibuprofen inhibits the activation of NF-kB and activates PPARa and PPARg.

Homocysteine, fibrinogen, and lipoprotein(a) levels are simultaneously reduced in patients with chronic renal failure treated with folic acid, pyridoxine, and cyanocobalamin.

Ischemic heart disease and other complications of atherosclerosis are the usual cause of death in patients with chronic renal failure. Important factors associated with early onset of atherosclerosis in these patients are hyperhomocysteinemia, hyperfibrinogenemia, and elevated levels of lipoprotein(a) (Lp(a)). Folic acid (15 mg/d), pyridoxine (150 mg/d), and cyanocobalamin (1 mg/wk) were administered for 4 weeks in 21 patients receiving dialysis, and a simultaneous, statistically significant reduction in the concentration of homocysteine, fibrinogen, and Lp(a) was found. A positive correlation between decreasing homocysteine and fibrinogen levels was also noted. The parameters studied approached presupplementation values 6 months after vitamins were discontinued. The results suggest that vitamin supplementation has a favorable effect on risk factors of atherosclerosis in patients with renal failure and that interactions may exist between homocysteine, fibrinogen, and Lp(a).

Selective inhibition by probucol of vascular cell adhesion molecule-1 (VCAM-1) expression in human vascular endothelial cells.

An early event in atherogenesis is the adhesion of monocytes to endothelium via adhesion molecules, such as VCAM-1 and intracellular adhesion molecule-1 (ICAM-1). It has been suggested that VCAM-1 plays a very important role in the recruitment of monocytes in atherosclerosis. Probucol is a potent inhibitor of atherosclerosis in animal models. However, the mechanism of its antiatherogenic effect is poorly understood. The aim of our study was to evaluate whether probucol can influence the expression of endothelial cell adhesion molecules and endothelial adhesiveness. The study was performed on cultured human umbilical vein endothelial cells (HUVEC). HUVEC were pretreated with probucol (50 microM) at different time periods before stimulation with TNFalpha (100 U ml(-1)) or IL-1beta (100 U ml(-1)). The protein expression of VCAM-1 and ICAM-1 was measured by flow cytometry. VCAM-1 mRNA expression was measured by reverse transcription polymerase chain reaction (RT PCR). Probucol time dependently reduced agonist-induced VCAM-1 ( approximately 45%, 48 h) surface protein and mRNA expression ( approximately 40%, 48 h) in HUVEC, but not ICAM-1 surface protein expression. Decreased VCAM-1 expression was associated with reduction ( approximately 40%) of adherence between cytokine-stimulated HUVEC and peripheral blood mononuclear leukocytes (PBMC). Our results suggest that the antiatherogenic effect of probucol may, in part, be due to a downregulation of VCAM-1 expression.

[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.

Ibuprofen inhibits adhesiveness of monocytes to endothelium and reduces cellular oxidative stress in smokers and non-smokers.

BACKGROUND: Cigarette smoking is a major risk factor in atherosclerosis and a useful model from which to study chronic inflammation. We compared monocyte function, lipid profiles and inflammatory markers in smokers and non-smokers, before and after oral ibuprofen intake. The adhesion of freshly isolated monocytes to native and tumour necrosis factor alpha (TNFalpha) stimulated human umbilical vein endothelial cells (HUVEC), as well as superoxide anion (O2-) levels and hydrogen peroxide (H2O2) production in resting and phorbol myristate acetate (PMA) stimulated monocytes were determined. MATERIALS AND METHODS: A group of nine smokers without any other coronary risk factor was compared with an age-matched group of 9 non-smokers. Tests were performed before and after a two-week course of oral ibuprofen (600 mg day-1). RESULTS: In smokers before ibuprofen, monocyte adhesion to native and TNFalpha-stimulated HUVEC was increased (P < 0001 and P < 0.01, respectively), and so were O2- levels in native and PMA-stimulated monocytes (P < 0.01 and P < 0.001, respectively). Ibuprofen reduced the adhesion of monocytes to native and stimulated HUVEC (P < 0.001) and O2- generation by resting and PMA-stimulated cells (P < 0.01) in both groups. H2O2 production by resting and PMA-stimulated monocytes was reduced in smokers and non-smokers (P < 0.01). Interestingly, ibuprofen increased HDL cholesterol levels in smokers (P < 0.01) and non-smokers (P < 0.001), and reduced the level of triglycerides in smokers (P < 0.05). CONCLUSION: Oral administration of ibuprofen reduced the adhesion of monocytes to HUVEC, suppressed oxidative stress and increased HDL cholesterol levels in smokers and non-smokers.