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Biomedical subjects

H Stepien

Publications and source records attributed to H Stepien.

At least 19 recordsLinked to original sources
PubMed2005

Effect of the growth hormone-releasing hormone [GHRH(1-44)NH2] on IL-6 and IL-8 secretion from human peripheral blood mononuclear cells in vitro.

OBJECTIVE: Bidirectional communication between the neuroendocrine and immune systems is now a subject of an intensive investigation. Growth hormone-releasing hormone (GHRH) is synthesized by the hypothalamus, but is present also in the immune cells. Some recent data indicate also an immunomodulatory role of the neuropeptide. The aim of the study was to examine the influence of GHRH(1-44)NH2 on interleukin-6 and interleukin-8 secretion from human peripheral blood mononuclear cells cultured in vitro. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated by centrifugation using Böyum technique and cultured in a humidified atmosphere of 5 % CO2 and 95 % O2 at 37 degrees C for 24 hours in the presence of lipopolysaccharide (LPS) at the concentration of 2 microg/ml and GHRH(1-44)NH2 (the final neuropeptide concentrations to be tested were 10(-12) to 10(-6) M). ELISA methods were used to measure IL-6 and IL-8 concentrations in the supernatants of cultured cells RESULTS: GHRH(1-44)NH2 influenced IL-6 secretion from cultured cells, but significant inhibition of IL-6 release was observed at 10-6 M (p < 0.001). The negative correlation between the GHRH concentration studied and the IL-6 level in the supernatants was found (r = -0.759; p < 0.001). GHRH had no influence on the secretion of IL-8 from activated PBMC. CONCLUSIONS: Our results demonstrate that GHRH in vitro modulates IL-6 secretion from the human peripheral blood mononuclear cells, without any significant effect on IL-8 secretion.

Adult↗
PubMed2005

P53 concentration and soluble FasL (sFasL) serum level as indicators of apoptosis in patients with benign and malignant thyroid tumors.

During embryonal development and morphogenesis, apoptosis may be induced by two pathways. The first is an external protein signal originating from other cell--also named as "death signal". The another one is a specific cell reaction to external stress factors. Plasma concentration of proteins regulating both apoptosis pathways may be useful in early diagnosis and staging of thyroid tumors. The aim of the study was to evaluate p53 and sFasL plasma concentration in patients with benign and malignant thyroid tumors. The study population was composed of 33 patients with thyroid carcinoma and 10 patients with follicular carcinoma (tumor types were verified by fine-needle biopsy). All patients underwent surgical procedures. p53 and sFasL levels were evaluated before surgery. Control group consists of 10 adult healthy volunteers. The results revealed high p53 and sFasL plasma concentration in patients with benign and malignant thyroid tumors. Such results confirm a significant role of p53 and sFasL in apoptosis in thyroid tumors. Expression of both proteins may be an indicator of an increased apoptosis and useful in preoperative diagnosis in thyroid tumors (Tab. 1, Ref. 31).

Adolescent↗
PubMed2001

Usefulness of VEGF, MMP-2, MMP-3 and TIMP-2 serum level evaluation in patients with adrenal tumours.

OBJECTIVE: To estimate serum levels of vascular endothelial growth factor (VEGF), metalloproteases MMP-2 (gelatinase A), MMP-3 (stromyelisine 1) and metalloprotease tissue inhibitors (TIMP-2) in patients with various benign and malignant adrenal tumours before and after surgery, as well as to evaluate if there is a correlation between serum levels of these agents and tumour types. METHODS: Serum levels of VEGF, MMP-2, -3 and TIMP-2 were estimated in 43 patients with adrenal tumour at the admission and, in case of surgery, again one month after surgery. The patients were divided into 6 groups according to the type of the tumour (I - patients with adrenal cortex carcinoma, II - with benign hormonally active adrenocortical adenomas, III - with benign, hormonally inactive adenocortical adenomas (incidentaloma), IV - with benign, hormonally active phaeochromocytomas, V - with hormonally quiescent phaeochromocytomas, VI - hormonally inactive adrenal tumours of extraglandular origin. The control group consisted of 10 healthy individuals. RESULTS: There was no correlation between MMP-2 serum levels and tumour types and no significant difference between MMP-2 level before and after surgery. There were no significant differences between TIMP-2 serum levels in patients with adrenal tumours and the control values. Significant increase of serum MMP-3 level was found in patients with cortex cancer and hormonally active benign adrenocortical tumours. The MMP-3 mean serum level was also significantly higher in patients with malignant incidentalomas than in those with benign ones. In all groups of patients with adrenal tumours the means serum VEGF level was significantly higher than in control patients, and it was also significantly higher in patients with malignant incidantalomas than in those with benign ones. After surgery the VEGF level decreased significantly in patients with extraglandular tumours and cortex cancers who had no recurrence. CONCLUSIONS: Since MMP-3 and VEGF serum levels were found significantly higher in patients with malignant adrenal incidentalomas than in those with benign ones, they might be applied as markers of malignancy of incidentalomas. VEGF and MMP-3 levels decreased after tumour resection in all patients with malignant tumors and increased significantly in patients with recurrence. Therefore, they are supposed to be of prognostic value in these patients.

Adenoma↗
PubMed1995

Effect of interleukin-1a, IL-1b and IL-1 receptor antibody on the proliferation and steroidogenesis of regenerating rat adrenal cortex.

Several data suggest that the endocrine and immune systems are closely interconnected, therefore, we investigated the effect of interleukin-1 on adrenocortical regeneration. The study was performed on adult rats subjected to left adrenal enucleation combined with contralateral adrenalectomy. The animals were given purified human recombinant IL-1 alpha (5 micrograms/kg), IL-1 beta (5 micrograms/kg) anti-human IL-1 receptor antibody (10 micrograms/kg) and combination of interleukins and antibodies. The cell proliferation measured by bromodeoxyuridine incorporation and plasma corticosterone determined by a RIA kit were evaluated six days after operation. The mean cell growth ratio expressed as number of BrdU-positive cells per 1,000 cells was 11.86 +/- 0.45 in the control group. IL-1b significantly stimulated the proliferation ratio (15.30 +/- 0.88; p < 0.01) and this effect could be prevented by addition of IL-1rAb. The antibody caused also a well-marked inhibition of cell growth ratio (8.23 +/- 0.67; p < 0.01). The plasma corticosterone concentration was higher in IL-1b-treated animals than in the control group, 107.79 +/- 2.82 vs. 61.08 +/- 2.0 ng/ml, respectively, p < 0.01. On the other hand, IL-1rAb decreased corticosterone secretion (31.53 +/- 2.58 ng/ml, p < 0.01) and reversed the stimulatory effect of of IL-1b. In contrast, IL-1a seemed to have no influence on adrenocortical regeneration. In conclusion, this study supported the thesis of close interconnection between immune and endocrine systems and revealed that IL-1b could act as a growth-promoting factor on regenerating adrenal cortex in the rat.

Adrenal Cortex↗
PubMed1993

Comparison of the antiproliferative effects of colon mitosis inhibitor, thyroliberin and the somatostatin analog octreotide on rat colonic mucosal epithelial cells.

The effects of colon mitosis inhibitor (CMI), thyroliberin (TRH), and the somatostatin analogue octreotide (SMS 201-995) on rat colonic mucosal epithelial cell proliferation were studied. As an index of cell proliferation the incorporation of bromodeoxyuridine (BrDU) into cell nuclei was used. It was found that all three peptides inhibited the colonic mucosal epithelial cells proliferation, but the time course of inhibition was different. The effect of SMS 201-995 occurred 12 h after the peptide injection, while CMI and TRH suppressed the proliferation after 24 h. These observations suggest that the mechanisms of the antiproliferative actions of somatostatin and of related tripeptides CMI and TRH are different.

Animals↗
PubMed1992

Effect of mesulergine on prolactin secretion and dopamine D2 receptors-adaptive changes in diethylstilbestrol-induced hyperplasia of the rat anterior pituitary.

Mesulergine (N,N-dimethylsulphamide-N'-1,6-dimethyl-ergoline-8 alpha-yl) is an active semisynthetic ergot derivative with lower antiprolactin potency compared with bromocriptine or pergolide. Since no data are yet available on the effects of mesulergine on pituitary dopamine receptors, the present study has been designated to elucidate the influence of this drug on prolactin secretion in vivo and in vitro and 3H-spiperone binding by the anterior pituitary gland in female Wistar rats with experimentally induced hyperprolactinemia. Three weeks after bilateral ovariectomy and subcutaneous implantation of silastic tubes, containing 10 mg of diethylstilbestrol, a dramatic rise in serum prolactin levels was observed (1.67 +/- 0.23 vs. 80.82 +/- 3.80 ng/ml; P less than 0.001). Mesulergine attenuated the stimulatory effect of diethylstilbestrol on serum prolactin level in a time- and dose-dependent fashion. At concentration range between 10(-5) and 10(-7) M it also inhibited prolactin secretion from cultured rat pituitary cells to the medium during 180 min incubation in a dose-dependent manner. Scatchard analyses performed on the in vitro 3H-spiperone binding kinetics in a dispersed anterior pituitary cell culture, prepared from the pituitaries from rats treated for four weeks with diethylstilbestrol, showed that chronic mesulergine treatment (in dose of 3.0 mg/kg injected s.c. for 10 days) induced a significant decrease in the number of dopamine D2-binding sites (Bmax 28.00 +/- 4.20 vs. 42.80 +/- 4.76 fmol/10(6) cells; P less than 0.01) without any changes in D2-receptor affinity. Our results suggested that antiprolactin activity of mesulergine in vivo and in vitro is probably associated with agonistic effect of this drug on D2-dopamine receptors.

Animals↗
PubMed1992

Synoviocyte derived granulocyte macrophage colony stimulating factor mediates the survival of human lymphocytes.

Synoviocytes have been shown to be effector cells capable of synthesizing and secreting a variety of cytokines and growth factors. We demonstrate here that synoviocyte derived conditioned medium has immunoregulatory properties as it enhances human peripheral blood lymphocyte survival in a dose dependent manner in vitro. The effect elicited by synoviocyte derived conditioned medium from patients with rheumatoid arthritis (RA) was greater than that induced by synoviocyte derived conditioned medium from patients with osteoarthritis. Granulocyte-macrophage colony stimulating factor (GM-CSF) was found in synoviocyte derived conditioned medium with significantly higher levels present in synoviocyte derived conditioned medium from patients with RA. Recombinant human GM-CSF induced survival of human lymphocytes in vitro and a monoclonal antibody to human GM-CSF fully abrogated synoviocyte derived conditioned medium induced survival. Our results demonstrate that synoviocyte derived GM-CSF may be important in the retention of lymphocytes, which is a central pathological characteristic of the rheumatoid joint.

Arthritis, Rheumatoid↗
PubMed1992

The effect of mesulergine on prolactin secretion and anterior pituitary cells morphology in diethylstilboestrol-treated female Wistar rats.

Mesulergine (Cu32-085) is an active semisynthetic ergot alkaloid with unusual biphasic antagonistic-agonistic effect on dopamine (DA) turnover in the rat striatum. The present study has been made to elucidate the influence of the long-term treatment of this drug on prolactin secretion and prolactin cells morphology in the female Wistar rats with experimentally-induced hyperprolactinemia. Additionally, the effect of this drug was compared with bromocriptine and pergolide activity, applied in the same experimental conditions. It has been shown that prolonged mesulergine treatment attenuated the stimulatory effect of stilboestrol on prolactin secretion in vivo. It also decreased mean prolactin cells density, above all cells and lactotroph mitotic indexes, estimated in immunohistochemically-stained slides. However, antiproliferative activity of Cu 32-085 was weaker, when compared with bromocriptine and pergolide.

Animals↗
PubMed1991

Inhibitory effect of thyrotropin releasing hormone on spontaneous proliferation of mouse spleen lymphocytes in vitro.

The effects of thyrotropin releasing hormone (TRH) and of TRH-like tripeptide pGlu-His-Gly-OH (colon mitosis inhibitor, CMI) on spontaneous proliferation of murine splenocytes were investigated in vitro. The 3H-thymidine incorporation into splenocyte DNA was used as an index of proliferation. It was found that TRH suppressed the proliferation of splenocytes. In contrast, CMI was ineffective by itself but used together with TRH blocked the effect of the latter.

Amino Acid Sequence↗
PubMed1991

Inhibitory effect of porphyrins on the proliferation of mouse spleen lymphocytes in vitro.

The influence of various porphyrins (deuteroporphyrin IX, mesoporphyrin IX, protoporphyrin IX, hematoporphyrin) and two related compounds (hemin, biliverdin) on the spontaneous proliferation of mouse spleen lymphocytes has been estimated in vitro by the 3H-thymidine uptake assay. It has been found that porphyrins (endogenous ligands for the mitochondrial benzodiazepine receptor) produce a concentration-dependent inhibition of 3H-thymidine incorporation into the DNA of these cells. Metalloporphyrin-hemin has been observed to evoke a weak inhibitory effect, in a high concentration (10(-4)M), whereas biliverdin, a porphyrins degradation product, was inactive in the same experimental conditions. Those findings indicate that endogenous porphyrins, presumably acting through the mitochondrial benzodiazepine receptor, could regulate the proliferation of mouse spleen lymphocytes in vitro.

Animals↗
PubMed1991

The effect of nerve growth factor on DNA synthesis, cyclic AMP and cyclic GMP accumulation by mouse spleen lymphocytes.

Nerve growth factor (NGF), a trophic neuropeptide, is known to stimulate development, and to be important in the maintenance and survival of sympathetic and sensory neurons. Considering the presence of specific receptors on the surface of spleen cells, the effect of 2.5s nerve growth factor on 3H-thymidine uptake, cAMP and cGMP accumulation in mouse spleen lymphocytes has been studied. It was found that NGF added in vitro at the concentrations between 4 x 10(-7) and 4 x 10(-8) M significantly inhibited the incorporation of 3H-thymidine into lymphocytes DNA and increased cAMP levels in a dose-dependent manner but had no effect on cGMP levels. The maximal stimulation of cAMP synthesis occurred between 5 and 30 min after the NGF addition to the culture medium. When NGF was administered in vivo a significant dose-dependent inhibition of the lymphocytes proliferation was observed. These results indicate that an early increase of cAMP concentration is responsible for the antiproliferative action of NGF on mouse spleen lymphocytes and suggest that NGF could play an important role in the regulation of immune system function.

Animals↗
PubMed1990

Effects of calcium channel modulators on the proliferation of mouse spleen lymphocytes in vitro.

The effects of nimodipine (voltage-dependent calcium channel blocker), CGP 28392 and BAY K 8644 (novel dihydropyridine derivatives that are considered as calcium entry stimulators) on the spontaneous proliferation of mouse spleen lymphocytes were studied in vitro. [3H]-thymidine incorporation into DNA of lymphocytes was used as an sensitive index of the cell proliferation. It has been found that nimodipine (10(-4) M-10(-6) M) significantly inhibited the [3H]-thymidine uptake in a dose dependent fashion with ED50 value of 2.4 x 10(-5) M. Unexpectedly, CGP 28392 (10(-4) M-10(-7) M) acts as a calcium entry blocker and produces a strong inhibitory effect on lymphocyte proliferation (ED50-2 x 10(-5) M). BAY K 8644 at a high concentration (10(-4) M) also has an inhibitory effect but at a lower concentration (10(-6) M-10(-10) M) significantly increased [3H]-thymidine uptake and abolished the inhibitory effect of nimodipine. This effect of nimodipine was also reversed by 5 x 10(-3) M calcium chloride. These findings indicate that calcium channel modulators can regulate the proliferation of mouse spleen lymphocytes in vitro.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

Effect of amantadine on prolactin secretion, pituitary DNA synthesis and 3H-spiperone binding in male estrogen-treated rats.

Amantadine, a well-known antiviral agent, causing an increase in dopamine synthesis, release and the inhibition of re-uptake of noradrenaline and dopamine in central and peripheral catecholaminergic neurons, is successfully used in the treatment of Parkinson's disease. In the present paper, we have studied the effect of various doses of amantadine on in vivo prolactin secretion and the incorporation of 3H-thymidine and 3H-spiperone binding by the anterior pituitary gland of long-term diethylstilboestrol-treated male Wistar rats. Four weeks after a subcutaneous implantation of Silastic tubes containing 10 mg of diethylstilboestrol, a dramatic rise in serum prolactin levels was observed, accompanied by an increased uptake of 3H-thymidine by DNA anterior pituitary cells. Amantadine, given in the subcutaneous doses of 50, 5 and 0.5 mg/kg of body weight attenuated the stimulatory effect of stilboestrol on serum prolactin concentration in a dose-dependent fashion. On the other hand, the incorporation of 3H-thymidine into DNA pituitary cells in all the groups of amantadine-treated rats was only slightly suppressed. In an additional experiment, Scatchard analyses were performed on the in vitro 3H-spiperone binding kinetics in a dispersed anterior pituitary cell culture prepared from the pituitaries of 6-week diethylstilboestrol-treated rats. It has been found that amantadine injected in the dose of 5 mg/kg of body weight for 14 days induced a twofold decrease in the density of dopamine D2 binding sites (36.6 +/- 9.4 vs. 70.3 +/- 3.4 fmol/10(6) cells; p less than 0.02), while the apparent affinity of the receptors was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Amantadine↗
PubMed1989

Inhibitory effect of calcium channel blockers on proliferation of human glioma cells in vitro.

The effects of 2 specific calcium channel blockers, verapamil and nimodipine, on the proliferation of human glioma tumour cells were investigated in vitro. Tumour tissues for primary cell cultures were obtained bioptically from 3 patients with the histopathological diagnosis of glioblastoma. The [3H]-thymidine incorporation into glioma tumour cells DNA was used as a sensitive index of the cell proliferation. It was found that verapamil (10(-4)-10(-5) M) and nimodipine (10(-4)-10(-6) M) significantly inhibited the [3H]-thymidine uptake in a dose-related manner. The inhibitory effect of both calcium channel antagonists was reversed by simultaneous addition of calcium chloride (5 x 10(-3) M). These results indicate that verapamil and nimodipine may exert an antiproliferative effect on glioma cells growth acting through a blockade of specific voltage-dependent calcium channels.

Calcium↗
PubMed1989

Effect of growth hormone-releasing hormone on human peripheral blood leukocyte chemotaxis and migration in normal subjects.

The effect of synthetic human growth hormone-releasing hormone (GHRH) on chemotactic response and migration inhibition of human peripheral blood leukocytes has been studied. In the assay performed by using modified Nelson methods, significant inhibition of chemotactic response was observed at 10(-6)M-10(-8) M concentrations of GHRH. There is a strong negative correlation (r = -0.519; p less than 0.001) between the chemotactic response of peripheral blood leukocytes and the concentration of GHRH. In contrast, GHRH tested at the same concentration range was not active in the migration inhibition assay. This finding provides additional evidence for the neuroimmunomodulatory action of GHRH.

Cell Migration Inhibition↗
PubMed1988

Effects of two neuropeptides, somatoliberin (GRF) and corticoliberin (CRF), on human lymphocyte natural killer activity.

The effect of corticoliberin (CRF) and somatoliberin (GRF) on the natural killer (NK) activity of human peripheral blood lymphocytes was investigated. NK activity was estimated by means of the radioactive chromium (51Cr) assay in which human leukemia K 562 cells serve as targets. Exposure of human lymphocytes (effector cells) to 10(-6) to 10(-10) M concentrations of CRF inhibited NK activity. NK activity was also suppressed by the same concentrations of GRF, but only when an effector:target cell ratio of 40:1 was used. In contrast, at effector:target ratios of 20:1 and 10:1, stimulatory effects of GRF were observed.

Corticotropin-Releasing Hormone↗
PubMed1988

Inhibition of cell proliferation of human gliomas by benzodiazepines in vitro.

The effects of several benzodiazepines (diazepam, clonazepam, Ro 15-1788 and Ro 5-4864) on cell proliferation of 2 human gliomas were estimated in vitro by means of [3H]-thymidine uptake assay. It was found that all tested benzodiazepines suppressed [3H]-thymidine incorporation into the DNA of glioma cells, the effects being stronger in case of peripheral-type benzodiazepine receptor ligands. The results indicated that benzodiazepines might exert an antiproliferative action on glioma tumour cells growth.

Astrocytoma↗