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S Mucha

Publications and source records attributed to S Mucha.

15 recordsLinked to original sources
PubMed2004

Expression of p65 gene in experimental colon cancer under the influence of 5-fluorouracil given alone and in combination with hormonal modulation.

The effect of tamoxifen (TAM), lanreotide (LAN) and 5-fluorouracil (5-FU), given separately or together, on p65 gene expression in murine Colon 38 cancer was investigated by RT-PCR method. The findings were compared with cell proliferation determined by bromodeoxyuridine (BrdU) labeling index, apoptosis visualized by TUNEL method and tumor mass. It was found that in the control group (mice bearing colon cancer without treatment) the expression of p65 gene was present in 57% of investigated samples. In the groups treated with TAM or LAN p65 gene expression was detected in 87.5% and 83.3% of analyzed cases, respectively. Both these substances increased apoptotic index in Colon 38 cancer and LAN also decreased the proliferation index. After a combined treatment with TAM and LAN a percentage of p65 positive cases was similar to that of the control group and equaled approximately 60%. This treatment did not increase proapoptotic effects of these drugs, and even reduced the antiproliferogenic effect of LAN. In the group treated with 5-FU and LAN p65 gene expression was also close to the control value (about 66%). Similarly in this group the combined treatment with these two drugs did not cause any favorable effect on proliferation and apoptosis. Moreover, in this group even reduced antiproliferogenic effect of LAN was observed. In the group with 5-FU alone the expression of p65 was present in about 80% of samples. The treatment with 5-FU increased apoptotic index and did not change proliferation. In the group treated with a combination of TAM and 5-FU all analyzed cases showed the presence of p65 gene expression. Previously, we observed in this group the most pronounced and synergistic effect of these substances on the inhibition of cell proliferation and tumor mass reduction. Based on these findings we conclude that p65 gene expression in murine Colon 38 cancer tissues can be modulated via chemotherapy (5-FU) and also via hormonal modulation (TAM and LAN).

Animals↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2000

Pituitary-adrenocortical responses to the chronic administration of granulocyte colony-stimulating factor in rats.

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor, but it may play a role in the regulation of the neuroendocrine system activity. Only few data are available about its possible influence on the pituitary gland. We have recently reported an acute stimulatory effect of G-CSF (and of GM-CSF) on adrenocorticotropic hormone (ACTH) secretion in rats in vivo. The purpose of the present study was to evaluate whether chronic administration of G-CSF affects ACTH and corticosterone secretion and growth processes of the rat anterior pituitary gland and adrenal cortex in vivo. We have demonstrated that G-CSF (at a dose of 10.0 microg/kg body weight (BW)) injected s.c. once daily (for 7 days), stimulated both ACTH and corticosterone secretion. Simultaneously, G-CSF treatment did not change the total anterior pituitary cell proliferation as revealed by immunohistochemical staining of proliferating cell nuclear antigen (PCNA). On the other hand, proliferative activity of corticotrophs, detected in the sections of the anterior pituitary using double-labeling. was significantly increased after treatment with G-CSF. Moreover, this growth factor induced an increase in the proliferation ratio in the entire adrenal equatorial section. These findings suggest an involvement of G-CSF in the regulation of pituitary-adrenal axis and support the hypothesis of bidirectional associations between the immune system and the endocrine glands.

Adrenal Cortex↗
PubMed1999

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↗
PubMed1999

Influence of granulocyte-macrophage colony stimulating factor on pituitary-adrenal axis (PAA) in rats in vivo.

We have studied the in vivo influence of granulocyte-macrophage colony stimulating factor (GM-CSF) on blood plasma concentration of adrenocorticotropic hormone (ACTH) and corticosterone in Wistar rats. The administration of 10 micrograms/kg b.w. GM-CSF at 45 (P < 0.01), 90 (P < 0.01) and at 45 (P < 0.001), 90 (P < 0.001) and 180 min (P < 0.001) increased the secretion of ACTH and corticosterone, respectively. Prolonged administration of 10 micrograms/kg b.w. of GM-CSF increased the ACTH (P < 0.001) and corticosterone (P < 0.001) concentration in blood plasma. We have also found that chronic treatment with 10 micrograms/kg b.w. of GM-CSF increased the proliferative activity of corticotrophs (P < 0.05), but it did not significantly change the total cell proliferation in the anterior pituitary gland. Moreover, this cytokine increased cell proliferation of the adrenal cortex (P < 0.001). These experiments suggest that GM-CSF activates the pituitary-adrenal axis and support the hypothesis of bidirectional associations between the immune and neuroendocrine systems.

Adrenal Cortex↗
PubMed1996

Inhibitory effects of fumagillin and its analogue TNP-470 on the function, morphology and angiogenesis of an oestrogen-induced prolactinoma in Fischer 344 rats.

The process of angiogenesis occurs in many physiological states, but it is also essential for the growth of solid tumours and metastasis formation. An abnormal arterial vascularization has been shown in prolactin-secreting pituitary adenomas induced by prolonged treatment with oestrogens in Fischer 344 (F344) rats. It is thought that anti-angiogenic agents might be useful in therapy for these tumours. Fumagillin and its analogue TNP-470 are known to inhibit endothelial cell proliferation selectively, but their effect on lactotroph cell secretory function and prolactinoma formation has not yet been described. The aim of the present study was to examine the effects of fumagillin and TNP-470 on prolactin secretion, and morphological and vascular changes within the anterior pituitary in long-term oestrogen-treated male F344 rats in vivo and in vitro. As expected, 7 weeks after s.c. implantation of Silastic tubes containing 10 mg diethyl-stilboestrol (DES), a very high rise in serum prolactin levels was found. Both angiogenesis inhibitors injected s.c. at doses of 10 mg/kg body weight for 24 days attenuated the stimulatory effect of DES on prolactin production and release. They also diminished prolactin cell density and inhibited cell proliferation expressed as the number of anterior pituitary cells labelled with bromodeoxyuridine (BrdU), but the effect of TNP-470 was minor compared with fumagillin. Both angioinhibitors suppressed neo-vascularization within the anterior pituitary with similar potency but, on the other hand, they did not affect DES-induced increases in prolactin secretion from cultured rat pituitary cells and cell proliferation in vitro. In conclusion, our results provide strong evidence for the anti-tumour and anti-prolactin activity of angiogenesis inhibitors in the experimentally oestrogen-induced pituitary adenoma; this might be mediated indirectly through the inhibition of angiogenesis.

Animals↗
PubMed1996

The effect of angiotensin II receptor antagonists on diethylstilbestrol-induced vascular changes in the rat anterior pituitary gland: a quantitative evaluation.

The effects if diethylstilbestrol (DES) and of angiotensin II (Ang II) receptor antagonists, such as losartan (selective AT1 receptor antagonist) or PD 123319 (selective AT2 receptor antagonist) on the anterior pituitary microvasculature were studied by means of computer-assisted image analysis. The vascularization was visualized using Selye's method modified by Poely et al. (1964). It was found that DES induced a sharp increase in vessel area, mean vessel diameter and perimeter, whereas mean vessel number was reduced. These DES-induced changes were inhibited by simultaneous administration of losartan. On the other hand, PD 123319 was less effective. These findings suggest an involvement of Ang II, acting mainly via AT1 receptors, in the mechanism of estrogen-induced vascular changes in the rat anterior pituitary gland.

Angiotensin II↗
PubMed1996

Effect of granulocyte-macrophage colony stimulating factor and granulocyte colony stimulating factor on prolactin and adrenocorticotropic hormone secretion in rats: dose- and time-response in vivo studies.

The in vivo effect of granulocyte-macrophage colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF) on the plasma levels of prolactin (PRL) and adrenocorticotropic hormone (ACTH) in rats were studied. The administration of 10 micrograms/kg G-CSF at 45 min (p < 0.05) and 90 min (p < 0.01) or 10 micrograms/kg GM-CSF at 45 and 90 min (p < 0.01) stimulated the secretion of ACTH. Moreover, G-CSF administration only, in doses of 10 micrograms/kg at 45 min (p < 0.05) and 90 min (p < 0.01) augmented PRL secretion into the blood. These experiments suggest that the human colony stimulating factors (GM-CSF and G-CSF) activate the anterior pituitary gland in vivo to ACTH secretion, but only G-CSF positively influenced PRL release in rats.

Adrenocorticotropic Hormone↗
PubMed1995

Effect of granulocyte-macrophage colony stimulating factor and granulocyte colony stimulating factor on melatonin secretion in rats in vivo and in vitro studies.

The study was performed in order to clarify whether granulocyte-macrophage colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF) affect melatonin production and release. We have found that both factors (GM-CSF at doses of 10.0 and 100.0 micrograms/kg, and G-CSF at doses of 1.0, 10.0, and 100.0 micrograms/kg) stimulate melatonin secretion in rats in vivo. Positive correlations between tested doses of GM-CSF and G-CSF and plasma melatonin levels were observed (P < 0.01). Moreover, GM-CSF at doses of 2.0 and 20.0 ng/ml activated in vitro the pineal gland to melatonin release (P < 0.05) in a dose-dependent manner.

Animals↗
PubMed1994

Influence of interleukin 1 and antihuman interleukin 1 receptor antibody on the growth and function of the thyroid gland in rats.

Cytokines seem to influence the hypothalamo-pituitary-thyroid axis. We have studied the effect of different doses of interleukin 1 alpha (IL-1 alpha) and IL-1 beta (given twice daily ip) alone or together with antihuman IL-1 receptor antibody (aIL-1ra) on the proliferation of thyroid follicular cells and thyroid hormone levels in male Wistar rats. We have examined the influence of IL-1 alpha and IL-1 beta at doses of 10.0, 1.0 and 0.1 micrograms/kg body wt of animal and aIL-1ra at a dose of 10.0 micrograms/kg body wt of animals. The incorporation of bromodeoxyuridine into thyroid follicular cell nuclei was used as an index of cell proliferation (labeling index: LI) and measured 24 h after the last of two injections of interleukin. Interleukin 1 beta, at all examined doses, increased thyroid follicular cell proliferation when compared to controls (p < 0.05), and a positive correlation between log of the dose of IL-1 beta used and LI (r = 0.62, p < 0.05) using Student's t-test was found. The administration of aIL-1ra alone also enhanced the thyroid follicular cell proliferation, whereas aIL-1ra used together with IL-1 beta exerted a less pronounced effect than each of these substances used separately (p < 0.05). Interleukin 1 alpha at the dose of 10.0 micrograms/kg body wt increased the proliferation of thyroid follicular cells (p < 0.05). Thyroid hormone levels did not change in any of the experiments. These results suggest a regulatory role of IL-1 upon the proliferation of thyroid cells.

Animals↗
PubMed1994

Interleukin-1 beta stimulates cell proliferation in the intermediate lobe of the rat pituitary gland.

Interleukin-1 (IL-1) is a multifunctional monokine which possesses an impressive array of diverse actions relating to the function of the immune system. IL-1 is present and formed locally in the brain as demonstrated by biochemical and immunocytochemical methods. Various immunomodulatory and neuroendocrine effects of IL-1 have been reported, including induction of several morphological changes in the endocrine cells of experimental animals and humans. IL-1 is present in two molecular forms (IL-1 alpha and IL-1 beta) that activate specific receptors for IL-1. In the present study we investigated the possible effect of recombinant human IL-1 alpha and IL-1 beta and recently cloned anti-human IL-1 receptor antibody (M10) on cell proliferation in the anterior and the intermediate lobe of the pituitary gland of the rat. In vivo labelling with bromodeoxyuridine (BrdU) and immunocytochemical staining with anti-BrdU monoclonal antibody were used as a sensitive index of cell proliferation. IL-1 beta was found to stimulate dose-dependently (0.1-10 micrograms/kg body weight) incorporation of BrdU into pituitary intermediate cell nuclei, and positive correlation between the tested doses of IL-1 beta and BrdU-labelling index was noted (r = 0.89; P < 0.01). This IL-1 beta-induced stimulation of pituitary pars intermedia cell proliferation was receptor specific, since stimulation was blocked by anti-IL-1 receptor antibody. On the other hand, recombinant human IL-1 alpha did not affect BrdU incorporation and the proliferation of pituitary pars intermedia cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Diabetic ketoacidosis in a patient with acromegaly.

Abnormalities of glucose metabolism are a common feature of acromegaly. Overt diabetes mellitus develops in about 10-15% of patients. We present an unusual complication of acromegaly: a 37-year old man with a 2-year history of acromegaly developed diabetic ketoacidosis 3 weeks after transsphenoidal adenomectomy. No specific cause for this sudden metabolic derangement could be demonstrated. Insulin need was very high in the first days after the onset of ketoacidosis, but was considerably reduced after initiation of treatment with octreotide and after successful re-operation.

Acromegaly↗