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Although associations between cholesterol and coronary heart disease (CHD) are well accepted, the association between cholesterol and stroke remains unclear. Epidemiological studies suggest lack of apparent correlation between cholesterol and cerebrovascular events, however meta-analyses of secondary prevention trials tested statins (HMG-CoA reductase inhibitors) efficacy in reducing cholesterol revealed a powerful statistically significant effect to reduce stroke as well as CHD (32%). Mechanism for stroke reduction can be connected with nonlipid mechanism of statins action: modifying endothelial function and inflammatory responses, plaque stabilisation and inhibition of plaque progression and thrombus formation in the intracranial and extracranial carotid arteries. Stroke events may be also reduced partially as a consequence of CHD reduction.

Gene therapy is based on the delivery of exogenous genetic material in order to influence the endogenous genetic components involved in disease development. This new therapeutic approach has been suggested to have great potential in the treatment of insufficient angiogenesis or in prevention of restenosis after balloon angioplasty of atherosclerotic arteries. As both vascular endothelial growth factor (VEGF) and nitric oxide (NO) exert beneficial effects on vascular physiology, we studied the generation of both compounds after in vitro transfection of relevant genes. The plasmid vectors, containing VEGF cDNA were constructed and lipotransfected into vascular smooth muscle cells (VSMC). Transfected cells generated up to a few nanograms of VEGF, which induced proliferation of endothelial cells. VSMC transfected with another plasmid, containing endothelial constitutive NO synthase (ecNOS) cDNA generated micromolar quantities of nitrite. Moreover, such NO-producing cells synthesized significantly more VEGF than VSMC transfected with control plasmids. Thus, the study demonstrated that transfer of VEGF and/or NOS genes to VSMC led to the production of measurable amounts of both VEGF protein and NO. Additionally, we evidenced that NO can enhance the endogenous generation of VEGF. A new protective mechanism of NO has been thus revealed.

In several renal diseases such as nephrotic syndrome or terminal renal insufficiency changes in lipids metabolism may lead to increase of cholesterol level or changes in its fractions proportions. There are many clinical and experimental observations demonstrating direct toxic effect of lipids on endothelium leading to impairment of endothelial function what can increase damage of glomeruli. It is associated with passive filtration of lipoprotein to mesangium and active fagocytosis by mesangial cells and infiltrating macrophages, which release cytokines and growth factors increasing mesangial proliferation. There are first publications suggesting possibility of application LDL-apheresis-radical cholesterol removing procedure in renal disease. Periodical cholesterol lowering in the blood reduces proteinuria in patients with resistant for pharmacotherapy nephrotic syndrome, especially with focal glomerulonephritis.

The article presents a new view on relations between obesity and ischaemic heart disease. The place of obesity among cardiovascular risk factors has been specified. Definition of obesity, methods of its diagnosis, its etiopathogenesis and therapeutic approach to it (according to statement of AHA) have been discussed.

There is a growing evidence on the relations between apoprotein E (apo E), in particular apoE4, cardiovascular disease and Alzheimer's disease. However, little is known on the prevalence of apoE in Polish population. The goal of this paper was to assess the frequency of apoE phenotypes and isoforms in the sample of elderly people. Studied group were 90 men and 92 women, residents of Polish rural province (Tarnobrzeg Voivodship) at age 65-78 years. Identification of apoE isoforms was done using the immunoblotting method. The most frequent phenotype was apoE3/3, which was found in 70% of men and 73% of women. Phenotype apoE3/2 was identified in 20% men and 15% women. Both in men and in women phenotypes apoE4/2 and apoE4/3 were more rare-in total 10% and 12% participants, respectively. There was nobody with phenotype apoE4/4. In women there was also nobody with phenotype apoE4/2, but in men phenotype apoE4/2 was found in 4% of participants. No person was found with phenotype apoE2/2. Frequency of homozygotes apoE4/4 was low in studied population and could little contribute to the epidemy of cardiovascular disease and dementia in the elderly. However, the 10% frequency of heterozygotes with isoform apoE4 could have more impact.

The aim of the study was to assess the relation between urinary excretion of epinephrine and norepinephrine, and stroke severity, prognosis and standard biochemical investigations in acute phase of ischaemic stroke. The study was done on the material of 36 patients (17 women and 19 men, aged 41-89 years, mean: 69 +/- 13 years) admitted to the stroke unit of the Neurology Department within 24 hours (mean: 7.7 hours), after the first ever ischaemic stroke affecting the territory of the internal carotid artery circulation, confirmed by CT. Patients with the history of diabetes mellitus, cardiac insufficiency and infection on admission were excluded from the study. The 24-hour urine collection for catecholamines (epinephrine and norepinephrine) was done on the first and third day of hospitalization. An even single increased daily excretion of epinephrine (10 micrograms/24 hr) was found in 21 and norepinephrine (50 micrograms/24 hr) in 10 of 36 patients. No correlation between daily excretion of epinephrine and norepinephrine was found. Statistical analysis revealed a significant relation between norepinephrine, but not epinephrine, and neurological deficit, prognosis and some biochemical parameters of investigated patients. Patients with increased daily excretion of norepinephrine showed worse neurological deficit (p0.01), greater mortality assessed on the 30-th and 90-th day of stroke (p0.05) and increased plasma glucose, sedimentation rate, white blood cells count, creatinine kinase activity as well as microalbuminuria and decreased plasma kalium concentration.

Background The association between apo E isoforms and insulin output during the oral glucose test (OGTT) in 60 non-diabetic, non-obese patients with essential hypertension and in control subjects (non-obese, non-diabetic normotensive subjects) was estimated. Methods According to low or high insulin output during OGTT, the subjects were divided into the following groups: normotensive subjects with low (NLI) and high (NHI) and hypertensive subjects with low (HLI) and high (HHI) insulin output. Results The apo E 4/2 phenotype was detected in 32% of hypertensive subjects but not in control subjects. The frequency of apo E 3/2 phenotype in hypertensive subjects was 5% and in normotensive subjects 15%. An increased frequency of phenotype apo E 4/3 was noticed both in HHI (46%) and in NHI (50%) compared with HLI (22%) and NLI (17%) groups. Conclusion The results suggest that the determination of phenotypes apo E and insulin output may contribute to an early detection of individuals at high risk of hypertension development.

The generation of nitric oxide is regulated by several factors, including the substrates and cofactors supplementation. Decreased expression and activity of nitric oxide synthase as well as diminished amount of L-arginine or enzyme cofactors results in the inhibition of nitric oxide generation in vascular wall cells. GTP cyclohydrolase 1 is a key enzyme involved in the synthesis of tetrahydrobiopterin, one of the most important cofactors of NO synthases. We have demonstrated that oxidized LDL inhibit not only inducible nitric oxide synthase gene expression but also GTP cyclohydrolase I gene expression in interleukin-1 beta activated rat vascular smooth muscle cells in vitro. It is postulated that diminished availability of tetrahydrobiopterin may additionally impair the generation of nitric oxide in atherosclerosis.

Selectin-P expression on platelets stimulated with thrombin was measured in terms of formation of "rosettes" according to Jungi et al. [9]. Selectin-P-mediated platelet/PMNs adhesion was inhibited by iloprost (IC50 = 5.0 nM), sodium nitroprusside (NaNP, IC50 = 0.93 microM) and interleukin-8 (IL-8, IC50 = 88 ng/ml), but activated dose-dependently by oxy-LDL (3-15 micrograms/ml). Glycogen-induced peritonitis in rats up-regulated the iNOS activity measured by the 2,3-[3H]-citrulline formation by the abdominal cavity PMNs up to 6 h after insult. Pretreatment with IL-8 (3 micrograms/300 g iv) decreased the amount of PMNs in ascites as well as its iNOS activity. Chemotaxis mediated iNOS gene expression of PMNs were measured by Northern blot hybridization. IL-8 (100 ng/ml) did not influence the PMNs iNOS gene expression induced by chemotaxis. We conclude that the decrease in iNOS activity by IL-8 involves postranslational modification of the enzyme activity.

The purpose of the study was to evaluate a relationship between HDL, triglyceride levels and insulinaemia in primary arterial hypertension. The study population consisted of 60 men aged 32-68 years (mean age 50.87 years, s.d. 8.4) with hypertension duration of 11.1 years (s.d. 6.4 years) who were compared with 60 normotensives matched for sex, age and BMI. We examined blood pressure, plasma lipoprotein content, sum of glucose and sum of insulinaemia (sum ins) during OGTT (oral glucose tolerance test). OGTT revealed insulin secretion almost twice as high in hypertensives (P0.001 sum ins 11002 microU min/ml, s.d. 4846) than in normotensives (sum ins 6662 microU min/ml, s.d. 3099). Comparison of concentration of selected VLDL components shows that hypertensives were characterised by markedly higher concentration of triglycerides (1.46 mmol/L, s.d. 0.87 in hypertensives and 1.04 mmol/L, s.d. 0.54 in normotensives), free and esterified cholesterol and protein, including apolipoprotein B than normotensives. It was also found that hypertensives had higher levels of apo CIII0 and lower levels of CIII1 VLDL than normotensives. Hypertensive patients showed also a higher frequency of apo E2 isoforms (three-fold) and apo E4 isoforms (two-fold) than healthy subjects. No changes were detected in the composition of LDL and HDL between the groups. Analysing the discriminating ability of biochemical parameters chosen in a step-wise manner it was found that sum ins and HDL, protein and cholesterol concentrations were the factors most powerfully differentiating men with hypertension from healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

In the present work we have demonstrated that the low NOS activity of circulating blood neutrophils is related to an endogenous inhibitory factor. This factor inhibits constitutive NOS (cNOS) of cerebellum and inducible NOS (iNOS) of macrophages in a concentration-dependent manner. Boiling only partially diminished its activity. The inhibition of cNOS was specific, since to some degree NADPH (0.5-4 mM) and more effectively L-arginine (0.1-1 mM), but not D-arginine, reversed the inhibition.

A rapid development of the knowledge about vascular endothelial cell function as an "endocrine gland" releasing the labile, highly biologically active products, caused a major reapprisal of our concepts concerning the pathophysiology of our body. The publication summarizes the present understanding of the involvement of nitric oxide (NO), endothelins (ETs) and arachidonic acid products in the mechanisms underlying the regulation of the tonus of vessels supplying blood to the CNS, their known modulatory and mediatory role in CNS functions such as a development and memory, peripheral nonadrenergic noncholinergic, or sensory neurotransmission. The regulation intracellular Ca+ +ion levels as a proposed mechanism for the neuroprotective, as well as the neurotoxic effect of the described endothelial products is presented. The supposed therapeutical usefullness of compounds which can modulate their biosynthesis, substitute their activity, or modify its degradation are also summarized.

Acid lipase activity (ALA) and neutral lipase activity (NLA) in lymphocytes of patients with primary hyperlipidemia (hypercholesterolemia or/and hypertriglyceridemia) were compared with that of an age-matched control group (blood donors). The specificity of lipase was confirmed by the use of cardiolipin the well known activator of acidic lipase. beta-D-glucuronidase activity was used as a marker of the lysosomal release reaction. ALA (by 33%) and beta-D-glucuronidase (by 55%) activity, but not NLA in lymphocytes of the group of hyperlipidemic patients, was significantly lower when compared to the control group. A negative correlation between the serum cholesterol level and ALA, NLA and beta-D-glucuronidase release from lymphocytes of hyperlipidemic subjects was observed. The serum HDL cholesterol level was positively correlated with ALA within this group. These results suggest that the high cholesterol level in serum can unspecifically supress ALA and (to the smaller degree) NLA activity in lymphocytes of hyperlipidemic subjects. The decrease of lipase activity may promote deposition of lipids in cells and the development of atherosclerosis. The parallel decrease of beta-D-glucuronidase activity in lymphocytes of hypercholesterolemic patients suggests the impairment of immune system in hypercholesterolemia.

The expression of Selectin-P was measured in terms of formation of "rosettes" by human gel-filtrated thrombin (30-50 mU)-stimulated platelets on the surface of isolated homologous neutrophilic leucocytes (PMNs) according to Jungi (1986). The monoclonal anti-Selectin-P antibody completely prevented the formation of "rosettes", proving the specificity of Selectin-P-mediated adhesion. The Selectin-P-mediated adhesion of platelets to PMNs was inhibited by both iloprost (ILO) (IC50 = 5.0 nM) and sodium nitroprusside (NaNP) (IC50 = 0.93 microM); thus ILO is ca. 180 times more potent an inhibitor of "rosette" formation than NaNP. The NOS-inhibitors L-NO2Arg (10-30 microM) and L-MetArg (3-30 microM) each suppressed the adhesion, while at lower and higher concentrations these NOS-inhibitors did not influence rosette formation. L-Arginine (up to 1 mM) was not able to influence significantly the Selectin-P-mediated adhesion of platelets to PMNs. The COX inhibitor aspirin (10-30 microM) promoted the adhesion. We conclude that the Selectin-P-mediated adhesion of platelets to PMNs is inhibited by both ILO and NaNP, whereas endogenous prostanoids and nitric oxide seem to exert an antagonist effect on the adhesion of platelets to PMNs.

The patients were divided by chance into 2 groups: the first one (15 persons) was given a natrium salt of prostacyclin (Epoprostenol Wellcome or Chinoin) in a dose of 5 mg/kg/min. intravenously by an infusion pump in 5 infusions; the control group (15 persons) received instead of prostacyclin a placebo (0.1 M glycine buffer of pH 10.5). Besides all the patients were given Doxium or Calcium dobesilate, Rutinoscorbin, Vitamin C, and Polopyrin S (Soluble Aspirin). Immediately after the completion of the treatment the authors did not find any essential differences between the examined groups. In prolonged observations however one demonstrated a significantly smaller frequency of the development of neovascularization in the eyes of persons treated by prostacyclin in comparison with the control group.

In isolated perfused ovalbumin-sensitized guinea-pig hearts modulating effects of nitric oxide (NO) on cardiac function and eicosanoid release were investigated. While the NO-donor SIN-1 exhibited a protective effect during cardiac anaphylaxis, inhibition of NO biosynthesis by NNA or NMMA aggravated anaphylactic changes of cardiac functions. Exogenous and endogenous NO seems to functionally antagonize the effects of vasoconstrictor mediators released during the anaphylactic reaction. In addition, inhibition of cysteinyl-leukotriene (cys-LT) release could contribute to the protective effect of SIN-1 observed.

Rabbit aortic strips superfused with Krebs buffer pH 7.3 were relaxed in an endothelium-dependent manner by both acetylcholine (0.01-0.3 microM) and an increase in pH up to 7.6-8.5. These vasorelaxant effects were abrogated by methylene blue (50 microM), lidocaine (1.3-640 microM) and verapamil (2.5-5.0 microM). Nitrendipine (2.5-5.0 microM) abolished only acetylcholine-induced, but not pH-induced relaxations. It is concluded that activation of Na+/H+ exchange might be involved in triggering the release of an endothelium-derived relaxing factor.

Prostacyclin (PGI2) connects all the pharmacologic properties of drugs being used till now in sudden deafness. 30 patients with sensori-neural sudden deafness were treated by prostacyclin and placebo in the double-blind test situation. In therapeutic group of 15 patients were 87% of complete recovery, but in placebo only 6%.