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Biomedical subjects

R Wyss

Publications and source records attributed to R Wyss.

At least 55 records · Page 3Linked to original sources

[Prevention for travel to the tropics].

The Swiss Working Group for Health Advice to Travellers regularly publishes its recommendations for malaria prophylaxis and vaccination as supplement to the 'Bulletin' of the Federal Office of Public Health. In this review the strategy with respect to information, to clever behavior abroad, to chemoprophylaxis and immunization prophylaxis is analyzed. A critical evaluation of emergency self-therapy describes remaining questions in particular.

Antimalarials↗

Quantitative analysis of retinoids in biological fluids by high-performance liquid chromatography using column switching. III. Determination of the arotinoid sumarotene and its Z-isomer in human and animal plasma.

A fully automated and sensitive high-performance liquid chromatographic method, using on-line solid-phase extraction, automated column switching and ultraviolet detection, was developed for the third-generation retinoid (arotinoid) sumarotene (methyl p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]phe nyl sulphone; Ro 14-9706) and its Z-isomer. Nearly quantitative recoveries for human, rat and dog plasma were obtained by addition of acetonitrile (final content ca. 17%) to the plasma sample prior to injection. No isomerization was observed when the samples were stored in the autosampler for more than 20 h. The injection volume was 0.5 ml, resulting in quantification limits of 1 ng/ml for sumarotene and 2 ng/ml for the Z-isomer. More than 40 injections could be made on to one precolumn, allowing routine overnight injections. Using a 1-ml injection volume, the limit of quantification for sumarotene could be improved to 0.5 ng/ml. The method was applied to toxicokinetic studies in rats and dogs, and was used to monitor human plasma samples after repeated topical application. The method could also be adapted to etarotene (Ro 15-1570), which was used as an internal standard, and which is at present in clinical development.

Animals↗

Use of direct injection precolumn techniques for the high-performance liquid chromatographic determination of the retinoids acitretin and 13-cis-acitretin in plasma.

A previously developed highly sensitive high-performance liquid chromatographic method for the determination of retinoids, using direct injection of large plasma volumes, on-line solid-phase extraction and ultraviolet detection, was improved and fully validated for the determination of acitretin and 13-cis-acitretin in plasma samples. The addition of acetonitrile to improve the recovery was performed on-line by a T-piece, avoiding any cis-trans isomerization which could occur when acetonitrile was added prior to storage in the autosampler. About 30 injections could be made onto one precolumn despite the large injection volume (1 ml of plasma containing the internal standard). Full automation was attained by the use of automated precolumn replacement. In addition, forward- and back-flush purging of the precolumn enhanced the longevity of the analytical column. This consisted of three coupled C18 columns of 125 mm length each. The quantification limit was 0.3 ng/ml, using ultraviolet detection at 360 nm, and the mean inter-assay precision was 3.8% for the two compounds.

Acitretin↗

A potentially new metabolic pathway: ethyl esterification of acitretin.

1. The acidic retinoid, acitretin, was esterified to etretinate (ethyl ester) by rat and human liver 12,000 g supernatant. The amount of etretinate formed was increased by adding ethanol to the rat preparation. 2. This esterification almost certainly involves enzymic catalysis, and the amounts of etretinate formed were increased by the use of fresh rat liver. 3. Co-administration of acitretin and ethanol to rats resulted in a maximum plasma concentration of etretinate at approximately 1 h after dosing. Secondary maxima were induced by administering ethanol alone at 5 and 8 h after dosing with acitretin. 4. Comparison of acitretin and etretinate concentrations in rat portal and jugular vein plasma after ethanol administration indicated that the ester was formed mainly systematically, rather than during absorption. 5. The results of our study in the rat could indicate that the presence of etretinate in plasma of some patients being treated with acitretin may result from the intake of alcohol.

Acitretin↗

[From malaria chemoprophylaxis to malaria self-treatment (1975-1989)].

Swissair's 3000-odd cockpit and cabin personnel spend an aggregate total of one year in the tropics for every ten years of flight service with the airline. Since 1975, company policy has been to issue all crews with a 'treatment dose' of anti-malaria medication to be taken if malaria contraction is suspected. Up until 1985, this treatment dose medication was recommended to crews for cases in which malaria was suspected even though chemoprophylactic medication had been taken. Since 1985, crews have been advised to rely solely on the treatment dose (i.e. not take any chemoprophylactic medication) if they are exposed to only low or moderate malaria risk. Experience so far has been encouraging: There has been no increase in incidences of malaria; the approach has been widely accepted among crews; the treatment dose (1%) has been judiciously used; the amount of chemoprophylactic tablets issued has declined; the number of repellents issued has increased; and the fear of side-effects from anti-malaria medication has decreased. The risk of contracting malaria-about one case per 200 to 300 years of service-is accepted. The question of whether and to what extent these experiences, which have been recorded among a small and selected group of the population, can be applied to other frequent flyers merits further investigation.

Animals↗

A newly discovered xenobiotic metabolic pathway: ethyl ester formation.

Formation of etretinate, ethyl ester of acitretin, can be confirmed in vitro and in vivo using acitretin as the substrate. Etretinate was identified by LC/MS. The in vitro incubation was performed using rat and human liver 12,000 g supernatant, and the in vivo experiment was conducted in rats after oral dosing of acitretin. The ethyl ester formation was greatly enhanced by addition of or dosing with ethanol.

Acitretin↗

Biological structures imaged in a hybrid scanning transmission electron microscope and scanning tunneling microscope.

A hybrid scanning transmission electron microscope (STEM) and scanning tunneling microscope (STM) is described which allows simultaneous imaging of biological structures adsorbed to electron-transparent specimen supports in both modes of scanning microscopy, as demonstrated on uncoated phage T4 polyheads. We further discuss the reproducibility and validity of height data obtained from STM topographs of biomacromolecules and present raw data from topographs of freeze-dried, metal-coated nuclear envelopes from Xenopus laevis oocytes.

Animals↗

Chromatography of retinoids.

This article reviews the determination of retinoic acids and their metabolites (first-generation retinoids), aromatic retinoids (second generation) and arotinoids (third generation) in biological samples. Because of the sensitivity of the retinoids to isomerization and oxidation, special care has to be taken from sample collection and storage, throughout extraction, till the final chromatographic separation. High and strong protein binding, and insolubility in aqueous solutions hamper the extraction from biological samples. Various extraction procedures are discussed, mainly involving liquid-liquid extraction of biological fluids or lyophilized tissue samples. The new technique involving direct injection of biological fluids or tissue homogenates, using high-performance liquid chromatography (HPLC) with automated column switching, provides full protection from light and simplifies sample work-up. HPLC with ultraviolet detection is the method of choice for the determination of retinoids, because it is rapid, sensitive and allows separation of geometric isomers and metabolites within a wide polarity range. Gas chromatography-mass spectrometry is not appropriate for first- and second-generation retinoids because of isomerization, but allows very sensitive determination of third-generation retinoids, although very extensive sample clean-up and derivatization are necessary. However, direct injection of large volumes of biological fluids into HPLC systems, using on-line solid-phase extraction and automated column-switching, results in very sensitive methods even with simple ultraviolet detection and may become the method of choice for routine analyses.

Body Fluids↗