Biomedical subjects

Jan Kowalski

Publications and source records attributed to Jan Kowalski.

44 records · Page 3Linked to original sources

PubMed2002

[Pleiotropic effects of micronized fenofibrate in patients with combined hyperlipidemia].

More and more recent studies demonstrate the pleiotropic effects of fibrates. Except lowering plasma lipid levels they can influence blood coagulation abnormalities and stabilise atherosclerotic lesions--a frequent result of the activation of inflammatory cells within the vascular wall. The anti-inflammatory action of fibrates includes inhibiting the release of many cytokines, such as Tumor Necrosis Factor e (TNF-alpha) by these cells. The aim of this study was to evaluate the effect of fenofibrate on the plasma levels of Plasminogen Activator Inhibitor type 1 (PAI-1) and fibrinogen in patients with combined dyslipidemia. Moreover, we assessed the amount of TNF-alpha released by peripheral blood isolated monocytes before and after therapy. Fourteen patients (8 women and 6 men) with hyperlipidemia IIb were treated with micronized fenofibrate (Lipanthyl 200 m, Fournier) in a daily dose of 200 mg for one month. The control group consisted of 12 individuals matched for age with biochemical confirmation of normolipemia. Plasma PAI-1 and TNF-alpha levels were measured by the ELISA method. Fibrinogen levels were measured according to the commonly used Clauss method. Before treatment the haemostatic compounds and TNF-alpha studied were significantly higher in the group with hyperlipidaemia IIb compared to the control group. One-month therapy with fenofibrate resulted in significant decrease of triglycerides and total cholesterol. After treatment, PAI-1 and fibrinogen levels also decreased significantly: PAI-1 from 101.18 +/- 9.74 ng/mL to 81.22 +/- 6.68 ng/mL, p < 0.01 and fibrinogen from 364.5 +/- 29.6 mg/dL to 294.7 +/- 19.3 mg/dL, p < 0.01. The study also revealed that the level of produced TNF-alpha decreased significantly from 2136.0 +/- 250.8 pg/mL to 1336.8 +/- 132.0 pg/mL, p < 0.05. These results may confirm new pathways of fibrates action.

Adult↗

PubMedDate not supplied

Evaluation of variations in sensory and pain threshold assessments by electrocutaneous stimulation.

Assessed sensory and pain thresholds can change consequently to disturbances associated with ongoing pain. Such assessments could be an additional method in the daily clinical evaluation of perceived pain. To study the test-retest variability within-day and between-day of such procedures a newly developed instrument producing electrocutaneous stimulation, PainMatcher (PM), was used to assess the electrical sensory thresholds (EST) and pain thresholds (EPT) in healthy volunteers and in patients with pain. The produced data were considered ordinal and analyzed with rank-invariant statistics with properties of analyzing systematic disagreement, bias, and individual variations. The percentage agreements within +/- 1PM value for EST were in the two groups of healthy volunteers and patients in pain 94% and 92%, and for EPT assessments 49% and 78%, respectively. The variability in the EST assessments is possibly explained by a slight bias while the individual variations were negligible between the two occasions. The assessed EPT were unbiased in both groups while individual variations were significant among the healthy volunteers but negligible among the patients in pain. The EST was found to be increased in pain patients compared to healthy volunteers, p < 0.03, and the EPT decreased in pain patients compared to healthy volunteers, p < 0.001. The results in this study indicate stable and reliable assessments of EST and EPT except for a possible bias. The threshold assessment procedure followed in this study may be a valuable tool in the clinical evaluation of sensory and pain assessments in pain patients.

Case-Control Studies↗

PubMedDate not supplied

Effect of simvastatin and fluvastatin on plasma fibrinogen levels in patients with primary hypercholesterolemia.

The aim of the study was to compare the effect of treatment with two different statins on plasma fibrinogen levels in patients with primary isolated hypercholesterolemia. Sixty three patients enrolled into the study were randomly divided into two groups, treated with simvastatin (20 mg/d) or fluvastatin (40 mg/d), respectively. Plasma lipid profile and fibrinogen levels were measured after 4 and 12 weeks of the therapy. Both drugs decreased total and LDL cholesterol and apoprotein B levels. Simvastatin additionally reduced triglyceride levels. After 4 weeks of treatment both drugs tended to increase plasma fibrinogen levels, while after 12 weeks fibrinogen level was significantly increased in the simvastatin-treated patients. The effect on fibrinogen did not correlate with their lipid-lowering potential, gender and was similar in patients positive and negative for anti-Helicobacter pylori or anti-Chlamydia pneumoniae antibodies. Our results support the findings about a relatively weak effect of statin therapy on plasma fibrinogen level and partially explain contradictory results of previous studies.

Adult↗

PubMedDate not supplied

Influence of antidepressant drugs on macrophage cytotoxic activity in rats.

The aim of the study was to evaluate the in vivo and in vitro effects of antidepressant drugs on cytotoxic activity of rat spleen macrophages. In the in vivo experiment, rats were injected subcutaneously with two different doses (2 or 10 mg/kg) of desipramine, fluvoxamine and fluoxetine. The drugs were given once, for 2, 4 or 8 weeks. In the in vitro experiment, spleen macrophages were cultured with three different concentrations of desipramine (3.75, 0.75, or 0.075 mM), fluvoxamine (3.14, 0.62, or 0.062 mM), and fluoxetine (3.23, 0.64, or 0.064 mM) for 72 h. The cytotoxic activity of macrophages was evaluated by measuring the lysis of ((51)Cr) chromate-labelled P-815 target cells. In the in vivo experiment, a single dose of fluvoxamine (2 and 10 mg/kg) and fluoxetine (10 mg/kg) significantly decreased macrophage cytotoxic activity. Fluvoxamine (2 and 10 mg/kg), fluoxetine (10 mg/kg) and desipramine (10 mg/kg) administrated for 14 days also decreased macrophage cytotoxic activity. Twenty-eight day treatment with desipramine (2 and 10 mg/kg) decreased macrophage cytotoxic activity. Desipramine, fluvoxamine and fluoxetine given for 56 days did not affect macrophage cytotoxic activity. In the in vitro experiment, antidepressant drugs did not affect the cytotoxic activity of macrophages. The results of the study indicate that the effects of antidepressant drugs on macrophage cytotoxic activity depend on the drug type, dose and duration of the treatment.

Animals↗

PubMedDate not supplied

Effect of kaempferol on the production and gene expression of monocyte chemoattractant protein-1 in J774.2 macrophages.

Monocyte chemoattractant protein-1 (MCP-1) is produced by activated macrophages, and is involved in pathogenesis of cardiovascular and neurodegenerative disorders. There is a need to develop drugs that inhibit excessive infiltration of monocytes and lymphocytes to the arterial wall and central nervous system. The aim of this study was to evaluate the effect of kaempferol on the (MCP-1) gene expression and MCP-1 protein release by J774.2 macrophage cultures in vitro. Kaempferol given both before and after lipopolysaccharide (LPS) administration reduced secretion of MCP-1. Kaempferol administered before LPS stimulation significantly decreased the number of copies of MCP-1 mRNA. The results suggest that kaempferol inhibits MCP-1 production at the transcriptional level, and that this is an additional anti-inflammatory mechanism of action of this flavonoid.

Animals↗

PubMedDate not supplied

Monocyte suppressing action of fenofibrate.

Since atherosclerosis has been proven to be an inflammatory disease, it is obvious that the proper treatment for dyslipidemia should not only correct lipid parameters but also inhibit inflammation. Monocytes and monocyte-derived proinflammatory cytokines are widely known to be involved in the formation and rupture of the atherosclerotic plaque. The aim of our study was to assess the effect of fenofibrate, a commonly used hypolipidemic drug, on the release of interleukin 1beta (IL-1beta), interleukin 6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1) by monocytes from patients with combined hyperlipidemia. Fourteen patients with biochemically confirmed type IIb dyslipidemia who did not respond to a low-fat diet were treated with micronized fenofibrate for 1 month. The control group included 12 healthy, normolipidemic, age-matched subjects. To accurately evaluate the levels of the inflammatory cytokines, we excluded patients with any inflammatory disease. Monocytes were isolated from peripheral blood before and after the treatment. IL-1beta, IL-6 and MCP-1 release was measured by enzyme-linked immunosorbent assay (ELISA) after lipopolysaccharide stimulation. IL-1beta, IL-6 and MCP-1 levels were significantly higher in hyperlipidemic patients compared to the control (143.9 +/- 6.5 vs. 74.4 +/- 4.4 pg/ml; 8212 +/- 285 vs. 6110 +/- 170 pg/ml; 19.6 +/- 0.9 vs. 12.3 +/- 0.6 ng/ml, respectively). Thirty-day fenofibrate treatment decreased the release of IL-1beta by 43% (143.9 +/- 6.5 vs. 86.2 +/- 5.9 pg/ml), of IL-6 by 22% (8212 +/- 285 vs. 6330 +/- 234 pg/ml), and of MCP-1 by 29% (19.6 +/- 0.9 vs. 14.0 +/- 0.8 ng/ml). The evaluated cytokines were markedly elevated in patients with type IIb dyslipidemia. Effective fenofibrate therapy had a significant inhibitory effect on the release of monocyte-derived inflammatory cytokines.

Adult↗

PubMedDate not supplied

Effect of apigenin, kaempferol and resveratrol on the expression of interleukin-1beta and tumor necrosis factor-alpha genes in J774.2 macrophages.

Flavonoids have been reported to bring benefits in lowering inflammation, oxidative stress and exert positive effects in cancer and cardiovascular and chronic inflammatory diseases. Apigenin, kaempferol and resveratrol present in fruits, vegetables and grain were investigated for their effect on the synthesis of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) at transcriptional level in lipopolysaccharide (LPS)-stimulated J774.2 macrophages. Apigenin (30 microM), kaempferol (30 microM) and resveratrol (50 microM) significantly decreased the number of TNF-alpha mRNA copies in LPS-activated J774.2 macrophages. Apigenin and kaempferol caused inhibition of IL-1beta gene expression in J774.2 macrophages, but resveratrol was ineffective. These results indicate that apigenin, kaempferol and resveratrol exert inhibitory effects on the TNF-alpha and except for of resveratrol on IL-1beta gene expression in J774.2 macrophages at the transcriptional level. In addition, the studied compounds may be the mediators responsible for protective role of a diet high in fruits and vegetables in the cardiovascular and inflammatory diseases.

Animals↗

PubMedDate not supplied

Plasma concentrations of adhesion molecules and chemokines in patients with essential hypertension.

Arterial hypertension vascular injury results in serious complications, such as left-ventricular hypertrophy and myocardial failure, ischemic heart disease and cerebral stroke. Currently, it is well known that inflammatory factors play a significant role in the mechanisms that trigger and enhance the remodeling of the vascular wall. A number of data suggest an important role of adhesion molecules and chemokines in this processes. The aim of this study was measuring the plasma levels of soluble Intercellular Adhesion Molecule 1 (sICAM-1) and Monocyte Chemoattractant Peptide1 (MCP-1) in patients with essential hypertension vs. healthy volunteers by ELISA method (R&D kits). sICAM-1 and MCP-1 levels were significantly higher in hypertensive patients compared to controls (sICAM-1: 279.2 +/- 8.8 ng/ml vs. 224.4 +/- 1.8 ng/ml; p < 0.001; MCP-1: 142.2 +/- 7 pg/ml vs. 95.4 +/- 36 pg/ml; p < 0.0001. Our results indicate that arterial hypertension alone (without inflammation, lipid and carbohydrate disorders) may increase the expression of these cytokines and contribute to the progression of endothelial injury.

Adult↗