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A Markowska

Publications and source records attributed to A Markowska.

At least 19 recordsLinked to original sources

Studies on leptin and leptin receptor gene expression in myometrium and uterine myomas of gnRH analogue-treated women.

AIM: To test if treatment with GnRH analogue, which leads to a significant reduction in myoma volume, changes expression of leptin genes and gene coding leptin receptor isoforms in uterine myomas and in the surrounding unaltered myometrium. METHODS: Using RT-PCR, expression of leptin genes and leptin receptor genes was studied in myomas and in the surrounding myometrium in women with uterine myomas, untreated or treated with GnRH analogue. In the randomly selected cases presence of leptin protein and of leptin receptor proteins was examined also by Western blotting. RESULTS: Expression of leptin genes was demonstrated both in myomas and in the surrounding myometrium, and a similar pattern of expression was found for leptin receptor isoforms. The results of RT-PCR were confirmed by Western blotting, which documented the identical distribution of leptin proteins and leptin receptor proteins in studied tissues. Treatment with GnRH analogue had no effect on the expression pattern of studied genes. CONCLUSION: The results of the present study on the administration of GnRH analogue to females with myomas suggest that no direct or immediate inter-relationship exists between expression of leptin genes in uterine myomas on one hand and estrogen, progesterone and leptin levels in the blood on the other. Expression seems to be of a more durable nature but factors that induce such expression remain unknown.

Adult↗

Further studies on leptin and leptin receptor expression in myometrium and uterine myomas.

AIM: Examination of the potential role of leptin in the development of uterine myomas. Expression of the leptin gene and leptin receptor gene was tested in the myometrium of healthy women, and in myomas and the surrounding myometrium of women with benign tumors. METHODS: Using RT-PCR, expression of the leptin gene and leptin receptor gene were studied in myomas and in the surrounding myometrium in 30 women with uterine myomas at various phases of the menstrual cycle, and in the myometrium of ten women in a control group. Presence of leptin gene proteins and leptin receptor gene proteins in the women was also examined by Western blotting. RESULTS: Using RT-PCR, expression of the leptin gene was demonstrated both in myomas and in the surrounding myometrium. In contrast, expression of the gene could not be detected in the myometrium of healthy women. The results were confirmed by Western blotting, which documented the identical distribution of leptin proteins and leptin receptor proteins in studied tissues. CONCLUSION: Demonstration of the expression of leptin genes and leptin proteins in uterine myomas and in the surrounding myometrium, and their absence in the myometrium of healthy women suggests the involvement of leptin in the development of uterine myomas.

Adult↗

The role of leptin in breast cancer.

Leptin, the protein hormone produced mainly by adipocytes, placenta and mammary epithelium plays a significant role in, e.g., control of metabolism, reproductive processes, immune processes, angiogenesis, haemopoiesis and oxidation of lipids. Since some authors link leptin to mechanisms of mammary cancer development, the clinical data has been screened to allow evaluation of the hypothesis.

Breast Neoplasms↗

Effect of pentagastrin on steroid secretion and proliferative activity of regenerating rat adrenal cortex.

The effects of three subcutaneous injections of 3 nmol/100 g body weight of the cholecystokinin type 2 (CCK2) receptor agonist pentagastrin on adrenocorticotrophic hormone (ACTH) and corticosterone secretion and proliferative activity of regenerating rat adrenal cortex were investigated. Pentagastrin did not alter either ACTH and corticosterone plasma concentrations or the adrenal mitotic index at day 5 of regeneration. In contrast, it increased (by about 50%) the adrenal mitotic index at day 8 of regeneration, and the effect was blocked by the simultaneous administration of equimolar doses of the CCK2-receptor antagonist PD-135,158. It is suggested that the activation of CCK2 receptors exerts a growth promoting action on the regenerating rat adrenal cortex.

Adrenal Cortex↗

Effects of galanin on the secretion and proliferative activity of the immature and regenerating adrenal glands of rats.

The effects of galanin and the galanin-receptor antagonist (galanin-A) [D-Thr(6),D-Trp(8,9),15-ol]-galanin(1-15) on the immature and regenerating rat adrenal glands have been investigated in vivo. Adult female rats with adrenal regeneration and their offpring (20-day-old) were given three subcutaneous injections (28, 16, and 4 h before being killed) of 2 nmol/100 g galanin and/or galanin-A, and 0.1 mg/100 g vincristin 3 h before being killed. Plasma corticosterone concentration was measured by radioimmunoassay, and the mitotic index ( per thousand of metaphase-arrested cells) was evaluated. In immature rats, galanin increased plasma corticosterone concentration, without affecting mitotic index; the secretagogue effect was reversed by galanin-A, which alone was ineffective. In rats with regenerating adrenal, galanin-A increased both blood level of corticosterone and mitotic index; galanin was ineffective, but blocked the effects of galanin-A. These findings allowed us to draw the following conclusions: 1) galanin exerts a moderate glucocorticoid secretagogue action on immature rat adrenals, but endogenous galanin does not play a major physiological role in the functional control of the gland; and 2) endogenous galanin exerts a maximal tonic inhibitory control on both glucocorticoid secretion and proliferative activity of regenerating rat adrenals, whose physiological relevance remains to be investigated.

Adrenal Glands↗

Cerebellin stimulates the secretory activity of the rat adrenal gland: in vitro and in vivo studies.

Cerebellin is a 16-aminoacid peptide widely distributed in the central nervous system, where it exerts neuromodulatory functions. Cerebellin is contained in human adrenal medulla, and it has been recently demonstrated that cerebellin elicits catecholamine release by human adrenal in vitro. Aim of the present study was to ascertain whether cerebellin affects adrenal function in the rat. Cerebellin concentration-dependently (from 10(-9)to 10(-7)M) increased norepinephrine (but not epinephrine) and cyclic-AMP production by adrenomedullary tissue in vitro. The norepinephrine response to 10(-7)M cerebellin was blocked by the protein kinase (PK) A inhibitor H-89, but not by the phospholipase C inhibitor U-73122 or the PKC inhibitor calphostin-C. Cerebellin did not affect aldosterone and corticosterone secretion of dispersed zona glomerulosa and zona fasciculata-reticularis adrenocortical cells. Cerebellin concentration-dependently (from 10(-8)to 10(-7)M) enhanced norepinephrine release by in situ perfused rat adrenals. Cerebellin (10(-7)M) also elicited a significant rise in aldosterone and corticosterone output, and this effect was annulled by either the beta1-adrenoceptor antagonist l -alprenolol or H-89. Collectively, the present findings allow us to conclude that cerebellin 1) directly stimulates norepinephrine release via the adenylate cyclase/PKA-dependent signaling pathway; and 2) indirectly enhances adrenocortical secretion in vivo, through a paracrine mechanism involving medullary catecholamine release.

Adrenal Cortex↗

Role of adrenal renin-angiotensin system in the control of aldosterone secretion in sodium-restricted rats.

This study examined the effect of the pharmacological manipulation of adrenal renin-angiotensin system (RAS) on aldosterone secretion from in situ perfused adrenals of rats kept on a normal diet and sodium restricted for 14 days. Neither the angiotensin-converting enzyme inhibitor captopril nor the nonselective angiotensin II receptor antagonist saralasin and the AT(1) receptor-selective antagonist losartan affected basal aldosterone output in normally fed rats. In contrast, they concentration dependently decreased aldosterone secretion in sodium-restricted animals, with maximal effective concentration ranging from 10(-7) to 10(-6) M. Captopril (10(-6) M), saralasin (10(-6) M), and losartan (10(-7) M) counteracted aldosterone response to 10 mM K(+) in sodium-restricted rats but not in normally fed animals. Collectively, these findings provide evidence that adrenal RAS plays a role in the regulation of aldosterone secretion, but only under conditions of prolonged stimulation of zona glomerulosa probably leading to overexpression of adrenal RAS.

Adrenal Glands↗

Adrenomedullin enhances cell proliferation and deoxyribonucleic acid synthesis in rat adrenal zona glomerulosa: receptor subtype involved and signaling mechanism.

The effect of adrenomedullin (ADM) on the proliferative activity of the rat adrenal cortex has been investigated in vivo, using an in situ perfusion technique of the intact left gland. ADM and other chemicals were dissolved in the perfusion medium, and the perfusion was continued for 180 min. ADM infusion concentration dependently increased the mitotic index and [3H]thymidine incorporation into DNA in the zona glomerulosa (ZG; the maximal effective concentration was 10(-8) M), but not in inner adrenocortical layers, where basal proliferative activity was negligible. The effect of 10(-8) M ADM was equipotently counteracted by both the calcitonin gene-related peptide (CGRP) type 1 receptor antagonist CGRP-(8-37) and ADM-(22-52). The adenylate cyclase inhibitor SQ-22536 (10(-4) M), the cAMP blocker Rp-cAMP-S (10(-3) M), and the protein kinase A inhibitor H-89 (10(-5) M), although counteracting the ZG proliferogenic action of 10(-9) M ACTH, did not affect the 10(-8) M ADM-elicited increase in ZG DNA synthesis. Similar results were obtained using the phospholipase C inhibitor U-73122 (10(-5) M), the inositol-1,4,5-trisphosphate antagonist D,L-myo-inositol-1,4,5-trisphosphothiate (10(-4) M), and the protein kinase C inhibitor calphostin C (10(-5) M), which, however, significantly inhibited the ZG proliferogenic effect of 10(-9) M angiotensin II. The growth-promoting action of 10(-8) M ADM was not affected by the phospholipase A2 inhibitor AACOCF3 (10(-5) M), the cyclooxygenase (COX) inhibitor indomethacin (10(-5) M), or the mixed COX/lipoxygenase inhibitor phenidone (10(-5) M). In contrast, the ZG proliferogenic effect of 10(-8) M ADM was abolished by either the tyrosine kinase (TK) inhibitor tyrphostin-23 (10(-5) M) or the mitogen-activated protein kinase (MAPK) antagonists PD-98059 and U0216 (10(-4) M). ADM (10(-8) M) stimulated TK and p42/p44 MAPK activity in dispersed ZG, but not ZF, cells, and the effect was reversed by either 10(-6) M CGRP-(8-37) and ADM-(22-52) or preincubation with 10(-5) M tyrphostin-23. Collectively, our findings indicate that 1) ADM stimulates cell proliferation in the rat ZG, through CGRP-(8-37)- and ADM-(22-52)-sensitive receptors, probably of the CGRP1 subtype; and 2) the mitogenic effect of ADM is mediated by activation of the TK-MAPK cascade, without any involvement of the adenylate cyclase/protein kinase A-, phospholipase C/protein kinase C-, and COX- or lipoxygenase-dependent signaling pathways.

Adenylyl Cyclase Inhibitors↗

[Total or subtotal hysterectomy?].

UNLABELLED: We compared the risk and benefits subtotal (supracervical) hysterectomy and total hysterectomy in women with nonmalignant conditions (perioperative mortality, intra- and postoperative complications, quality of life, long-term effects on other diseases). The main disadvantage of subtotal hysterectomy over total one is the fact, that in 1 per 1000 women develops carcinoma in cervical stump. CONCLUSION: Total hysterectomy is recommended in benign conditions of the uterine corpus.

Adult↗

Molecular modelling, synthesis and antitumour activity of carbocyclic analogues of netropsin and distamycin--new carriers of alkylating elements.

A series of netropsin and distamycin analogues was synthesised and investigated by molecular modelling. The lowest-energy conformations of four carbocyclic lexitropsins, potential carriers of alkylating elements, were obtained using the HyperChem 4.0 program, and compared with the DNA-lexitropsin crystal structures from the Brookhaven National Laboratory Protein Data Bank. A method for synthesis of carbocyclic lexitropsins was elaborated, with the use of a nitro group or azobenzene as precursors for the aromatic amino group. The influence of methoxy group in ortho position with respect to amide groups on the activity of the new compounds was investigated. All of the compounds tested showed high antitumour activity in the standard cell line of mammalian tumour MCF-7.

Alkylating Agents↗

[Cesarean section for the second twin during the course of delivering twins].

We have analysed 6 cases of twin pregnancies with vertex presentation of the first foetus. In this cases after delivery of the first twin by vaginal route caesarean, section was made. Caesarean section of the second twin was made because of: transversal presentation with fetal distress syndrom (four cases), umbilical cord drop (one case), and premature placenta ablation (one case). We have determined acid base balance and Apgar score. We have noted worse results for the second twin, independently too of the time between deliveries both twins. Caesarean section of the second twin is the rarely clinical situation, but in motivated situation is accepted and reasonable solution.

Acid-Base Equilibrium↗

Synthetic analogues of netropsin and distamycin. VI. Synthesis of carbocyclic lexitropsins containing a bioreductive element.

Carbocyclic derivatives of lexitropsines containing of two aromatic rings, N-dimethylaminopropyl group lonked to carboxyl terminus and 5-[bis(2-chloroethyl)-amino]-2,4-dinitrobenzamide group linked to the amino terminus group were synthesed. The N-terminal group should present selective alkylating activity on the DNA of cancer cells in conditions of hypoxia.

Alkylation↗

Effects of neurotensin and bombesin on the secretory and proliferative activity of regenerating rat adrenal cortex.

Neurotensin (NT) and bombesin (BM)-like peptides are known to be involved in the regulation of the rat hypothalamo-pituitary-adrenal axis. By using selective NT- and BM-receptor antagonists (NT-A and BM-A, respectively) we investigated whether endogenous NT and BM-like peptides play a role in the control of rat adrenal secretion and growth during enucleation-induced regeneration. At day 5 of regeneration, NT-A did not affect the plasma concentrations of aldosteronc (PAC) and corticosterone (PBC), but at day 8, it raised both PAC and PBC over the respective baseline value; the simultaneous administration of NT abolished this effect of NT-A. BM-A did not alter PAC and PBC at day 5 of regeneration, while at day 8 it enhanced PBC, an effect reversed by BM. NT-A did not alter mitotic index, and BM-A lowered it at both day 5 and day 8 of regeneration, an effect suppressed by the simultaneous administration of BM. Collectively, these findings allow us to draw the following conclusions: 1) endogenous NT and BM-like peptides influence adrenocortical regeneration in rats; 2) NT exerts a tonic inhibitory action on both aldosterone and corticosterone secretion, without affecting cell-proliferation rate; and 3) BM-like peptides exert a tonic suppressive effect on corticosterone production, coupled with a clear-cut stimulating effect on cell proliferation.

Adrenal Cortex↗

Cholecystokinin, acting through the A receptor subtype, stimulates the proliferative activity of adrenocortical cells and thymocytes in the rat.

Cholecystokinin (CCK) is a multifunctional regulatory peptide, which acts through two main subtypes of receptors, named CCK-A and CCK-B. Evidence indicates that CCK modulates cell proliferation in various tissues in a paracrine manner, and proofs are available of the presence of CCK in both adrenal glands and thymus. Hence, we have investigated the possible mitogenic action of this peptide on these two tissues, by evaluating the /1000 of metaphase-arrested cells after vincristin injection (mitotic index). The systemic administration of CCK (three subcutaneous injections of 20 nmol/kg, 28, 16 and 4 h before the sacrifice) increased the mitotic index in both the outer adrenal and thymus cortexes of immature (20-day-old) rats and the enucleated adrenal gland of adult (2-month-old) animals at day 5 and 8 of regeneration. The simultaneous administration of equimolar doses of a selective CCK-A receptor antagonist blocked the effect of CCK, while a CCK-B antagonist was ineffective. These findings indicate that CCK exerts a marked CCK-A-mediated proliferogenic effect on both adrenal cortex and thymus in the rat, the physiological relevance of which, however, remains to be demonstrated. In fact, the administration of the CCK-A antagonist alone was ineffective, thereby casting doubts on the role played by endogenous CCK in the maintenance and stimulation of adrenal and thymus growth.

Adrenal Cortex↗

[The evaluation of nitrate and nitrite contents in diets of preschool children].

The contents of nitrites and nitrates in whole day's food of children at preschool age have been examined. Meals consisted of three dishes were taken from one of the day nurseries in Lódź in January 1996. In the evaluation of the degree of exposure the highest permissible daily intake was considered of nitrites (0.2 mg NaNO2) and nitrates (5 mg KNO3) for kg of body weight and assumed average body weight was 20 kg for children. The contents of nitrites and nitrates were determined spectrophotometrically on the basis of Griess reaction. Nitrates were reduced to nitrites passing anaquelos extract of the studied sample through a column filled with cadium dust. The range of quality of collected nitrates in meals in wide and the quantity oscillate between 8.9 and 127, mg KNO3, the average quantity is 55.01 mg KNO3. The quantity of collected nitrites is between 0.5 and 3.8 mg NaNO2 and the average quantity is 1.58 mg NaNO2.

Child↗

[The evaluation of nitrates and nitrites in daily food intake of adults].

During the research work the contents of nitrates and nitrites in whole day's food of adults were examined. The study were carried out in February 1996. In the evaluation of the degree of exposure highest permissible daily intake was considered of nitrites (0.2 mg NaNO2) and nitrates (5 mg KNO3) for one kg of body weight, and the assumed average body weight was 60 kg for adults. The contents of nitrites and nitrates were determined spectrophotometrically of the basis of Griess reaction. Nitrate was determined colorimetrically using sulphanic acid and N-1-naphtyl-ethylene-diamine. The quantity of collected nitrates and nitrites in whole day's food oscillates between 69.5 and 737.5 mg KNO3 and the average quantity is 304.55 mg KNO3. The quantity of collected nitrites is in the average 1.8-8.4 mg NaNO2, and the average quantity is 4.39 mg NaNO2.

Adult↗

Synthetic analogues of netropsin and distamycin. V. Synthesis of a carbocyclic bis-lexitropsin as potential DNA cleaving agent.

A carbocyclic analogue of bis-distamycin, in which N-methylpyrroles were replaced by two trisubstituted benzene moieties joined by tetramethylenedioxy linkage, has been prepared. This compound bearing photosensitive benzotriazole moieties at the N-terminal residues. The synthetic method for the preparation of the bis-benzotriazolyllexitropsin was accomplished in twelve steps starting from 2-hydroxy-5-phenylazobenzoic acid.

Antineoplastic Agents↗