[Effect of pineal peptides on neuroendocrine system after pinealectomy]. / Vliianie peptidov pineal'noi zhelezy na neiroéndokrinnye vzaimosviazi posle pinealéktomii.

Removal of the pineal gland leads to structural and functional rearrangement of gastric endocrine cells and thyroid C-cells in albino rats, as was shown by immunohistological methods and morphometry. Injection of pineal peptides epithalone and epithalamine eliminated these changes. Biological activity of epithalone is believed to be higher than that of epithalamine.

Pulmonary endocrine cell hyperplasia and papilloma in rats induced by intratracheal injections of extract from particulate air pollutants.

We investigated the effect of intratracheal injections of an extract of suspended particulate matter (SPM) obtained from the urban ambient air of Tokyo, upon the development of proliferative lesions of pulmonary endocrine cells (PECs) in the rat. We also examined the modification effects of nitrogen dioxide, sulfur dioxide, or both of them on the PEC lesions. Male F344 rats were divided into six experimental groups of 5 animals each. Twenty animals were treated with intratracheal instillations of SPM admixed with carbon once a week for 4 weeks with or without additional gaseous exposure (6 ppm nitrogen dioxide or 4 ppm sulfur dioxide) 16 hrs a day for 11 months. Five animals were given intratracheal injections of carbon suspended in saline and the other five were untreated. The subcardiac lobes of the right lung were fixed with 4% paraformaldehyde, and embedded in paraffin. PEC hyperplasias and papillomas were counted in 200 serial sections, 4 microns thick. The average incidences of PEC hyperplasia in the untreated animals and in those treated with carbon were 194 and 200/cm3, respectively. The average incidences of PEC hyperplasia in the animals exposed to SPM tar only, SPM tar plus nitrogen dioxide and sulfur dioxide, SPM tar with nitrogen dioxide and SPM tar with sulfur dioxide were 376, 378, 372 and 349/cm3, respectively. These were significantly higher than the levels of the control animals, and additional gaseous stimuli had no effect on the incidence of PEC hyperplasia. Besides PEC hyperplasia, a few PEC papillomas were found in the animals treated with SPM tar, regardless of gaseous exposure, but in the control animals no papilloma was evident. Thus, compounds in airborne particulates are considered to be responsible for the development of PEC hyperplasias and papillomas.

[The effect of choleragen poisoning on the intestinal apudocytes of gnotobiotic minipigs]. / Vliianie kholerogennoi intoksikatsii na apudotsity kishechnika gnotobioticheskikh mini-porosiat.

Intragastric administration of the cholera toxin to gnotobiotic mini-pigs results in cyclic morphofunctional alterations of intestinal apudocytes followed by their degranulation, a decrease in their number from 1 to 3 hrs and after 18 hrs, while a slight increase in their number occurred from 3 to 12 hrs. The response of APUD-system cells is similar in large and small intestine. Products of apudocyte secretion may be involved in the diarrheogenic effect of the cholera toxin.

Gastric endocrine cell evolution in patients with Zollinger-Ellison syndrome. Influence of gastrinoma growth and long-term omeprazole treatment.

Evolution of gastrinoma tumoral mass, fasting serum gastrin concentrations, and gastric endocrine cells has been analyzed in 21 patients with the Zollinger-Ellison syndrome committed to long-term omeprazole treatment (up to 7.75 years, median 37 months). Gastrinoma growth was seen in eight patients. Significant increase in serum gastrin was only observed in the group of patients with gastrinoma growth. Fundic argyrophil cell densities were correlated with serum gastrin (r' = 0.68, P = 0.002). Argyrophil and antral gastrin cell densities significantly increased during the survey, but increases were greater in the group with gastrinoma growth (respectively, +136% and +131%) than in the other group (respectively, +34% and +43%). Progression in the degree of argyrophil cell hyperplasia, noted qualitatively, was observed in 11 patients. Fundic carcinoids developed in three of these 11 patients, all three having multiple endocrine neoplasia type 1 (MEN 1). Positive linear individual correlations (r > or = 0.85) between argyrophil cell densities and corresponding durations of omeprazole treatment were found in nine of the 10 patients studied at least three times and who had a clear-cut increase in those cell densities. Thus, increase in serum gastrin and fundic argyrophil cell densities appeared closely associated with gastrinoma growth; however, duration of drug-induced hypochlorhydria may also affect cell proliferation.

[Structural-functional characteristics of the renal endocrine system after alpha-1 adrenoreceptor blockade]. / Strukturno-funktsional'naia kharakteristika éndokrinnoi sistemy pochek pri blokade alfa-1 adrenoreceptorov.

Research Institute of Cardiology, Uzbek Health Ministry Structural and functional peculiarities of the renal juxtaglomerular and interstitial cells were studied after alpha 1-adreno-blockers were used. The endocrine cells were studied after a single and prolonged introduction of the agents. Administration of a single dose of the drugs led to hypergranulation in juxtaglomerular cells thus decreasing their functional activity and release of the granules from the cells. The interstitial cells function intensified. Prolonged administration of alpha 1-adrenoblockers caused a degranulation process in the juxtaglomerular cells and a decrease in their protein-synthetizing structures, namely, renin synthesis, and elevation of synthetic process in the interstitial cells.

Investigations of endocrine cells in the gastrointestinal tract and pancreas during the metamorphosis of an anuran (Alytes obstetricans L.): histochemical detection of APUD cells.

Endocrine cells were detected at premetamorphosis, prometamorphosis, climax, and juvenile stages using an amine-inducing fluorescence technique with or without previous L-3,4-dihydroxyphenylalanine (L-DOPA) treatment. At premetamorphosis, serotonin cells exhibited yellow fluorescence in the gut primary epithelium of the L-DOPA untreated animals. In the treated animals, green fluorescent APUD cells could be seen in addition to the serotonin cells. In the pancreas, numerous clusters of fluorescent APUD cells were observed. At prometamorphosis the number of fluorescent cells increased in the intestinal primary epithelium and, close to the basal membrane, numerous small regenerative buds devoid of fluorescent cells appeared. In the pancreas of L-DOPA-treated animals, two types of APUD cells could be distinguished by their different fluorescence intensities. At the climax stage, the stomach developed and APUD cells were detectable in the gastric glandular buds. The degenerated primary intestinal epithelium was progressively removed in the intestinal lumen. At this stage, the regenerative buds of the secondary epithelium exhibited APUD cells. In the disorganized pancreas, the induced fluorescence decreased strongly. At the juvenile stage, cords of APUD cells displayed a cytoplasmic green fluorescence in the pancreas. In the stomach and intestine, serotonin and APUD cells were numerous.

[Ultrastructure of cells of the rat entero-endocrine system during exposure to cholera toxin]. / Ul'trastruktura kletok éntero-éndokrinnoi sistemy krysy pri kholerogennoi intoksikatsii.

Horse radish peroxidase-labelled cholera toxin (choleragen) binds to the receptors of entero-endocrine cell (Ec-cells) plasmalemma. Unlike columnar epitheliocytes, the effect of choleragen on Ec-cells.

Studies on in vitro effect of serotonin on calcitonin secretion by rat thyroid C cells.

Thyroid glands of young rats were incubated for 3 h in Eagle's solution supplemented with 5-hydroxy-l-tryptophan (5-HTP) or with serotonin. Following control incubations or incubations with serotonin, no serotonin could be demonstrated in C cells using immunocytochemical techniques. However, serotonin was demonstrated in the secretory granules of all C cells following incubation with 5-HTP. The secretory function of C cells was evaluated by ultrastructural and immunocytochemical studies, and by calcitonin radioimmunoassays of the incubation medium. Following incubation with 5-HTP, the secretory function of the majority of C cells was inhibited, and calcitonin levels in the media were decreased. Incubation with serotonin produced an increased secretory function of C cells and higher calcitonin levels in the media. The results indicate that serotonin and its direct precursor, 5-HTP, affect calcitonin secretion by rat thyroid C cells by distinct mechanisms.

Effect of 1-DOPA on calcitonin secretion by thyroid C cells.

After administering 1-DOPA for 7 d a decreased number of secretory granules as well as pronounced rough endoplasmic reticulum and Golgi apparatus were noted in C cells. A single dose of 1-DOPA did not inhibit C cell stimulation induced by a single dose of calcium gluconate. On the other hand, parallel administration of alpha-methyl-DOPA and calcium gluconate did not decrease the number of C cell secretory granules, which were observed after administration of calcium gluconate alone. The data suggest that the presence of DOPAmine (formed the 1-DOPA) in the secretory granules is a prerequisite for normal functioning of secretory processes in thyroid C cells.

Occurrence of APUD-type cells in the ciliated cyst of the parathyroid gland of ozone-exposed dogs.

Presence of APUD-type cells in the ciliated cysts of the parathyroid glands of ozonized dog is described in this report. These cells were present on the abluminal side of the cyst wall and contained secretory granules with dense core, homogeneous matrix and coated vesicles throughout the cytoplasm. Intermixed with the granules were sheaves of microfilaments which were mostly seen in the perinuclear area. The APUD cells formed hemidesmosomes with the basal lamina.

Effects of diethylnitrosamine on lung neuroendocrine cells.

Diethylnitrosamine is known to cause squamous cell carcinoma and adenocarcinoma of the lung in Syrian golden hamsters. Sections of lungs obtained from hamsters treated with the systemic carcinogen diethylnitrosamine revealed a significant increase in the number of argyrophilic cells of neuroepithelial bodies. These affected cells also exhibited enhanced survival in vitro. After 7 days in culture, argyrophilia, dense-core vesicles, and corticotropin-like immunoreactivity were observed in many of the cells derived from the lungs of carcinogen-exposed hamsters by dissociation with pronase. In addition, nuclei of argyrophilic cells in neuroepithelial bodies of the exposed hamsters were labeled at 60 min following administration of [3H]thymidine. This suggests that the carcinogen stimulates the pulmonary neuroendocrine-like cells to divide. Normally, the component cells of neuroepithelial bodies may originate from nonargyrophilic precursor cells in the surrounding epithelium, as in control hamsters the argyrophilic cells of neuroepithelial bodies appeared labeled only at 8 days after the administration of thymidine. The relationship of the diethylnitrosamine-induced reactions to bronchial carcinoid tumors or small-cell carcinomas of the lung remains to be established.

Immunocytochemical studies of APUD cells in airways: effects of nitrosodiethylamine and nitrogen dioxide.

The amine precursor uptake and decarboxylase (APUD) cells and neuroepithelial bodies (NEBs) in airways of adult rats have been studied by immunocytochemical methods for the presence of adrenocorticotropic hormone (ACTH), growth hormone (hGH), calcitonin, and bombesin in control animals and following exposure to nitrosodiethylamine and nitrogen dioxide (NO2). Calcitonin-like immunoreactivity (CLIR) is present in APUD cells of the trachea and bronchioles and in NEBs in the lung. Rats treated with nitrosodiethylamine and NO2 exhibit increased numbers of argyrophilic cells but no increase in cells containing specific intracytoplasmic CLIR. The presence of ACTH, hGH, and bombesin in respiratory tract APUD cells was not observed. These studies indicate that APUD cells in the trachea and bronchioles of adult rats harbor endocrine cells with immunohistochemical characteristics similar to C cells of the thyroid, and that these cell do not appear to be altered in number when rats are treated with agents known to produce an increase in APUD cells.

Quantitative studies of argyrophilic APUD cells in airways: II. The effects of transplacental diethylnitrosamine.

The effects of transplacental administration of diethylnitrosamine (DEN) on the densities of epithelial and APUD cells in the large and small airways of developing hamsters have been studied quantitatively. The APUD cells are quantitated by relating them to the number of airway epithelial cells; APUD cells are present in similar densities in the large airways (0.12 APUD cells/100 cells) and small airways (0.14) of 2-day-old control hamsters. At 4 days an increase in the densities of APUD cells and an increase in epithelial cells is observed in the small airways, whereas those in the large airways decrease slightly. At later periods there is a progressive decline in the density of APUD cells in the control hamsters. Exposure in utero to DEN results in a generalized increase in APUD cells in 2-day-old hamsters, which is more pronounced in bronchioles (fivefold increase). The effect disappears in older animals. It also results in a transient increase in tracheal epithelial cell density in 7-day-old hamsters. Whether the selective and transient APUD cell hyperplasia induced by transplacental administration of DEN results from proliferation of these cells or from differentiation of other types of epithelial cells into APUD cells requires further study.