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Biomedical subjects

L Heintz

Publications and source records attributed to L Heintz.

4 recordsLinked to original sources

Simultaneous determination of cross-reactive leukotrienes in biological matrices using on-line liquid chromatography immunochemical detection.

Sulfidopeptide leukotrienes, which are important biomarkers for several diseases, are commonly measured by microtiter plate immunoassays. These immunoassays, however, cannot distinguish between several structurally similar leukotrienes and their cross-reactive metabolites and, therefore, need extensive sample handling and fractionation by means of liquid chromatography (LC). This paper describes the development and automation of a continuous-flow immunochemical detection (ICD) system and its subsequent on-line coupling to LC. The on-line LC-ICD system based on fluorescence-labeled leukotriene E4 (LTE4) was used to determine sulfidopeptide leukotrienes and their cross-reactive metabolites in a single run. Furthermore, biological matrices, e.g., urine and human cell extracts, were analyzed, the only sample pretreatment being on-line solid-phase extraction (SPE) on a novel RP-C4 restricted-access support. The determination limit of LTE4 in urine was 0.2 ng/mL (800 fmol; injection volume, 2000 microL; signal-to-noise ratio, 10). The system was linear from 0.2 to 1.0 ng/mL LTE4. Using nonlinear curve-fitting, the range could be expanded to 2.5 ng/mL. It is shown that, besides quantitation of known analytes, on-line LC-ICD is useful in the discovery of cross-reactive LTE4 metabolites.

Antigen-Antibody Reactions

An efficient way to do the wrong thing.

Britain's national health system (NHS) has been embattled since Thatcherism undertook to privatize it. This Britannic version of the new medicine is a hybrid of a neglected, underfunded shadow of the NHS and robust free-market capitalism. The NHS that the Tory government administers is aptly described as topless, bulging in the middle, and suffering chronic battle fatigue at the bottom. The quality of leadership in the NHS has plummeted at the same time thousands of middle managers have been added to prod the frontline caregivers.

Economics

Toxic effects of some xanthine derivatives with special emphasis on adverse effects on rat testes.

Testicular toxicity and effects on thymus and body weights of 4 xanthine derivatives (D4026: 1,8-dimethyl-3-phenylxanthine, D4152: 8-methyl-3-phenylxanthine, D4160: 1,8-dimethyl-3-(2-methylbutyl)-xanthine, D4173: 8-methyl-3-(2-methylbutyl)-xanthine) were studied in Sprague-Dawley rats and cellular toxicity in human embryonal cells. The effect on toxicity by variation of substituent at positions 1 and 3 was tested. The compounds were administered orally to the rats once a day for 1 month. Mortalities were noted only with D4160. Dose related decreases in body weight gain were found for all substances, but only marginally with D4152. A significant decrease in thymus weight relative to control was observed with all substances, D4152 being the least potent. No effects on testes weights were found with any treatment but histological examination disclosed degeneration of germ producing epithelium of all rats given 100 mumol/kg of D4026 but not at 25 mumol/kg. One rat out of 5 showed testicular damage at 400 mumol/kg of D4173 or D4152. Plasma analysis for unchanged compounds showed significantly higher plasma concentrations at the high dose compared with the low dose with the exception for D4152 showing unexpectedly low levels. In the cellular toxicity test, D4160 was the most potent while D4152 was the least potent. D4026 had a steeper dose-response curve than the others but was less potent than D4160. The 1-methylated xanthine derivatives seemed to be more toxic than the two in position 1 unsubstituted analogues. Mechanisms for testicular toxicity of xanthine derivatives in the rat and clinical relevance of animal data are discussed.

Animals

Absorption of sustained-release theophylline tablets.

Three different sustained-release tablets of theophylline (Theo-Dur, Phyllocontin continus, Euphyllin Retard) and an oral elixir of aminophylline were administered to 12 healthy volunteers according to a crossover scheme. Plasma concentration of theophylline was monitored for 33 h after each administration using an HPLC reversed-phase method. The mean values and SD for total body clearance (0.054 +/- 0.010 l/[h X kg]), elimination half-life (6.0 +/- 1.2 h), and volume of distribution (0.455 +/- 0.046 l/kg) were calculated from the plasma concentration curves after the administration of elixir. The mean bioavailability of Theo-Dur was 94%, Phyllocontin continus 88%, and Euphyllin Retard 84%. The absorption was faster from Phyllocontin continus than from Theo-Dur or Euphyllin Retard. The time of peak concentration varied considerably after Euphyllin Retard but was less fluctuating among the subjects after Phyllocontin continus or Theo-Dur. In some subjects an extremely delayed peak (up to 24 h after administration) was observed after Euphyllin Retard.

Adult