Biomedical subjects

R R Streiff

Publications and source records attributed to R R Streiff.

At least 19 recordsLinked to original sources

PubMed1992

A comparison of the iron-clearing properties of 1,2-dimethyl-3-hydroxypyrid-4-one, 1,2-diethyl-3-hydroxypyrid-4-one, and deferoxamine.

A comparative study of the iron-clearing properties of subcutaneously (SC) administered deferoxamine (DFO) with those of orally administered 1,2-dimethyl-3-hydroxypyrid-4-one (CP20) and 1,2-diethyl-3-hydroxypyrid-4-one (CP94) is presented. The studies were performed in both a non-iron-overloaded, bile duct-cannulated rat model and an iron-loaded Cebus monkey model. All three drugs performed well in the rodent, promoting the excretion of iron in both the urine and the bile, with total iron output efficiencies of 2.8%, 1.2%, and 7.1%, respectively. The efficiency of DFO increased slightly in the Cebus model, while that of the hydroxypyridones was essentially the same in the monkey, with total iron output efficiencies of 5.5%, 2.1%, and 7.4%, respectively. Iron balance studies showed that both DFO and CP94 were able to maintain the animals in a negative iron balance, while CP20 had little impact.

Animals↗

PubMed1990

A comparative evaluation of iron clearance models.

A comparative study of the non-iron-overloaded, bile duct-cannulated rat and of the Cebus monkey as iron-clearance models is presented. The ability of desferrioxamine, desferrithiocin, and a pyridoxal isonicotinoyl hydrazone (PIH) analogue to clear the metal from these two animals is evaluated. Data suggest that although rodents represent a viable first-line animal screen, there is no strict correspondence between the effectiveness of a chelator in rodents and that in primates. Rodent data should be interpreted carefully as it relates to potential human trials. Iron-loading response, the similarity between multiple human and Cebus serum and hematological values, and the ability to easily observe changes in behavioral patterns clearly render the Cebus monkey the best preclinical screen.

Animals↗

PubMed1985

Influence of iron on in vivo proliferation and lethality of L1210 cells.

The ability of iron to stimulate the growth of L1210 cells both in DBA-2 mice and in cell culture is evaluated. Although in vitro stimulation is absent, in vivo studies clearly indicate higher numbers of tumor cells in the presence of supplemental iron. When mice were given iron i.p., at levels comparable to clinical doses for humans (24 mg/kg body weight), the tumor load recovered from their peritoneum was substantially greater than from controls without iron supplements. Furthermore, at higher levels of supplemental iron (250 mg Fe/kg body weight), the pretreated animals inoculated with L1210 cells died in 9.7 d whereas controls died in 12.2 d (i.e., 25% faster). As expected, the lower iron dose (24 mg/kg) also resulted in shorter life spans, although the effects were less striking. It is the belief of these authors that these data support the opinion that "anemia of chronic disease" associated with leukemia and possibly other malignancies may represent a host defense mechanism as has been postulated by others (1, 8).

Animals↗

PubMed1983

The effect of diphenylhydantoin (phenytoin) on the sequential stages of intestinal folate absorption.

The drug diphenylhydantoin (phenytoin) (DPH) is thought to interfere with the bioavailability of dietary folate through an effect on intestinal folate deconjugation and/or monoglutamate folate transport. In order to determine whether DPH inhibition occurs in the sequential steps of folate deconjugation, uptake, or reduction-methylation, the effect of the drug on the intestinal absorption of hexaglutamate folate (PteGlu6), pteroylmonoglutamate folate (PGA), and N-5-methyltetrahydrofolate (CH3FH4) was studied. Folate absorption was directly quantified by the method of triple lumen tube perfusion in 12 subjects serving as their own controls. All 12 received PGA mixed with and without DPH (20 micrograms/ml), while 6 of the 12 subjects received hexaglutamate and 6 received reduced methylated folate with and without added DPH. With this model DPH was shown not to impair significantly folate absorption by any action upon the process of folate deconjugation, absorption, or reduction-methylation. The previously reported association between DPH intake and reduced levels of serum folate remains unexplained by these studies.

Adult↗

PubMed1979

Folate antagonism following teratogenic exposure to diphenylhydantoin.

Previous studies have reported indirect evidence for the mediation of folate antagonism in the induction of malformations by diphenylhydantion. We have demonstrated that a teratogenic regimen of folate-deficiency and antagonism using 9-methyl PGA in the rat produces significantly decreased rates of oxygen consumption in the maldeveloping embryos. The present study reports similar reductions in oxygen uptake by mouse embryos from mothers treated with teratogenic doses of diphenylhydantoin, and documents a significant depression of the actual folate levels in such embryos. The differences are less significant with lower doses of diphenylhydantoin, and do not occur with a nonteratogenic dose.

Abnormalities, Drug-Induced↗

PubMed1978

Effect of diphenylhydantoin on the bioavailability of citrus folate.

Long term use of the drug diphenylhydantoin (DPH) has been associated with biochemical evidence of folic acid deficiency and rarely with megaloblastic anemia. The mechanism of this nutritional deficiency is uncertain but is thought to result from DPH-induced alteration in the intestinal absorption of conjugated and/or free dietary folate. The effect of DPH on the intestinal absorption of free folates from a food source has heretofore not been reported. In this study triple lumen tube perfusion of the human jejunum was used to quantitate folate absorption from a control solution of orange juice and from an identical solution containing DPH. The results in eleven volunteers serving as their own controls indicate no effectof DPH at a concentration of 20 microgram/ml on folate absorption from this food source. The predominant form of folate in orange juice as determined by differential microbiologic assay is N-5-methyltetrahydrofolate. DPH does not appear to interfere with the absorption of free food folate which is both methylated and reduced.

Adult↗

PubMed1975

Comparative bioavailability of folate and vitamin C from a synthetic and a natural source.

Intraluminal perfusion of the human small intestine has not been used extensively to study comparative bioavailability of vitamins. In this study a triple lumen tube with a 30-cm study segment was used to measure absorption of water-soluble vitamins from the human proximal jejunum. Fifteen normal subjects served as their own controls to quantitate absorption of folic acid and vitamin C from an orange juice solution and from a solution of synthetic vitamins. Despite a predictably greater water absorption from the glucose containing orange juice solution, the absorption of the two water-soluble vitamins did not differ significantly from the two solutions. Natural and synthetic ascorbate and folate were avidly absorbed in the first 30 cm of jejunum and with the exception of synthetic folate correlated positively with water absorption. This method, previously applied to the absorption of sugars, amino acids, and electrolytes, can be reliably applied to the study of comparative bioavailability of nutrients from food sources. The advantages of triple lumen perfusion over previous methods are: 1) it overcomes the necessity for urine collections in metabolic studies, 2) it can be used to study sites and mechanism of absorption, and 3) it is a direct measurement of absorption capacity.

Adult↗

PubMed1973