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M Pawlikowski

Publications and source records attributed to M Pawlikowski.

At least 19 recordsLinked to original sources

Angiotensins II and IV modulate adrenocortical cell proliferation in ovariectomized rats.

Effects of angiotensins II (AngII), angiotensin IV (AngIV, 3-8 fragment of angiotensin II) and losartan (an antagonist of angiotensin receptor type 1) on the proliferation of adrenocortical cells in ovariectomized rats have been studied. The incorporation of bromodeoxyuridine (BrdU) into cell nuclei was used as an index of cell proliferation. AngIV decreased BrdU labeling index mainly in the reticularis zone and losartan (Los) was able to partially reverse this inhibitory effect of AngIV. AngII had no effect on the adrenocortical cell proliferation when given alone, however Los given simultaneously diminished BrdU incorporation into nuclei of glomerulosa and reticularis zones as compared with AngII. These findings suggest that AngII and AngIV modulate adrenocortical cell proliferation in ovariectomized rats.

Adrenal Cortex↗

The effect of selective sst1, sst2, sst5 somatostatin receptors agonists, a somatostatin/dopamine (SST/DA) chimera and bromocriptine on the "clinically non-functioning" pituitary adenomas in vitro.

The aim of the work was to investigate the effects of somatostatin analogs acting selectively on sst1 (BIM-23926), sst2 (BIM-23120) and sst5 (BIM-23206) receptor subtypes on the viability of "clinically non-functioning" pituitary adenomas in vitro. The effects of native SST (SST-14), a SST/DA chimera (BIM-23A387) and a D(2)-dopamine receptor agonist bromocriptine (BC) were also examined. The study was performed on 10 surgically removed pituitary macroadenomas, diagnosed before surgery as "non-functioning". A part of each tumor was mechanically dispersed and digested with collagenase to isolate the tumoral cells. Another part of each tumor was fixed, embedded in paraffin and immunostained to reveal the pituitary hormones and SST receptor subtypes (sst1, sst2A, sst2B, sst3, sst4, sst5). The tumoral cell suspensions were incubated for 24 h with the substances mentioned above. The quantity of viable cells was estimated using the EZ4U system. The results were compared with the immunohistochemical evaluation of the hormonal profile of adenoma and the sst receptor subtype immunoreactivities present. The findings indicate that selective sst1, sst2 and sst5 receptors agonists, SST/DA chimera and D(2)-dopamine receptor agonist bromocriptine affect the viability of some, but not all, "clinically non-functioning" pituitary adenomas in vitro. The most effective was bromocriptine. The investigated somatostatin analogs including SST/DA chimera exerted roughly similar inhibitory effects. Further studies are needed to fully evaluate the potential usefulness of these compounds in the pharmacological treatment of "non-functioning" pituitary tumors.

Adenoma↗

Effect of thyroliberin on the course of experimental candidosis in mice.

Thyroliberin (TRH) is one of the hormones, which affect immunologic processes. This hormone was studied in experimental subacute candidosis in mice. BALB/c males were given intraperitoneally single dose of Candida albicans cells (1 x 10(7) to 1 x 10(9) cfu of strain no. 244-33 ATCC). The animals from the experimental groups were injected subcutaneously, after 24 h from inoculation, dose of 10 microg TRH in 0.2 ml 0.9% NaCl, seven times at 24 h intervals. The control animals were given respectively 0.2 ml of physiologic NaCl solution. We have found that the examined hormone significantly decreases mortality in these animals (LD50 C. albicans for mice treated with TRH was three times higher than that in the control groups), prolongs mean survival time for mice and decreases the intensity of fungal invasion of the animal organs.

Animals↗

Angiotensin IV stimulates the activity of tyrosine kinases in rat anterior pituitary gland acting via AT1-like receptors?

Angiotensin II (Ang II) is known to modulate tyrosine kinases (PTKs) activity in pituitary tumor cells. It is known that AngII is acting via AT1 receptors in many tissues. The aim of this study was to see whether 3-8 fragment of AngII, called angiotensin IV (AngIV) has a similar effect on tyrosine kinase activity in normal pituitary gland and what type of angiotensin receptor is involved in this process. The homogenates of normal rat pituitaries was a source of enzymes. The PTKs activity was determined using the synthetic substrate poly GluTyr and gamma-(32)P-ATP. Ang IV was found to increase the PTK activity in the rat anterior pituitary tissue, with the maximal effect at concentration of 10(-10) M. AngII was ineffective at all concentrations studied. Losartan, a selective AT1 receptor blocker, added together with Ang IV abolished the effect of the latter, however losartan diminished also the PTK activity when applied together with Ang II, but only when it was added immediately before, but not after, the addition of Ang II. The involvement of a non-classic AT1-like receptor is suggested.

Angiotensin II↗

Pregnenolone sulfate modulates angiotensin II-induced inositol 1,4,5-trisphosphate changes in the anterior pituitary of female rat.

The present study was designed to test whether pregnenolone sulfate can influence the angiotensin II (AngII) action in the anterior pituitary. Female rats were ovariectomized and 10 days after operation were treated with either 50 or 250 microg per animal in one of the following substances: oil (control), pregnenolone sulfate (PREG-S), estradiol benzoate (E(2),) progesterone (P), or dehydroepiandrosterone sulfate (DHEA-S), given in single intraperitoneal injection. Because AngII is known to act in the anterior pituitary through the phosphatidiloinositol breakdown, thus increasing the level of inositol-1,4,5-trisphosphate (IP(3)), the IP(3) concentration was determined 24 h after the injection in the anterior pituitary homogenate after in vitro exposure to AngII. Among the tested steroids only PREG-S enhanced the basal (without AngII) and AngII-induced level of IP(3) in both doses used. There was no difference between the effect of a high and low dose of PREG-S. These results show that PREG-S may modulate AngII action in the anterior pituitary, regardless of the presence of ovary.

Adjuvants, Immunologic↗

Melatonin and RZR/ROR receptor ligand CGP 52608 induce apoptosis in the murine colonic cancer.

The effects of melatonin and the thiazolinidinedione derivative CGP 52608 on apoptosis of Colon 38 cancer cells were investigated. Male mice were implanted subcutaneously with a suspension of Colon 38 cells. Ten days after induction of tumors, the animals were treated with melatonin or CGP 52608. Both substances were given in subcutaneous injections in daily doses of 10 or 100 microg in the evening for 6 days. The control group received solvent. The apoptotic cells were visualized in paraffin sections by means of the transferase-mediated dUTPnick end-labeling method. Both treatments increased significantly and to the same degree the number of apoptotic cells in tumors. This finding confirms our earlier observation that melatonin exerts a pro-apoptotic effect on murine colonic cancer cells. Moreover, because CGP 52608 is a ligand of RZR/ROR receptors and the latter are considered by some investigators as nuclear binding sites for melatonin, our data suggest the involvement of these receptors in the pro-apoptotic effect of melatonin.

Animals↗

Anti-inflammatory effects of somatostatin analogs on zymosan-induced earlobe inflammation in mice: comparison with dexamethasone and ketoprofen.

The aim of the present study was the estimation of the anti-inflammatory effects of the somatostatin analogs, octreotide (OCT) and vapreotide (RC-160), in zymosan-induced mice ear inflammation and to compare their effects with those of the glucocorticoid dexamethasone (DX) and the non-steroid anti-inflammatory drug ketoprofen (KP), which are the well-known and potent suppressors of the inflammatory reaction. The inflammation was induced by injecting 20 microl of 1% suspension of zymosan intradermally into one of the earlobes of the mouse. The control animals received a vehicle 0.9% NaCl. The zymosan-treated animals were injected subcutaneously with one of the following substances: 0.9% NaCl, OCT, RC-160, DX, KP or with OCT plus DX and OCT plus KP. The edema of earlobes, the area of inflammatory focus and the area of vascular profiles in the inflamed tissues were estimated. A reduction of the ear edema in the mice treated with OCT, DX, KP, OCT + DX and OCT + KP was observed. The administration of all drugs caused the decrease of the area of the inflammatory focus and of the area of vascular profiles. The antiphlogistic activity was more pronounced in the OCT-treated animals in comparison to those treated with RC-160. The joint treatment with either OCT plus DX or OCT plus KP almost totally inhibited the zymosan-induced inflammatory reaction. In summary, the somatostatin analog OCT possesses antiphlogistic activity roughly comparable with classical anti-inflammatory drugs such as DX and KP. The somatostatin analogs may constitute a new promising group of anti-inflammatory agents.

Analgesics↗

Correlation between PCNA expression and AgNOR dots in pituitary adenomas.

Nucleolar organizer regions are segments of DNA associated with argyrophilic proteins (AgNORs). Our previous findings showed that the number, the area, and the intranuclear localization of AgNOR dots differ according to tumor aggressiveness and to the hormone-immunopositivity of pituitary adenomas. Proliferating cell nuclear antigen (PCNA) is a nuclear protein, whose expression is correlated with cell proliferation. The aim of the present paper was to examine PCNA-labeling indexes in pituitary adenomas and to correlate them with AgNOR dots in various immunohistochemical types of the tumors. Histological slides from 32 pituitary tumors and one normal pituitary were silver-stained and analyzed with a computerized system for microscopic image analysis. We found that the percentage of PCNA-positive cells did not differ significantly among examined groups of monohormonal adenomas. However, tumors immunopositive for alpha-subunit (alpha-SU) showed a significantly higher (p < 0.05) PCNA index than adenomas immunonegative for that unit. PCNA index in recurrent tumors was significantly higher than in primary adenomas. There was a moderate positive correlation between the PCNA index and the mean area of AgNOR dots and a similar correlation between the PCNA index and the area of the biggest dot in the nucleus. The obtained results reveal that the PCNA indexes and estimated parameters of AgNOR dots differ according to tumor aggressiveness.

Adenoma↗

Immunocytochemical prognostic markers in pituitary tumors.

The value of different immunocytochemical markers in the evaluation of the pituitary tumor aggressiveness is discussed on the basis of the data from the literature and the author's personal experience. The usefulness of the proliferation markers (PCNA, Ki-67), prothymosin-alpha, the endothelial markers revealing the intratumoral vascularization and of the expression or co-expression of glycoprotein hormones in predicting the aggressive behaviour of the tumor is likely, but still needs further studies.

Biomarkers↗

Anti-tumoral action of octreotide and bromocriptine on the experimental rat prolactinoma: anti-proliferative and pro-apoptotic effects.

OBJECTIVES: The purpose of the study was to compare the effects of bromocriptine (BC) - D-2 receptor agonist and octreotide (OCT) - somatostatin analog on the tumor weight, prolactin (PRL) secretion, cell proliferation and apoptosis in the diethylstilboestrol (DES)-induced rat prolactinoma. MATERIAL AND METHODS: Male four-week Fisher 344 rats were used in the experiment. The animals were implanted subcutaneously (s.c.) with capsules containing DES. Six weeks after the implantation the rats were given OCT (2 x 25 microg/animal/24 h s.c.) or BC (3 mg/kg b.w./24 h s.c.) for 10 days. The incorporation of bromodeoxyuridine (BrDU) into the tumor cell nuclei was used as an index of cell proliferation (labeling index - LI). The labeling of nuclear DNA fragmentation according to the TUNEL method was considered as an index of apoptosis (AI). PRL was measured by radioimmunoassay (RIA). RESULTS: It has been found that OCT and BC significantly decreased the tumor weight and LI of tumor cells to the same extent. Both OCT and BC suppressed the PRL levels, but the inhibitory effect of BC was stronger than that of OCT. BC and OCT significantly enhanced the number of apoptotic cells in the tumor, but the pro-apoptotic effect of BC was more pronounced. The joint treatment exerted additive effects on tumor mass reduction, PRL secretion and cell proliferation, but OCT attenuated the pro-apoptotic effect of BC. CONCLUSIONS: Summing up, both OCT and BC inhibit PRL secretion and cell proliferation. The anti-tumoral action of BC, and to some extent the action of OCT, is also connected with induction of apoptosis.

Animals↗

Angiotensins II and IV stimulate the rat adrenocortical cell proliferation acting via different receptors.

OBJECTIVE: The effects of angiotensins II (Ang II) and IV (Ang IV,3-8 fragment of angiotensin II) on the adrenocortical cell proliferation have been investigated in the rat. METHODS: The male adult Wistar rats were injected subcutaneously with saline, captopril or captopril together with either Ang II or Ang IV. A part of animals received additionally losartan - an antagonist of AT1 subtype of angiotensin receptors. Bromodeoxyuridine (BrDU) incorporation into cell nuclei was used as the index of cell proliferation. RESULTS: It was found that both Ang II and Ang IV increased the BrDU labeling in the adrenal cortex of captopril-pretreated rats. This effect involved mainly the zona glomerulosa cells. The proliferogenic effect of Ang II was blocked by AT1 receptor antagonist losartan. In contrast, losartan did not block the effect of Ang IV. CONCLUSION: Both Ang II and Ang IV stimulate the adrenocortical cell proliferation in the rat, but they act via different receptors - AT1 in the case of Ang II and non-AT1 (probably AT4) in the case of Ang IV.

Adrenal Cortex↗

The involvement of angiotensins in the control of prostatic epithelial cell proliferation in the rat.

The effects of captopril (the inhibitor of the angiotensin-converting enzyme) and of angiotensins II and IV (3-8 fragment of angiotensin II) on cell proliferation of the prostatic epithelium was investigated in the rat. The incorporation of bromodeoxyuridine into cell nuclei was used as an index of cell proliferation. It was found that the treatment with captopril resulted in the suppression of prostatic epithelial cell proliferation. The antiproliferative effect of captopril was reversed (at least partially) by a simultaneous treatment with either angiotensin II or angiotensin IV. The effects of angiotensins were not blocked by the administration of losartan--AT1 angiotensin receptor blocker. These findings suggest the involvement of angiotensins in the control of prostatic growth, acting via the receptors different from the AT1-subtype (presumably via AT4 receptors).

Angiotensin II↗

Effect of 17-beta-estradiol and progesterone on angiotensin II-induced changes in inositol-1,4,5-trisphosphate content and protein kinase C activity in anterior pituitary.

Angiotensin II (AngII) is known to act in the anteriorpituitary through phosphatidiloinositol breakdown, increasing the level of inositol-1,4,5-trisphosphate (IP(3)) and diacyloglycerol (DAG), a potential activator of protein kinase C (PKC). We examined the effect of estradiol and progesterone treatment in vivo on IP(3) levels and activity of PKC under the influence of AngII. Three groups of intact female rats received in vivo injections of 17-beta-estradiol, progesterone, and oil (control) for five days, and then the in vitro effect of AngII was examined using homogenate of the anterior pituitary. AngII increased either the IP(3) concentration or the synapsin I phosphorylation catalyzed by PKC. Estradiol enhanced the basal (without AngII) IP(3) level and PKC activity induced by AngII. Progesterone did not change the basal and AngII-induced IP(3) concentrations. On the other hand, it decreased the basal PKC activity and blocked the effect of AngII. Our data suggest that ovarian steroids can modulate the effect of AngII on the anterior pituitary gland.

Angiotensin II↗

Time of day-dependent effects of thyroliberin and thyrotropin on thymocyte proliferation in rats.

Our earlier studies have shown that thyroliberin (TRH) as well as thyrotropin (TSH) enhanced thymus cell proliferation. The aim of the present study was to investigate whether the effects of TRH and TSH on thymocyte proliferation depend on time of day. A single subcutaneous injection of TRH (25 microgram/animal) or TSH (3 IU/animal) was made at 9:00 h (1 h after light onset) or at 18:00 h (10 h after light onset) in 3-month-old male Wistar rats. The animals were killed 24 h later. The proliferation of thymocytes was assessed by incorporation of bromodeoxyuridine into cell nuclei. Thymocyte proliferation was significantly increased by TSH administration at 9:00 h, whereas treatment given at 18:00 h was ineffective. TRH enhanced the proliferation when injected at 9:00 h, but had an inhibitory effect when administered at 18:00 h. These data indicate that the effects of TRH and TSH on thymocyte proliferation are dependent on time of day.

Animals↗

The involvement of the renin-angiotensin system in the regulation of cell proliferation in the rat endometrium.

Oestrogens are known to enhance angiotensin biosynthesis by increasing the elaboration of its precursor, angiotensinogen. On the other hand, we found that inhibition of angiotensin-converting enzyme (ACE) suppressed the proliferative response of the rat anterior pituitary gland to oestrogens. To answer the question whether the angiotensin system is involved in the control of the cell proliferation of the uterine epithelium, the effects of an ACE inhibitor, enalapril maleate, and of angiotensins II and IV, alone or together with losartan, an antagonist of angiotensin receptor type 1 (AT1), on endometrial epithelial cell proliferation have been studied. The experiments were performed on ovariectomized female Wistar rats. In the first experiment the animals were injected with a single dose of oestradiol benzoate or received an injection of solvent only. Half of the oestrogen-treated rats were injected additionally with enalapril maleate (EN, twice daily). The incorporation of bromodeoxyuridine (BrDU) into endometrial cell nuclei was used as an index of cell proliferation. It was found that oestradiol alone dramatically increased the BrDU labelling index (LI) of endometrial cell nuclei, and this effect was partially blocked by the simultaneous treatment with EN. In the second experiment, the animals were injected intraperitoneally with angiotensin II (AII), angiotensin IV (AIV) or saline, alone or together with losartan. It was found that AIV induced an increase in the LI in uterine epithelium, and this effect was not blocked by the simultaneous treatment with losartan. The increase in LI in uterine epithelium was also observed in the rats treated with AII and with losartan. These findings suggest an involvement of angiotensin IV in the control of uterine epithelium cell proliferation.

Angiotensin II↗

Does the impairment of the hypothalamic-pituitary-gonadal axis in anorexia nervosa depend on increased sensitivity to endogenous melatonin?

The authors hypothesize that the impairment of hypothalamic-pituitary-gonadal axis in patients suffering from anorexia nervosa depends (at least in part) on the increased sensitivity to endogenous melatonin. The hypothesis is based mainly on the following facts: (1) melatonin is well known to exert an inhibitory effect on gonadotropin secretion; (2) melatonin binding is increased in brains of fasted rats; (3) undernutrition dramatically increases the inhibitory effect of exogenous melatonin on gonadotropin-releasing hormone-induced gonadotropin secretion in female rats; (4) the administration of propranolol in girls suffering from anorexia nervosa diminishes the nocturnal peak of melatonin and, in parallel, restores the gonadotropin response to gonadotropin-releasing hormone.

Adolescent↗