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Arne K Sandvik - One of the best experts on this subject based on the ideXlab platform.
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somatostatin receptor 2 sst2 mediated effects of endogenous somatostatin on exocrine and endocrine secretion of the rat stomach
British Journal of Pharmacology, 2005Co-Authors: Vidar Fykse, Helge L. Waldum, Arne K SandvikAbstract:1 Somatostatin is a potent inhibitor of gastric acid secretion. Its effects are mediated through five specific receptor subtypes (sst1–5), of which sst2 is dominant on the enterochromaffin-like (ECL) cell and the parietal cell. To study the paracrine mechanisms of somatostatin, the sst2-specific antagonist PRL-2903 was used. 2 Effects of PRL-2903 on acid secretion and Release of histamine were studied in the totally isolated, vascularly perfused rat stomach. Further, the Release of histamine and Gastrin after bombesin, alone and in combination with PRL-2903, were studied. Results are presented as mean±standard error of the mean (s.e.m.). 3 PRL-2903 concentration-dependently increased the venous histamine concentration from basal 55.6±7.5 to 367±114 nM at 50 μM PRL-2903. With 10 μM PRL-2903, venous histamine output increased from baseline 6.2±0.5 to 20.9±4.9 nmol h−1; P=0.008. The combination of 520 pM Gastrin and 10 μM PRL-2903 increased venous histamine output from 41.7±7.3 nmol h−1 with Gastrin alone to 95.2±9.8 nmol h−1; P=0.016. Further, 10 μM PRL-2903 increased acid output from baseline 8.5±1.8 to 37.4±11 μmol h−1; P=0.017. When combined with 10 μM ranitidine, PRL-2903 did not significantly stimulate acid secretion. Bombesin/PRL-2903 increased venous histamine concentration from 50.4±14.8 to 292±64.2 nM; P=0.008, and Gastrin concentration from 38.6±13.1 to 95.8±20.3 pM; P=0.037. 4 Endogenous somatostatin exerts a continuous restraint on histamine and Gastrin Release from the gastric mucosa and significantly reduces baseline acid secretion. British Journal of Pharmacology (2005) 144, 416–421. doi:10.1038/sj.bjp.0706094
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Somatostatin-receptor 2 (sst2)-mediated effects of endogenous somatostatin on exocrine and endocrine secretion of the rat stomach
British journal of pharmacology, 2005Co-Authors: Vidar Fykse, Helge L. Waldum, David H. Coy, Arne K SandvikAbstract:1 Somatostatin is a potent inhibitor of gastric acid secretion. Its effects are mediated through five specific receptor subtypes (sst1–5), of which sst2 is dominant on the enterochromaffin-like (ECL) cell and the parietal cell. To study the paracrine mechanisms of somatostatin, the sst2-specific antagonist PRL-2903 was used. 2 Effects of PRL-2903 on acid secretion and Release of histamine were studied in the totally isolated, vascularly perfused rat stomach. Further, the Release of histamine and Gastrin after bombesin, alone and in combination with PRL-2903, were studied. Results are presented as mean±standard error of the mean (s.e.m.). 3 PRL-2903 concentration-dependently increased the venous histamine concentration from basal 55.6±7.5 to 367±114 nM at 50 μM PRL-2903. With 10 μM PRL-2903, venous histamine output increased from baseline 6.2±0.5 to 20.9±4.9 nmol h−1; P=0.008. The combination of 520 pM Gastrin and 10 μM PRL-2903 increased venous histamine output from 41.7±7.3 nmol h−1 with Gastrin alone to 95.2±9.8 nmol h−1; P=0.016. Further, 10 μM PRL-2903 increased acid output from baseline 8.5±1.8 to 37.4±11 μmol h−1; P=0.017. When combined with 10 μM ranitidine, PRL-2903 did not significantly stimulate acid secretion. Bombesin/PRL-2903 increased venous histamine concentration from 50.4±14.8 to 292±64.2 nM; P=0.008, and Gastrin concentration from 38.6±13.1 to 95.8±20.3 pM; P=0.037. 4 Endogenous somatostatin exerts a continuous restraint on histamine and Gastrin Release from the gastric mucosa and significantly reduces baseline acid secretion. British Journal of Pharmacology (2005) 144, 416–421. doi:10.1038/sj.bjp.0706094
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marked increase in gastric acid secretory capacity after omeprazole treatment
Gut, 1996Co-Authors: Helge L. Waldum, J S Arnestad, E Brenna, I Eide, Unni Syversen, Arne K SandvikAbstract:BACKGROUND: In contrast with the histamine2 (H2) blockers, proton pump inhibitors have not been shown to give rebound hypersecretion of acid. Taking into consideration the hyperplasia of the enterochromaffin-like (ECL) cell provoked by hyperGastrinaemia secondary to profound acid inhibition and the central role of histamine from ECL cells in the regulation of acid secretion, the lack of any rebound acid hypersecretion after treatment with proton pump inhibitors has been questioned. AIMS: To reassess the effect of treatment with omeprazole on post-treatment acid secretion. METHODS AND PATIENTS: Basal and pentaGastrin stimulated acid secretion were determined in nine patients with reflux oesophagitis before and 14 days after termination of a 90 day treatment period with the proton pump inhibitor omeprazole (40 mg daily). Basal Gastrin Release were determined before and during omeprazole treatment. Furthermore, biopsy samples from the oxyntic mucosa were taken before and at the end of the treatment period for chemical (histamine and chromogranin A (CgA)) evaluation of the ECL cell mass. RESULTS: A substantial increase in meal stimulated Gastrin Release during omeprazole treatment resulted in an increased ECL cell mass. Furthermore, CgA in serum increased during omeprazole treatment suggesting that serum CgA may be used as a test to evaluate ECL cell hyperplasia. A significant increase in basal and a marked (50%) and significant increase in pentaGastrin stimulated acid secretion were found after treatment with omeprazole. CONCLUSIONS: Increased acid secretion after a conventional treatment period with a proton pump inhibitor is probably due to ECL cell hyperplasia and may have negative consequences for acid related diseases.
Helge L. Waldum - One of the best experts on this subject based on the ideXlab platform.
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The Enterochromaffin-like [ECL] Cell—Central in Gastric Physiology and Pathology
International Journal of Molecular Sciences, 2019Co-Authors: Helge L. Waldum, Øystein Sørdal, Patricia MjønesAbstract:Background: Studies on the regulation of gastric and pancreatic secretion began more than 100 years ago. Secretin was the first hormone postulated to exist, initiating the field of endocrinology. Gastrin produced in the antral mucosa was the second postulated hormone, and together with histamine and acetylcholine, represent the three major gastric acid secretagogues known since 1920. For a long time, the mast cell was the only recognized histamine-producing cell in the oxyntic mucosa and, in the mid-1980s, the ECL cell was recognized as the cell producing histamine, taking part in the regulation of gastric acid secretion. Methods: This review is based upon literature research and personal knowledge. Results: The ECL cell carries the Gastrin receptor, and Gastrin regulates its function (histamine Release) as well as proliferation. Long-term hyperGastrinemia results in gastric neoplasia of variable malignancies, implying that gastric hypoacidity resulting in increased Gastrin Release will induce gastric neoplasia, including gastric cancer. Conclusions: The trophic effect of Gastrin on the ECL cell has implications to the treatment with inhibitors of acid secretion.
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somatostatin receptor 2 sst2 mediated effects of endogenous somatostatin on exocrine and endocrine secretion of the rat stomach
British Journal of Pharmacology, 2005Co-Authors: Vidar Fykse, Helge L. Waldum, Arne K SandvikAbstract:1 Somatostatin is a potent inhibitor of gastric acid secretion. Its effects are mediated through five specific receptor subtypes (sst1–5), of which sst2 is dominant on the enterochromaffin-like (ECL) cell and the parietal cell. To study the paracrine mechanisms of somatostatin, the sst2-specific antagonist PRL-2903 was used. 2 Effects of PRL-2903 on acid secretion and Release of histamine were studied in the totally isolated, vascularly perfused rat stomach. Further, the Release of histamine and Gastrin after bombesin, alone and in combination with PRL-2903, were studied. Results are presented as mean±standard error of the mean (s.e.m.). 3 PRL-2903 concentration-dependently increased the venous histamine concentration from basal 55.6±7.5 to 367±114 nM at 50 μM PRL-2903. With 10 μM PRL-2903, venous histamine output increased from baseline 6.2±0.5 to 20.9±4.9 nmol h−1; P=0.008. The combination of 520 pM Gastrin and 10 μM PRL-2903 increased venous histamine output from 41.7±7.3 nmol h−1 with Gastrin alone to 95.2±9.8 nmol h−1; P=0.016. Further, 10 μM PRL-2903 increased acid output from baseline 8.5±1.8 to 37.4±11 μmol h−1; P=0.017. When combined with 10 μM ranitidine, PRL-2903 did not significantly stimulate acid secretion. Bombesin/PRL-2903 increased venous histamine concentration from 50.4±14.8 to 292±64.2 nM; P=0.008, and Gastrin concentration from 38.6±13.1 to 95.8±20.3 pM; P=0.037. 4 Endogenous somatostatin exerts a continuous restraint on histamine and Gastrin Release from the gastric mucosa and significantly reduces baseline acid secretion. British Journal of Pharmacology (2005) 144, 416–421. doi:10.1038/sj.bjp.0706094
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Somatostatin-receptor 2 (sst2)-mediated effects of endogenous somatostatin on exocrine and endocrine secretion of the rat stomach
British journal of pharmacology, 2005Co-Authors: Vidar Fykse, Helge L. Waldum, David H. Coy, Arne K SandvikAbstract:1 Somatostatin is a potent inhibitor of gastric acid secretion. Its effects are mediated through five specific receptor subtypes (sst1–5), of which sst2 is dominant on the enterochromaffin-like (ECL) cell and the parietal cell. To study the paracrine mechanisms of somatostatin, the sst2-specific antagonist PRL-2903 was used. 2 Effects of PRL-2903 on acid secretion and Release of histamine were studied in the totally isolated, vascularly perfused rat stomach. Further, the Release of histamine and Gastrin after bombesin, alone and in combination with PRL-2903, were studied. Results are presented as mean±standard error of the mean (s.e.m.). 3 PRL-2903 concentration-dependently increased the venous histamine concentration from basal 55.6±7.5 to 367±114 nM at 50 μM PRL-2903. With 10 μM PRL-2903, venous histamine output increased from baseline 6.2±0.5 to 20.9±4.9 nmol h−1; P=0.008. The combination of 520 pM Gastrin and 10 μM PRL-2903 increased venous histamine output from 41.7±7.3 nmol h−1 with Gastrin alone to 95.2±9.8 nmol h−1; P=0.016. Further, 10 μM PRL-2903 increased acid output from baseline 8.5±1.8 to 37.4±11 μmol h−1; P=0.017. When combined with 10 μM ranitidine, PRL-2903 did not significantly stimulate acid secretion. Bombesin/PRL-2903 increased venous histamine concentration from 50.4±14.8 to 292±64.2 nM; P=0.008, and Gastrin concentration from 38.6±13.1 to 95.8±20.3 pM; P=0.037. 4 Endogenous somatostatin exerts a continuous restraint on histamine and Gastrin Release from the gastric mucosa and significantly reduces baseline acid secretion. British Journal of Pharmacology (2005) 144, 416–421. doi:10.1038/sj.bjp.0706094
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marked increase in gastric acid secretory capacity after omeprazole treatment
Gut, 1996Co-Authors: Helge L. Waldum, J S Arnestad, E Brenna, I Eide, Unni Syversen, Arne K SandvikAbstract:BACKGROUND: In contrast with the histamine2 (H2) blockers, proton pump inhibitors have not been shown to give rebound hypersecretion of acid. Taking into consideration the hyperplasia of the enterochromaffin-like (ECL) cell provoked by hyperGastrinaemia secondary to profound acid inhibition and the central role of histamine from ECL cells in the regulation of acid secretion, the lack of any rebound acid hypersecretion after treatment with proton pump inhibitors has been questioned. AIMS: To reassess the effect of treatment with omeprazole on post-treatment acid secretion. METHODS AND PATIENTS: Basal and pentaGastrin stimulated acid secretion were determined in nine patients with reflux oesophagitis before and 14 days after termination of a 90 day treatment period with the proton pump inhibitor omeprazole (40 mg daily). Basal Gastrin Release were determined before and during omeprazole treatment. Furthermore, biopsy samples from the oxyntic mucosa were taken before and at the end of the treatment period for chemical (histamine and chromogranin A (CgA)) evaluation of the ECL cell mass. RESULTS: A substantial increase in meal stimulated Gastrin Release during omeprazole treatment resulted in an increased ECL cell mass. Furthermore, CgA in serum increased during omeprazole treatment suggesting that serum CgA may be used as a test to evaluate ECL cell hyperplasia. A significant increase in basal and a marked (50%) and significant increase in pentaGastrin stimulated acid secretion were found after treatment with omeprazole. CONCLUSIONS: Increased acid secretion after a conventional treatment period with a proton pump inhibitor is probably due to ECL cell hyperplasia and may have negative consequences for acid related diseases.
F Halter - One of the best experts on this subject based on the ideXlab platform.
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effects of helicobacter pylori on gastritis pentaGastrin stimulated gastric acid secretion and meal stimulated plasma Gastrin Release in the absence of peptic ulcer disease
The American Journal of Gastroenterology, 1998Co-Authors: S Hurlimann, L Varga, P Schwab, L Mazzucchelli, R Brand, F HalterAbstract:Effects of Helicobacter pylori on Gastritis, PentaGastrin-Stimulated Gastric Acid Secretion, and Meal-Stimulated Plasma Gastrin Release in the Absence of Peptic Ulcer Disease
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long term effects of helicobacter pylori infection on acid and pepsin secretion
Yale Journal of Biology and Medicine, 1996Co-Authors: F Halter, Rowen K ZettermanAbstract:Abstract Chronic Helicobacter pylori infection causes a slight postprandial hypergastinemia, generally referred to as exaggerated or inappropriate Gastrin Release. This can be ablated by eradication of this infective agent. The expectations that this would further unravel the mysteries of the pathogenesis of peptic ulcer disease have not been fulfilled. It is now well established that of conventional acid secretory patterns such as basal acid secretion, maximum Gastrin-stimulated acid secretion, and of sensitivity of the parietal cell to Gastrin, only basal acid is modified by chronic H. pylori colonization. This particularly relates to basal secretion in duodenal ulcer patients, as basal secretion of otherwise healthy, chronically H. pylori-infected subjects appears to be affected in only a small proportion of subjects. It is of particular interest, however, that chronic H. pylori infection supplies a solid explanation why acid inhibitory pathways are deficient in duodenal ulcer disease, since this is reversible following H. pylori eradication as demonstrated by elegant studies with Gastrin-releasing, peptide-stimulated acid secretion. Furthermore, it has gradually become apparent that exaggerated Gastrin response is probably no more than an innocent bystander of chronic H. pylori infection. Paradoxically, in a small subset of patients, hypo-or anacidity accompanying chronic H. pylori infection can be reverted by H. pylori eradication, for currently unknown reasons.
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cholecystokinin type b receptor antagonist pd 136 450 is a partial secretory agonist in the stomach and a full agonist in the pancreas of the rat
Gut, 1994Co-Authors: A Schmassmann, L Varga, A Garner, Beatrice Flogerzi, M Y Hasan, M Sanner, F HalterAbstract:Gastrin (cholecystokinin type B (CCK-B)) receptor antagonists may help to elucidate the physiological role of Gastrin, have therapeutic potential as acid antisecretory drugs, and may be of use as adjuvant therapy for Gastrin sensitive tumours. In binding studies, the Gastrin receptor antagonist PD-136,450 had at least 1000 fold greater affinity for Gastrin (CCK-B) than CCK-A receptors. In this study the biological activity of PD-136,450 was evaluated in conscious and anaesthetised rats. PD-136,450 antagonised Gastrin stimulated acid secretion after subcutaneous (IC50: 0.28 mumol/kg; conscious rats) and intravenous (IC50: 0.17 mumol/kg; anaesthetised rats) administration. In basal secreting fistula animals, the compound stimulated acid output to 30 (5)% of the maximal response to Gastrin. Stimulant activity was not caused by Gastrin Release. As an agonist PD-136,450 was about 350 times less potent than Gastrin-17 on a molar basis. In addition, PD-136,450 was a powerful agonist of pancreatic secretion in anaesthetised rats. The specific Gastrin antagonist L-365,260 inhibited the (partial) agonist activity of PD-136,450 in the stomach and the specific CCK-A receptor antagonist L-364,718 inhibited the agonist activity of PD-136,450 in the pancreas. It is concluded that the agonist effect of PD-136,450 is mediated via interaction with the Gastrin (CCK-B) receptor in the stomach and the CCK-A receptor in the pancreas.
Vidar Fykse - One of the best experts on this subject based on the ideXlab platform.
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somatostatin receptor 2 sst2 mediated effects of endogenous somatostatin on exocrine and endocrine secretion of the rat stomach
British Journal of Pharmacology, 2005Co-Authors: Vidar Fykse, Helge L. Waldum, Arne K SandvikAbstract:1 Somatostatin is a potent inhibitor of gastric acid secretion. Its effects are mediated through five specific receptor subtypes (sst1–5), of which sst2 is dominant on the enterochromaffin-like (ECL) cell and the parietal cell. To study the paracrine mechanisms of somatostatin, the sst2-specific antagonist PRL-2903 was used. 2 Effects of PRL-2903 on acid secretion and Release of histamine were studied in the totally isolated, vascularly perfused rat stomach. Further, the Release of histamine and Gastrin after bombesin, alone and in combination with PRL-2903, were studied. Results are presented as mean±standard error of the mean (s.e.m.). 3 PRL-2903 concentration-dependently increased the venous histamine concentration from basal 55.6±7.5 to 367±114 nM at 50 μM PRL-2903. With 10 μM PRL-2903, venous histamine output increased from baseline 6.2±0.5 to 20.9±4.9 nmol h−1; P=0.008. The combination of 520 pM Gastrin and 10 μM PRL-2903 increased venous histamine output from 41.7±7.3 nmol h−1 with Gastrin alone to 95.2±9.8 nmol h−1; P=0.016. Further, 10 μM PRL-2903 increased acid output from baseline 8.5±1.8 to 37.4±11 μmol h−1; P=0.017. When combined with 10 μM ranitidine, PRL-2903 did not significantly stimulate acid secretion. Bombesin/PRL-2903 increased venous histamine concentration from 50.4±14.8 to 292±64.2 nM; P=0.008, and Gastrin concentration from 38.6±13.1 to 95.8±20.3 pM; P=0.037. 4 Endogenous somatostatin exerts a continuous restraint on histamine and Gastrin Release from the gastric mucosa and significantly reduces baseline acid secretion. British Journal of Pharmacology (2005) 144, 416–421. doi:10.1038/sj.bjp.0706094
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Somatostatin-receptor 2 (sst2)-mediated effects of endogenous somatostatin on exocrine and endocrine secretion of the rat stomach
British journal of pharmacology, 2005Co-Authors: Vidar Fykse, Helge L. Waldum, David H. Coy, Arne K SandvikAbstract:1 Somatostatin is a potent inhibitor of gastric acid secretion. Its effects are mediated through five specific receptor subtypes (sst1–5), of which sst2 is dominant on the enterochromaffin-like (ECL) cell and the parietal cell. To study the paracrine mechanisms of somatostatin, the sst2-specific antagonist PRL-2903 was used. 2 Effects of PRL-2903 on acid secretion and Release of histamine were studied in the totally isolated, vascularly perfused rat stomach. Further, the Release of histamine and Gastrin after bombesin, alone and in combination with PRL-2903, were studied. Results are presented as mean±standard error of the mean (s.e.m.). 3 PRL-2903 concentration-dependently increased the venous histamine concentration from basal 55.6±7.5 to 367±114 nM at 50 μM PRL-2903. With 10 μM PRL-2903, venous histamine output increased from baseline 6.2±0.5 to 20.9±4.9 nmol h−1; P=0.008. The combination of 520 pM Gastrin and 10 μM PRL-2903 increased venous histamine output from 41.7±7.3 nmol h−1 with Gastrin alone to 95.2±9.8 nmol h−1; P=0.016. Further, 10 μM PRL-2903 increased acid output from baseline 8.5±1.8 to 37.4±11 μmol h−1; P=0.017. When combined with 10 μM ranitidine, PRL-2903 did not significantly stimulate acid secretion. Bombesin/PRL-2903 increased venous histamine concentration from 50.4±14.8 to 292±64.2 nM; P=0.008, and Gastrin concentration from 38.6±13.1 to 95.8±20.3 pM; P=0.037. 4 Endogenous somatostatin exerts a continuous restraint on histamine and Gastrin Release from the gastric mucosa and significantly reduces baseline acid secretion. British Journal of Pharmacology (2005) 144, 416–421. doi:10.1038/sj.bjp.0706094
Bianchi G Porro - One of the best experts on this subject based on the ideXlab platform.
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effect of helicobacter pylori eradication on gastric histology serum Gastrin and pepsinogen i levels and gastric emptying in patients with gastric ulcer
The American Journal of Gastroenterology, 1997Co-Authors: G Maconi, M Lazzaroni, O Sangaletti, S Bargiggia, Luca Vago, Bianchi G PorroAbstract:OBJECTIVE: The evolution of gastritis and the behavior of basal and meal-stimulated Gastrin Release, pepsinogen levels, and gastric emptying of solids were studied in a series of consecutive patients with Helicobacter pylori-positive, uncomplicated, non-NSAID-related type I gastric ulcer over a follow-up period of 3 months after eradication therapy was begun. METHODS: Before starting treatment (consisting of omeprazole 40 mg a day for 1 month and amoxycillin 1 g three times daily for 14 days), and for 3 months after ulcer healing, 16 patients had a series of functional examinations, including basal and meal-stimulated serum Gastrin concentration, serum pepsinogen I levels, evaluation of gastric emptying of solids by means of serial ultrasonographic measurement of the gastric antrum area, and histological assessment of antral and corpus gastritis. RESULTS: Double therapy resulted in the successful eradication of H. pylori in eight of 16 evaluable patients. In the group of H. pylori-eradicated patients, the mean scores of gastritis activity and inflammation in the antrum and corpus had fallen, 3 months after eradication. No significant changes in mean gastritis scores were observed in the case and control group with regard to intestinal metaplasia and atrophy in the antrum and corpus. In H. pylori-eradicated patients, the integrated Gastrin response to meal, but not fasting Gastrin concentration, fell significantly during follow-up, and serum pepsinogen I levels significantly decreased, compared with baseline. In contrast, the fasting and maximal antral area and the gastric emptying of solids remained unchanged over time. In the control group (but not the H. pylori-eradicated group), no significant modifications of any of the above-mentioned parameters were observed during follow-up. CONCLUSION: Our findings suggest that in non-NSAID-related type I gastric ulcers, the eradication of H. pylori significantly reduces gastritis activity and inflammatory scores, but not atrophy and intestinal metaplasia, and modifies Gastrin and pepsinogen I Release in a short follow-up period. In contrast, H.pylori eradication does not significantly affect gastric emptying of solids, at least within a period of 3 months from therapy.
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behaviour of acid secretion Gastrin Release serum pepsinogen i and gastric emptying of liquids over six months from eradication of helicobacter pylori in duodenal ulcer patients a controlled study
Gut, 1995Co-Authors: F Parente, G Maconi, O Sangaletti, Luca Vago, M Minguzzi, Bianchi G PorroAbstract:The behaviour of basal and stimulated acid secretion, Gastrin Release, serum pepsinogen I, and gastric emptying of liquids was studied in 19 consecutive patients with Helicobacter pylori positive duodenal ulcer, over a follow up period of six months. Eleven patients were studied before and at three and six months after eradication with lansoprazole plus amoxicillin and tinidazole (case group), whereas the remainder, with persistent H pylori infection, were studied before and after three and six months from ulcer healing, thus constituting the control group. In the case group, three months after eradication, fasting serum pepsinogen I fell from (mean (SEM)) 91.9 (6.9) (pretreatment) to 72.2 (5.1) ng/l and the integrated Gastrin response to a meal reduced from 11,470 (1174) (pretreatment) to 8130 (608) pg/ml/h (p < 0.05). Fasting serum Gastrin concentrations and maximal acid output reduced significantly only six months after eradication. In contrast, no significant change of any of these measurements was seen in the control group either at three or six months from healing compared with the pretreatment values. Gastric emptying of liquids did not change over the entire period of follow up in both study groups. In conclusion, eradication of H pylori in duodenal ulcer patients is accompanied by a rapid fall in serum pepsinogen I and plasma Gastrin concentrations, whereas a slight but significant reduction of maximal acid secretion takes place later on. In contrast, gastric emptying of liquids does not seem to be influenced by H pylori status.
