Sacolene in cholera: a double blind randomized controlled trial.

Methylated casein (Sacolene), a diarrhoea remedy used in Europe, has shown an antisecretory effect in cholera-induced secretion in animals and benefit in diarrhoea in humans. In this placebo controlled trial Sacolene was evaluated in 78 male adults with severe cholera who, after initial i.v. therapy received Sacolene or placebo, 4 g at start and 2 g 4 hourly until cessation of diarrhoea, along with oral rehydration therapy and repeat i.v. therapy if indicated. No antibiotics were given during the study. The purging rate and diarrhoea duration were similar in the 2 groups. The proportion of patients requiring repeat courses of i.v. therapy in the study group was 46% compared with 69% in controls (i.e. reduced by 23%, p = 0.04). While the severity of purging was not reduced, the proportion of patients requiring repeat i.v. therapy was reduced by Sacolene therapy. The latter finding may indicate some benefit from Sacolene in cholera, though this requires confirmation.

The effect of L-glutamine on salt and water absorption: a jejunal perfusion study in cholera in humans.

OBJECTIVES: To assess the efficacy of an L-glutamine solution on jejunal salt and water absorption in cholera patients. DESIGN: A randomized double-blind jejunal perfusion study. SETTING: International Centre for Diarrhoeal Disease Research, Bangladesh. PATIENTS: Nineteen adults with acute cholera. INTERVENTIONS: Perfusion of balanced salt solutions alternated with defined glucose salt solution and glutamine glucose salt or alanine glucose salt solutions. MAIN OUTCOME MEASURES: Net jejunal water and sodium secretion. RESULTS: Perfusion of glutamine in the presence of glucose significantly reduced net water secretion (JnetH2O = -2.6 +/- 1.3 ml/h/cm) and also reduced net sodium secretion (JnetNa = -213 +/- 153 mumol/h/cm). Similar results were observed during the perfusion of solutions that contained alanine in addition to glucose (JnetH2O = -4.2 +/- 1.1 ml/h/cm and JnetNa = -444 U +/- 142 mumol/h/cm, respectively) or glucose alone (JnetH2O = -4.3 +/- 1.7 ml/h/cm and JnetNa = -452 +/- 212 mumol/h/cm, respectively). In addition, a higher basal secretion was associated with a greater stimulation of water absorption (F = 17, P < 0.001). CONCLUSION: Glutamine in the presence of glucose significantly reduces net water secretion and also reduces sodium secretion; higher basal secretion is associated with greater water absorption. As glutamine is able to stimulate water absorption to the same degree as glucose and alanine, and because it has the theoretical advantage of providing fuel for the mucosa, the inclusion of glutamine as the sole substrate in oral rehydration solution warrants further study.

Enhanced sodium absorption by citrate: an in vivo perfusion study of rat small intestine.

The effect of citrate on sodium, potassium chloride, and water absorption in the presence of glucose from the whole rat small intestine was studied by an in vivo marker perfusion technique. The perfusion solutions contained glucose and were similar in their electrolyte composition to the currently recommended oral rehydration solution for the treatment and prevention of diarrheal dehydration. Significantly more sodium and water absorption occurred from the citrate-containing solution than from the one without citrate. It is concluded that citrate enhances net sodium absorption from a glucose electrolyte solution in the rat small intestine independent of glucose-stimulated absorption.

Bicarbonate enhances sodium absorption from glucose and glycine rehydration solutions. An in vivo perfusion study of rat small intestine.

Sodium, potassium and water absorption was studied over the whole length of rat jejunum and ileum by an in vivo marker perfusion technique. The composition of solutions were similar to the oral rehydration solution currently in use for the treatment of acute diarrhoeal diseases. The study shows that bicarbonate and chloride containing glucose or glycine electrolyte solutions induce a significantly greater absorption of sodium, potassium and water compared to those containing chloride only. The study also confirms that an amino acid such as glycine is as efficient as glucose in promoting the absorption of sodium, potassium and water from rat small intestine.

Oral rehydration formula containing alanine and glucose for treatment of diarrhoea: a controlled trial.

OBJECTIVE: To determine whether adding L-alanine to the glucose based oral rehydration solution recommended by the World Health Organisation would improve its efficacy in treating acute diarrhoea. DESIGN: Randomised double blind controlled trial of oral rehydration solution containing L-alanine and glucose. SETTING: Inpatient service of a hospital treating diarrhoea. PATIENTS: 97 Male patients aged 6-59 years admitted to the hospital with acute and severe dehydration due to diarrhoea associated with Vibrio cholerae or enterotoxigenic Escherichia coli. Forty nine received the standard glucose based oral rehydration solution (control group) and 48 this solution with alanine added (study group). INTERVENTIONS: All of the patients received rapid intravenous acetate solution for the initial four hours after admission, which fully corrected the signs of dehydration. They were then admitted to the study and randomised. Immediately after the intravenous treatment oral rehydration treatment was started. All of the patients received oral tetracycline for 48 hours, starting 24 hours after start of the study. If signs of dehydration reappeared during oral treatment patients were given rapid intravenous acetate solution until they were fully corrected and then continued to take the assigned oral rehydration solution. END POINT: Passage of the last watery stool. MEASUREMENTS AND MAIN RESULTS: The median stool output/kg body weight during the initial 24 hours of oral rehydration treatment and until diarrhoea stopped was reduced in the study group compared with the control group from 309 ml to 196 ml and from 393 ml to 236 ml respectively. Intake of oral rehydration solution and intravenous acetate solution was reduced from 455 ml to 308 ml and from 616 ml to 425 ml respectively. Two patients in the study group compared with 18 patients in the control group required unscheduled rapid intravenous acetate solution to correct signs of dehydration during oral rehydration treatment. CONCLUSION: Oral rehydration solution containing L-alanine was considerably better than standard oral rehydration solution at reducing the severity of symptoms and the need for fluid of male patients with diarrhoea associated with V cholerae and enterotoxigenic E coli.

Preserved exocrine function in patients with acute cholera and acute non-cholera diarrhoea.

Exocrine pancreatic function was assessed by means of the Lundh test in 14 patients with acute cholera and 18 patients with acute infectious non-cholera diarrhoea within the first 24 h of their admission. Mean tryptic activity amounted to 39.8 +/- 4.8 microEq/min/ml in the cholera group and to 64.4 +/- 11.0 microEq/min/ml in the non-cholera group. None of these patients shared a value below the lower limit of normal. In fact, the mean tryptic activity per 2 h was significantly higher than that reported previously in a control group from the Bengal area. It is therefore concluded that the exocrine pancreatic function is preserved and responds to food stimulation in various types of acute infectious diarrhoea, including cholera. These findings provide the pathophysiological background for the recent observation that oral rehydration solutions containing high-molecular-weight nutrients such as rice powder are at least as efficient or even more potent than the WHO-recommended glucose-electrolyte formula in acute diarrhoea.

In search of a super solution: controlled trial of glycine-glucose oral rehydration solution in infantile diarrhoea.

In a double blind trial a glycine fortified oral glucose electrolyte solution was evaluated in a group of infants and small children (n=25) with moderate to severe dehydration due to acute diarrhoea, and was compared with a matched control group (n=26) receiving only glucose based oral rehydration solution. It is seen that the diarrhoea stool output, duration of diarrhoea, and volume of oral rehydration fluid required to achieve and maintain hydration are significantly lower in the group receiving glycine fortified glucose electrolyte solution. The possibility of developing an oral rehydration solution which could also act as an absorption promoting drug is discussed.

PIP: In a double-blind study, a glycine fortified oral glucose electrolyte solution as evalutaed in a group of infants and small children (n=25) with moderate to severe dehydration due to acute diarrhea, and was compared to a matched control group (n=26) receiving only glucose based oral rehydration solution. It was observed that diarrhea stool output, duration of diarrea, and volume of oral rehydration fluid required to achieve and maintain hydration are significantly lower in the group receiving glycine fortified glucose electrolyte solution. The possibility of developing an oral rehydration solution which could also act as a absorption promoting drug is also discussed.

Stimulation of sodium and water absorption by sucrose in the rat small intestine.

This study described the absorption of Na, K, Cl, H2O and sugars from an isosmotic sucrose electrolyte solution and compares it with the absorption of these substances from an isosmotic glucose electrolyte solution and a mannitol electrolyte solution, by an in vivo perfusion technique in the rat jejunum and ileum. The composition of the solutions was similar to the oral rehydrating solutions, currently in use for the treatment of acute diarrhoeal diseases. The study shows that an isosmotic sucrose containing electrolyte solution induces a significantly greater Na, Cl, and K absorption compared to glucose electrolyte solution. Water absorption however, is significantly less from the former solution probably due to osmotic drag of water into the lumen by the slowly absorbed fructose released from sucrose hydrolysis. These findings underline the clinical importance of using hyposmotic sucrose electrolyte solution for oral rehydration.