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Petersen KU. Pepsin and Its Importance for Functional Dyspepsia: Relic, Regulator or Remedy? Dig Dis 2017; 36:98-105. [PMID: 28982106 DOI: 10.1159/000481399] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 09/06/2017] [Indexed: 02/02/2023]
Abstract
BACKGROUND Functional dyspepsia is a heterogeneous disorder lacking an established therapeutic strategy. Historical treatment attempts with pepsin products were shrugged off, as a simple calculation shows that quantitative substitution is pointless. However, such attempts might have been right for the wrong reason. SUMMARY Today, the role of pepsins is primarily seen in the provision of signalling amino acids (especially phenylalanine and tryptophan) and peptides, which initiate processes promoting digestion. Proteolysis benefits from pepsin variants showing, contrary to common belief, activities of up to a pH value of 5.0. Non-clinical and clinical studies support the view that liberated amino acids produce a variety of direct and indirect effects. Signal chains stimulated by (mostly aromatic) amino acids lead to secretion of gastrin and cholecystokinin (CCK), mediated, respectively, by CCK2 (gastrin) and Ca2+-sensing receptors in the parietal cell, and Ca2+-sensing receptors in the antral and duodenal mucosa. Thus, CCK effects such as secretion of pancreatic enzymes and promotion of gastric accommodation are (also) consequential to peptic liberation of amino acids. Key Message: As functional dyspepsia represents a heterogeneous disorder, it may be intriguing to view pepsin as a potential (although still to be proven) treatment modality, distinguished by a diversity of pro-digestive effects.
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Montoya CA, Hindmarsh JP, Gonzalez L, Boland MJ, Moughan PJ, Rutherfurd SM. Dietary actinidin from kiwifruit (Actinidia deliciosa cv. Hayward) increases gastric digestion and the gastric emptying rate of several dietary proteins in growing rats. J Nutr 2014; 144:440-6. [PMID: 24431326 DOI: 10.3945/jn.113.185744] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Dietary actinidin influences the extent to which some dietary proteins are digested in the stomach, and it is hypothesized that the latter modulation will in turn affect their gastric emptying rate (GE). In this study, the effect of dietary actinidin on GE and gastric digestion of 6 dietary protein sources was determined in growing rats. Each dietary protein source [beef muscle, gelatin, gluten, soy protein isolate (SPI), whey protein isolate, and zein] was included in 2 semisynthetic diets as the sole nitrogen source. For each protein source, 1 of the 2 diets contained actinidin [76.5 U/g dry matter (DM)] in the form of ground freeze-dried green kiwifruit (Actinidia deliciosa cv. Hayward), whereas the other diet contained freeze-dried gold kiwifruit (Actinidia chinensis cv. Hort16A), which is devoid of actinidin (3.4 U/g DM). For both diets, dietary kiwifruit represented 20% of the diet on a DM basis. The real-time GE was determined in rats gavaged with a single dose of the diets using magnetic resonance spectroscopy over 150 min (n = 8 per diet). Gastric protein digestion was determined based on the free amino groups in the stomach chyme collected from rats fed the diets (n = 8 per diet) that were later killed. GE differed across the protein sources [e.g., the half gastric emptying time (T(½)) ranged from 157 min for gluten to 266 min for zein] (P < 0.05). Dietary actinidin increased the gastric digestion of beef muscle (0.6-fold), gluten (3.2-fold), and SPI (0.6-fold) and increased the GE of the diets containing beef muscle (43% T(½)) and zein (23% T(½); P < 0.05). There was an inverse correlation between gastric protein digestion and DM retained in the stomach (r = -0.67; P < 0.05). In conclusion, dietary actinidin increased gastric protein digestion and accelerated the GE for several dietary protein sources. GE may be influenced by gastric protein digestion, and dietary actinidin can be used to modulate GE and protein digestion in the stomach of some dietary protein sources but not others.
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Actinidin from kiwifruit (Actinidia deliciosacv. Hayward) increases the digestion and rate of gastric emptying of meat proteins in the growing pig. Br J Nutr 2013; 111:957-67. [DOI: 10.1017/s0007114513003401] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
The present study aimed to investigate the effect of dietary actinidin on the kinetics of gastric digestion of beef muscle proteins and on the rate of stomach emptying in growing pigs. For this purpose, 120 pigs (mean body weight 28 (sd2·9) kg) were fed beef muscle protein-based diets containing either actinidin (fresh green kiwifruit pulp or gold kiwifruit pulp supplemented with purified actinidin) or no actinidin (fresh gold kiwifruit pulp or green kiwifruit pulp with inactivated actinidin). Additionally, fifteen pigs were fed with a protein-free diet to determine the endogenous protein flow. Pigs were euthanised at exactly 0·5, 1, 3, 5 and 7 h postprandially (n6 per time point for each kiwifruit diet andn3 for protein-free diet). Stomach chyme was collected for measuring gastric retention, actinidin activity, individual beef muscle protein digestion based on SDS–PAGE and the degree of hydrolysis based on the appearance of free amino groups. The stomach emptying of DM and N was faster when actinidin was present in the diet (P< 0·05): the half gastric emptying time of DM was 137v. 172 min ( ± 7·4 min pooled standard error) for the diets with and without actinidin, respectively. The presence of dietary actinidin in the stomach chyme increased the digestion of beef muscle protein (P< 0·05) and, more specifically, those proteins with a high molecular weight (>34 kDa;P< 0·05). In conclusion, dietary actinidin fed in the form of fresh green kiwifruit increased the rate of gastric emptying and the digestion of several beef muscle proteins.
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Farré R, Tack J. Food and symptom generation in functional gastrointestinal disorders: physiological aspects. Am J Gastroenterol 2013; 108:698-706. [PMID: 23458851 DOI: 10.1038/ajg.2013.24] [Citation(s) in RCA: 86] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The response of the gastrointestinal tract (GIT) to ingestion of food is a complex and closely controlled process, which allows optimization of propulsion, digestion, absorption of nutrients, and removal of indigestible remnants. This review summarizes current knowledge on the mechanisms that control the response of the GIT to food intake. During the cephalic phase, triggered by cortical food-related influences, the GIT prepares for receiving nutrients. The gastric phase is dominated by the mechanical effect of the meal volume. Accumulation of food in the stomach activates tension-sensitive mechanoreceptors, which in turn stimulate gastric accommodation and gastric acid secretion through the intrinsic and vago-vagal reflex pathways. After meal ingestion, the tightly controlled process of gastric emptying starts, with arrival of nutrients in the duodenum triggering negative feedback on emptying and stimulating secretion of digestive enzymes through the neural (mainly vago-vagal reflex, but also intrinsic) and endocrine (release of peptides from entero-endocrine cells) pathways. Several types of specialized receptors detect the presence of all main categories of nutrients. In addition, the gastrointestinal mucosa expresses receptors of the T1R and T2R families (taste receptors) and several members of the transient receptor potential channel family, all of which are putatively involved in the detection of specific tastants in the lumen. Activation of nutrient and taste sensors also activates the extrinsic and intrinsic neural, as well as entero-endocrine, pathways. During passage through the small bowel, nutrients are progressively extracted, and electrolyte-rich liquid intestinal content with non-digestible residue is delivered to the colon. The colon provides absorption of the water and electrolytes, storage of non-digestible remnants of food, aboral propulsion of contents, and finally evacuation through defecation.
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Affiliation(s)
- Ricard Farré
- Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium
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Montoya CA, Hindmarsh JP, Moughan PJ, Rutherfurd SM. A magnetic resonance spectroscopy technique to determine the stomach emptying rate of mixed diets in growing rats. J Nutr 2013; 143:541-7. [PMID: 23427332 DOI: 10.3945/jn.112.171223] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
A rapid technique allowing the accurate determination of stomach emptying rate (SER) would be useful for understanding the process of digestion. The development of a rapid magnetic resonance spectroscopy (MRS) technique based on the marker AlCl(3)-6H(2)O (Al-MRS) to determine the real-time SER of foods in a rat model is described. Experiments were conducted to establish several variables for the Al-MRS technique and validate the technique against the traditional serial slaughter method. Overnight feed-deprived rats (n = 8/treatment) were gavaged with a single dose of a semisynthetic meat or soy bean protein isolate-based diet containing the marker AlCl(3)-6H(2)O in acidified water (pH 2). Rats were either placed individually in the magnetic resonance spectrometer to estimate the SER from the real-time decrease in the aluminum (Al) signal or killed and their stomach chyme collected at prescribed times postprandially to determine the SER. The concentration of diet in the gavage mixture did not influence the SER. In contrast, rat body weight (BW), gavage volume, and dietary marker concentration affected SER (P < 0.05). The optimal BW range, gavage volume, and marker concentration that gave repeatable SER values were 280-320 g, 2-4 mL, and 55 g/L, respectively. Correlations were found for SER between Al-MRS and serial slaughter methods (r = 0.81-0.95; P < 0.001). Al-MRS is a robust, rapid, and straightforward technique for predicting the SER of food.
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Affiliation(s)
- Carlos A Montoya
- Riddet Institute, Nutrition and Human Health, Massey University, Palmerston North, New Zealand.
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Ghosh S, Pellett PL, Aw-Hassan A, Mouneime Y, Smriga M, Scrimshaw NS. Impact of Lysine-Fortified Wheat Flour on Morbidity and Immunologic Variables among Members of Rural Families in Northwest Syria. Food Nutr Bull 2008; 29:163-71. [DOI: 10.1177/156482650802900302] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background Previous studies have shown an effect of lysine fortification on nutrition and immunity of poor men, women, and children consuming a predominantly wheat-based diet. Objective To examine the lysine value of diets and the effect of lysine fortification on functional protein status, anthropometry, and morbidity of men, women, and children in rural Syria. Methods At baseline of a two-phase study using 7-day household food intake inventories ( n = 98), nutrient availabilities per adult male equivalent were estimated. In the intervention phase, a 16-week double-blind trial, households ( n = 106) were randomly assigned to control and lysine groups. Hematologic and anthropometric data were collected from men ( n = 69; 31 control, 38 lysine), women ( n = 99; 51 control, 48 lysine), and children ( n = 69; 37 control, 32 lysine) at baseline, 12 weeks, and 16 weeks. Total CD3 T lymphocytes as well as T lymphocytes bearing the receptors CD4, CD8, and CD56, IgM, IgG, IgA, complement C3, C-reactive protein, serum albumin, prealbumin, transferrin, retinol-binding protein, hemoglobin, and hepatitis B surface antigen were determined. Health status and flour usage were monitored. Paired- and independent-sample t-tests and chi-square tests were performed. Results Mean nutrient availability per adult equivalent was 2,650 ± 806 kcal, 70.1 ± 26.4 g protein, 65 ± 14% cereal protein, and 41.9 ± 0.8 mg lysine per gram of protein. Complement C3 was significantly higher in men receiving lysine than in controls ( p < .05). Among women, there were significant differences between the control and lysine groups in diarrhea period prevalence (total number of diarrheal episodes during the period of intervention divided by the total number of observations), (20 in the control group, 6 in the lysine group; p = .014), the mean number of days ill (0.4 ± 0.7, control, 0.14 ± 0.4, lysine, p = 0.03), and the number of diarrheal episodes per person per year (1.39 in the control group, 0.47 in the lysine group). No other significant differences between the lysine and the control groups were observed. Conclusions Lysine fortification of wheat flour demonstrated a positive effect on diarrheal morbidity in women. The effect could be attributed to an improvement in protein utilization but possibly also to a direct effect of lysine in gastrointestinal tract. Studies in populations with higher diarrheal prevalence and significant dietary lysine deficiency are needed to determine whether the reported effects on diarrheal prevalence are replicable and whether they are pharmacological or nutritional. It would be particularly desirable to study the effect of lysine on diarrhea in preschool children, who have much higher morbidity and mortality rates from this disease than school-age children or adults.
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Nguyen NQ, Fraser RJ, Bryant LK, Chapman M, Holloway RH. Diminished functional association between proximal and distal gastric motility in critically ill patients. Intensive Care Med 2008; 34:1246-55. [PMID: 18297265 DOI: 10.1007/s00134-008-1036-5] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2007] [Accepted: 12/27/2007] [Indexed: 12/21/2022]
Abstract
OBJECTIVE This study examined the effects of critical illness on the relationship between proximal and distal gastric motor activity during fasting and duodenal nutrient stimulation. DESIGN Prospective, case-controlled study. PATIENTS AND PARTICIPANTS Ten critically ill patients and ten healthy volunteers. INTERVENTIONS Concurrent proximal gastric (barostat) and antro-pyloro-duodenal (manometry) motility were recorded during fasting and during two 60-min duodenal nutrient infusions (Ensure at 1 kcal/min and 2 kcal/min) in random order, separated by a 2-h wash-out period. RESULTS Baseline proximal gastric volumes were similar between the two groups. At 10 min nutrient-induced fundic relaxation was lower in patients than healthy subjects (45 +/- 26 vs. 196 +/- 29 ml). In patients the frequency and volume amplitude of fundic waves were also lower. There were fewer propagated antral waves in patients than in healthy subjects during both fasting and nutrient infusion. These were more retrograde, shorter in length and associated with a pyloric contraction. The proportion of fundic waves followed by a distally propagated antral wave was significantly less in patients (0%, 0-8%) than controls 36% (11-44%). CONCLUSIONS In critical illness, in addition to impairment of proximal and distal gastric motor activity, the association between the two gastric regions is abnormal. This disturbance may interfere with meal distribution and further contribute to slow gastric emptying in these patients.
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Affiliation(s)
- Nam Q Nguyen
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, North Terrace, SA, Australia.
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Deane A, Chapman MJ, Fraser RJ, Bryant LK, Burgstad C, Nguyen NQ. Mechanisms underlying feed intolerance in the critically ill: Implications for treatment. World J Gastroenterol 2007; 13:3909-17. [PMID: 17663503 PMCID: PMC4171161 DOI: 10.3748/wjg.v13.i29.3909] [Citation(s) in RCA: 87] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Malnutrition is associated with poor outcomes in critically ill patients. Although nutritional support is yet to be proven to improve mortality in non-malnourished critically ill patients, early enteral feeding is considered best practice. However, enteral feeding is often limited by delayed gastric emptying. The best method to clinically identify delayed gastric emptying and feed intolerance is unclear. Gastric residual volume (GRV) measured at the bedside is widely used as a surrogate marker for gastric emptying, but the value of GRV measurement has recently been disputed. While the mechanisms underlying delayed gastric emptying require further investigation, recent research has given a better appreciation of the pathophysiology. A number of pharmacological strategies are available to improve the success of feeding. Recent data suggest a combination of intravenous metoclopramide and erythromycin to be the most successful treatment, but novel drug therapies should be explored. Simpler methods to access the duodenum and more distal small bowel for feed delivery are also under investigation. This review summarises current understanding of the factors responsible for, and mechanisms underlying feed intolerance in critical illness, together with the evidence for current practices. Areas requiring further research are also highlighted.
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Nguyen NQ, Fraser RJ, Bryant LK, Holloway RH. Functional association between proximal and distal gastric motility during fasting and duodenal nutrient stimulation in humans. Neurogastroenterol Motil 2007; 19:638-45. [PMID: 17640178 DOI: 10.1111/j.1365-2982.2007.00919.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
A functional integration exists between proximal and distal gastric motor activity in dogs but has not been demonstrated in humans. To determine the relationship between proximal and distal gastric motor activity in humans. Concurrent proximal (barostat) and distal (antro-pyloro-duodenal (APD) manometry) gastric motility were recorded in 10 healthy volunteers (28 +/- 3 years) during (i) fasting and (ii) two 60-min duodenal infusions of Ensure((R)) (1 and 2 kcal min(-1)) in random order. Proximal and APD motor activity and the association between fundic and propagated antral waves (PAWs) were determined. During fasting, 32% of fundic waves (FWs) were followed by a PAW. In a dose-dependent fashion, duodenal nutrients (i) increased proximal gastric volume, (ii) reduced fundic and antral wave (total and propagated) activity, and (iii) increased pyloric contractions. The proportion of FWs followed by a distal PAW was similar between both infusions and did not differ from fasting. During nutrient infusion, nearly all PAWs were antegrade, propagated over a shorter distance and less likely to traverse the pylorus, compared with fasting. In humans, a functional association exists between proximal and distal gastric motility during fasting and duodenal nutrient stimulation. This may have a role in optimizing intra-gastric meal distribution.
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Affiliation(s)
- N Q Nguyen
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, SA 5000, Australia.
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Multifunctional roles of dietary proteins in the regulation of metabolism and food intake: Application to feeding infants. The journal The Journal of Pediatrics 2006. [DOI: 10.1016/j.jpeds.2006.06.056] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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Nguyen NQ, Fraser RJ, Chapman M, Bryant LK, Holloway RH, Vozzo R, Feinle-Bisset C. Proximal gastric response to small intestinal nutrients is abnormal in mechanically ventilated critically ill patients. World J Gastroenterol 2006; 12:4383-8. [PMID: 16865782 PMCID: PMC4087751 DOI: 10.3748/wjg.v12.i27.4383] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the response of the proximal stomach to small intestinal nutrients in critically ill patients.
METHODS: Proximal gastric motility was measured in 13 critically ill patients (49.3 ± 4.7 years) and 12 healthy volunteers (27.7 ± 2.9 years) using a barostat technique. Recordings were performed at baseline, during a 60-min intra-duodenal infusion of Ensure® (2 kcal/min), and for 2 h following the infusion. Minimum distending pressure (MDP), intra-bag volume and fundic wave activity were determined.
RESULTS: The MDP was higher in patients (11.7 ± 1.1 vs 7.8 ± 0.7 mmHg; P < 0.01). Baseline intra-bag volumes were similar in the 2 groups. In healthy subjects, a ‘bimodal’ proximal gastric volume response was observed. In patients, the initial increase in proximal gastric volume was small and delayed, but eventually reached a maximal volume similar to that of healthy subjects. In healthy subjects, the proximal gastric volume rapidly returned to baseline level after nutrient infusion (median 18 min). In contrast, the recovery of volume to baseline was delayed in critically ill patients (median 106 min). In 6 patients, the volume had not returned to baseline level 2 hours after nutrient infusion. In patients, fundic volume waves were less frequent (P < 0.05) and had lower amplitude (P < 0.001), compared to healthy subjects.
CONCLUSION: In critical illness, proximal gastric motor responses to small intestinal nutrient stimulation are abnormal.
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Affiliation(s)
- Nam-Q Nguyen
- Department of Gastroenterology, Hepatology and General Medicine, Royal Adelaide Hospital, South Australia
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Castillo EJ, Delgado-Aros S, Camilleri M, Burton D, Stephens D, O'Connor-Semmes R, Walker A, Shachoy-Clark A, Zinsmeister AR. Effect of oral CCK-1 agonist GI181771X on fasting and postprandial gastric functions in healthy volunteers. Am J Physiol Gastrointest Liver Physiol 2004; 287:G363-9. [PMID: 15246968 DOI: 10.1152/ajpgi.00074.2004] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
CCK influences satiation and gastric and gallbladder emptying. GI181771X is a novel oral CCK-1 agonist; its effects on gastric emptying of solids, accommodation, and postprandial symptoms are unclear. Effects of four dose levels of the oral CCK-1 agonist GI181771X and placebo on gastric functions and postprandial symptoms were compared in 61 healthy men and women in a randomized, gender-stratified, double-blind, double-dummy placebo-controlled, parallel group study. Effects of 0.1, 0.5, and 1.5 mg of oral solution and a 5.0-mg tablet of GI181771X on gastric emptying of solids by scintigraphy, gastric volume by (99m)Tc-single photon emission computed tomographic imaging, maximum tolerated volume of Ensure, and postprandial nausea, bloating, fullness, and pain were studied. On each of 3 study days, participants received their randomly assigned treatment. Adverse effects and safety were monitored. There were overall group effects of GI181771X on gastric emptying (P < 0.01) and fasting and postprandial volumes (P = 0.036 and 0.015, respectively). The 1.5-mg oral solution of GI181771X significantly delayed gastric emptying of solids (P < 0.01) and increased fasting (P = 0.035) gastric volumes without altering postprandial (P = 0.056) gastric volumes or postprandial symptoms relative to placebo. The effect of the 5.0-mg tablet on gastric emptying of solids did not reach significance (P = 0.052). Pharmacokinetic profiles showed the highest area under the curve over 4 h for the 1.5-mg solution and a similar area under the curve for the 0.5-mg solution and 5-mg tablet. Adverse effects were predominantly gastrointestinal and occurred in a minority of participants. GI181771X delays gastric emptying of solids and exhibits an acceptable safety profile in healthy participants. CCK-1 receptors can be modulated to increase fasting gastric volume.
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Demarchi B, Vos R, Deprez P, Janssens J, Tack J. Influence of a lipase inhibitor on gastric sensitivity and accommodation to an orally ingested meal. Aliment Pharmacol Ther 2004; 19:1261-8. [PMID: 15191507 DOI: 10.1111/j.1365-2036.2004.02003.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Intraduodenal administration of lipids, through lipid digestion and release of cholecystokinin (CCK), induces viscero-visceral reflexes that affect gastric tone and sensitivity. It is unclear whether the same mechanisms control gastric function after an orally ingested meal. AIM To evaluate the effect of orlistat, a selective lipase inhibitor, on gastric response to an orally administered meal. METHODS Eighteen healthy volunteers participated in this study. They were treated for 5 days with orlistat (120 mg) or placebo t.d.s. in a double-blind randomized crossover design. During treatment, all subjects underwent a gastric barostat study, measurement of plasma CCK levels and a satiety drinking test. RESULTS Although CCK plasma levels were significantly decreased, pre-treatment with orlistat failed to affect gastric compliance (72 +/- 6 mL/mm Hg and 64 +/- 6 mL/mm Hg, NS), gastric sensitivity (discomfort threshold 12.2 +/- 0.6 mm Hg vs. 10.9 +/- 0.6 mm Hg above minimal distending pressure, NS) or gastric accommodation (172 +/- 41 mL vs. 206 +/- 49 mL, NS) to an orally ingested meal. Furthermore, orlistat pre-treatment had no significant effect on the amount of calories ingested during a satiety drinking test (1329 +/- 88 kcal vs. 1217 +/- 115 kcal, NS). CONCLUSION Administration of a lipase inhibitor does not affect gastric compliance, sensitivity to distension and accommodation to an orally ingested meal, and does not influence meal-induced satiety.
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Affiliation(s)
- B Demarchi
- Department of Internal Medicine, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium
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Le Blanc-Louvry I, Savoye G, Maillot C, Denis P, Ducrotté P. An impaired accommodation of the proximal stomach to a meal is associated with symptoms after distal gastrectomy. Am J Gastroenterol 2003; 98:2642-7. [PMID: 14687810 DOI: 10.1111/j.1572-0241.2003.08725.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The aim of this study was to assess gastric emptying and postprandial proximal gastric tone variations depending on the presence of postoperative symptoms after Billroth II gastrectomy (BII). METHODS A total of 16 consecutive patients were prospectively studied 10 +/- 3 months after distal gastrectomy for antral cancer. No evidence of cancer recurrence was detected at the time of the study. Ten patients were asymptomatic after surgery, whereas six patients were considered as symptomatic because of at least one weekly epigastric pain, postprandial fullness, nausea, or vomiting. The fasting fundus volume and tone, the onset of a gastric relaxation after a standard 200-kcal liquid meal, and the characteristics of this relaxation (delay of occurrence, amplitude) were determined with a barostat. Patient results were compared to normal values obtained in 12 healthy volunteers. Gastric emptying studies were performed in all patients using the C(13) acid octanoic breath test after a 250-kcal meal. RESULTS In the patients, both fasting fundus tone (BII 7.0 +/- 0.5, controls 8.4 +/- 2.4 mm Hg) and volume (BII 108 +/- 11, controls 119 +/- 29 ml) were not different from controls. Fasting fundus tone was lower in asymptomatic patients than in symptomatic patients (6.5 +/- 0.4 vs 8.1 +/- 0.5 mm Hg, p < 0.04). Gastric relaxation was observed immediately after the meal in all asymptomatic patients as well as in controls. In contrast, gastric relaxation occurred in only two of six symptomatic patients (p < 0.01); when it occurred it was delayed by the meal and was observed only 23 +/- 1 min after food intake. When a relaxation occurred, its amplitude was higher than that observed in controls both in asymptomatic and symptomatic patients (294 +/- 21 vs 179 +/- 53 ml, p < 0.02). CONCLUSIONS After distal gastrectomy, gastric accommodation is impaired (i.e., absent or delayed) in symptomatic patients. When relaxation exists in these patients, its amplitude is higher than in control subjects.
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Affiliation(s)
- Isabelle Le Blanc-Louvry
- Digestive Tract Research Group, Appareil Digestif Environnement Nutrition (ADEN) EA 3234/IFRMP 23, Rouen University Hospital, Rouen, France
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Feinle C, Christen M, Grundy D, Faas H, Meier O, Otto B, Fried M. Effects of duodenal fat, protein or mixed-nutrient infusions on epigastric sensations during sustained gastric distension in healthy humans. Neurogastroenterol Motil 2002; 14:205-13. [PMID: 11975721 DOI: 10.1046/j.1365-2982.2002.00318.x] [Citation(s) in RCA: 58] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Duodenal fat modulates sensory and motor responses to gastric distension and raises plasma cholecystokinin compared with glucose. The effects of protein (also releasing cholecystokinin), or mixed nutrients (with a balanced macronutrient composition), on gastrointestinal sensations in relation to gastric relaxation and plasma cholecystokinin concentrations are not known. The aim of this study was therefore to compare the effects of duodenal infusion of fat, protein or mixed nutrients during sustained gastric distension (mimicking the intragastric presence of food) on these parameters. In 10 healthy subjects, gastric distension to fullness was maintained for 90 min, while gastric volume, sensations and plasma cholecystokinin were monitored during duodenal infusion of isotonic saline or nutrients (2 kcal min-1). During saline infusion, all parameters remained unchanged for 90 min. Initially, only lipid increased plasma cholecystokinin, gastric volume and scores for sensations. Cholecystokinin and gastric volume responses to protein and mixed nutrients were delayed and not associated with significant changes in sensations. In conclusion, the intensity of gastrointestinal sensations is related to, but not entirely explained by, the magnitude in intragastric volume and plasma cholecystokinin changes. Our results offer new insights into the role of dietary nutrient composition in gastrointestinal sensations, and may have implications for the dietary management of digestive symptoms.
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Affiliation(s)
- C Feinle
- Gastroenterology Division, University Hospital Zurich, Switzerland.
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