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Biomedical subjects

A Markowska

Publications and source records attributed to A Markowska.

At least 37 records · Page 2Linked to original sources
PubMed1998

Role of endothelins in regulation of vascular tone in the in situ perfused rat adrenals.

This study examined the role of endothelins (ETs) and their receptor subtypes ETA and ETB in the regulation of vascular tone in the in situ perfused rat left adrenal gland. Endothelin-1 (ET-1), which binds both ETA and ETB receptors, decreased adrenal flow rate of the perfusion medium, and its effect was reversed by the ETA antagonist BQ-123 and enhanced by the ETB antagonist BQ-788. ET-3, which preferentially binds ETB, and the selective ETB agonist BQ-3020 increased adrenal flow rate of perfusate, and their effects were annulled by BQ-788. BQ-123 magnified the effect of ET-3 and did not affect that of BQ-3020. The ETA-mediated decrease and the ETB-mediated rise in the rate of collection of perfusate were abolished by Ro-31-8220, an inhibitor of protein kinase C (PKC), and by N(G)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase (NOS), respectively. Collectively, these findings suggest that ETs can regulate vascular tone in the in situ perfused rat adrenals via both PKC-coupled ETA and NOS-coupled ETB receptors, the activation of which evokes vasoconstriction and vasodilation, respectively.

Adrenal Glands↗
PubMed1998

[Spontaneous tumor regression].

Spontaneous remission of cancer is a rare but definitely observed phenomenon. Spontaneous remission is defined by partial or total disappearance of a proven malignant tumor, without adequate medical treatment. It has been estimated that it occurs no more than once in 60,000 to 100,000. The cause of phenomenon is multifold: immunologic, hormonal and psychological mechanism as well as elimination of carcinogen (action of oncogenes, growth factors, cytokines) and apoptosis are postulated. In gynecological malignancies, excluding chorionepithelioma and breast cancer, spontaneous remission is rare.

Breast Neoplasms↗
PubMed1998

Synthetic analogues of netropsin and distamycin--synthesis of a new pyridine and carbocyclic analogues of the pyrrolecarboxamide antitumour antibiotics.

A new series of pyridine-containing analogues III-XXII of distamycin A and netrop sin was investigated by the molecular mechanics technique and molecular modelling. A pyridine analogue of netropsin (VII) is described, the first compound based on molecular studies, and two carbocyclic analogues of distamycin A with an N-terminal chloro- or bromoacetyl group (VIa, VIIa) were synthesized, as well as carbocyclic analogues of netropsin (VIIIb, Xb), potential carriers of alkylating elements. The potential use of VIa, VII, VIIa, VIIIb and Xb as carriers to place into the minor groove of DNA chemical groups capable of modifying DNA, is discussed.

Acids, Carbocyclic↗
PubMed1997

Distribution and functional significance of the endothelin receptor subtypes in the rat adrenal gland.

Endothelins (ET) are a family of vasoactive peptides that act via two subtypes of receptors, named ETA and ETB. ET-1 binds to both ETA and ETB, whereas the isopeptide ET-3 preferentially binds to ETB. The localization of ETA and ETB receptors in the rat adrenal gland and their involvement in the adrenal secretagogue effect of ETs has been studied in vitro. Autoradiographic assessment of the selective displacement of [125I]ET-1, [125I]ET-3 and [125I]BQ-3020 (an ETB agonist) by BQ-123 or BQ-788 (specific antagonists of ETA and ETB, respectively) indicates that the zona glomerulosa and adrenal medulla possess both ETA and ETB, whereas the zona fasciculata/reticularis is exclusively provided with ETB. ET-1, ET-3 and BQ-3020 enhance aldosterone and corticosterone secretion by dispersed cells of the zona glomerulosa and zona fasciculata/reticularis, respectively. BQ-123 does not affect the secretagogue action of these three agonists, whereas BQ-788 completely annuls it. ET-1 induces a marked rise in catecholamine release by fragments of the adrenal medulla, and both BQ-123 and BQ-788 partially reverse this effect. ET-3 and BQ-3020 elicit a catecholamine release that is less intense than that produced by ET-1; this response is unaffected by BQ-123 and abolished by BQ-788. Thus, in the rat, the corticosteroid secretagogue effect of ETs seems to be exclusively mediated by the ETB receptor subtype, and the catecholamine secretagogue action by both ETA and ETB. The functional relevance of ETA receptors present in the zona glomerulosa remains to be investigated.

Adrenal Glands↗
PubMed1997

Effects of endothelin-1 on the rat pituitary-adrenocortical axis under basal and stressful conditions.

Endothelins (ETs) and their receptor subtypes A and B (ETA and ETB) are expressed in the various components of the mammalian hypothalamo-pituitary-adrenal (HPA) axis, but their involvement in the functional regulation of HPA is controversial. To gain insight into this topic, we have investigated the effects of ET-1 and/or the specific antagonists of ETA and ETB receptors (BQ-123 and BQ-788, respectively) on the plasma concentrations of ACTH, corticosterone and aldosterone of non-stressed (control) and ether- or cold-stressed rats. The study of the effects of the administration of the two ET-receptor antagonists alone could provide informations about the possible action of endogenous ETs on the HPA axis. Exogenous ET-1 increased ACTH, corticosterone and aldosterone blood levels in control rats, as well as evoked a sizable enhancement of the HPA axis response to ether stress and a marked depression of the response to cold stress. BQ-123 and BQ-788 did not prevent the stimulatory effect of exogenous ET-1 in control rats, but when administered alone, raised the plasma concentrations of ACTH, corticosterone and aldosterone. Both ET-receptor antagonists magnified the HPA axis response to ether and cold stresses, but their effect was not counteracted by exogenous ET-1. Although very difficult to interpret, our present findings allow us to conclude that endogenous ETs play a role in the maintenance of the basal activity of rat HPA axis acting through ETA and ETB receptor subtypes, which are partially insensitive to BQ-123 and BQ-788. Conversely, the involvement of ETs in the modulation of the HPA axis responses to various stresses is very doubtful.

Adrenocorticotropic Hormone↗
PubMed1997

Endothelins stimulate deoxyribonucleic acid synthesis and cell proliferation in rat adrenal zona glomerulosa, acting through an endothelin A receptor coupled with protein kinase C- and tyrosine kinase-dependent signaling pathways.

The effects of endothelins (ET) on the proliferative activity of the rat adrenal cortex have been investigated in vivo, using an in situ perfusion technique of the intact left gland. The chemicals were dissolved in the perfusion medium, and the perfusion continued for 120 min. ET-1 concentration dependently increased the mitotic index and [3H]thymidine incorporation into DNA in the zona glomerulosa (ZG; 6- and 3-fold increases, respectively, at a 10(-8) M concentration), but not in the inner adrenocortical layers, where the basal proliferative activity was negligible. The effect of 10(-8) M ET-1 was blocked by the ETA receptor antagonist BQ-123, whereas the ETB receptor antagonist BQ-788 was ineffective. ET-2 and ET-3 (10(-8) M) enhanced DNA synthesis in the ZG, but their effects were less intense than that of 10(-8) M ET-1 and were directly related to their binding potency for the ETA receptor subtype (ET-1 > ET-2 >> ET-3). The selective ETB receptor agonists BQ-3020, IRL-1620, and sarafotoxin-6B were ineffective. The ZG proliferogenic action of 10(-8) M ET-1 was reversed by both the protein kinase C inhibitor Ro31-8220 and the tyrosine kinase inhibitor tyrphostin-23; a complete blockade was obtained at a 10(-6)-M concentration of each inhibitor. In contrast, neither the protein kinase A inhibitor H-89 (10(-5) M) nor the cyclooxygenase and lipoxygenase inhibitors indomethacin and phenidone (10(-5) M) affected ET-1 action. Collectively, our findings indicate that ETs stimulate the proliferation of rat adrenal ZG cells, acting through ETA receptors coupled with protein kinase C- and tyrosine kinase-dependent signaling pathways. The results of the present study are in keeping with the view that in mammals, ZG is the proliferative layer involved in the maintenance of growth of the entire adrenal cortex and with the previous autoradiographic demonstration that ZG is the only adrenocortical layer provided with ETA receptors.

Animals↗
PubMed1997

Effects of pneumadin (PNM) on the adrenal glands. 6. Further studies on the inhibitory effect of PNM on dexamethasone-induced atrophy of the rat adrenal cortex.

Pneumadin (PNM) is a biologically active decapeptide, which has previously been found to enhanced rat adrenal growth; the mechanism is indirect and probably involves the stimulation of both arginine-vasopressin (AVP) and ACTH release. The effects of 2- and 6-day PNM administration on the atrophic adrenal cortices of rats treated for 8 and 12 days, respectively, with daily subcutaneous injections of 15 or 40 g/100 g body weight of dexamethasone (Dx) were investigated. Morphometry showed that PNM counteracted Dx-induced adrenal atrophy, by preventing the decrease in volume and number of the parenchymal cells. PNM raised aldosterone and corticosterone production of adrenal quarters from Dx-treated rats, but it did not evoke significant changes in the plasma concentrations of the two hormones. The preventive effect of PNM was only partial and almost exclusively evident in rats administered the lower dose of Dx. In light of these findings the following conclusions are drawn: (i) PNM is able to partially overcome the Dx-induced inhibition of the rat hypothalamo-pituitary-adrenal axis, probably by stimulating the pituitary release of AVP and ACTH, that in turn enhance adrenocortical growth; (ii) the PNM-induced improvement of the secretory capacity of atrophic adrenocortical cells is not sufficient to raise the blood level of corticosteroid hormones; and (iii) Dx exerts a direct inhibitory action on adrenocortical cells, which is not counteracted by PNM.

Adrenal Cortex↗
PubMed1996

In vitro studies of the subtypes of endothelin (ET) receptors present in the rat testis, and of their involvement in the secretory response of Leydig cells to ET-1.

The distribution of the endothelin (ET)-receptor subtypes ET(A) and ET(B) in the rat testis and their involvement in the secretory response of Leydig cells to ET-1 have been investigated by the use of specific ligands. Autoradiography showed that [125I]ET-1 binding was intense in the interstitial area of the testis, containing Leydig cells, and virtually absent in the walls of seminiferous tubules. Labelling was almost completely displaced by BQ-123, a selective ETA receptor antagonist, while sarafotoxin-6C and BQ-788, two specific ET(B) ligands, were ineffective. ET-1 concentration-dependently enhanced testosterone secretion of dispersed rat Leydig cells, and the response was suppressed by BQ-123, but not by BQ-788. Both antagonists per se did not affect either basal and hCG stimulated secretion of Leydig cells. Taken together our findings indicate that rat Leydig cells are mainly, provided with ETA, and that this ET-receptor subtype mediates their secretory response to ET-1.

Animals↗
PubMed1996

The possible role of endogenous substance P in the modulation of the response of rat pituitary-adrenal axis to stresses.

The role played by endogenous substance P (SP) in the regulation of hypothalamo-pituitary-adrenal (HPA) axis was investigated in the rat. Normal and ether-stressed (2 min ether-vapor inhalation) or cold-stressed (20 min at 4 degrees C) animals were given a bolus subcutaneous injection of 100 nmol spantide (SPA) a specific antagonist of SP; their blood concentrations of ACTH, aldosterone (ALDO) and corticosterone (B) were measured by specific RIA, 1, 2 or 4 h after the injection. SPA did not evoke significant changes in the basal plasma levels of the three hormones. Ether and cold stresses markedly raised the blood concentrations of ACTH, ALDO and B, being maximal response observed after 1 or 2 h. SPA notably enhanced the responses of the three hormones to ether stress. SPA magnified ALDO and B responses to cold stress, but it notably depressed ACTH one. In light of these findings, it may be concluded that (i) endogenous SP does not affect basal activity of rat HPA axis, but it exerts an inhibitory action on its response to the stresses, especially the ether-inhalation one: and (ii) different mechanisms are involved in the cold and ether stress-induced activation of the HPA axis.

Adrenocorticotropic Hormone↗
PubMed1996

Effects of pneumadin (PNM) on the adrenal glands. 5. Potent stimulating action of PNM on adrenocortical growth of dexamethasone-administered rats.

Pneumadin (PNM) is a biologically active decapeptide, originally isolated from mammalian lungs, that has been previously found to acutely stimulate pituitary-adrenocortical axis in rats. The effects of 2-day PNM administration on the atrophic adrenal cortices of rats treated for 8 days with dexamethasone (DX) were investigated. PNM significantly raised adrenal weight and the average volume of adrenocortical cells. The decapeptide strikingly increased ACTH plasma concentration; however, the blood levels of aldosterone and corticosterone, as well as steroid output by adrenal quarters were not apparently affected. In light of these findings the following conclusions can be drawn: (i) PNM enhances the growth of adrenal cortex in DX-administered rats by a mechanism involving the stimulation of ACTH release; and (ii) PNM treatment is probably too short to allow DX-atrophied adrenocortical cells to re-acquire all their differentiated secretory capacities.

Adrenal Cortex↗
PubMed1996

Effects of the prolonged administration of bradykinin on the rat pituitary-adrenocortical axis.

The effects of a prolonged administration of bradykinin (BK) and/or D-Arg, [Hyp3, D-Phe7]-BK, a specific antagonist of BK receptors (BK-A) (daily subcutaneous injections of 4 nmol/rat for 6 days) on the function of the pituitary-adrenocortical axis were investigated. BK did not change plasma aldosterone concentration (PAC), but markedly lowered that of corticosterone (PBC) and consequently induced a compensatory hypersecretion of ACTH by the pituitary gland. BK-A did not apparently affect the function and growth of the adrenal gland, but, when administered together with BK, markedly raised both PAC and PBC, and provoked a significant atrophy of the adrenal gland, probably due to loss of parenchymal cells. Taken together, these rather puzzling findings do not appear to provide clear evidence for the involvement of BK in the physiological regulation of adrenocortical growth and steroidogenic capacity in rats.

Adrenal Glands↗
PubMed1996

Neuropeptide Y-related peptides and hypothalamo-pituitary-adrenal axis function.

Current data on the localization of neuropeptide Y-related peptides in the hypothalamo-pituitary-adrenal gland (HPA) axis as well as the effects of these peptides on the function of cells comprising HPA axis are presented and discussed. The action of neuropeptide Y, peptide YY, and pancreatic polypeptide on HPA axis are evaluated. Moreover, we report the presence of pancreatic polypeptide immunoreactivity in subset of chromaffin cells in the medulla of rat adrenal gland.

Adrenocorticotropic Hormone↗
PubMed1995

Effects of neuromedin-K on the rat hypothalamo-pituitary-adrenal axis.

The effects of neuromedin-K (NMK) on the rat hypothalamo-pituitary-adrenal (HPA) axis were studied both in vivo and in vitro. A subcutaneous injection of 1 nmol/100 g NMK evoked a rise in plasma ACTH level at 30 min, increased plasma corticosterone (B) concentration (PBC) at 60 and 120 min, and did not alter plasma aldosterone (ALDO) concentration (PAC). The administration of 3 nmol/100 g NMK induced a rise in plasma ACTH level at 120 min and a drop of PBC at 30 min; it increased PBC and PAC at 60 and 120 min. NMK did not affect basal B secretion of dispersed zona fasciculata/reticularis (ZF/R) cells, but markedly enhanced basal ALDO production by dispersed zona glomerulosa (ZG) cells (minimal and maximal effective concentrations were 10(-9) M and 10(-7) M). Video-imaging analysis showed that NMK (10(-8) M) increased intracellular Ca2+ concentration in dispersed ZG cells, but not in ZF/R ones. These findings indicate that NMK exerts a complex modulatory action on the rat HPA axis: low doses of NMK appear to evoke a transient stimulation of ACTH release, while high doses seem to exert a short-term inhibition of glucocorticoid synthesis followed by the compensatory hypersecretion of ACTH; moreover, elevated doses of NMK also exert a strong ALDO secretagogue action by acting directly on the ZG cells.

Adrenal Glands↗
PubMed1995

Investigations on the acute effects of neuropeptides on the pituitary-adrenocortical function in normal and cold-stressed rats. II. Neurotensin and neuromedin N.

The effects of a subcutaneous bolus injection of 2 micrograms neurotensin (NT) or neuromedin N (NMN) on the function of the hypothalamo-pituitary-adrenocortical axis were investigated in both normal and cold-stressed rats. The blood concentrations of ACTH, corticosterone (B) and aldosterone (ALDO) were measured by specific radioimmunoassays 1, 2 or 4 h after the neuropeptide administration. Cold stress enhanced plasma levels of ACTH, B and ALDO, and these rises lasted unchanged until 4 h. NT did not affect either basal or stress-stimulated plasma levels of ACTH and B, while it lowered the plasma ALDO concentration at 4 h in normal rats and increased it at 1 h in stressed animals. NMN did not change the basal plasma level of ACTH, but it did markedly raise blood levels of both B and ALDO; on the other hand, in cold-stressed rats NMN strongly depressed ACTH response and decreased B plasma concentration at 2 h, without evoking apparent changes in ALDO response. In light of these findings the following conclusions and hypotheses can be drawn and suggested: (i) NT and NMN, when administered at a relatively high dose, do not affect ACTH release in rats under basal conditions; (ii) NMN, but not NT, is able to prevent cold stress-induced stimulation of ACTH secretion, probably by inhibiting hypothalamic thermoregulatory centers; and (iii) NT and NMN exert direct adrenocortical antisecretagogue and secretagogue effects, respectively, which could explain the evident lack of correlation between the levels of circulating ACTH and the plasma concentrations of the main adrenal steroid hormones in both normal and stressed rats after neuropeptide administration.

Adrenocorticotropic Hormone↗
PubMed1995

[Content estimation of nitrates and nitrites in vegetables from the province of Lodz].

The contents of nitrates and nitrites in selected vegetables reaped in summer and autumn in 1993 were investigated. The samples of vegetables were collected directly from the producers from area of Lódź and from outside of the city. Nitrates were reduced on a cadmium column to nitrites, where-upon they were determined colorimetrically using sulfanilic acid and N-1-Naphthylethylenediamine. It has been found that the contents of nitrates in tested vegetables are mostly higher than the allowable values published in the Ordinance of Minister of Health and Social Welfare from 8th of October 1993. The average contents of nitrates and nitrites in most of tested vegetables were higher in the vegetables from the outskirts of the city than in ones from outside of the city in the province.

Colorimetry↗
PubMed1995

[Studies on the contents of nitrates and nitrites in selected fresh and heat processed vegetables].

The levels of nitrates and nitrites were determined in fresh vegetables and the same products subjected to culinary processing such as boiling. Nitrates were reduced on a cadmium column to nitrites, where upon they were determined colorimetrically using sulfanilic acid and N-1-naphthyl-ethylenediamine. Thermal processing of these vegetables reduced the level of nitrates by about 50% and the nitrites loss reached even 100%.

Colorimetry↗
PubMed1994

Neuropeptide K enhances glucocorticoid release by acting directly on the rat adrenal gland: the possible involvement of zona medullaris.

Neuropeptide K (NPK), a member of the kassinin-like tachykinin family, is contained in the rat hypothalamus and is known to stimulate pituitary ACTH release. The intraperitoneal bolus administration of NPK dose-dependently enhanced corticosterone blood level not only in intact rats, but also in hypophysectomized/ACTH replaced animals. NPK did not affect corticosterone secretion of dispersed rat adrenocortical cells; however, it concentration-dependently raised basal corticosterone production by decapsulated adrenal quarters (including both cortical and medullary tissues). Minimal and maximal effective concentrations were 10(-9) and 10(-8) M, respectively. 10(-8) M NPK potentiated corticosterone response of adrenal quarters elicited by 10(-12) M ACTH, but not that evoked by higher concentrations of ACTH. The direct corticosterone secretagogue effect of 10(-8) M NPK is annulled by 10(-6) M alpha-helical-CRH or corticotropin-inhibiting peptide, competitive inhibitors of CRH and ACTH, respectively. In light of these findings, the hypothesis is advanced that NPK exerts a direct stimulatory action on adrenocortical secretion and that the mechanism underlying this effect of NPK may involve the activation of the intra-medullary CRH/ACTH system.

Adrenal Cortex↗