Rational assessment of the interaction profile of cerivastatin supports its low propensity for drug interactions.
For biotherapeutic agents, there is a lack of information on dose-response relationships and mechanism of action. The present study was designed to address these issues for Saccharomyces boulardii using the rat model of castor oil-induced diarrhea. A single dose of Saccharomyces boulardii at 12 x 10(10) CFU/kg of viable cells given 1 hr before castor oil administration significantly reduced the onset of diarrhea. Repeated ingestion of the yeast, twice daily between 1.2 and 12 x 10(10) CFU/kg for 5 days before castor oil, showed a dose-response relationship. The percentage of rats with diarrhea decreased and a stronger protection was afforded by the repeated treatment. The mechanism of action of Saccharomyces boulardii in this model was investigated with two classes of antagonists, naloxone and L-arginine. The effect of Saccharomyces boulardii was not inhibited by naloxone but was significantly reduced by L-arginine. This last result suggests a novel mechanism of action for Saccharomyces boulardii involving a possible inhibition of nitric oxide production by the yeast.
For the treatment of acute uncomplicated traveler's diarrhea - more than 90 % of all cases - the secretion inhibitor racecadotril is considered first choice, based on our evaluation criteria. The previously usual practice of recommending the antimotility drug loperamide as first choice should be reconsidered, in favor of the recent active ingredient racecadotril. Antibiotics should be used only in complicated cases. A large number of travelers who generally demand antibiotic therapy should be disabused of their expectations. Other therapeutic measures that are currently available for the treatment of acute diarrhea while traveling play a subordinate role.
Twenty five Swedish hospitals have contributed to this patient register, which comprises 163 histopathologically verified cases. Clinical data were retrospectively analysed.
Department of Medicine, Bristol Royal Infirmary.
Several methods are used to evaluate gastric motility in rodents, but they all have technical limitations. Recent technical developments enable a convenient method to evaluate gastric motility. The (13)C-acetic acid breath test in rodents is a non-invasive and repeatable method that can be used without physical restraints. The present study aimed to validate the (13)C-acetic acid breath test by measuring the effects of loperamide, morphine, mosapride, and itopride on gastric emptying in mice. Loperamide (1-10 mg/kg) and morphine (1.25-10 mg/kg) slowed gastric emptying and decreased the maximum concentration (C(max)) and area under the curve (AUC(90 min)) value in a dose-dependent manner. Mosapride (0.2-5 mg/kg) accelerated gastric emptying and increased C(max) value. Mosapride (20 mg/kg) did not accelerate gastric emptying on the (13)C-breath test. Itopride (30 mg/kg, per os) significantly accelerated gastric emptying compared with the vehicle group. In a comparison with the conventional phenol red test, there was a correlation between the C(max) value of breath test and gastric emptying (%) of phenol red tests in treatment with loperamide or mosapride. These results indicate that the (13)C-acetic acid breath test is an accurate, noninvasive, and simple method for monitoring gastric emptying in mice. This method is useful to assess the effect of drugs and gut function pharmacologically.
High-stoma output is a common problem that can lead to dehydration and electrolyte disturbance. The following report describes three patients with end ileostomy who had high-stoma outputs where conventional medical management was unsuccessful in controlling stoma output. All three patients responded to high-dose loperamide, resulting in significant clinical improvement. High-dose loperamide therapy should be considered in patients with high-stoma output who have failed conventional medical management.
Subtotal colectomy for severe slow-transit constipation is justified provided anorectal function is normal. In spite of normal rectal emptying very high rectal volume tolerability may be an indicator of functional megarectum and impaired rectal emptying postoperatively.
Mangifera indica is commonly grown in many parts of the world. Its seeds have been used for anti-diarrhoeal activity in Indian traditional medicine. This study evaluates the potential anti-diarrhoeal activity of methanolic (MMI) and aqueous (AMI) extracts of seeds of M. indica in experimental diarrhoea, induced by castor oil and magnesium sulphate in mice. Both MMI and AMI were given orally in the dose of 250 mg/kg, showed significant anti-diarrhoeal activity comparable with that of the standard drug loperamide. However, only MMI significantly reduced intestinal transit in charcoal meal test as compared with atropine sulphate (5 mg/kg; im). The in vitro antimicrobial activity of MMI and AMI showed variable results. While, AMI significantly inhibited growth of Streptococcus aureus and Proteus vulgaris, both MMI and AMI did not show any significant effect on growth of E. coli and Klebsiella. The results illustrate that the extracts of M. indica have significant anti-diarrhoeal activity and part of the activity of MMI may be attributed to its effect on intestinal transit.