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H Marcus

Publications and source records attributed to H Marcus.

70 records · Page 4Linked to original sources

Markers for detection of supplementation in narcotic programs--deuterium-labeled methadone.

Specific deuterium labeling of methadone and use of gas chromatography-mass spectroscopy technique permits rapid and quanitative determination of the ratio of the labeled to unlabeled drug in body fluids. A trideuertiomethadone (methadone-d3) was shown to have exactly the same analgesic activity and toxicity in mice as methadone. The rates of absorption, distribution, and excretion of methadone-d3 and methadone were identical in rats. These observations suggest that methadone-d3 may be used as an in vivo marker for monitoring methadone intake of patients, and thus may improve the effectiveness of methadone treatment programs.

Animals↗

Effect of sympathectomy on ontogeny of small intestinal disaccharidases in the rat.

In the present study the effect of chemical sympathectomy on the development of small intestinal enzymes in the rat was analyzed. Eight doses of guanethidine sulfate were administered subcutaneously every 48 h to 34 newborn rats, starting at birth. The last dose was given at 14 days of age. Twenty-two littermates served as controls. Intestinal lactase, maltase, sucrase, and alkaline phosphatase were determined at 15, 17, 20, 23, and 25 days of age. Sympathectomy was demonstrated by reduction of the number of perikarya in the superior cervical ganglia in treated rats as compared with control rats. A normal developmental pattern of activities of the disaccharidases in the small intestine was observed in both groups. The activity of alkaline phosphatase was significantly lower (p less than 0.01) in the 15- and 17-day-old treated animals.

Animals↗

Application of recovery tests in the validation of immunoassays for assessing the immunogenicity of B. anthracis PA vaccine.

In the quantitative assessment of polyclonal serum antibodies, the complex composition and characteristics of the analyte population (serum antibodies) restricts the capability of constructing appropriately defined calibration standards. This fact limits the application of the conservative recovery tests to the validation of immunoassays aimed at determining serum antibody levels. The present report describes a modification of recovery tests that overcomes this impediment. The modified approach is based on a dilution analysis system, where a given immune serum is serially diluted in normal serum and the antibody titers in each of the derived diluted samples are then determined. Expected sample titers (calculated on the basis of the relevant dilution factors) are plotted against the respective observed results, and the resulting recovery curve is then examined by means of a regression analysis, according to the standard rules of the conservative recovery analysis. This approach was tried with two immunoassay systems, Enzyme Linked Immunosorbent Assay (ELISA) and Neutralizing Antibodies (NtAb) immunoassays, aimed at assessing the immunogenicity in guinea pigs of B. anthracis protective antigen (PA) vaccine. In a series of feasibility studies using a recovery simulation model (dilutions made in the immunoassay diluent, rather than in normal serum) the average recovery levels in ELISA and NtAb immunoassays were 0.99 +/- 0.011 and 1.02 +/- 0.04 respectively, and the 99% confidence intervals contained the target 100% value. Regression lines were proved to be linear demonstrating R > 0.97 in all cases. The 99% confidence intervals around the observed slopes and intercepts always contained the corresponding target values 1 and 0. The relative standard deviation (RSD) in the ELISA and NtAb immunoassays was found to be 0.01 and 0.025 respectively. All of the above experimental results were not affected by the serum antibody titer, or by day-to-day variations embodied in these immunoassay systems. When true recovery tests were applied to the above immunoassays, essentially identical results were obtained. In both assays the correlation coefficients were in the range of 0.96-1, recoveries were found to be in the range of 0.90-1.06, and RSD values were in the range of 0.02-0.025. All the recovery deviations from the target value of 1 were not statistically significant. The hitherto observed experimental findings illustrate the capability of the dilution analysis system to allow the application of recovery tests to the validation of quantitative immunoassays, which are based on the procedure of serum titrations.

Animals↗