Synthesis of desfluorinated nebivolol isomers.

The syntheses of all possible stereoisomers of desfluorinated side products of the potent antihypertensive β-blocker nebivolol are reported. A straightforward approach using a common racemic precursor was employed to obtain the desired optically active building blocks. For one series of compounds, a Sharpless asymmetric epoxidation (SAE) route yielded in a direct fashion the required compounds whereas a Mitsunobu reaction was selected to obtain the other series of compounds.

A predictive mathematical model of the DNA damage G2 checkpoint.

A predictive mathematical model of the transition from the G2 phase in the cell cycle to mitosis (M) was constructed from the known interactions of the proteins that are thought to play significant roles in the G2 to M transition as well as the DNA damage- induced G2 checkpoint. The model simulates the accumulation of active cyclin B1/Cdk1 (MPF) complexes in the nucleus to activate mitosis, the inhibition of this process by DNA damage, and transport of component proteins between cytoplasm and nucleus. Interactions in the model are based on activities of individual phospho-epitopes and binding sites of proteins involved in G2/M.

A mathematical model for human nucleotide excision repair: damage recognition by random order assembly and kinetic proofreading.

A mathematical model of human nucleotide excision repair was constructed and validated. The model incorporates cooperative damage recognition by RPA, XPA, and XPC followed by three kinetic proofreading steps by the TFIIH transcription/repair factor. The model yields results consistent with experimental data regarding excision rates of UV photoproducts by the reconstituted human excision nuclease system as well as the excision of oligonucleotides from undamaged DNA.

Feedback-mediated dynamics in two coupled nephrons.

Previously, we developed a dynamic model for the tubuloglomerular feedback (TGF) system in a single, short-looped nephron of the mammalian kidney. In that model, a semi-linear hyperbolic partial differential equation was used to represent two fundamental processes of solute transport in the nephron's thick ascending limb (TAL): chloride advection by fluid flow along the TAL lumen and transepithelial chloride transport from the lumen to the interstitium. An empirical function and a time delay were used to relate glomerular filtration rate to the chloride concentration at the macula densa of the TAL.

[Tuberculosis in asylum seekers].

In this prospective study conducted by 9 Public Health Offices in North Rhine Westphalia 1992 to 1994, among the analysed 4058 asylum seekers aged 1-89 years the chest radiographs showed in 444 cases old specific changes and in 48 cases active tuberculosis. This was verified microbiologically. 81% of the evaluated tuberculin skin test were positive with variations between the different countries of origin, which is significantly higher than among persons born in the Fed.

Synthesis and biological activity of new HMG-CoA reductase inhibitors. 3. Lactones of 6-phenoxy-3,5-dihydroxyhexanoic acids.

A group of 43 optically active sodium carboxylates (11a-qq and the corresponding lactones 4 were prepared from respective phenols 8 according to Schemes I-III. Phenols 8 were synthesized from commercially available compounds according to Schemes IV-IX. A number of these HMG-CoA reductase inhibitors 11 exceeded mevinolin's activity in vitro (Tables II and III).

Synthesis and biological activity of new HMG-CoA reductase inhibitors. 1. Lactones of pyridine- and pyrimidine-substituted 3,5-dihydroxy-6-heptenoic (-heptanoic) acids.

Lactones of pyridine- and pyrimidine-substituted 3,5-dihydroxy-6-heptenoic (-heptanoic) acids 2-4 have been synthesized. Extensive exploration of structure-activity relationships led to several compounds exceeding the inhibitory activity of mevinolin (1b) on HMG-CoA reductase, both in vitro and in vivo. First clinical trials with 2i (HR 780) are in preparation.

Synthesis and biological activity of new HMG-CoA reductase inhibitors. 2. Derivatives of 7-(1H-pyrrol-3-yl)-substituted-3,5-dihydroxyhept-6(E)-enoic (-heptanoic) acids.

A series of 7-(1H-pyrrol-3-yl)-substituted-3,5-dihydroxyhept-6(E)- enoates (-heptanoates) 1 and 2 have been prepared and tested for inhibiti 3-hydroxy-3-methylglutaryl-coenzyme A reductase. The most potent compounds exceeded mevinolin's activity in vitro and in vivo.

[Amino acid losses in human sweat. Influence of oral contraceptives, physical exercise and sex on the excretion of amino acids in sweat (author's transl)].

Unlabelled: With the aid of ion exchange column chromatography we determined quantitatively the free amino acids in thermal sweat of the total human body surface. Sweat of 60 healthy men and 63 healthy women (aged 18-31 years) collected during 12 min of sauna bathing was investigated. Thirty men and 31 women were well trained, 33 women were taking oral, hormonal contraceptives.

A quantitative study of free amino acids in eccrine sweat collected from the forearms of healthy young men during sauna bathing.

Using ion-exchange column chromatography we measured the free amino acids in eccrine sweat collected from the forearms of 20 healthy young men at intervals of 15, 30, and 45 min during sauna bathing. In comparison with the amino acid concentrations determined after 15 min of sweating (100%) a significant and uniform decrease occurred in the concentrations of all amino acids examined after a further 15 min (65%), with a further decrease after another 15 min (45%). These results indicate that either the mechanism of excretion of amino acids in the secretory cells of the eccrine sweat glands, or the reabsorption of amino acids by the ductular cells, or the combination of both mechanisms are similar for all the amino acids examined here.

Quantitative study of free amino acids in human eccrine sweat excreted from the forearms of healthy trained and untrained men during exercise.

The free amino acids in eccrine sweat collected from the forearms of 20 healthy trained and 20 healthy untrained men during controlled exercise were determined quantitatively using ion exchange column chromatography. Sweat was deproteinized by adding an equal volume of 5% sulphosalicylic acid. The amino acid concentrations showed a constant qualitative pattern in sweat and large individual differences.