Lab Anim Sci. 1996 Dec;46(6):612-8.
Increased survival of CFTR knockout mice with an oral osmotic laxative.
Clarke LL, Gawenis LR, Franklin CL, Harline MC.
Cardiovascular Research Center, Department of Veterinary Biomedical Sciences, University of Missouri-Columbia, 65211, USA.
Mouse models of cystic fibrosis that are generated by targeted disruption (knockout) of the cystic fibrosis transmembrane conductance regulator gene, cftr(-/-), typically die shortly after weaning, from intestinal obstruction/rupture caused by an inability to secrete fluid into the bowel lumen. We investigated the use of a commercial osmotic laxative, Colyte, provided continuously in the drinking water, to increase the survival of cftr(-/-) mice. Genotype analysis of 623 offspring surviving at 10 days of age yielded 28.1% cftr(+/+), 59.6% cftr(+/-), and 12.4% cftr(-/-) mice (25% predicted), suggesting that cftr(-/-) mice have a significant perinatal mortality rate. However, of the 77 cftr(-/-) mice alive at 10 days of age, >98% survived weaning and were maintained in apparent health to a minimum of 56 days of age (arbitrary age for experimentation). In intestinal bioelectric studies Colyte-treated drinking water, compared with tap water, had no significant effect on basal short-circuit current, cyclic AMP-stimulated Cl- secretion, Na+-coupled glucose absorption, or electrogenic Na+ absorption across intestinal sections from cftr(+/+ or +/-) mice. Other than a mild dilatation of the distal portion of the colon in the Colyte-treated animals, examination of jejunal and colonic sections revealed no histologic differences between the two treatments. These findings indicate that the chronic use of Colyte osmotic laxative in drinking water is an economical means of greatly increasing the survival of CFTR knockout mice without altering the major electrolyte transport processes or histomorphologic integrity of the intestine.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9001172&dopt=Abstract constipation laxative
Mutat Res. 1996 Dec 20;371(3-4):165-73.
Genotoxicity of the laxative drug components emodin, aloe-emodin and danthron in mammalian cells: topoisomerase II mediated?
Muller SO, Eckert I, Lutz WK, Stopper H.
Department of Toxicology, University of Wurzburg, Germany.
1,8-Dihydroxyanthraquinones are under debate as plant-derived carcinogens that are found in laxatives, food colors, and possibly vegetables. Published genotoxicity data are controversial, and so three of them (emodin, danthron and aloe-emodin) were tested in a number of in vitro assay systems. All three compounds induced tk-mutations in mouse lymphoma L5178Y cells. Induction of micronuclei also occurred in the same cell line, and was dose-dependent, with the potency ranking being danthron > aloe-emodin > emodin. In a DNA decatenation assay with a network of mitochondrial DNA of C. fasciulata, all three test compounds inhibited the topoisomerase II-mediated decatenation. Danthron and aloe-emodin, but not emodin, increased the fraction of DNA moving into comet tails when tested at concentrations around 50 microM in single-cell gel-electrophoresis assays (SCGE; comet assay). Comet assays were also used in modified form to determine whether pretreatment of the cells with the test compounds would reduce the effects of etoposide, a potent topoisomerase II inhibitor. All three test chemicals were effective in this pretreatment protocol, with danthron again being the most potent. Given clearcut evidence of their genotoxic activity, further research on the human cancer risk of these compounds may be warranted.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9008718&dopt=Abstract constipation laxative
Eur J Pediatr Surg. 1996 Dec;6 Suppl 1:32-4.
Treatment of defecation disorders by colonic enemas in children with spina bifida.
Scholler-Gyure M, Nesselaar C, van Wieringen H, van Gool JD.
Spina Bifida Team, University Children's Hospital, Utrecht, The Netherlands.
Faecal incontinence and constipation are well known problems in children with spina bifida. Effective treatment can be difficult and this gave the condition a low priority despite the obvious physical and psychological sequelae. Positive experience with colonic enemas (CE) in the paediatric post-operative care have led us to adopt this method as the treatment of choice for defecation disorders in children with spina bifida. In 41 spina bifida children (mean age 8.4 years, range 7 months to 22 years), retrograde CEs with hand-warm tap water were given at home from once a day to twice per week. Satisfaction with the procedure was evaluated with a questionnaire sent out after a mean follow-up period of 33 months (range 6 to 55 months). The indications to start CEs were faecal incontinence (27%), constipation (27%) or both. 34% of 41 children also had other gastrointestinal complaints, 7% had headaches, 29% had poor appetite and 15% felt generally unwell. Before the start of CE 22% of the children had been on a diet, 37% on oral laxatives, 31% on a rectal laxative and 44% had to have manual evacuations. 90% used diapers on a daily basis. At the end of the follow-up period 27% of the children were still on a diet and 17% still used oral laxatives but rectal laxatives were no longer used nor were manual evacuations necessary. 66% of the 41 children were completely faecally continent and constipation occurred only occasionally, no child had faecal retention or impaction. At follow-up 39% still used diapers regularly and 20% used a panty-line and complaints of abdominal pain, headache and poor appetite were rare. Satisfaction with the procedure was rated highly by 63% of parents and children and good by 37% but 15% of the children found regul
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