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A K Sandvik

Publications and source records attributed to A K Sandvik.

At least 37 records · Page 2Linked to original sources
PubMed2000

Gastrin has a specific proliferative effect on the rat enterochromaffin-like cell, but not on the parietal cell: a study by elutriation centrifugation.

Gastrin has a general growth-promoting effect on gastric oxyntic mucosa, and a more pronounced one on the enterochromaffin-like (ECL) cell. Whether gastrin has a proliferative effect on the parietal cell lineage beyond the general effect is uncertain. Hypergastrinaemia was evoked in rats using pantoprazole (group II: 100 micromol kg-1, group III: 400 micromol kg-1) for 45 days. Plasma gastrin was 43 +/- 8 pmol L-1 (control), 283 +/- 54 pmol L-1 (group II) and 577 +/- 63 pmol L-1 (group III). Gastric mucosal cells were isolated and fractionated by elutriation centrifugation. Total cell number, percentage and number of ECL and parietal cells, and histamine were determined in each fraction. The number of mucosal cells increased 1.5-fold in both hypergastrinaemic groups. Enterochromaffin-like cell content was 2.6 +/- 0.5% (control), 6.0 +/- 0.6% (group II) and 9.0 +/- 0.8% (group III). Histamine concentration in oxyntic mucosal cells rose similarly. The size of the ECL cells was 8.5 +/- 0.1 microm (control), 10.8 +/- 0.2 microm (group II) and 12.1 +/- 0.2 microm (group III), and the increased size was confirmed by shifted distribution in elutriation fractions. Histamine per ECL cell increased with cell size. The number of parietal cells increased parallel to the total number of mucosal cells (1.5-fold). Parietal cell size and percentage, assessed by image analysis and distribution in elutriation fractions, were unchanged after pantoprazole dosing. Gastrin has a pronounced, concentration-dependent specific trophic effect on ECL cells and a general proliferative effect on gastric mucosa, including parietal cells.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Oxyntic lesions may be provoked in the rat both by the process of acid secretion and also by gastric acidity.

BACKGROUND: Gastric ischaemia appears to be a common pathogenetic factor for stress ulcers. These ulcers occur predominantly in the oxyntic mucosa, suggesting that the acid secretory process or its stimulation is involved in the pathogenesis. METHODS: We examined separately the role of the acid secretory process and gastric luminal acidity in the pathogenesis of gastric lesions using the isolated vascularly perfused acid-secreting rat stomach. RESULTS: Pentagastrin-stimulated acid secretion induced submucosal bleeding in the oxyntic mucosa whether accompanied by perfusion of the gastric lumen with saline or a phosphate buffer at pH 7.0. On the other hand, acidity, whether endogenous or introduced by luminal perfusion, induced erosions in both the oxyntic and antral mucosa. CONCLUSION: It is concluded that the acid secretory process itself contributes to the particular vulnerability of the oxyntic mucosa to ischaemia. Histamine released upon stimulation of gastric acid secretion or shortage of energy due to the requirements for acid secretion may both contribute to this vulnerability. Furthermore, these findings suggest that inhibition of gastric acid secretion should be superior to antacids in preventing stress ulcers.

1-Methyl-3-isobutylxanthine↗
PubMed2000

Spontaneous ECLomas in cotton rats (Sigmodon hispidus): tumours occurring in hypoacidic/hypergastrinaemic animals with normal parietal cells.

We have identified cotton rats with a high female-predominant occurrence of spontaneous gastric carcinomas localized to the oxyntic mucosa, classified as malignant enterochromaffin-like (ECL) omas. The present study was made to further characterize these ECLomas and surrounding oxyntic mucosa, both morphologically using histochemical and immunohistochemical methods, and for gene expression by northern blot analysis. Among eight female cotton rats, three had an irregularly thickened oxyntic mucosa, increased stomach weight and a high serum gastrin level. Histopathological examination showed adenomatous hyperplasia of the thickened oxyntic mucosa with areas of an invasive neoplastic tumour. Immunohistochemistry, using the general neuroendocrine cell marker chromogranin A (CgA) and the specific ECL cell marker histidine decarboxylase (HDC), showed a considerably increased ECL cell density. These ECL cells displayed active proliferation, with hyperplasia, dysplasia and neoplasia. Parietal cells were not found in the tumour tissue. Parietal cell density was only slightly reduced in the surrounding oxyntic mucosa. The antral mucosa was histopathologically normal with a normal number of gastrin-immunoreactive cells. Likewise, somatostatin-immunoreactive cells did not show any differences in the antral and oxyntic mucosa between rats with pathological and normal oxyntic mucosa. Northern blot analysis revealed increased expression of CgA and HDC mRNA in the thickened oxyntic mucosa, whereas H(+)/K(+) ATPase mRNA was similar in the oxyntic mucosa of those with thickened and normal oxyntic mucosa. Gastrin mRNA in the antral mucosa was high in animals with thickened oxyntic mucosa. Somatostatin mRNA expression was similar in the antral mucosa of control animals and animals with a thickened oxyntic mucosa. We conclude that the spontaneous gastric carcinoma occurring in female cotton rats is an ECLoma developing secondary to hypergastrinaemia due to reduced intragastric pH. The mechanism for reduced acidity is not known, but is not gastric atrophy.

Animals↗
PubMed2000

Octreotide inhibits the enterochromaffin-like cell but not peroxisome proliferator-induced hypergastrinemia.

The peroxisome proliferator ciprofibrate induces hypergastrinemia and as a consequence, enterochromaffin-like (ECL) cell hyperplasia. The mechanism for the gastrin cell stimulation is unknown. The somatostatin analog octreotide LAR (long-acting release) was used to see if the stimulating effects of ciprofibrate could be attenuated. Female Fischer rats were dosed with ciprofibrate (50 mg/kg body weight per day) alone or combined with octreotide LAR (10 mg/30 days) for 60 days. Plasma gastrin and histamine, gastric endocrine cell densities and mRNA abundances were measured. Ciprofibrate increased gastrin mRNA abundance (P<0.05), gastrin cell number (P<0. 001) and cell area (P<0.01), and induced hypergastrinemia (P<0.001). These rats had profound ECL cell hyperplasia, confirmed by an increase in chromogranin A (CgA) and histidine decarboxylase (HDC) mRNA, density of neuroendocrine and ECL cells and plasma histamine levels (all P<0.001). Octreotide LAR did not affect ciprofibrate stimulation of gastrin cells, but all parameters of ECL cell hyperplasia were reduced (P<0.001). Octreotide LAR also significantly inhibited basal ECL cell function and growth. Ciprofibrate stimulates gastrin cell activity by a mechanism unaffected by octreotide, but octreotide does inhibit basal and gastrin-stimulated ECL cell function and growth.

Animals↗
PubMed1999

Pre- and postnatal testosterone administration induces proliferative epithelial lesions with neuroendocrine differentiation in the dorsal lobe of the rat prostate.

BACKGROUND: Androgens are implicated in the pathogenesis of prostatic carcinoma. We have elucidated the role of pre- and postnatal testosterone administration in the occurrence of proliferative lesions as well as neuroendocrine (NE) cells in the rat prostatic complex. METHODS: Female rats were given a single dose of 9 mg testosterone enantate i.m. on day 15 of pregnancy; it gave a high testosterone exposure to the fetus in the early organogenetic period of the rat prostatic complex. One group of the male offspring was followed without further testosterone treatment; a second group received testosterone only in the pubertal period; a third group was given testosterone from puberty and throughout life (46 weeks). These groups were compared to parallel groups (1A-1C) of male offspring without a testosterone supplement in pregnancy. RESULTS: The serum testosterone concentrations in the rats receiving testosterone were significantly higher than those of control rats. Histopathologically, the testosterone-induced proliferative lesions, mainly hyperplastic, were almost exclusively located in the dorsal lobe. Chromogranin A-immunoreactive (CgA-IR) cells were rarely found normally, but occurred more often in the proliferative lesions (P < 0.001). CONCLUSIONS: The incidence of proliferative lesions in rats exposed to testosterone only in puberty was comparable to the incidence found in those rats receiving testosterone in puberty and throughout life. This finding may have clinical implications for young athletes, who use testosterone as an anabolic drug. The occurrence of CgA-IR cells increased in proliferative lesions in the dorsal lobe of the rat prostatic complex.

Aging↗
PubMed1999

Biological activity of carboxy-terminal gastrin analogs.

Amidated forms of gastrin are derived by post-translational processing of a large precursor peptide and stimulate gastric acid secretion via the gastrin/CCK(B) receptor. Non-amidated biosynthetic intermediates may exert biological effects through other mechanisms, but their effect on gastric acid secretion is unclear. Amidated gastrins stimulate acid secretion mainly by releasing histamine from mucosal enterochromaffin-like cells. This study examines the effects on histamine release from the vascularly perfused rat stomach of amidated gastrin-17, COOH-terminal glycine-extended gastrin-17, gastrin-17 extended at the COOH-terminal including the remaining progastrin sequence, and carboxy-terminal progastrin fragments (SAEDEN and GRRSAEDEN). Carboxy-terminal extended gastrins induced histamine release which was inhibited by the gastrin/CCK(B) antagonist L-740,093, but had to be given in concentrations 100-fold higher than amidated gastrin-17 to produce comparable effects. These progastrin-derived peptides are found in high concentrations in some patients with the Zollinger-Ellison syndrome and may contribute to acid hypersecretion and other gastrin/CCK(B) receptor mediated responses.

Amino Acid Sequence↗
PubMed1999

Vagal stimulation augments maximal (penta) gastrin-stimulated acid secretion in humans.

Since the late sixties, the pentagastrin test has been the standard method to examine maximal gastric acid secretion in humans. However, studies on rats and dogs have shown that maximal pentagastrin-stimulated acid secretion can be augmented by concomitant cholinergic stimulation. The aim of this study was to examine whether the combined stimulation of the vagal nerves and pentagastrin infusion could increase maximal gastric acid secretion compared with pentagastrin alone. Eight healthy medical students (seven males) were included in the study. Gastric acid secretion was determined thrice in each subject. On day one, pentagastrin (6 microg kg(-1) h(-1)) was infused. On day two, insulin-induced hypoglycaemia (plasma glucose approximately 2.3 mM during 30 min) was obtained by applying the glucose clamp technique. On day three, pentagastrin infusion and insulin induced-hypoglycaemia were combined. The combination of insulin-induced hypoglycaemia and pentagastrin infusion increased peak acid output about 20% (P = 0.018) compared with pentagastrin alone. The hypoglycaemia did not cause significant release of gastrin. It is concluded that vagal stimulation of gastric acid secretion may be safely obtained by insulin-induced hypoglycaemia when applying the glucose clamp technique. In addition, maximal pentagastrin-stimulated acid secretion does not represent the maximal acid secretory capacity in humans.

Adult↗
PubMed1999

Chronic carbon monoxide exposure in vivo induces myocardial endothelin-1 expression and hypertrophy in rat.

Smoking is associated with endothelial dysfunction and increased plasma levels of endothelin-1. The component of tobacco smoke inducing these effects is unknown. Carbon monoxide induces hypoxia, and there is evidence of carbon monoxide acting as a local mediator in both endothelial and smooth muscle cells. The purpose of this study was to determine whether chronic carbon monoxide exposure similar to that experienced by smokers affects myocardial endothelin-1 expression. Sprague-Dawley female rats were exposed to carbon monoxide 100 ppm for one week or to 100 ppm for one week and 200 ppm for a second week. Carboxyhaemoglobin was 12+/-0.9% in the low and 23+/-1.1% in the high carbon monoxide exposure group. Endothelin-1 expression was measured by competitive reverse transcriptase polymerase chain reaction. High carbon monoxide exposure increased endothelin-1 mRNA by 54+/-12% (P<0.001) in the left ventricle and by 53+/-12% (P<0.001) in the right ventricle. In the low carbon monoxide exposure group corresponding changes were 43+/-14% (P=0.06) and 12+/-16%(P=0.29). Right ventricular weight increased by 18+/-7% (P=0.02) after high and by 16+/-5% (P=0.02) after low exposure. Left ventricular weight was elevated by 5+/-2% (P=0.05) when both exposure groups were compared to controls. We conclude that chronic carbon monoxide exposure leading to carboxyhaemoglobin levels similar to those observed in smokers increases endothelin-1 gene expression and induces myocardial hypertrophy in the rat.

Animals↗
PubMed1998

Neuroendocrine differentiation in human gastric carcinoma.

BACKGROUND: Distinguishing between neuroendocrine carcinoma and adenocarcinoma may be difficult. METHODS: In the current prospective study blood and tumor tissue from patients with gastric carcinoma were collected. The tissue was fixed in different ways to allow examination for neuroendocrine markers by multiple methods such as various histochemical and immunohistochemical methods and electron microscopy. Blood and tumor homogenates were examined by radioimmunoassay for specific hormones and general neuroendocrine markers. RESULTS: Based on examination of general neuroendocrine markers such as chromogranin A (by immunohistochemistry, Northern blot analysis, and tissue concentration), neuron specific enolase (immunohistochemistry) as well as electron microscopy, it was possible to conclude that approximately 10% of the tumors were actually neuroendocrine malignant tumors. Among these tumors, the enterochromaffin-like (ECL) cell was the most preponderant cell of origin (Sevier-Munger positive and serotonin negative immunoreactive tumor cells with secretory granules resembling those observed in normal ECL-cells). As reported previously, tumors of the diffuse type (according to the classification of Laurén) most often were reclassified as neuroendocrine carcinomas. CONCLUSIONS: The current study shows that neuroendocrine and particularly ECL cell-derived tumors are more common in the stomach than previously recognized.

Adenocarcinoma↗
PubMed1998

Carbachol stimulation of gastric acid secretion and its effects on the parietal cell.

1. The acid secretagogue effect of gastrin is mainly mediated by the release of enterochromaffin-like (ECL) cell histamine, but the mechanism of muscarinic stimulation of acid secretion remains unclear. The results of studying aminopyrine uptake in isolated parietal cells, and histamine release in isolated ECL cells suggest that muscarinic agents may act both directly on the parietal cell and indirectly via histamine release from ECL cells. 2. We examined parietal and ECL cell responses to the muscarinic agent carbamylcholine (carbachol) in conscious rats and in rat isolated vascularly perfused stomachs. 3. Intravenous carbachol stimulated acid secretion in conscious gastric fistula rats and increased H+K+ ATPase mRNA abundance, indicating activation of parietal cells. In these experiments there was no increase in portal venous histamine, or in oxyntic mucosal histidine decarboxylase (HDC) enzyme activity and HDC mRNA abundance. 4. In rat isolated stomachs stimulated with carbachol in the dose range 10 nM(-1) mM only the 1 microM concentration increased venous histamine significantly. 5. We concluded that the muscarinic agent carbachol stimulates acid secretion and H+K+ ATPase mRNA in vivo by a direct effect on the parietal cell, that does not depend on the release of ECL cell histamine.

Animals↗
PubMed1998

Potentiating hypergastrinemic effect by the peroxisome proliferator ciprofibrate and omeprazole in the rat.

BACKGROUND: Profound inhibition of gastric acid secretion induces enterochromaffin-like (ECL) cell carcinoids due to hypergastrinemia. Peroxisome proliferators also lead to hypergastrinemia and ECL cell carcinoids but without reducing gastric acidity. Since the peroxisome proliferator ciprofibrate is still in use as lipid-reducing agent, and proton pump inhibitors are among the most commonly used drugs, we found it of interest to evaluate both the effect of a combination of these drugs on serum gastrin and the expression of gastrin and somatostatin mRNA in antral mucosa. METHODS: The drugs were given by gastric gavage once daily for 4 weeks to female rats. Blood was drawn by vein puncture before and at the end of the 4-week period for determination of gastrin by radioimmunoassay. At death the stomachs were removed, the antral mucosa homogenized, and the density of gastrin and somatostatin mRNA determined by Northern blot, using 32P-labelled probes. RESULTS: Omeprazole dosing increased serum gastrin 4-fold, ciprofibrate 5-fold, and the combination 24-fold. Serum gastrin during ciprofibrate dosing increased gradually, reaching significance after 14 days. Antral gastrin mRNA density increased similarly to the increase in serum gastrin, whereas antral somatostatin mRNA tended to be reduced in the omeprazole and increased in the ciprofibrate-dosed rats. CONCLUSION: A potentiating hypergastrinemic effect of the peroxisome proliferator ciprofibrate and the inhibitor of gastric acid secretion omeprazole is shown, indicating different mechanisms of action.

Animals↗
PubMed1998

NGF-beta, NE-cells and prostatic cancer cell lines. A study of neuroendocrine expression in the human prostatic cancer cell lines DU-145, PC-3, LNCaP, and TSU-pr1 following stimulation of the nerve growth factor-beta.

Neuroendocrine (NE) cells are present in both benign and malignant human prostate. However, their function is poorly understood, mainly due to the lack of suitable experimental models. The nerve growth factor-beta (NGF-beta) promotes the rat pheochromocytoma cell line PC-12 to differentiate into neuronal like cells. We have studied the effect of NGF-beta on four human prostate cancer cell lines, LNCaP, DU-145, PC-3, and TSU-pr1. NGF-beta stimulates the growth rate in all these cell lines, but does not induce a neuronal phenotype. NE tumour markers (chromogranin A [CgA] and chromogranin B[CgB]) could not be demonstrated by immunocytochemistry (CgA and CgB), Northern blotting (CgA), or ELISA techniques (CgA), neither in control nor in NGF-beta stimulated cells. Consequently, other experimental models have to be sought in the study of NE cells in the human prostate.

Blotting, Northern↗
PubMed1998

The effect of the peroxisome proliferator ciprofibrate on the gastric mucosa and particularly the gastrin cell.

The peroxisome proliferator ciprofibrate induces hypergastrinemia without inhibiting acid secretion. The present study was carried out to assess the effect of ciprofibrate on serum gastrin and gastrin (G) cells in different strains of rats and to compare the effect of ciprofibrate with other lipid-reducing agents (lovastatin and simvastatin) which have a different mechanism of action. Serum gastrin was determined by a radioimmunoassay method, G cell density by histomorphometry after immunostaining for G cells, and gastrin, somatostatin and histidine decarboxylase (HDC) mRNA abundance by Northern blot analysis. Ciprofibrate (100 mg/kg/day for three weeks) induced a marked hypergastrinemia (P < 0.01) in male and female Fischer rats as well as in female Wistar rats. Simvastatin and lovastatin did not affect serum gastrin. Antral G cell density increased significantly in female Wistar rats (P < 0.05) and non-significantly in the other rats after ciprofibrate. Both gastrin and somatostatin mRNA abundance in antral mucosa increased markedly and significantly (P < 0.01) after ciprofibrate treatment. The present study shows that the peroxisome proliferator ciprofibrate induces hypergastrinemia secondary to an increased storage and synthesis of antral gastrin. Since somatostatin mRNA abundance also increased, the present study suggests that ciprofibrate and possibly other peroxisome proliferators in sufficient concentrations have a stimulatory effect on endocrine cells.

Animals↗