Acute effects of coffee consumption on self-reported gastrointestinal symptoms, blood pressure and stress indices in healthy individuals.

BACKGROUND: It has been suggested that coffee may affect the gut-brain axis with conflicting outcomes. Moreover, there is insufficient evidence to determine whether the type or temperature of coffee consumed will have a different impact on the gut-brain axis. The purpose of this study was to investigate the effects of acute coffee consumption on the following: 1. self-reported GI symptoms and salivary gastrin, 2. stress indices [salivary cortisol and alpha-amylase (sAA)] and psychometric measures, and 3. blood pressure (BP), in healthy, daily coffee consuming individuals in non-stressful conditions. METHODS: This was a randomized, double blind, crossover clinical trial, in which 40 healthy individuals (20 men, 20 women), 20-55 years of age, randomly consumed four 200 ml coffee beverages containing 160 mg caffeine (hot and cold instant coffee, cold espresso, hot filtered coffee), 1 week apart. Salivary samples and psychometric questionnaires were collected at baseline and post-coffee consumption at 15,30, and 60 min for salivary gastrin and sAA measurements and at 60,120, and 180 min for cortisol measurements. BP was measured at beginning and end of each intervention. ClinicalTrials.gov ID: NCT02253628 RESULTS: Coffee consumption significantly increased sAA activity (P = 0.041), with significant differences only between cold instant and filter coffee at 15 and 30 min post-consumption (P < 0.05). Coffee temporarily increased salivary gastrin, without differences between coffee types. Coffee did not affect salivary cortisol or self-reported anxiety levels. Coffee consumption significantly increased BP, within the healthy physiological levels, in a gender specific manner at the end of the experimental periods, without differences between coffee types. CONCLUSION: Acute coffee consumption in non-stressful conditions activated sAA and BP but not salivary cortisol, indicating activation of the sympathetic nervous system. Post-coffee sAA increase without a concomitant cortisol increase may also indicate that coffee may have some anti-stress properties.

Gut peptide profile and chemotherapy-associated dyspepsia syndrome in patients with breast cancer undergoing FEC60 chemotherapy.

AIM: The association of motilin, ghrelin, leptin, gastrin, pepsinogen (PG) I and II with cancer chemotherapy-associated dyspepsia syndrome (CADS) was investigated in 35 patients with breast cancer receiving first cycle of 5-fluorouracil, cyclophosphamide, epirubicin (FEC60) chemotherapy. PATIENTS AND METHODS: The onset of dyspeptic symptoms on days 3 and 10 after chemotherapy identified patients with and without CADS. Gastrointestinal symptoms were scored with the Gastrointestinal Symptom Scoring Rate (GSRS) questionnaire. Gastrointestinal peptides were evaluated by enzyme-linked immunosorbent assay. RESULTS: Twenty-one patients (60%) had CADS. The area under the curve (AUC) of ghrelin was higher, whereas that of PGI, PGII and motilin were lower in patients with CADS compared to those without. In patients with CADS, the AUC of PGI and PGII negatively correlated with the GSRS indigestion cluster. CONCLUSION: Impairment of gastrointestinal motility suggested by low motilin concentrations and mucosal damage mirrored by an increase of ghrelin seem to be involved in the onset of CADS in patients during chemotherapy for breast cancer.

Activation of the calcium sensing receptor stimulates gastrin and gastric acid secretion in healthy participants.

UNLABELLED: In 17 adults on a fixed metabolic diet, an 11-day course of cinacalcet increased serum gastrin and basal gastric acid output, but not maximal gastric acid output, compared with a placebo. These findings indicate that the calcium sensor receptor plays a role in the regulation of gastric acid. INTRODUCTION: Gastric acid secretion is a complex process regulated by neuronal and hormonal pathways. Ex vivo studies in human gastric tissues indicate that the calcium sensing receptor (CaR), expressed on the surface of G and parietal cells, may be involved in this regulation. We sought to determine whether cinacalcet, a CaR allosteric agonist, increases serum gastrin and gastric acid secretion. METHODS: Seventeen healthy adults with normal gastric acid output were placed on an 18-day metabolic diet. On day 8 (baseline), participants were given cinacalcet (15 then 30 mg/day) or placebo for 11 days. Changes in gastric acid output, serum gastrin, and other measures were compared in the two groups. RESULTS: Changes in serum gastrin and basal acid output (adjusted for baseline body weight) were significantly more positive in the cinacalcet group compared with placebo (P = 0.004 and P = 0.039 respectively). Change in maximal acid output was similar in the two groups (P = 0.995). As expected, cinacalcet produced significant decreases in serum PTH (P < 0.001) and ionized calcium levels (P = 0.032), and increases in serum phosphorus levels (P = 0.001) and urinary calcium (P = 0.023). CONCLUSIONS: This study provides in vivo evidence that activation of the CaR increases serum gastrin levels and basal gastric acid secretion in healthy adults.

Effects of estradiol and progesterone on gastric mucosal response to early Helicobacter pylori infection in female gerbils.

BACKGROUND: Gender differences have been shown regarding the changes in the inflammatory response, gastrin secretion, and gastric acidity during Helicobacter pylori infection. AIM: To investigate the role of estradiol and progesterone in the changes of the gastric mucosa induced by H. pylori during the early stage of infection in female gerbils. MATERIALS AND METHODS: Thirty-three adult ovariectomized female gerbils were infected with H. pylori (SS1); 7 days after infection they were treated with low and high doses of estradiol (50 and 250 microg/60 days pellet), progesterone (15 and 50 mg/60 days pellet) and vehicle. Non-ovariectomized infected gerbils were used as control. Gerbils were euthanized after 6 weeks of infection. Histologic evaluation, immunohistochemical detection of proliferation cell nuclear antigen (PCNA), gastrin, and apoptosis by terminal deoxynucleotide nick end labeling (TUNEL) assay were performed. Positive cells for PCNA, TUNEL, and gastrin were counted in 10 oriented glands per animal. Two-sided p = .05 was considered significant. RESULTS: Estradiol-treated groups showed more intense and extended acute and follicular gastritis compared to the vehicle group, whereas progesterone-treated groups presented less gastritis than the other groups. Proliferation and apoptosis indexes were significantly lower in the vehicle group when compared with those of the control; both indexes were increased in the high-dose estradiol and progesterone groups as compared with those of the vehicle. Grade I nonmetaplastic atrophy was observed in the vehicle and progesterone groups. The high-dose progesterone group showed a significant reduction in the number of gastrin cells. CONCLUSIONS: Estradiol and progesterone participate in the gastric mucosal response to early H. pylori infection in gerbils.

The effect of different dietary fats on gastrin levels in the pyloric antrum and plasma of weaner and adult Wistar rats.

The effect of dietary fats on gastrin in the pyloric antrum and plasma of Wistar rat was examined. Two different age groups of rats were fed 3 different diets in which fat was in the form of menhaden oil (MO), hydrogenated coconut oil (CO) and safflower oil (SO) respectively. Control groups were fed on normal laboratory diet. Each diet was isoenergetic and no group showed significant differences in either food intake or weight gain during the experiment. Weaner rats fed on MO diet exhibited significant reduction in both antral (P = 0.047) and plasma (P = 0.002) gastrin concentrations when compared with age-matched controls. Likewise, adult rats fed the MO diet exhibited significant reduction in both antral (P = 0.008) and plasma (P = 0.002) gastrin concentrations. In addition, adult rats fed the CO diet exhibited significant reduction in both antral (P = 0.047) and plasma gastrin (P = 0.002) concentrations. Rats from both age groups fed the SO diet exhibited no significant differences in gastrin concentration when compared with their respective control groups. These data indicate that the composition of dietary fat can have profound effects on both tissue and plasma concentrations of gastrin in rats.

Histamine H2 receptor antagonist-refractory oesophagitis: the efficacy of long-term omeprazole maintenance treatment.

BACKGROUND: Erosive oesophagitis refractory to high dose histamine H2 receptor antagonists (definition: failure to heal fully after > or = 3 months' treatment with cimetidine 3.2 g or ranitidine 0.9 g) responds well to omeprazole 40 mg daily but frequently relapses when the patients are put back on maintenance H2 receptor antagonists at medium or even high dose (e.g. cimetidine 1.6 g and 3.2 g, respectively). AIM: To investigate the efficacy of maintenance omeprazole 20 mg daily in refractory erosive oesophagitis. PATIENTS & METHODS: In this open, sequential study, patients with H2 receptor antagonist-refractory oesophagitis were healed on omeprazole 40 mg daily and then put on maintenance H2 receptor antagonists (cimetidine 1.6 g or 3.2 g). Relapses were re-treated with omeprazole 40 mg; upon rehealing, patients were put on maintenance omeprazole 20 mg daily for up to 4.5 years. RESULTS: Healing on omeprazole occurred in 38 out of 39 patients (97%) at 12 weeks. Only six of the 38 patients (16%) relapsed (asymptomatic in half) during subsequent maintenance treatment, whereas all had relapsed earlier on high dose H2 receptor antagonists. CONCLUSION: Within the limits of interpretation of an open study, omeprazole 20 mg daily seems effective in maintaining prolonged remission in this group of patients with H2 receptor antagonist-refractory oesophagitis.

[A study on two gut hormones in breast milk].

OBJECTIVE: To determine if motilin and gastrin are present in breast milk and to measure their concentrations in human milk and cow milk. METHODS: The concentration of motilin was measured in 17 samples of human colostrum, 18 samples of human mature milk, 8 samples of cow colostrum and 20 samples of cow mature milk by radioimmunoassay. The concentration of gastrin in human milk was also determined by radioimmunoassay. RESULTS: Motilin concentration in human colostrum was the highest (416.34 +/- 183.95ng/L), being higher than that in human mature milk (272.91 +/- 148.73ng/L, that in cow colostrum (229.51 +/- 63.68ng/L) and that in cow mature milk (35.46 +/- 16.94ng/L). Evidently the difference in motilin concentration was very significant between human milk and cow milk. The gastrin concentration in human colostrum was 17.20 +/- 11.98ng/L, being higher than that in human mature milk (5.62 +/- 2.33ng/L). CONCLUSION: Human milk, especially human colostrum, contains high concentrations of motilin and gastrin. Breast feeding, especially early breast feeding, may promote the maturation of the developing gut in neonates and infants.

[Effect of prolonged treatment with proton pump inhibitors on serum gastrin levels and the fundus mucosa. Preliminary results]. / Influence des traitements prolongés par inhibiteurs de la pompe à protons sur la gastrinémie et la muqueuse fundique. Résultats préliminaires.

OBJECTIVES: To evaluate the evolution of fundic argyrophil cell density and hyperplasia grading, fundic chronic gastritis grading and serum gastrin levels in patients treated with proton pump inhibitors. METHODS: Thirty-two patients treated with proton pump inhibitors for gastroesophageal reflux and/or duodenal ulcer were studied. No patient had a gastric ulcer. The studied parameters were serum gastrin levels, fundic argyrophil cell density, the degree of fundic argyrophil cell hyperplasia, the grade of fundic atrophic gastritis and the presence of Helicobacter pylori. The first point of the study was 7 months (range: 0-42 months) and the last point 33 months (range: 7-72 months) after the beginning of the treatment. RESULTS: Serum gastrin levels significantly increased with treatment. Fundic argyrophil cell density did not change significantly. In 3 patients (9%), serum gastrin levels were twice the normal upper limit. The highest serum gastrin levels (249 and 665 pg/mL) were noted in the 2 patients treated with the highest doses of proton pump inhibitors. Micronodular hyperplasia of the fundic argyrophil cells was observed in 2 patients treated with omeprazole 20 mg/d for 4 years and lansoprazole 90 mg/d for 6 years, respectively. Non active superficial chronic gastritis was noted in 2 patients. Serum gastrin levels were significantly correlated with cell densities. CONCLUSION: There were minor modifications of fundic argyrophil cell population and of gastrinaemia during the study period. They were not related to chronic atrophic gastritis. However, survey is mandatory in patients treated with high dose proton pump inhibitors, in those in whom gastrinaemia is elevated and when treatment duration is longer than 5 years.

Gastrin receptor genes are expressed in gastric parietal and enterochromaffin-like cells of Mastomys natalensis.

Although gastric enterochromaffin-like (ECL) carcinoid tumors are known to develop in patients with long-standing hypergastrinemia, the expression of the gastrin receptor gene in ECL cells has not yet been demonstrated. Therefore, this study was designed to examine gastrin receptor gene expression in ECL cells. Mastomys gastric mucosal cells isolated by enzyme dispersion were separated into 10 fractions (F1-10) by centrifugal elutriation. Each fraction was examined histologically to determine whether they contained ECL and/or parietal cells and Northern blot analysis was used to confirm the presence of histidine decarboxylase and H+, K(+)-ATPase gene expression. ECL cells were found only in fractions 1 and 2, whereas parietal cells were detected in fractions 6-10. Gastrin receptor gene expression was demonstrated in both parietal cell-rich and ECL cell-rich fractions. In addition, the gastrin receptor cDNA sequences obtained from the two of the fractions (F1 and 8) were identical. These results suggest that gastrin receptor genes are expressed in ECL cells as well as in parietal cells and that these receptors are identical.

Sensitive detection of rat gastrin mRNA by in situ hybridization with chemically biotinylated oligodeoxynucleotides: validation, quantitation, and double-staining studies.

Chemically biotin-labeled oligonucleotides form attractive reagents, as large quantities of stable and well-defined probes can easily be produced. Their usefulness for in situ hybridization was tested using rat gastrin cells as a model. Two probes recognizing two different regions of rat gastrin mRNA were synthesized and produced specific and equally strong hybridization signals. A probe complementary to human gastrin mRNA, but with mismatches to the rat gastrin mRNA sequence, failed to reveal rat gastrin cells under the stringency conditions used. Northern blotting revealed that the rat gastrin mRNA probes reacted exclusively with the appropriately sized (approximately 650 bases) mRNA. Model systems demonstrated that the hybridization signal, as revealed by alkaline phosphatase-based detection, varied linearly with the 10logarithm of target concentration and also showed that a new detection system was much more sensitive than previously used systems. In agreement with previous biochemical data, image analysis showed that starvation of rats led to a progressive decrease in cell staining intensities and cell numbers. Double staining for rat gastrin mRNA and gastrin immunoreactivity showed that in adult rats almost all gastrin cells expressed both mRNA and protein. Similar studies on developing rat gastrin cells revealed discrepancies between gastrin mRNA and gastrin-immunoreactive cells during the first week of newborn life. Subsequently, expression of mRNA and protein in the cells became gradually more concordant.

Production of immunoreactive corticotropin-releasing hormone in various neuroendocrine tumors.

The concentrations of immunoreactive (IR) corticotropin-releasing hormone (CRH) in 218 neuroendocrine tumors were determined by CRH radioimmunoassay. The tumors examined were 86 pancreatic endocrine tumors (PET), 22 neuroblastic tumors (NBT), 26 carcinoid tumors (CA), 24 pheochromocytomas (PHEO), 40 small cell lung carcinomas (SCLC) and 20 medullary thyroid carcinomas (MTC). IR-CRH was detectable in 21 neuroendocrine tumors (10 PET, four NBT, three CA, two PHEO and two SCLC) at levels of 10-2,700 ng/g wet weight (9.6%). The 21 patients with these CRH-producing tumors showed no clinical symptoms suggestive of Cushing's syndrome. The levels of plasma IR-CRH extracted by immunoaffinity chromatography were < 7.5 pg/ml in five normal subjects and a patient with a neuroblastic tumor containing 55 ng/g wet weight IR-CRH, but in a patient with a thymic carcinoid tumor containing 1,000 ng/g wet weight IR-CRH, the plasma level was elevated to 180 pg/ml. This patient did not have Cushing's syndrome nor an elevated plasma adrenocorticotropic hormone (ACTH) level. The concentrations of nine peptides (growth hormone-releasing hormone, somatostatin, ACTH, calcitonin, gastrin-releasing peptide, glucagon, vasoactive intestinal peptide, neuropeptide tyrosine and pancreatic polypeptide) were determined in extracts of the 21 IR-CRH-producing tumors. Some of these peptides were frequently found to be produced concomitantly with CRH. The results indicate IR-CRH to be produced by various neuroendocrine tumors, but Cushing's syndrome, due to the CRH, to be very rare. The results also show that CRH-producing tumors produce multiple hormones.

[The stereologic-quantitative analysis of gastric antrum G cells in patients with splenic diseases].

In this paper, 89 Spleen deficiency (SD) patients' gastric mucosa specimens obtained during fibrogastroscopy mucosal biopsy were observed with immunocytochemical-stereologic-quantitative analysis method. The number of G cells counted and the content of basic gastrin in serum measured. This study found that the difference of the number of G cells and the content of gastrin in serum possessed statistical significance between two types of SD. The results suggested the hyperplasia and hypersecretion of G cells in gastric antrum might be an important pathological mechanism for different types of SD.

Satiety, hunger and regional brain content of cholecystokinin/gastrin and met-enkephalin immunoreactivity in sheep.

Cholecystokinin (CCK) and met-enkephalin (MEK) related peptides have been shown to alter feeding behavior subsequent to their injection into the peripheral circulation or directly into the brains of several species. To evaluate the potential role of endogenous brain pools of these peptides in feeding, groups of sheep were sacrificed either immediately following a meal (satiated) or after various intervals of food deprivation (hungry). Content of CCK-gastrin immunoreactivity in the anterior hypothalami of satiated sheep was elevated compared to 2, 4, or 24 hours of food deprivation. Content of MEK increased progressively with longer intervals of fasting (4 and 24 hours) in the amygdala and basomedial hypothalamus, whereas olfactory bulb content decreased with a similar time course. The results support a potential role for anterior hypothalamic CCK/gastrin in behaviors of satiety, whereas MEK neurons of limbic/rhinencephalic regions appear to form part of a separate circuit gradually activated by increasing hunger. Results are discussed in terms of potential target regions of the peptides, as well as the regional levels and feeding response of sheep as compared to available data from other species.

Co-existence of cholecystokinin- or gastrin-like peptides with other peptides in the hypophysis and the hypothalamus.

The presence of cholecystokinin and gastrin has been reported in the hypothalamohypophyseal system. These peptides present a peculiar distribution in the hypothalamic nuclei, the median eminence, and the neurohypophysis. CCK and gastrin have close relationships with other peptides like oxytocin, CRF, vasopressin, and the enkephalins; these relationships vary in different projecting areas and in different types of hypothalamic neurons. The functional role of G-CCK in neurosecretion seems to be linked to the role of these closely associated peptides and certainly deserves further investigation.

Localization by immunofluorescence of a gastrin-like substance in the brain of the rainbow trout, Salmo gairdneri.

With the aid of an indirect immunofluorescence technique neurons containing a gastrin-like substance were identified in the brain of Salmo gairdneri. The perikarya of these neurones appear to be located along the periventricular part of the nucleus lateralis tuberis between the hypophysial stalk and the most rostral tip of the saccus vasculosus. The fibres of these perikarya run rostrally toward the hypophysis, where they can be followed in the protrusions of the neurohypophysis into the proximal pars distalis. Here the bundle of immunoreactive fibres divides into numerous smaller bundles and into single fibres. Immunohistochemical specificity test have shown this immunoreactive substance to belong to the gastrin group, sharing an antigenic determinant with cholecystokinin (CCK) and pentagastrin (common amino-acid sequence Trp-Met-Asp-Phe). A possible function of these gastrin (or CCK)-containing neurones in the rainbow trout is discussed.

Immunohistochemical localization of a gastrin-like peptide in the brain of an amphibian, Xenopus laevis Daud.

The indirect immunofluorescence technique was used to demonstrate a substance reacting with gastrin antisera in the brain of Xenopus laevis. Immunoreactive material was found in two sites: (1) In the caudal hypothalamus more precisely in the nucleus infundibularis ventralis, (NIV) of the pars ventralis of the tuber cinereum, (PVTC). The fluorescent axons of the reactive parikarya of the NIV give rise to two symmetrical tracts which run rostro-ventrally and join, in the infundibular floor, the preoptico-hypophysial tract, where they form an uneven median tract coursing caudally and running along the medio-tuberal area before entering the external zone of the median eminence. (2) In the anterior preoptic area (APOA), where numerous nerve fibers and endings form a dense network near the preoptic recess. The exact origin of these terminals has not yet been determined. Control of immunohistochemical specificity shows that the labeling by gastrin antisera is suppressed by gastrin (2--17), but also by cholecystokinin (CCK) and pentagastrin (Peptavlon). These results indicate that the immunoreactive substance revealed belongs to the gastrin group and has an antigenic determinant composed of the amino acid sequence or a protion thereof common to gastrin, CCK and Peptavlon (Trp-Met-Asp-Phe). It should be emphasized that, in the brain of Xenopus laevis, both gastrin-immunoreactive sites correspond to the sites of uptake of steroid hormones (Kelley et al., 1975; Morrell et al., 1975).