The fate of cyclamate in man and other species

1. 14C-labelled cyclamate has been administered to guinea pigs, rabbits, rats and humans. When given orally to these species on a cyclamate-free diet, cyclamate is excreted unchanged. In guinea pigs some 65% of a single dose is excreted in the urine and 30% in the faeces, the corresponding values for rats being 40 and 50%, for man, 30–50% and 40–60%, and for rabbits, 90 and 5%, the excretion being over a period of 2–3 days. 2. Cyclamate appears to be readily absorbed by rabbits but less readily by guinea pigs, rats and humans. 3. If these animals, including man, are placed on a diet containing cyclamate they develop the ability to convert orally administered cyclamate into cyclohexylamine and consequently into the metabolites of the latter. The extent to which this ability develops is variable, the development occurring more readily in rats than in rabbits or guinea pigs. In three human subjects, one developed the ability quite markedly in 10 days whereas two others did not in 30 days. Removal of the cyclamate from the diet caused a diminution in the ability to convert cyclamate into the amine. 4. In rats that had developed the ability to metabolize orally administered cyclamate, intraperitoneally injected cyclamate was not metabolized and was excreted unchanged in the urine. The biliary excretion of injected cyclamate in rats was very small, i.e. about 0.3% of the dose. 5. The ability of animals to convert cyclamate into cyclohexylamine appears to depend upon a continuous intake of cyclamate and on some factor in the gastrointestinal tract, probably the gut flora.

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Nutritional programming of gastrointestinal tract development. Is the pig a good model for man?

Nutrition Research Reviews ◽

10.1017/s0954422410000077 ◽

2010 ◽

Vol 23 (1) ◽

pp. 4-22 ◽

Cited By ~ 172

Author(s):

Paul Guilloteau ◽

Romuald Zabielski ◽

Harald M. Hammon ◽

Cornelia C. Metges

Keyword(s):

Gastrointestinal Tract ◽

Animal Models ◽

Animal Studies ◽

Reference Model ◽

Human Subjects ◽

Mammalian Species ◽

Epidemiological Studies ◽

Long Term Effects ◽

Nutritional Programming ◽

The Impact

The consequences of early-life nutritional programming in man and other mammalian species have been studied chiefly at the metabolic level. Very few studies, if any, have been performed in the gastrointestinal tract (GIT) as the target organ, but extensive GIT studies are needed since the GIT plays a key role in nutrient supply and has an impact on functions of the entire organism. The possible deleterious effects of nutritional programming at the metabolic level were discovered following epidemiological studies in human subjects, and confirmed in animal models. Investigating the impact of programming on GIT structure and function would need appropriate animal models due to ethical restrictions in the use of human subjects. The aim of the present review is to discuss the use of pigs as an animal model as a compromise between ethically acceptable animal studies and the requirement of data which can be interpolated to the human situation. In nutritional programming studies, rodents are the most frequently used model for man, but GIT development and digestive function in rodents are considerably different from those in man. In that aspect, the pig GIT is much closer to the human than that of rodents. The swine species is closely comparable with man in many nutritional and digestive aspects, and thus provides ample opportunity to be used in investigations on the consequences of nutritional programming for the GIT. In particular, the ‘sow–piglets’ dyad could be a useful tool to simulate the ‘human mother–infant’ dyad in studies which examine short-, middle- and long-term effects and is suggested as the reference model.

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The importance of skeletal muscles as a distribution volume for digitalis glycosides in guinea-pigs and human subjects

Cardiac Glycosides 1785–1985 ◽

10.1007/978-3-662-11292-2_32 ◽

1986 ◽

pp. 245-255 ◽

Cited By ~ 1

Author(s):

Keld Kjeldsen

Keyword(s):

Guinea Pigs ◽

Skeletal Muscles ◽

Human Subjects ◽

Distribution Volume ◽

Digitalis Glycosides

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Immunohistochemical study of CD44 immunopositive cells in the muscular layers of the gastrointestinal tract in adult guinea pigs and mice

Acta Histochemica ◽

10.1016/j.acthis.2008.12.003 ◽

2009 ◽

Vol 111 (4) ◽

pp. 383-391 ◽

Cited By ~ 2

Author(s):

Bin Yu ◽

Juan Han ◽

Yang-tao He ◽

Sheng Guo ◽

Shi-feng Li ◽

...

Keyword(s):

Gastrointestinal Tract ◽

Guinea Pigs ◽

Immunohistochemical Study

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Autonomic nerve receptors in the allergic nasal mucosa in the human subjects and the sensitized guinea pigs.

Nippon Jibiinkoka Gakkai Kaiho ◽

10.3950/jibiinkoka.88.1153 ◽

1985 ◽

Vol 88 (9) ◽

pp. 1153-1161

Author(s):

NOBUHISA TERADA ◽

AKIYOSHI KONNO ◽

YOSHITAKA OKAMOTO

Keyword(s):

Nasal Mucosa ◽

Guinea Pigs ◽

Human Subjects ◽

Autonomic Nerve

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Glucagon induces biliary protein excretion in guinea pigs

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1993.264.5.g961 ◽

1993 ◽

Vol 264 (5) ◽

pp. G961-G966

Author(s):

R. Lenzen ◽

N. Tavoloni

Keyword(s):

Biliary Excretion ◽

Guinea Pigs ◽

Lysosomal Enzymes ◽

Fluid Transport ◽

Dependent Manner ◽

Canalicular Membrane ◽

Protein Excretion ◽

Endogenous Protein ◽

Camp System ◽

Protein Output

This study was done to determine glucagon's effect on protein biliary excretion in anesthetized, bile duct-cannulated guinea pigs. Glucagon (1.4 nmol.min-1.kg-1) induced choleresis and increased protein biliary concentration from 0.12 +/- 0.04 to 0.20 +/- 0.6 mg/ml and protein output from 22.8 +/- 3.8 to 54.5 +/- 16.1 micrograms.kg-1.min-1. Protein biliary excretion increased during the first 10 min of glucagon infusion and progressively declined thereafter. Biochemical analysis of biliary protein revealed that the increase could be accounted for primarily by an increase in the lysosomal enzymes acid phosphatase and beta-glucuronidase. Biliary excretion of the canalicular membrane enzymes 5'-nucleotidase and alkaline phosphatase only modestly increased, whereas that of [14C]sucrose, a marker of paracellular fluid transport, was unaffected. On the other hand, glucagon enhanced biliary entry of horseradish peroxidase in a fashion similar to that observed with total endogenous protein. These effects were mediated by the adenosine 3',5'-cyclic monophosphate (cAMP) system, since infusion of dibutyryl-cAMP at 0.5 mumol.kg-1.min-1 increased bile flow and biliary protein excretion in a time-dependent manner, as observed with glucagon. Glucagon's failure to sustain enhanced protein biliary output was not due to declining hepatic concentrations of cAMP or to depletion of hepatocellular lysosomal enzymes. These studies provide evidence that glucagon stimulates biliary excretion of protein in guinea pigs that can be accounted for by biliary discharge of enzyme originating from the canalicular membrane and, primarily, from the lysosomal compartment. Although the precise mechanism(s) underlying these effects remains to be elucidated, it is suggested that the increase in canalicular membrane enzyme excretion is due to glucagon's effect on exocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)

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Intact biliary excretion of gastrically administered prostaglandin F2 alpha in rats: developmental differences

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1987.253.6.g787 ◽

1987 ◽

Vol 253 (6) ◽

pp. G787-G792

Author(s):

A. D. Bedrick ◽

M. A. Wells ◽

D. L. Ford ◽

O. Koldovsky

Keyword(s):

Gastrointestinal Tract ◽

Bile Duct ◽

Biliary Excretion ◽

Enterohepatic Circulation ◽

Developmental Differences ◽

Orogastric Tube ◽

Prostaglandin F2 Alpha ◽

Age Related ◽

Weanling Rats

Tritium-labeled prostaglandin F2 alpha was administered via orogastric tube to bile duct-cannulated suckling and weanling rats to determine if maturational differences were present in the biliary excretion of prostaglandin F2 alpha and metabolites. Animals were killed 2 h after radioactivity administration. Characterization of radioactivity present in bile revealed age-related differences in biliary prostaglandin F2 alpha excretion. Suckling rats had a greater proportion of radioactivity migrating in chromatographic regions of greater polarity than prostaglandin F2 alpha. Compared with the weanling, a significantly greater amount of radioactivity cochromatographed with intact, unmetabolized prostaglandin F2 alpha (33.08 +/- 1.99 vs. 21.38 +/- 1.46). These results indicate that orogastrically administered prostaglandin F2 alpha can be absorbed from the gastrointestinal tract, transported to the liver, and subsequently excreted into bile and detected in an unmetabolized form in suckling and weanling rats. The enterohepatic circulation of milk-derived prostaglandin present in bile may contribute to the overall content of intestinal prostaglandins.

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