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Biomedical subjects

M Pawlikowski

Publications and source records attributed to M Pawlikowski.

At least 37 records · Page 2Linked to original sources

Differential effects of somatostatin and its analog on protein tyrosine kinases activity in the rat pituitary and the murine colonic tumors.

The effects of the native somatostatin-14 (SST-14) and of its analog octreotide (OCT) on the activity of protein tyrosine kinases (PTK) in the normal rat anterior pituitary gland, diethylstilbestrol (DES)-induced rat pituitary tumor and murine colonic cancer Colon 38 were studied in vitro. PTK activity was estimated in tissue homogenates using gamma-[32P]ATP and poly (Glu80, Tyr20) as a substrate. It was found that both SST-14 and OCT suppressed the PTK activity in all examined tissues. The suppressive effect was more pronounced in DES-induced pituitary tumor than in normal anterior pituitary gland, and in the former, OCT was more effective than SST-14. In contrast, SST-14 stronger suppressed PTK activity in colonic cancer than OCT. We hypothesize that SST-14 acts on PTK activity in colonic cancer mainly via SSTR-1 subtype of somatostatin receptors.

Animals↗

Effects of octreotide on propylotiouracil-induced goiter in rats: a quantitative evaluation.

To evaluate the possible antigoitrogenic effect of somatostatin, the influence of long-acting somatostatin analog--octreotide--on experimental goiter developed in rats treated with propylthiouracil was examined. Goiter formation was assessed by measurement of the main histological compartments of the thyroid as well as by morphometric analysis of the vascularization and blood supply of the gland. Although treatment with octreotide did not prevent the goiter formation, it clearly reduced blood supply and vascularization of the thyroid and counteracted propylthiouracil-induced increase in the relative volume of follicular epithelium. To conclude, the somatostatin analog--octreotide--is effective in reduction of goiter vascularisation. This finding provides a rationale for the clinical trials of the treatment of hypervascular goiter by somatostatin analogs.

Animals↗

Angiotensin IV stimulates the proliferation of rat anterior pituitary cells in vitro.

The effects of angiotensins II (A II) and IV (A IV) and of A II receptor antagonists losartan (Los) and PD 123319 on [3H]-thymidine incorporation into DNA of the rat anterior pituitary cells in vitro have been studied. The anterior pituitary cells were isolated from the pituitaries of male rats implanted chronically by diethylstilboestrol (DES). It has been found that A IV, like A II, stimulated the tritiated thymidine incorporation into pituitary cells. The effect has not been blocked by antagonists of AT1 and AT2 receptors, Los and PD 123319, respectively.

Angiotensin II↗

[Mineral changes in the intervertebral disc and facet joints during aging].

The mineralogic examinations of intervertebral disc and cartilages of facet joints, taken from corps of the accidents victims, from the level L4-L5, were performed. At the moment of accident the middle age of victim was 41.2 years (4-87 years). Scanning microscopy, atom absorption, chemical analyses and electron microprobe analyses were used in the examinations. As the result of examinations we found: demineralisation of nucleus pulposus in the intervertebral disc and two kinds of mineralisation of anulus fibrosus--invisible and visible. Invisible mineralization was found as the initial stage of visible mineralization. In the cartilages of fact joints, similarly as in the anulus fibrosus, the visible mineralization was found, characterised by the presence of the different shaped mineral deposits in the microscope. The invisible mineralization characterised by increased content of Ca and P and by changes in the chemical composition of basic cartilage substance Fe, Cu, Pb, Zn, Sr, Na, K. It was detected with very sensitive methods. The very close relations between mineralogic changes in the intervertebral disc and facet joints cartilages were also found. Mineralogic changes in degenerative changes of vertebral column outstrip the radiologic ones.

Adolescent↗

The effect of somatostatin analog octreotide on diethylstilbestrol-induced prolactin secretion, cell proliferation and vascular changes in the rat anterior pituitary gland.

The effects of diethylstilbestrol (DES) and of long-acting somatostatin analog, octreotide (SMS) on the rat anterior pituitary microvasculature have been studied by means of computer-assisted image analysis. Additionally, the effects of DES and SMS on prolactin secretion and anterior pituitary cell proliferation have been studied, as well. The vascularization was visualized using Selye's method modified by Poely et al. (1964). The prolactin serum levels were estimated by radio-immunoassay. The proliferation indices were assessed using bromodeoxyuridine incorporation assay. As expected, it was found that DES sharply increased serum prolactin levels and enhanced cell proliferation in the anterior pituitary gland. DES also induced changes in parameters of vascularization. Simultaneous treatment of rats with SMS inhibited the DES-induced elevation of prolactin levels and pituitary cell proliferation. It also suppressed some but not all DES-induced changes in the anterior pituitary vascularization. These data suggest that the angio-inhibitory activity of SMS might be involved in its anti-tumor action on pituitary adenomas, but not as a sole or principal mechanism.

Animals↗

Differential effects of somatostatin analogues on proliferation of murine colonic cancer cells in vitro.

The effects of somatostatin analogues octreotide (SMS 201-995), ASS-51 and ASS-52 on [3H]-thymidine incorporation into DNA of the murine colon 38 cancer cells in vitro were investigated. It was found that SMS 201-995 and ASS-51 inhibited the tritiated thymidine incorporation in a dose-dependent manner. In contrast, analogue ASS-52 in spite of a very similar structure to ASS-51, which differed from the latter only by one CH2OH group, was devoid of remarkable antiproliferative activity. These results indicate that slight modification of the molecule of somatostatin analogues may deeply influence their antiproliferative activity.

Amino Acid Sequence↗

Effects of TRH, prolactin and TSH on cell proliferation in the intermediate lobe of the rat pituitary gland.

The effect of TRH on cell proliferation in the anterior lobe of the pituitary is well known and documented. On the other hand, there are no data on the effects of TRH on the intermediate lobe of the pituitary gland. The aim of this study was to investigate the effect of TRH and its analogues (pGlu-HIs-Gly, pGlu-His-Gly-NH2) on cell proliferation in the intermediate pituitary lobe. The bromodeoxyuridine technique was used to detect the proliferating cells. It was found that TRH stimulated cell proliferation 24 h after a single injection at a dose of 100 micrograms/kg body weight. The TRH analogues did not exert any significant stimulatory effect either 12 h or 24 h after the injection. The second experiment was carried out to distinguish the probable mechanism of the action of TRH. The effects of TSH and prolactin (PRL) on intermediate lobe cell proliferation were examined. It was found that both PRL and TSH exerted a significant stimulatory effect 24 h after a single s.c. injection of PRL at a dose of 150 IU/kg body weight or TSH at a dose 20 IU/kg body weight. It therefore appears that the stimulatory effect of TRH on intermediate pituitary lobe cell proliferation is mediated by PRL and TSH.

Animals↗

Mineral-cholesterol concentrations of the aortic aneurysmatic wall.

Mineralogical investigations were performed on specimens from the aneurysmatic wall of ascending and descending thoracic and abdominal aortas collected intraoperatively from 10 patients (8 male, 2 female) aged 40-80 years. Scanning electron microscopy with energy dispersive x-ray analyses (microprobe-SEM/EDXA), and atomic absorption spectroscopy (AAS) showed incipient mineral and cholesterol depositions in the tissues of the patients when compared with the normal aorta of the young individual. Grains and crystals of cholesterol, and spherulitic mineralization, probably apatitic, were detected. It is suggested that localized cations imbalance precedes mineralization and is the potential co-factor of aortic wall pathology and aneurysm formation.

Adult↗

[Use of mineralogic methods for examination of human tissues. I. Methods of mineralogic examination].

Pathologic mineralization in the human body may produce severe morbidity. Application of mineralogic methods of investigation makes possible closer cognizance of this process, and facilitates prophylaxis and treatment. The principles and employment of following methods are discussed: polarized light microscopy, transmission and scanning electron microscopy, infrared spectroscopy, X-ray diffraction, atomic absorption spectroscopy, electron microprobe, and neutron activation analysis.

Bone and Bones↗

[Use of mineralogic methods for examination of human tissues. II. Mineralization of heart structures].

Using mineralogic methods of investigation there were analyzed 8 mitral and 6 aortic valves, removed during surgical replacement, and 18 concretions which occluded coronary arteries, removed during surgical revascularization procedures. In all samples two kinds of mineralization were stated: 1. secret-observed as higher than normal content of elements in the tissue, and detected using chemical methods only, and 2. apparent-observed as grains and crystals, composed mainly of hydrated phosphates and hydroxyapatite, often with deposits of lipids and cholesterol.

Adult↗

Somatostatin-14 increases the inositol-1,4,5-trisphosphate content in various areas of the brain.

The effects of somatostatin-14 on inositol-1,4,5-trisphosphate (IP3) content were examined in rat pituitary, hippocampus and cortex homogenates. Somatostatin increased IP3 concentration in all these investigated regions in a dose- and time-dependent manner. Maximal increase of IP3 content was found in the pituitary homogenate, and in the hippocampal and cortex homogenates the IP3 argumentation was slightly smaller. Time-response studies showed that this effect declined with extended time of incubation. These results suggest that IP3 is involved in the mechanism of action of somatostatin in brain.

Analysis of Variance↗

Stimulatory effect of angiotensin II on the proliferation of mouse spleen lymphocytes in vitro is mediated via both types of angiotensin II receptors.

The influence of different concentrations of angiotensin II (ANG II) and two specific nonpeptide ANG II receptor antagonists losartan (AT1 receptor blocker) and PD 123319 (AT2 receptor blocker) on the spontaneous proliferation of mouse spleen lymphocytes has been estimated in vitro by the [3H]thymidine uptake assay. It was found that ANG II (10(-6)-10(-12)M) significantly enhanced the [3H]thymidine incorporation into DNA of mouse splenocytes with the maximal effect at 10(-10)M. This stimulatory effect of ANG II on the proliferation of mouse spleen lymphocytes was completely blocked when ANG II receptor antagonists losartan (10(-8)M) or PD 123319 (10(-8)M) were added together with ANG II (10(-10)M). Losartan or PD 123319 tested alone were inactive in this experimental conditions. This findings indicate for the first time the stimulatory effect of ANG II on the proliferation of mouse spleen lymphocytes in vitro. This effect seems to be mediated by both types of ANG II receptors.

Angiotensin II↗

Increased interleukin-2 levels during standard TRH test in man.

Interleukin-2 (IL-2) is a pluripotential cytokine that, besides its role in the regulation of immunocompetent cells function, also stimulates hormone secretion. On the other hand, several factors, including cytokines (interleukin-1, IL-1; interleukin-6, IL-6) and pituitary hormones (thyrotropin, TSH; prolactin, PRL), exert stimulatory effects on T-cell connected IL-2 production. In order to evaluate the role of both pituitary hormones in the activation of the immune system, the following two standard diagnostic tests were performed: TRH test (0.2 mg) in 8 healthy human subjects (4F/4M) aged 18-50 years, and oral metoclopramide (MCP) test (10 mg) in 8 females with galactorrhea and regular menstruation aged 18-52 years. The mobilization (peak response) of PRL, TSH, triiodothyronine (T3), thyroxin (T4), IL-1 beta, IL-2, IL-6 in TRH test, and PRL, IL-1 beta, IL-2, IL-6 for MCP test were evaluated. The responses of TSH (2.0 +/- 0.3 vs 12.3 +/- 2.2 microlU/ml, p < 0.01), PRL (15.3 +/- 2.3 vs 46.4 +/- 8.8 ng/ml, p < 0.01), T3 (178.0 +/- 16.4 vs 248.7 +/- 21.1 ng/dl, p < 0.001), T4 (7.9 +/- 0.4 vs 9.6 +/- 0.5 micrograms/dl, p < 0.001), and IL-2 (45.6 +/- 7.8 vs 79.9 +/- 16.4 fmol/ml, p < 0.05) in TRH test were noted. The peak response of PRL (16.3 +2- 2.6 vs 107.7 +/- 22.4 ng/ml, p < 0.01) in MCP test was also observed, but without any changes in interleukin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Inhibition of rat pituitary tumor cell proliferation by benzodiazepines in vitro.

The effect of various benzodiazepines (peripheral-type receptor ligands: Ro 5-4864, PK 11135; central-type receptor ligands: clonazepam, Ro 15-1788, Ro 15-4513; mixed type: diazepam) on the proliferation of estrogen-induced rat pituitary prolactin-secreting tumor cells was studied in vitro. [3H]thymidine incorporation into DNA was used as an index of cell proliferation. It was found that tested peripheral- and mixed-type benzodiazepine receptor ligands significantly suppressed the pituitary cell proliferation in a dose-dependent manner (10(-4)-10(-8) M). The inhibitory effect of Ro 5-4864 was reversed by 5 x 10(-3) M calcium chloride. On the other hand, central-type benzodiazepine receptor ligands suppressed tumor cell proliferation only at the highest concentration studied (10(-4) M). Our results indicate that benzodiazepines might exert an antiproliferative action on pituitary tumor cell growth, and that this effect seems to be a calcium-dependent process.

Animals↗