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Detrimental effects on villus form during conventional oral rehydration therapy for diarrhoea in calves; alleviation by a nutrient oral rehydration solution containing glutamine.

This paper examines the possibility that treatment of diarrhoea with conventional oral rehydration solutions (ORSs) may be detrimental to villus structure by imposing nutrient deprivation and that such detrimental effects may be reduced or avoided by using a nutrient ORS. A conventional WHO-type ORS (W) was compared with two nutrient solutions (N and G) both containing high glucose concentrations and the latter containing glutamine; their effects on enteric structure were assessed by morphometric analysis of samples obtained from diarrhoeic calves after 96 h treatment. Comparisons were also made with samples from controls and diarrhoeic calves at the stage where oral rehydration would have begun in the treated groups. As in our previous ORS studies, diarrhoea was induced with enterotoxigenic Escherichia coli (09:K30:K99). We measured villus length and width, crypt depth and width and calculated villus surface area in proximal, mid and distal small intestine (PSI, MSI, DSI), using standard morphometric techniques. Proximal and distal spiral colon samples (PC, DC) were examined for crypt depth and width; mitoses per crypt were counted in samples from all regions. Non-diarrhoeic calves showed the expected gradient of villus length through PSI, MSI and DSI, hence data for each region are normalized as a percentage of the control value for that region. PSI showed the greatest loss of villus length and surface area (50%) with diarrhoea. In MSI and DSI the villus loss was greater with solution W and N or G, as were increased mitoses and crypt depth. Crypt depth and mitoses also increased in the colon with solution W. Colonic crypt width increased with diarrhoea and conventional oral rehydration but less so with G; there is reason to believe that such changes have functional significance. Crypt changes in colon, MSI and DSI were least with solution G. The changes developing in diarrhoeic calves prior to treatment were thus less apparent in those treated with a nutritional ORS, particularly if it contained glutamine.

Animals↗

Oral rehydration solutions: enhanced sodium absorption with gum arabic.

OBJECTIVE: To assess whether the addition of gum arabic (GA) to oral rehydration solutions (ORS) of either 60 or 90 mM sodium enhances net water and sodium absorption in rats. METHODS: Perfusion of a jejunal segment of male juvenile rats under anesthesia, and determination of net water and sodium absorption, and unidirectional fluid movements using appropriate markers. RESULTS: Addition of 5 and 10 g/L of GA increased the rates of sodium removal from the intestinal lumen perfused with ORS containing either 60 or 90 mM sodium. Net water absorption was unaffected, although GA tended to facilitate bidirectional fluid movement. The alteration of solute transport rates by the addition of 10 g/L GA was associated with an expansion of the basolateral intercellular spaces. CONCLUSIONS: A soluble fiber such as GA appears to be an effective enhancer of sodium absorption from ORS when tested in experimental animals. Since GA does not affect viscosity, an alteration of solute diffusibility through the brush border membrane and changes in intercellular compartments may underlie the observed improvement of sodium absorption.

Animals↗

Evidence of a dominant role for low osmolality in the efficacy of cereal based oral rehydration solutions: studies in a model of secretory diarrhoea.

Clinical trials suggest that including naturally occurring complex carbohydrate in oral rehydration solutions (ORS) in place of glucose increases water absorption and reduces stool volume during acute diarrhoea. The mechanisms for this greater clinical efficacy has not been established. This study examined the ability of two hypotonic rice based ORS, RS-ORS (137 mOsm/kg) and RP-ORS (143 mOsm/kg), and HYPO-ORS (240 mOsm/kg) a glucose equivalent ORS, to effect water absorption by in vivo perfusion of normal and secreting rat small intestine. The results were compared with those for two widely used conventional hypertonic ORS, WHO-ORS (331 mOsm/kg) and UK-ORS (310 mOsm/kg). In the normal intestine, water absorption was similar from WHO-ORS (87.4 (45.1-124.6) microliters/min/g; median and interquartile range) and UK-ORS (57.6 (41.5-87)) but less than from the hypotonic solutions (p < 0.02); water absorption from RS-ORS (181.8 (168.5-193.8)) and RP-ORS (195.7 (179.3-207.9)) was similar but less than from HYPO-ORS (241.3 (230.6-279.7); p < 0.005). In the secreting intestine, all ORS reversed net secretion of fluid to net absorption; the hypotonic solutions, HYPO-ORS (105.2 (95.2-111)), RS-ORS (127.7 (118.3-169.4)) and RP-ORS (133.7 (122.1-174.5)), produced more water absorption (p < 0.005) than the hypertonic solutions WHO-ORS (47.1 (29-75.9)) and UK-ORS (24.9 (18.4-29.4)). The rice based ions promoted most water absorption in secreting intestine (p < 0.007). These data indicate that low osmolality is of primary importance in mediating the increased water absorption from cereal based ORS.

Animals↗

Comparative bacterial study of oral rehydration solution (ORS) prepared in plain unboiled and boiled drinking water of Kathmandu valley.

Result of bacterial study on Oral Rehydration Solution (ORS) prepared in plain unboiled and boiled drinking water of Kathmandu valley is reported. Of the total 100 water samples collected from different sources and area all the samples, as a base line study, were subjected for the examination of bacterial presence. Eighty eight percent of the water samples studied were found to be unsatisfactory for drinking. Thirty five percent of the ORS prepared in unboiled water and kept for 24 hours at room temperature showed increased bacterial count whereas none of the ORS prepared in 5 minute boiled water and kept for 24 hour at room temperature showed any bacterial growth. Decreased bacterial count was not found in any of the ORS prepared in unboiled water. Typical coliform bacilli were found grown in 57.0% of the ORS prepared in unboiled water samples.

Child↗

High-calorie, rice-derived, short-chain, glucose polymer-based oral rehydration solution in acute watery diarrhea.

In this study, we have compared the effects of the World Health Organization oral rehydration solution (WHO ORS) and an ORS containing short polymers of glucose (Amylyte ORS) at a high caloric density (five times) and comparable osmolality, on stool output, duration of diarrhea, weight gain and fluid and electrolyte balance, in randomized, open-labeled, controlled clinical trials in five centers. A total of 198 male children (4 months to 10 years) with acute diarrhea ( <72 h after onset) were assigned by random allocation to either WHO ORS or Amylyte ORS at five centers in Asia. Children were stratified according to grade of dehydration (mild, moderate or severe) and the initial purging rates during the first 6 h (low ( < 2 ml/kg/h), moderate (2-5 ml/kg/h) and high ( > 5 ml/kg/h) purgers). The clinical characteristics of the children in the two treatment groups were comparable. Amylyte ORS reduced stool volumes significantly in children with severe dehydration (285.4 +/- 74.2 versus 75.5 +/- 20.0 ml/kg; p < 0.05) and in children with a high initial purging rate (200.3 +/- 42.8 versus 130.5 +/- 9.1 ml/kg; p < 0.05). This was accompanied by a significant (276.4 +/- 14.6 versus 227.6 +/- 11.8 ml/kg; p < 0.01) reduction in ORS requirements in the Amylyte ORS treated group, the effect being greatest in children with severe dehydration (491.5 +/- 108.5 versus 155.7 +/- 27.3 ml/kg; p < 0.01) or high initial purging rates (394.2 +/- 66.2 versus 316.8 +/- 34.8 ml/kg; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

The benefits of the very early introduction of powdered rice and dried edible seeds (Dal moong) in the oral rehydration solution during the treatment of acute infectious diarrhoea of infancy.

We have examined whether the addition of powdered rice and pulses (Dal moong) to oral rehydration solution will decrease the purging rate and thereby increase the efficacy of the oral rehydration therapy. The study was carried out on 60 male infants, with acute watery diarrhoea, moderate dehydration but without fever, vomiting, or other conditions like septicaemia and meningitis. The infants were treated with either the standard WHO oral rehydration salt solution (ORS) or with a modified solution where glucose was removed and powdered rice and Dal moong were added. We found that the infants receiving ORS with powdered rice and Dal moong had significantly lower fluid losses in the stools, a significant and more rapid weight gain, and needed significantly less fluid than the infants receiving ORS only.

Acute Disease↗

Evaluation of oral rehydration solution by whole-gut perfusion in rats: effect of osmolarity, sodium concentration and resistant starch.

BACKGROUND: Reduced osmolarity oral rehydration solution (ORS) improved small bowel absorption of fluid and electrolytes in segmental perfusion in experimental animals; this was borne out in clinical practice. Adding amylase-resistant starch (RS) to ORS is expected to increase colonic fluid absorption. This study used combined small and large bowel perfusion to evaluate combinations of reduced osmolarity and starch in ORS. METHODS: Single-pass steady-state perfusions of the whole gut at 30 mL/h, using the nonabsorbable marker C-polyethylene glycol 4000, were performed in Wistar rats after exposure to cholera toxin or Escherichia coli heat-stable enterotoxin (STa). RESULTS: Steady state was established within 90 minutes after commencing perfusion. Net secretion of water, sodium and chloride induced by cholera toxin was partially reversed by standard glucose-ORS (G-ORS). Substituting glucose in G-ORS with RS (RS-ORS) substantially increased net water absorption (P < 0.001) as did reduced osmolarity ORS (RO-ORS) (P < 0.001); addition of RS to RO-ORS further increased water absorption (P < 0.001). In STa-treated intestine, RO-ORS and RS-ORS significantly improved water absorption compared to G-ORS (P < 0.005). RO- and RS-RO-ORS did not significantly augment net electrolyte absorption compared with G-ORS. RS-ORS was associated with highest net absorption of sodium and chloride compared with all other groups. CONCLUSIONS: RS increased net water (and sodium) absorption from isosmolar and reduced osmolar ORS consistent with increased absorption by the colon. RS in reduced osmolar ORS may have advantages to reduce severity of diarrhea and prevent hyponatremia in severe diarrhea and may be applicable to diarrhea of different etiologies.

Animals↗

Clinical experience with a hypotonic oral rehydration solution for treatment of pediatric gastroenteritis in the United Kingdom.

Animal and human perfusion studies suggest that water absorption can be optimized by glucose-electrolyte solutions with low total osmolality. A new oral rehydration solution (ORS), reformulated Dioralyte (RD), containing 60 mmol/L of sodium and 90 mmol/L of glucose with an osmolality of 240 mosm/kg, was tested for safety and efficacy in children in the United Kingdom with acute gastroenteritis. In a double-blind, controlled trial, RD was compared with standard Dioralyte (SD), a widely used low-sodium, high-glucose solution containing 35 mmol/L of sodium and 200 mmol/L of glucose, with an osmolality of 310 mosm/kg. Infants and children aged 2 weeks to 3 years admitted with acute gastroenteritis of less than five days' duration and mild to moderate dehydration were randomized to receive either RD or SD. Clinical and laboratory assessments were made on admission and 12, 24, and 48 hours after treatment. Thirty-two children were enrolled in the study; 14 received RD and 18 SD. No adverse effects from either ORS were reported. Efficacy was evaluated in 24 patients, of whom eight received RD and 16 SD. Total ORS intake and intake in milliliters per kilogram were similar in both treatment groups. Mean fluid balance, mean percentage weight change, and median stool frequency did not differ between the groups at 12, 24, and 48 hours after onset of treatment. Three (12.5%) patients had greater than or equal to 0.05% reducing substances in the stool during treatment, and the incidence was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗

Rice starch low sodium oral rehydration solution (ORS) in infantile diarrhoea.

The relative efficacy and incidence of hypernatremia of a rice starch based low sodium (sodium of 60 mmol/L) oral electrolyte solution was compared to the standard WHO oral rehydration solution (ORS; sodium 90 mmol/L) in 60 infants with non choleragenic acute diarrhoea. Both solutions were found to be equally effective in correcting dehydration as determined by the respective post hydration weight gain which was 150 +/- 175 gms in the rice starch low sodium ORS group and 164 +/- 125 gms in the standard WHO ORS group. However, the mean frequency of stools was greater and the duration of stay longer in the WHO ORS group compared to the rice starch low sodium group. There were 5 cases of hypernatremia in the WHO ORS group as opposed to only one in the rice starch low sodium ORS group. The present study shows that a rice starch low sodium ORS was as effective as the standard WHO ORS and had a lower incidence of hypernatremia in the fluid and electrolyte management of infants with non choleragenic diarrhoea.

Diarrhea, Infantile↗

A randomized double-blind clinical trial of a maltodextrin-containing oral rehydration solution in acute infantile diarrhea.

A double-blind, randomized controlled study was used to compare the efficacy and safety of an oral rehydration solution either with minimally hydrolyzed maltodextrins or the standard recommended glucose. One hundred twenty pediatric patients with acute watery diarrhea (60 in each group) were studied, but only 116 patients were included in the final analysis. After rehydration, outcome variables did not differ significantly at p < 0.05. Mean duration of diarrhea was 52.5 +/- 32.2 h for the control group (median, 50.8 h) and 57.2 +/- hours for the study group (median, 45.3 hours). Comparisons of the mean stool output, weight gain, and ORS intake on the 24th h and from admission to discharge were not statistically significant. Differences in laboratory parameters consisting of mean serum sodium, potassium, total CO2, hematocrit, plasma total solids, urine specific gravity, and random blood sugar were likewise not significant. Differences in stool pH and reducing sugars were statistically significant; however, the observed values were still within normal range. All laboratory values improved upon rehydration. Replacement of glucose with maltodextrins did not offer added advantages in reducing the duration and severity of diarrhea.

Blood Glucose↗

Zinc as a potential enteroprotector in oral rehydration solutions: its role in nitric oxide metabolism.

Zinc has been recognized as an antioxidant with potential for chronic and acute effects. Oxidative damage produced by free radicals, including nitric oxide (NO), is responsible for certain types of intestinal malabsorption syndromes and diarrhea. Under physiologic or mildly stimulatory conditions for NO synthesis, the small intestine characteristically is in a proabsorptive state; however, an excessive production of NO triggers formation of cyclic nucleotides, which cause secretion and malabsorption. In this study, we hypothesized that low-molecular-weight, soluble zinc chelates could modulate the effects of induced NO excess on the small intestine. In vitro experiments demonstrated that zinc-citrate or zinc-histidine at > or =0.66 mM, as well as a known NO scavenger, 2-[carboxyphenyl]-4,4,4,4-tetramethylimidazoline-1-oxyl-3-oxide, at 2 microM, were effective at removing chemically generated NO. In vivo jejunal perfusions, conducted in healthy rats under anesthesia, showed that c-PTIO reduced the proabsorptive effects produced by 1 mM L-arginine, the precursor of NO. In a standard oral rehydration solution, 1 mM zinc-citrate partially reversed the antiabsorptive effects on potassium caused by an excess of NO generated from 20 mM L-arginine but did not alter sodium or water absorption. The data are consistent with the view that soluble zinc compounds incorporated into an oral rehydration solution may deserve further attention as a means to scavenge NO with fluids used for the treatment of chronic or acute diarrhea, especially in malnourished children who are often zinc deficient.

Animals↗

Evaluation of home-made salt-sugar oral rehydration solution in a rural Nigerian population.

Standardized local measures for preparing oral rehydration solution (ORS) in Nigeria were re-evaluated under laboratory conditions. Our results confirm those of the standardization team in respect of granulated and cube sugar. However, our mean weight of one salt measure (2.8155 +/- 0.292 g) is about 20% greater than their value. Consequently, correct use of the measures in our study gave solutions of 211-297 mmol-1 total concentration and 60-80 mmol-1, Na+ as against their values of 173-251 mmol 1-1 and 45-70 mmol-1, respectively. This discrepancy is most likely due to differences in salt type. Analysis of home-made solutions prepared by 40 illiterate mothers showed that 60% of them made accurately composed solutions. All the rest made hypertonic solutions. Salt type, spoon size and levelling technique are all possible causes of their error. The tendency to err only on the side of greater rather than lower salt concentration may be culture based or simply due to natural maternal instinct. To combat this trend, health education programmes in Nigeria should emphasize the danger in feeding a hypernatremic solution to a dehydrated child.

Adult↗

Symptomatic hyponatremia during treatment of dehydrating diarrheal disease with reduced osmolarity oral rehydration solution.

CONTEXT: In May 2002, the World Health Organization and the United Nations Children's Fund recommended that the formulation of oral rehydration solution (ORS) for treatment of patients with diarrhea be changed to one with a reduced osmolarity and that safety of the new formulation, particularly development of symptomatic hyponatremia, be monitored. OBJECTIVE: To measure the rates of symptomatic hyponatremia during treatment of patients with diarrhea with reduced osmolarity ORS. DESIGN, SETTINGS, AND PATIENTS: A phase 4 trial conducted at the Dhaka hospital (December 1, 2002-November 30, 2003) and Matlab hospital (February 2, 2003-January 31, 2004) of the International Centre for Diarrhoeal Disease Research Bangladesh: Centre for Health and Population Research, Dhaka, Bangladesh. All patients admitted with uncomplicated watery diarrhea were treated with the newly recommended ORS and monitored. Patients developing neurological symptoms (seizure or altered consciousness) were transferred to the special care ward for treatment and investigated to identify the cause of the symptoms. Patient records of the Dhaka hospital were reviewed during the previous year when the old ORS formulation was used. INTERVENTION: Reduced osmolarity ORS. MAIN OUTCOME MEASURE: Incidence rate of symptomatic hyponatremia in a 1-year period. RESULTS: A total of 53,280 patients, including 22,536 children younger than 60 months, were monitored at the Dhaka and Matlab hospitals. Twenty-four patients, none older than 36 months, developed seizures or altered consciousness associated with hyponatremia, with an overall incidence rate of 0.05% (95% confidence interval [CI], 0.03%-0.07%) at the Dhaka hospital and 0.03% (95% CI, 0.01%-0.09%) at the Matlab hospital. During the previous year, 47 patients at the Dhaka hospital had symptoms associated with hyponatremia, for an estimated incidence rate of 0.10% (95% CI, 0.07%-0.13%). The reduction in the rates was statistically significant (odds ratio, 0.50; 95% CI, 0.29-0.85; P = .009). CONCLUSION: The risk of symptoms associated with hyponatremia in patients treated with the reduced osmolarity ORS is minimal and did not increase with the change in formulation.

Adolescent↗

Clinical trial of fermented maize-based oral rehydration solution in the management of acute diarrhoea in children.

In an effort to identify appropriate fluids available in the home for oral rehydration therapy in Ghana, a study was designed to investigate the efficacy of fermented maize gruel, a popular Ghanaian traditional food, in the management of acute diarrhoea. Altogether 108 children aged between 4 and 27 months presenting with acute diarrhoea at the Princess Marie Louise Children's Hospital in Accra, with mild to moderately severe dehydration, were randomly assigned to treatment with either WHO/UNICEF oral rehydration solution (ORS) or fermented and unfermented maize solutions. About 35 children were admitted to each of the three treatment groups. Treatment with the rehydration fluid was maintained for 24 h. Efficacy of the various treatments, assessed in terms of fluid intake, stool output, stool frequency, weight gain and duration of diarrhoea, showed no significant variation among the three groups. The results indicate that the maize solutions were as effective as WHO/UNICEF ORS for oral rehydration therapy. However, the fermented maize was more readily accepted by the children than the unfermented solution. Because fermented maize gruel is widely consumed, inexpensive, readily available, and culturally acceptable to most communities in Ghana, it may be recommended as an appropriate home-available fluid for the management of acute diarrhoea in children at the community level.

Acute Disease↗

Neonatal hyperparathyroidism. Conservative treatment with intravenous and oral rehydration solutions.

A neonate with primary hyperparathyroidism was successfully managed by conservative medical treatment. This treatment consisted of intravenous saline load, followed by oral rehydration solutions containing between 60-90 mmol/l of sodium. The combined administration of sodium and diuretics maintained normal levels of serum calcium. Similar cases were previously treated by parathyroidectomy with or without autotransplantation. In selected patients, medical treatment should be considered as the initial approach in mild neonatal hyperparathyroidism. It poses no specific risks and offers an alternative to surgical intervention.

Fluid Therapy↗

Efficacy and safety of oral rehydration solution with reduced osmolarity in adults with cholera: a randomised double-blind clinical trial. CHOICE study group.

BACKGROUND: The effects of oral rehydration solution (ORS) with reduced osmolarity on children with acute watery diarrhoea are known, but little is known about the effects of such ORS on adults with cholera. We aimed to compare the efficacy and safety of an ORS with reduced osmolarity with that of standard WHO ORS in adults with cholera. METHODS: We undertook a double-blind, controlled clinical trial in adults with severe cholera at the International Centre for Diarrhoeal Disease Research, Bangladesh. Our primary outcomes were mean stool output in the 24 h after randomisation, proportion of patients who needed unscheduled intravenous therapy, and proportion of patients with biochemical hyponatraemia 24 h after randomisation. FINDINGS: 147 patients received ORS with reduced osmolarity and 153 received standard WHO ORS. There was no significant difference between the two groups in terms of main outcome variables: mean initial 24 h and total stool output (reduced osmolarity vs standard WHO ORS 212 [SE 8] vs 207 [8] and 284 [13] vs 273 [13] g/kg respectively), duration of diarrhoea (46 [1.5] vs 43 [1.5]). The proportion of patients vomiting during the first 24 h and the proportion who received unscheduled intravenous infusion during the first 24 h was similar between groups. More patients on reduced osmolarity ORS than on standard WHO ORS developed hyponatraemia during the first 24 h, defined as serum sodium concentration below 130 mmol/L (29 of 142 vs 16 of 150; odds ratio 2.1 [95% CI 1.1-4.1]). However, all hyponatraemic patients in both groups were symptom-free and the proportion of patients with serum sodium concentration below 125 mmol/L was similar between groups. INTERPRETATION: There was no difference in clinical outcome between cholera patients treated with reduced osmolarity ORS solution and those treated with standard WHO ORS. The risk of increased incidence of symptom-free hyponatraemia in patients with cholera treated with an ORS with reduced osmolarity should be further assessed by meta-analysis. The risk should be taken into account when choice of ORS is made in areas in which cholera is endemic.

Administration, Oral↗

Outpatient use of oral rehydration solutions in Apache population: effect of instructions on preparation and contamination.

Oral Rehydration Solutions (ORS) containing 90 and 50 mmol/L sodium have recently been recommended for use in ambulatory children in the U.S. These solutions are now marketed in powder form by some commercial companies. However, few data are available in the U.S. on the accuracy with which the solutions are mixed at home or on the bacterial contamination that may occur during mixing. We evaluated the effect of various forms of instructions on the occurrence of bacterial contamination and accuracy of mixing ORS at home by mothers of patients who were dispensed the dry ingredients of an ORS containing 90 mmol/L sodium at the U.S. Public Health Service Hospital, Whiteriver, Arizona. Patients were randomized to one of the four following groups: group I (23 patients) was given written instructions for mixing the solution along with a pre-marked container; group II (22 patients) was given written instructions only; group III (22 patients) was given a premarked container only; and group IV (19 patients) was given neither. All patients were given oral instructions in the preparation of ORS and were asked to refrigerate the reconstituted ORS. We collected samples of ORS at the patient's home 1 day after the clinic visit, to measure their electrolyte content and to identify any bacterial contamination. Mean Na+ concentrations were significantly lower in the ORS prepared by mothers/guardians in groups that were not given a premarked container [82 +/- 13 (II) and 79 +/- 21 (IV) mmol/L vs. 88 +/- 13 (I) and 92 +/- 14 (III) mmol/L; p less than 0.01].(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Oral rehydration solutions: increased water and sodium absorption by addition of a viscosity-enhancing agent in a rat model of chronic osmotic diarrhea.

Viscosity-enhancing agents such as carboxymethylcellulose (CMC) can alter absorption of solutes and fluid exchange in the small intestine. We investigated whether the standard World Health Organization oral rehydration solution (WHO-ORS) with the addition of CMC would improve net water and sodium absorption in rats using an in vivo intestinal perfusion technique. Four WHO-ORS, containing either 0, 2.5, 5.0, or 10.0 g/L of CMC, were perfused in rats with a well-tested model of cathartic-induced chronic osmotic diarrhea (D) and in normal controls (C). In D rats, the ORSs with CMC improved sodium absorption at the three concentrations used (p < 0.01). The same effect was shown in C rats. Net water absorption was also enhanced in D rats given ORSs with CMC, although the changes in C animals were less marked. The improvement in sodium and water absorption in both C and D rats positively correlated with the log of relative ORS viscosity. Ultrastructural examination of tissues perfused with 10 g/L of CMC showed an extended brush border glycocalyx. This study indicates that CMC added to WHO-ORS in the perfused rat jejunum improves the effectiveness of the solution by increasing sodium and water absorption.

Animals↗