Biomedical subjects

R Dickerson

Publications and source records attributed to R Dickerson.

23 records · Page 2Linked to original sources

PubMed1983

Synthesis and evaluation of 3-halocyclophosphamides and analogous compounds as novel anticancer "pro-prodrugs".

3-Fluoro-, 3-chloro-, and 3-bromocyclophosphamide were prepared from the reaction of trifluoromethylhypofluorite, sodium hypochlorite, and bromine with the anticancer drug cyclophosphamide. Treatment of cis- and trans-4-phenylcyclophosphamide and 5,6-benzocyclophosphamide with sodium hypochlorite afforded cis- and trans-3-chloro-4-phenylcyclophosphamide and 3-chloro-5,6-benzocyclophosphamide, respectively. 31P-NMR spectroscopy was used to study the reactivity of these compounds: the fluoro derivative was reduced to cyclophosphamide on incubation with mouse liver slices, and the reactivity order for sulfhydryl-induced reduction of the 3-halocyclophosphamides was Br approximately equal to Cl much greater than F. Compared with the therapeutic efficacy of cyclophosphamide against L-1210 and P-388 cancers in mice, 3-fluoro- and 3-chlorocyclophosphamide were less active, although the fluoro derivative was more efficacious than the 3-chloro compound. The individual R and S enantiomers of 3-chlorocyclophosphamide, prepared from (S)- and (R)-cyclophosphamide, respectively, showed no significant difference in therapeutic activity in the P-388 test system.

Animals↗

PubMed1981

Synthesis of 3-hydroxycyclophosphamide and studies related to its possible role in the metabolism of cyclophosphamide.

Hydrogenolysis of 3-(benzyloxy)cyclophosphamide (10) using Pd/C catalyst and ethyl acetate as solvent leads to the formation of 3-hydroxycyclophosphamide (3, approximately 20%) and cyclophosphamide (1, approximately 10%), accompanied by regioselective hydrogen-exchange reactions at the C-4 and C-5 positions in 3 and 1. A variety of oxidizing reagents and liver microsomal incubation failed to provide evidence (31P NMR) for conversion of 1 into 3, whereas identical incubation of 3 led to its reduction to 1. Compound 3 is stable at pH 6.5-8.2, 37 degrees C, and exhibits anticancer activity comparable to 1 when tested against L1210 leukemia in mice. Data are discussed with regard to a previously reported suggestion that metabolism of 1 may involved oxidation to give 3 followed by rearrangement of 3 to 2.

Animals↗

PubMed1980

Air or CO2 for knee arthrography?

Both air and carbon dioxide (CO2) have been advocated for use as the negative agent in double-contrast knee arthrography. In 39 patients examined, 40 knee arthrograms were obtained, using CO2 as the negative agent for 20 studies and room air in the other 20. In addition, the change in pH of the joint fluid was measured. Of the 20 patients in the CO2 group, 12 had pain, five of whom described it as severe. Of the 20 in the air group, two reported only moderate discomfort. Regardless of the gas used, the incidence of pain was directly related to the amount of decrease in pH. Air is believed superior to CO2 primarily because it produces less pain, persists in the joint longer (allowing for refilming), costs less, and is readily available.

Air↗

PubMedDate not supplied

Effects of environmentally relevant concentrations of 2,3,7,8-TCDD on domestic chicken immune function and CYP450 activity: F1 generation and egg injection studies.

Domestic chickens (Gallus gallus) were used as a surrogate species for wild turkey to assess risk from environmental 2,3,7,8-TCDD exposure. Lymphocyte proliferation and CYP450 induction were assessed in adults exposed via i.m. injection, in F1 14-day old hatchlings, in F1 adults (30-weeks old), and in 14-day old hatchlings exposed via yolk sac injections. Hatchlings from injected eggs exhibited a dose-response in lymphocyte proliferation, IgM titers, EROD, and PROD endpoints. Exposed adults showed a significant dose-dependent increase in CYP450 induction. F1 14-day old chicks exhibited a significant dose-dependent suppression of B-cell proliferation and induction of CYP450 enzymes. F1 adult proliferative responses exhibited B-cell suppression, that was not statistically significant. Significant sex-dependent EROD and MROD induction was also observed in F1 adults, indicating mixed-function oxidase imprinting from maternal exposure.

Animals↗

PubMedDate not supplied

Pesticide residues in composited milk collected through the U.S. Pasteurized Milk Network.

The U.S. Food and Drug Administration (FDA) has implemented a comprehensive monitoring program to determine the incidence and levels of organohalogen pesticide residues in milk representing most of the U.S. supply consumed in metropolitan areas. Residue findings for 806 composite milks collected through the Pasteurized Milk Program by the U.S. Environmental Protection Agency (EPA) in 1990-1991 are reported. Milk was collected on a monthly basis from 63 stations selected by EPA for radionuclide monitoring. These stations provide an estimated 80% of the milk delivered to U.S. population centers. At each station, milk from selected sources had been composited to represent the milk routinely consumed in its metropolitan area. Portions of these composites were forwarded to an FDA contract laboratory for pesticide residue analysis. Pesticide residues were found in 398 (49.4%) of 806 test samples, on the basis of a 0.0005 ppm limit of detection for each residue on a whole-product basis. A total of 455 occurrences of pesticide residues were found; p,p'-DDE and dieldrin accounted for 384 (84.4%) of these occurrences. The highest level was 0.019 ppm p,p'-DDE.

Animals↗