A controlled trial comparing the efficacy of rice-based and hypotonic glucose oral rehydration solutions in infants and young children with gastroenteritis

A prospective randomized trial was conducted to compare the efficacy of a rice-based oral rehydration solution (ORS) with glucose ORS in infants and children under 5 years of age with acute diarrhoea and mild to moderate dehydration (< 10%). One hundred children presenting to a large metropolitan teaching hospital were eligible for entry to the study and were randomized to receive rice ORS or glucose ORS. Outcome measures were stool output (SO), duration of illness (DD) and recovery time to introduction of other fluids (RTF) and diet (RTD). Significant differences were found for all outcome measures in favour of the rice ORS group. Mean SO was lower (160 vs 213 mL; P < 0.02), mean DD was reduced (17.3 vs 24.3 h; P = 0.03) and median RTF was decreased (12.7 vs 18.1 h; P < 0.001) in the rice ORS group compared with the glucose ORS group. The median time to introduction of diet and mean length of hospital stay showed similar significant reductions. Our study has shown rice ORS to be an acceptable alternative to glucose ORS in young children and have shown that it is significantly more effective in reducing the course of diarrhoeal illness and the time taken to return to normal drinking and eating habits.     

Gum arabic promotes rat jejunal sodium and water absorption from oral rehydration solutions in two models of diarrhea

BACKGROUND & AIMS: We have shown that addition of gum arabic (GA) to a 90 mmol/L sodium-111 mmol/L glucose oral rehydration solution (ORS) enhances its effectiveness for water and electrolyte absorption in normal rats. The present study extends these observations on GA in ORS to two rat models of diarrheal disease. METHODS: Juvenile rats were either treated for 1 week with magnesium citrate-phenolphthalein to produce chronic osmotic-secretory diarrhea or luminally exposed to 10 mmol/L theophylline to induce jejunal secretion. In both models jejunal perfusion was used to assess absorption. RESULTS: Addition of 2.5 or 5.0 g/L GA to ORS increased roughly twofold absorption of sodium, potassium, and water in the model of chronic osmotic-secretory diarrhea. Rats perfused with GA-supplemented ORS showed an expansion of the basolateral intercellular spaces between villus absorptive epithelial cells and the lamina propria, reflecting enhanced water and sodium absorption. Similarly, addition of 2.5, 5.0, or 10.0 g/L GA to the ORS neutralized theophylline-induced abolition of net sodium and potassium absorption and reversed water and glucose malabsorption. CONCLUSIONS: These experimental studies in models of diarrhea suggest that GA may be a useful additive to ORS for the potentiation of water and electrolyte absorption. (Gastroenterology 1997 Jun;112(6):1979-85)     

Omeprazole Does Not Interfere with the Antiplatelet Effect of Low-Dose Aspirin in Man

Background: Experimental studies have shown that omeprazole and other anti-inflammatory agents compromise the therapeutic activity of nonsteroidal anti-inflammatory drugs and aspirin in rats. It is not known whether this effect will occur in humans. Our aim was to determine whether omeprazole affects the antiplatelet effects of low-dose aspirin in humans. Methods: Platelet lumiaggregation, skin bleeding time, plasma levels of aspirin and salicylic acid, and serum gastrin levels were determined in 14 healthy men before and after the ingestion of 125 mg aspirin with or without previous treatment with 20 mg/day of omeprazole for 4 days before testing. Results: Omeprazole increased serum gastrin levels from 64 (median; range, 52-91) pg/ml to 80.5 (median; range, 56-455) pg/ml (P &lt; 0.05) but did not significantly affect the plasma concentration of aspirin or salicylic acid. Aspirin increased skin bleeding time in all subjects, and the increase was similar with and without previous omeprazole treatment. Aspirin inhibited platelet aggregation in response to both collagen and arachidonic acid regardless of omeprazole treatment. Conclusion: A single dose of 20 mg omeprazole daily does not interfere with the biologic activity of 125 mg aspirin on platelets in humans.     

Cholera Toxin-Induced Secretion in Rats Is Reduced by a Soluble Fiber, Gum Arabic

Gum arabic (GA), a soluble fiber with emulsifying properties, enhances intestinal water and electrolyte absorption in normal and secreting rats. Our aim was to assess the effect of GA, 2.5 and 5.0 g/liter, on cholera toxin-induced water and electrolyte secretion in rat jejunum in vivo. After a 2-hr exposure to cholera toxin, jejunal segments of adult rats were perfused in vivo with a plasma electrolyte solution containing GA, 0, 2.5 or 5.0 g/liter. ²⁴Na was used as a marker of sodium influx. Cholera toxin-induced secretion was reduced by GA, 2.5 and 5.0 g/liter. ²⁴Na secretion into the lumen was reduced by GA. GA caused a morphological expansion of intercellular spaces in the villi but not crypts. In conclusion, GA promotes lumen to blood intestinal transport of water and sodium despite cholera toxin activation. These observations support a potential role for GA in enhancing the efficacy of ORS.     

Duodenal nutrients inhibit canine jejunal fasting motor patterns through a hormonal mechanism

Ingestion of a meal converts the fasting motor pattern, the migrating motor complex (MMC), to a fed pattern of motility. The role of specific anatomic gut regions involved in these changing patterns of motility and the neurohormonal factors which mediate these changes, however, are unknown. Our aim was to determine the neurohormonal mechanisms by which nutrients within the duodenal lumen alter proximal jejunal motility. Fifteen dogs were prepared with a gastric cannula, duodenal infusion catheter, duodenal and proximal jejunal manometry catheters, and a totally diverting cannula in the most proximal portion of the jejunum. Ten of the dogs also underwent completein situ neural isolation of the entire jejunoileum. Experiments were performed in the fasting state with no infusion (0 ml/min) and during a 5-hr duodenal infusion (3 ml/min) of either a nonnutrient electrolyte solution or a mixed nutrient solution while diverting distal duodenal chyme from the jejunum. During sham infusion (0 ml/min), the MMC was present in neurally intact dogs (group 1) and dogs with neurally isolated jejunoileum (group 2). Nonnutrient infusion did not inhibit or consistently alter the MMC in either group. Nutrient infusion limited to the duodenum inhibited the MMC in both duodenum and jejunum in dogs with neurally intact and neurally isolated jejunoileum. Latency of onset of the fed pattern in the duodenum and jejunum did not differ between groups. We conclude that postprandial inhibition of the MMC in the jejunum is mediated, in part, by a hormonal mechanism induced by duodenal lumenal nutrients.This work was supported in part by the USPHS (NIH Grant DK39337), the Ethicon Corporation, and Mayo Foundation.This work was presented at the Annual Meeting of the Association of Academic Surgeons on November 11, 1993, in Hershey, Pennsylvania.     

L-arginine in low concentration improves rat intestinal water and sodium absorption from oral rehydration solutions.

BACKGROUND: The nitric oxide (NO) precursor L-arginine has been shown to produce variable effects on intestinal absorptive function, including ion transport. AIMS: To determine whether there is an optimal concentration of L-arginine, promoting proabsorptive effects from oral rehydration solutions (ORS) with 90 or 60 mM sodium. SUBJECTS AND METHODS: In vivo perfusion of rat jejunum with determination of net water absorption, unidirectional fluid exchanges, sodium and calcium transport, and glucose absorption. RESULTS: L-Arginine (1 mM) added to the 90 mM sodium ORS increased intestinal absorption of both sodium and water. Higher concentrations of L-arginine (2 to 10 mM) lacked this stimulatory effect. At 20 mM, L-arginine decreased sodium absorption below baseline. With a 60 mM sodium ORS, 2 mM L-arginine had a maximal fluid and electrolyte proabsorptive effect. At 20 mM L-arginine, net water absorption was indistinguishable from that obtained in the absence of L-arginine, and lower than with 2 mM L-arginine. Sodium absorption remained raised above baseline in perfusions with 10 and 20 mM L-arginine. Morphologically, villi from perfusions with increased absorption showed a large expansion of intercellular and lamina propria intercellular spaces. CONCLUSIONS: Low concentrations of L-arginine seem to stimulate water and electrolyte absorption by the small intestine. This effect is consistent with NO induced vasodilation, may be vaso-constrictive and thereby reverse fluid and electrolyte transport.     

Gastric emptying of oral rehydration solutions in acute cholera

Gastric emptying of rice powder electrolyte solution and of glucose electrolyte solution was measured by a marker dilution double sampling technique in 14 and in 16 adult patients respectively after intravenous rehydration during an attack of acute cholera. Six patients who received rice powder electrolyte solution and seven who received glucose electrolyte solution re-attended for a repeat study with the same test meal 16 days later, when fully recovered from cholera. No differences in gastric emptying patterns of the two electrolyte solutions were observed, either in the acute or in the recovered patients. Similarly, gastric emptying of both solutions was rapid during acute cholera and comparable to that observed in recovered patients. This study indicates that gastric emptying is not impaired in acute cholera and that the rate of emptying of oral rehydration solutions is adequate to account for their observed clinical efficacy in fast purging patients with acute cholera.     

Alterations in carrier-mediated glutamine transport after a model of canine jejunal autotransplantation

The effects of small bowel transplantation (SBTx) on absorptive function are unknown. Preliminary experiments showed a decrease in absorption of glutamine. Our aim was to determine mechanisms of decreased ileal transport of glutamine utilizing a model of intestinal autotransplantation. Seven dogs were studied before and after a model of jejunoileal autotransplantation.In vivo absorption experiments were performed before and two and eight weeks postoperatively with an electrolyte solution containing glutamine (20 mM).In vitro glutamine transport was studied using brush-border membrane vesicles (BBMV) prepared from ileal mucosa obtained from six other dogs and compared to a controls.In vivo net absorptive flux of glutamine decreased at two weeks but returned toward baseline by eight weeks (P=0.06). Transport of glutamine into BBMVs was decreased at two weeks and remained decreased at eight weeks. , a measure of carrier affinity was unchanged but , a function of the number of transporter was decreased at two and eight weeks. Glucose transport was unchanged. It is concluded that jejunoileal autotransplantation decreases ileal absorption of glutamine by a decrease in carrier-mediated transport of glutamine.Supported in part by NIH DK39337 (M.G.S.), NIH CA45327 (W.W.S.), and the Mayo Foundation.Presented at the Society of Surgery of the Alimentary Tract, May 1995, in San Diego, California. An abstract of this work was published inGastroenterology 108:A1235, 1995.     

The use of oral rehydration solutions in children and adults

The observation that the intestinal Na⁺-glucose cotransporter remains intact in most diarrheal illnesses led to development of the life-saving, low-cost technology of oral rehydration salt (ORS) solutions. The primary therapeutic role of ORS solutions is in prevention and treatment of dehydration during management of acute gastroenteritis. Successful oral rehydration therapy involves early use of ORS with maintenance or timely resumption of regular feeding. Since the inception of the oral rehydration approach more than three decades ago, the widespread use of ORS solutions has revolutionized the management and outcomes of acute gastroenteritis in children and adults. The efficacy of the World Health Organization ORS solution and of commercial ORS formulations has been enhanced by reducing osmolarity. Newer formulations of ORS are under active investigation, with promise of added benefits, including promotion of intestinal healing. This article reviews fluid and electrolyte transport in the gastrointestinal tract, the pathophysiologic mechanisms of acute diarrhea, and the basis and formulation of current and newer ORS solutions. Guidelines for efficacious use of ORS in the management of acute gastroenteritis and short gut syndrome are also provided.     

Effect of proinflammatory interleukins on jejunal nutrient transport

AIM: We examined the effect of proinflammatory and anti-inflammatory interleukins on jejunal nutrient transport and expression of the sodium-glucose linked cotransporter (SGLT-1). METHODS: 3-O-methyl glucose and L-proline transport rates were examined in New Zealand White rabbit stripped, short circuited jejunal tissue. The effects of the proinflammatory cytokines interleukin (IL)-1alpha, IL-6, and IL-8, IL-1alpha plus the specific IL-1 antagonist, IL-1ra, and the anti-inflammatory cytokine IL-10 were investigated. In separate experiments, passive tissue permeability was assessed and brush border SGLT-1 expression was measured by western blot in tissues exposed to proinflammatory interleukins. RESULTS: The proinflammatory interleukins IL-6, IL-1alpha, and IL-8 significantly increased glucose absorption compared with control levels. This increase in glucose absorption was due to an increase in mucosal to serosal flux. IL-1alpha and IL-8 also significantly increased L-proline absorption due to an increase in absorptive flux. The anti-inflammatory IL-10 had no effect on glucose transport. The receptor antagonist IL-1ra blocked the ability of IL-1alpha to stimulate glucose transport. IL-8 had no effect on passive tissue permeability. SGLT-1 content did not differ in brush border membrane vesicles (BBMV) from control or interleukin treated tissue. CONCLUSIONS: These findings suggest that intestinal inflammation and release of inflammatory mediators such as interleukins increase nutrient absorption in the gut. The increase in glucose transport does not appear to be due to changes in BBMV SGLT-1 content.     

Use of commercially available oral rehydration solutions in Lima, Peru

Caregivers' practices concerning oral rehydration of young children during diarrheal illness were investigated in a periurban community of low socioeconomic level in Lima, Peru. Data of 330 caregivers of children aged 6-36 months were analyzed; 72.7% of all caregivers would give commercially available oral rehydration solutions (ORSs). However, only 58.6% of those caregivers with children that had experienced diarrhea during the previous week stated that they had used commercially available ORSs, a significantly lower percentage. The main reason for not using commercially available ORSs was that caregivers did not know about them. Of all recipes caregivers provided for homemade ORS, none contained the recommended concentrations of sugar and salt. Educating caregivers about availability, benefits, and use of commercially available ORSs as well as correct preparation of homemade ORS is urgently needed.     

Enhanced absorption of macromolecules

We explored the function of the intestine's mucosal barrier to foreign antigen entry in Crohn's disease. Macroscopically and microscopically uninvolved areas of the small intestines of patients with Crohn's disease were examined. We studied 27 endoscopic biopsy samples from 17 patients with Crohn's disease and 14 samples from nine controls. The absorption and degradation of horseradish peroxidase (molecular weight 40,000 Da) were studied in Ussing chambers. The absorption of intact horseradish peroxidase was significantly increased in patients with moderate or severe Crohn's disease: 271 (95% confidence interval 119–616) ng/hr/cm², but not in those with slight disease activity: 42 (18–98), compared with controls: 45 (32–64);F=10.90,P=0.0002. The transport rates of degraded horseradish peroxidase were comparable in the Crohn's disease samples and controls. Our results indicate that enhanced absorption of macromolecules is associated with clinical activation of Crohn's disease, and impairment of the mucosal barrier function is a secondary phenomenon in Crohn's disease.The study was supported by grants from the Academy of Finland and the Foundation for Nutrition Research (Finland).     

Effect of a model of canine jejunoileal orthotopic autotransplantation on jejunal and ileal transport of water and electrolytes

Canine jejunoileal transplantation induces an early profuse watery diarrhea of uncertain etiology. Our aim was to determine the temporal effects of a canine model of jejunoileal autotransplantation (a model devoid of confounding effects of ischemia-reperfusion or immune rejection) on basal jejunal and ileal absorption of water and electrolytes to determine if impaired absorption is responsible for the diarrhea. Our hypothesis was that net absorption of water and electrolytes in an enterically isolated loop would decrease after jejunoileal transplantation. Four groups of dogs (N 6) were prepared with 80-cm modified Thiry-Vella loops: group I, neurally intact jejunum; group II, autotransplanted jejunum; group III, neurally intact ileum; and group IV, autotransplanted ileum. The loops were perfused for 3 hr with 150 mM NaCl at 3 ml/min under fasted conditions; transit time through the loop was determined by bolus of a nonabsorbable marker. Dogs were studied on three separate days at one, two, eight, and nine weeks postoperatively. Net absorptive fluxes of water and electrolytes and transit times were similar (P>0.05) between neurally intact and autotransplant groups (group I vs II and group III vs IV) at each time point. Ileal loops absorbed more than jejunal loops, and transit was slower in ileal loops (eachP<0.05). Our findings suggest that, despite the obligate disruption of extrinsic innervation, enteric (intrinsic) neural continuity, and lymphatic drainage that accompanies this canine model of jejunoileal autotransplantation, net basal absorptive function of water and electrolytes during the fasted state was not decreased nor was transit altered either in jejunum or ileum. These findings have important implications for clinical small intestinal transplantation in man.Supported by NIH RO1 DK39337 (M.G.S.), Ethicon Corporation, and Mayo Foundation.     

Independence of in vitro iron absorption from mucosal transferrin content in rat jejunal and ileal segments

Summary Isolated non blood-perfused intestinal segments from normal and irondeficient rats were used in vitro. A modification of the luminal perfusion method according to Fisher and Parsons allowed the comparison of iron and transferrin quantities in the serosal fluid at 15 min intervals. Iron transfer in jejunal and ileal segments was directly proportional to the luminal iron concentration within a dose range of 1 to 100 mol/l, did not show saturation characteristics and was linear over time. Jejunal segments from iron-deficient rats transfered about twice as much iron as the jejunal controls. In ileal segments there was no difference in iron transfer between iron-deficient and control rats; in both cases transfer amounted to approx. 10% of jejunal controls. An exponential correlation was found, when the decreasing transferrin content of the tissue was plotted against the cumulative water transport. Transferrin and albumin release from jejunal and ileal segments into the absorbate cumulated asymptotically, which is typical for wash-out phenomena. As iron transfer cumulated linearly while transferrin release cumulated in an asymptotic manner, the capacity of transferrin to bind iron ions is exceeded roughly 100 times by molar equivalents of iron in the last absorbate fractions. Independence of iron transfer from mucosal transferrin quantities is concluded. As the molar transferrin/albumin ratios do not show significant differences between plasma and the sequence of absorbate samples, a wash-out from the gut's interstitial space is assumed, which makes plasma the most likely origin of transferrin in the mucosa.Supported by a grant of the Deutsche Forschungsgemeinschaft Fo 58/8-2. Part of the results has been presented during the VIth Meeting of the European Intestinal Transport Group [16]     

Effects of enteral infusion of hypertonic saline and nutrients on canine jejunal motor patterns

The aim of the study was to clarify the effects of hypertonic solutions on jejunal motility. The study focused on differential effects of hypertonic saline and nutrients. Motility of the canine proximal jejunum was recorded with closely spaced strain-gauge transducers. During fasting, hyperosmotic solutions (up to 1520 mosmol/liter) of saline or nutrients (1 kcal/ml) were infused into the proximal jejunum (0.5–1.5 ml/min) up to 6 hr. The hyperosmotic solutions stimulated jejunal motility. With both increasing osmolarity of saline or increasing energy load of nutrients, jejunal motility linearly declined. The reduction of motility was associated with a change in motor pattern from a propulsive to a more segmenting one. Hypertonic glucose evoked a significantly smaller level of motor activity compared with both saline (at given osmolarities) and an elemental diet (at given energy loads). Motility parameters were not different between glucose and maltose, although osmolarity of maltose was less than half (760 vs 1520 mosmol/liter). In contrast, a mixture of glucose-fructose exerted a smaller inhibition of jejunal motility than glucose. The hypertonic solutions of saline or nutrients were tolerated over 2 hr; with hypertonic saline retrograde power contractions with or without vomiting occurred, whereas with hypertonic nutrients vomiting was preceded by strong inhibition of jejunal motility. Three conclusions can be derived from the present results: (1) The behavior of jejunal motility suggested that the motor activity was the result of both a local stimulation and an inhibitory feedback mechanism. (2) The different degree of inhibition between glucose and saline indicated that the nutrient itself played a major role in the inhibitory feedback regulation, whereas osmolarity was of minor importance. (3) Comparisons between different nutrients suggested a linkage between inhibitory control of motility and the absorptive capacity of the gut for the single nutrient.     

Effect of cholera toxin on small intestinal motor activity in the fed state

We sought to determine the effect of cholera toxin on small intestinal transit and motor activity in the fed state. Mean transit time increased after cholera toxin, but there was no change in mean amplitude, duration, and area of contractions. In contrast, there was a reduction in the total amplitude, duration, and area of contractions, and this was due to a decrease in frequency of contractions. The reduction in the total parameters of all contractions could be accounted for by a reduction in the same parameters for propagating contractions. The parameters of nonpropagating contraction were not different after cholera toxin. Also, there was a decrease in the distance of propagation of contractions. Our findings demonstrate that during the secretory state due to cholera toxin the small intestinal motor activity works in a compensatory mode to decrease transit and allow more time for absorption.This work was supported in part by grant DK32346 from the National Institute of Diabetes and Digestive and Kidney Diseases and in part by Department of Veterans Affairs Medical Research Service.     

Does oral rehydration therapy alter food consumption and absorption of nutrients in children with cholera?

In order to estimate consumption of food and absorption of nutrients, a metabolic balance study was conducted in 47 children between 1 and 5 years old, suffering from acute cholera. Twenty-two of the children were treated by intravenous solution (IV) only and 25 others by oral rehydration along with intravenous solution (ORS/IV) when necessary. After initial rehydration a nonabsorbable charcoal marker was fed to the patients followed by a typical Bangladeshi home food of known composition offered ad libitum. Appearance of the first marker in the faeces was taken as zero hour (0 h); at 72 h a second marker was fed. Faeces, urine and vomitus were collected up to the appearance of the second marker. Intake of IV fluid, ORS and any other fluid or food were recorded accurately. Samples of faeces, urine and vomitus were analysed for energy, fat and nitrogen. Consumption of nutrients and absorption in both groups were calculated. There was no significant difference in the intake or absorption of energy or carbohydrate between the two groups. The consumption of fat and protein was slightly, but significantly, lower in the ORS/IV group during the acute stage of diarrhoea than in the IV group. Absorption of nitrogen was significantly lower in the ORS/IV group, but absorption of fat was not significantly impaired. Vomiting was significantly higher in the ORS/IV group. The differences in the consumption and absorption of nutrients between the two groups were transient and came to the same level within 2 weeks after recovery.     

Modulation of jejunal flow by solutions of varying osmolality and acidity in the intact canine jejunum

Because gastric emptying is modulated by the osmolality or hydrogen ion concentration of intraduodenal solutions, we hypothesized that similar mechanisms exist to regulate flow within the small intestine and that the altered flow is associated with changes in intestinal motility. Sodium chloride solutions with higher and lower osmolality than plasma and both isotonic and hypotonic hydrochloric acid solutions flowed more slowly into segments of jejunum in conscious dogs than isotonic neutral salt solutions. The altered flow was associated with increased frequency of spike bursts in the segment with the salt solutions of varied osmolality, but with only increased force of contractions with both isotonic and hypotonic acid solutions. Some evidence exists to suggest that the changes in motility are mediated by a neural mechanism. If similar mechanisms exist in the duodenum, they may play a role in the regulation of gastric emptying.This work was supported in part by Veterans Administration Research Funds and grant AM 08901 from the National Institute for Arthritis, Metabolism and Digestive Diseases, National Institution of Health, Bethesda, Maryland.     

Haemochromatosis: understanding the mechanism of disease and implications for diagnosis and patient management following the recent cloning of novel genes involved in iron metabolism

Haemochromatosis, a common recessive genetic disorder in people of Northern European descent, is an iron storage disorder characterized by excessive hepatic iron accumulation resulting from disruption of the regulation of intestinal iron absorption. The identification of novel genes involved in the control of iron absorption from the diet has allowed improved understanding of iron metabolism in health and disease. In particular, the identification of the haemochromatosis gene (HFE) and more recently the transferrin receptor 2 gene (TfR2) together with the specific mutations in these genes which result in hepatic iron overload, has enhanced our understanding of the pathophysiology of haemochromatosis. However, because of the wide variation in phenotypic expression of the disease, there now exists a considerable challenge to diagnosis and patient management.