Biomedical subjects

Andrzej Madej

Publications and source records attributed to Andrzej Madej.

11 recordsLinked to original sources

PubMed2006

[Markers of inflammatory process in stable and unstable coronary artery disease].

Clinical studies performed in last few years proved great role of inflammatory processes in development of atherosclerosis. Inflammatory markers indicating unstable atherosclerotic plaque were isolated. These biomarkers are used in diagnostics and identification of patients with unstable angina pectoris and miocardial infarct. Moreover usefulness of proinflammatory markers in indicating patients with high cardiovascular risk was confirmed. In result different markers of inflammation found their use in diagnostics of patients with stable and unstable coronary artery disease.

Angina Pectoris↗

PubMed2005

Delayed effects on plasma concentration of testosterone and testicular morphology by intramuscular low-dose di(2-ethylhexyl)phthalate or oestradiol benzoate in the prepubertal boar.

The immediate and delayed effects of prepubertal exposure to di(2-ethylhexyl)phthalate (DEHP) or oestradiol benzoate on the plasma concentrations of testosterone, oestradiol and LH, as well as testicular morphology were examined in prepubertal boars. In a split litter design experiment, prepubertal boars were intramuscularly exposed to DEHP, oestradiol or vehicle during five weeks, starting at six weeks of age. The dose of DEHP was 50mg/kg of bodyweight twice weekly, which is in the same range as recently used oral doses in rodents. Oestradiol-benzoate was administered at 0.25mg/kg of bodyweight twice weekly. One set of animals was examined immediately after the exposure, and the other set was examined at an age of 7.5 months. During the exposure period concentrations of LH in plasma were lower (p=0.02) in the oestradiol-treated animals than in the control group. In the group exposed to oestradiol, the relative to the body weight of the testicles tended to be lower (p=0.07) than control immediately after five weeks of exposure, and the relative to the body weight of the seminal vesicles tended to be lower (p=0.05) than control at 7.5 months of age. In the DEHP-exposed group an elevated (p=0.005) concentration of testosterone and increased (p=0.04) area of the Leydig cells in the testicles compared to the control group were seen at 7.5 months of age. These data suggest that DEHP early in life causes delayed effects on the reproductive system in the adult.

Aging↗

PubMed2005

Hypolipidemic drugs affect monocyte IL-1beta gene expression and release in patients with IIa and IIb dyslipidemia.

Because atherosclerosis has been proven to be an inflammatory disease, it became obvious that the proper treatment of dyslipidemic patients should not only correct lipid parameters but also inhibit the inflammatory state. One of the crucial proinflammatory and procoagulant cytokines participating in the pathogenesis of atherosclerosis is interleukin-1beta (IL-1beta). Therefore, the aim of the study was to asses the effect of statin and fibrate therapy (for dyslipidemia IIa and IIb, respectively) on IL-1beta gene expression and monocyte release evaluated in each patient. Additionally, the effect of hypolipidemic therapy on fibrinolysis was evaluated. The study was carried out in 37 patients: 12 with biochemically confirmed type IIa dyslipidemia (treated with atorvastatin), 12 with type IIb dyslipidemia (treated with fenofibrate), and 13 age- and sex-matched normolipidemic persons (control). IL-1beta concentrations in cultured monocytes and PAI-1 (Plasminogen Activator Inhibitor) plasma levels were measured using the ELISA method. To evaluate the expression of IL-1beta gene in monocytes, a semiquantitive RT-PCR procedure was performed. The results were normalized with the expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a housekeeping gene. Although IL-1beta monocyte release was markedly elevated in patients with atherogenic dyslipidemias, IL-1beta gene expression was only slightly and nonsignificantly higher in the studied groups versus control. We have observed significant reduction of IL-1beta mRNA expression after 30-day treatment with the examined drugs (atorvastatin, 2.10 +/- 0.50 versus 1.05 +/- 0.15; P < 0.001, fenofibrate; 2.27 +/- 0.48 versus 1.23 +/- 0.27; P < 0.01). There was no significant difference between statin and fibrate effect on IL-1beta mRNA expression. Similarly, we have noticed significant reduction of IL-1beta release by cultured monocytes after 30-day statin therapy (133.0 +/- 5.7 pg/mL versus 77.0 +/- 3.6 pg/mL; P < 0.01) and fibrate therapy (143.9 +/- 6.5 pg/mL versus 86.2 +/- 5.9 pg/mL; P < 0.01). Besides this antiinflammatory effect, we have observed a 30% reduction of PAI-1 plasma levels in both treated groups. In conclusion, effective 1-month hypolipidemic therapy with atorvastatin or fenofibrate diminished plasma levels of proinflammatory and procoagulatory state markers.

Atorvastatin↗

PubMed2005

Monocyte release of tumor necrosis factor-alpha and interleukin-1beta in primary type IIa and IIb dyslipidemic patients treated with statins or fibrates.

Both 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) as well as peroxisome proliferator-activated receptor (PPAR)alpha activators (fibrates) proved to be effective in the primary and secondary prevention of cardiovascular diseases. The benefits of hypolipemic therapy in cardiovascular diseases cannot be explained only by the lipid-lowering potential of these agents. The aim of this study was to clarify the effect of hypolipemic agents on proinflammatory cytokine release from human monocytes in relationship with their action on plasma levels of sensitive systemic marker of low-grade vascular inflammation. Plasma lipid and high-sensitivity C-reactive protein (hsCRP) levels, and the release of tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta from monocytes were assessed at baseline and 30 and 90 days following randomization of IIa dyslipidemic patients into fluvastatin or simvastatin groups and randomization of type IIb dyslipidemic patients to the micronized form of either ciprofibrate or fenofibrate. Lipopolysaccharide-stimulated monocytes from dyslipidemic patients released significantly more TNFalpha (types IIa and IIb dyslipidemias) and interleukin-1beta (type IIa dyslipidemia) in comparison with monocytes in 59 age-, sex-, and weight-matched control subjects. Their baseline hsCRP levels were also higher. Both statins and fibrates reduced the release of TNFalpha and interleukin-1beta, and lowered plasma hsCRP levels. The effects of hypolipemic agents on cytokine release and plasma hsCRP were unrelated to their lipid-lowering action. Our results have demonstrated that type IIa and IIb dyslipidemic patients exhibit the abnormal pattern of TNFalpha and interleukin-1beta production by activated monocytes. Both HMG-CoA reductase inhibitors and PPARalpha activators normalize monocytic secretion of these cytokines, and this action may partially contribute to the systemic antiinflammatory effect of hypolipemic agents. The statin- and fibrate-induced suppression of proinflammatory cytokine release from monocytes seems to play a role in their beneficial effect on the incidence of cardiovascular events.

Adult↗

PubMed2004

The effect of statins and fibrates on interferon-gamma and interleukin-2 release in patients with primary type II dyslipidemia.

The aim of the study was to assess the effect of two major groups of hypolipemic drugs, HMG-CoA reductase inhibitors (statins) and PPARalpha activators (fibrates), on the secretory function of T-lymphocytes in patients with primary type II dyslipidemia. Sixty-three patients with type IIa dyslipidemia were randomized to fluvastatin (40 mg daily; n = 33) or simvastatin (20mg daily; n = 30), while 68 type IIb dyslipidemic patients were treated with micronized ciprofibrate (100mg daily; n = 34) or micronized fenofibrate (200mg daily; n = 34). Lipid profile and cytokine (interferon-gamma and interleukin-2) release by phytohemagglutinin-stimulated lymphocytes were determined at the beginning of the study and after 30 and 90 days of treatment. Compared to healthy subjects (n = 59), both type IIa and IIb dyslipidemic patients exhibited higher baseline release of interferon-gamma and interleukin-2. Fluvastatin, simvastatin and, to a less extent, ciprofibrate and fenofibrate inhibited the release of both cytokines, but this effect did not correlate with their lipid-lowering potential. Hypolipemic agents also slightly reduced plasma interleukin-2 levels. Our study suggests that the beneficial effect of hypolipemic drugs involves their inhibitory action on the secretory function of T-lymphocytes. This lipid-independent action is stronger for statins than for fibrates and probably results from their "class" effect. The treatment-induced reduction in the release of both cytokines may contribute to the clinical effectiveness of statins and fibrates in the therapy of atherosclerosis and in the management of organ transplant recipients.

Adult↗

PubMed2004

Effects of intracerebroventricular infusion of genistein on gonadotrophin subunit mRNA and immunoreactivity of gonadotrophins and oestrogen receptor-alpha in the pituitary cells of the anoestrous ewe.

The present study was designed to demonstrate whether genistein, a synthetic phytoestrogen, infused into the third ventricle of the brain could affect the gonadotrophic cells regarding the presence of oestrogen receptor-alpha immunoreactivity and gonadotrophin subunit mRNA hybridising reaction in the ewe. Ewes (n=7), aged 2 years, in early anoestrous season were infused with Ringer-Locke solution (control, n=3) or 10 microg/100 microl/h of genistein (n=4) into the third ventricle over a 5 h period and slaughtered the following morning. Immunoreactivity of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and oestrogen receptor-alpha (ERalpha) was determined in the adenohypophysis by immunohistochemistry using antibodies raised against LHbeta, FSHbeta, and ERalpha. Messenger RNA analyses were performed by non-isotope in situ hybridisation using sense and antisense riboprobes produced from beta subunits of LH and FSH cDNA clones. Computer image analysis was used to determine the percent of cells exhibiting immunohistochemical and/or hybridising reaction. It was found that in ewes infused with genistein, the percentage of LH-positive cells and the density of immunoreactive-LHbeta material decreased significantly (P<or=0.001), but the percentage of mRNA LHbeta-expressing cells and the intensity of the hybridisation signal increased significantly (P<or=0.001), compared to the vehicle-infused animals. The genistein infusions had no effect on the immunoreactivity of FSH cells or on the expression of mRNA for FSHbeta. The percentage of ERalpha-positive cells increased significantly after genistein infusions (P<or=0.001) and this increase was significant in the LH but not in FSH cells (P<or=0.001). In conclusion, we suggest that genistein can stimulate the expression of immunoreactive ERalpha in the pituitary LH-cells but not in FSH-cells and change the endocrine activity of LH-producing cells of anoestral ewes.

Anestrus↗

PubMed2002

Thyroid gland function in ovariectomized ewes exposed to phytoestrogens.

Phytoestrogens are by definition plant-derived substances that are able to activate the mammalian oestrogen receptors. We examined the possible effects of phytoestrogens on the secretion of thyroid hormones as well as on the immunoreactivity to oestrogen receptor alpha (ER alpha) in the thyroid glands of ovariectomized ewes. Eight ovariectomized ewes were fed 3.5 kg of 100% red clover silage for 14 days. Blood samples were collected before and on day 14 of exposure to phytoestrogens. After 5 months, four of the ewes were re-exposed to red clover silage as described above and the other four served as controls. Blood samples were collected as above. All ewes were slaughtered at the end of the experiment and the thyroid glands were weighed and examined for macroscopical changes. Tissue samples were taken for immunohistochemistry and image analysis. Ewes exposed to red clover silage had significantly higher plasma concentrations of total T(3) and free T(3) than ewes fed hay. The cross-section area of thyroid follicles tended to be larger in ewes fed red clover silage than in the control animals. ER alpha immunoreactivity was stronger in thyroid glands from ewes exposed to phytoestrogens than in ewes fed hay. In conclusion, daily ingestion of 81-95 mg phytoestrogens per kg body weight for 14 days stimulated secretion of thyroid hormones and tended to increase follicle size and ER alpha immunoreactivity of thyroid glands of ovariectomized ewes.

Animals↗

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

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↗

PubMedDate not supplied

Extralipid effects of micronized fenofibrate in dyslipidemic patients.

The aim of this study was to evaluate the levels of lipid and extralipid parameters in patients with atherogenic dyslipidemia. We investigated the lipid-lowering therapeutic efficacy of fenofibrate and its extralipid influence on oxidized low-density lipoprotein (oxLDL), C-reactive protein (CRP), Fibrinogen, factor VII and plasminogen activator type 1 (PAI-1) during 1-month treatment. Fourteen individuals with HLPIIb were treated with micronized fenofibrate (267 mg/d) for 1 month. The control group included twelve volunteers. Lipidograms were determined with enzymatic kits. ELISA method was used to measure oxLDL and PAI-1. Plasma CRP levels were measured spectrophotometrically. Fibrinogen and factor VII serum levels were evaluated with automatic coagulometer. After 1-month therapy with micronized fenofibrate, we observed a significant reduction of total cholesterol (TC) (277.2 to 217.8 mg/dl, p < 0.05), LDL (183.6 to 129.4 mg/dl, p < 0.05), trigliceryde (TG) (316.7 to 220.6 mg/dl, p < 0.05), oxLDL (68.7 +/- 5.5 to 39.7 +/- 3.7 U/l, p < 0.001) and increase in high-density lipoprotein (HDL) (35.1 to 41.9 mg/dl, p < 0.05). Fibrate treatment also decreased CRP(5.81 +/- 0.26 to 5.08 +/- 0.06 mg/l, p < 0.001), PAI-1 (120.4 +/- 9.7 to 84.7 +/- 5.9 ng/ml; p < 0.05), fibrinogen (3.65 +/- 0.17 to 3.44 +/- 0.16 g/l, ns) and factor VII (159.7% +/- 56.7 to 141% +/- 42.4, ns). The micronized fenofibrate at a daily dose of 267 mg demonstrated a highly beneficial effect on all lipid parameters and advantageous influence on inflammatory and thrombogenic plasma risk factors in patients with dyslipidemia HLPIIb.

Adult↗