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Biomedical subjects

F Herman

Publications and source records attributed to F Herman.

At least 19 recordsLinked to original sources
PubMed2001

Evaluation of pollution-related stress factors for forest ecosystems in central Europe.

Since the early eighties air pollution by SO2 and Pb and, to a lesser degree by NOx and NH3, have been significantly reduced in Europe. This was done in part for the protection of forest ecosystems. The reductions are reflected in the pollutant impacts and inputs and have been verified through the bioindicator Norway spruce. In contrast, ozone concentrations increased at most of the evaluated measuring locations and trends were calculated based on the results of about 100 stations in Austria and Germany. Despite reduced emissions, large parts of the forest ecosystems are still affected by air-pollution impacts. Negative effects can be assessed using different legal standards and Critical Levels and Critical Loads, respectively: The legal standard for the evaluation of SO2 impact, as used in Austria, is well suited. The provisional European Critical Level for ozone, the AOT40 must, in order to be a meaningful criterion for field applications, be further refined. Continuing the Critical Load concept, the spatial risk of acid depositions in areas of high geomorphic variability were evaluated using the new parameter of 'critical soil depth'. With the help of the newly defined 'lead accumulation index', the accumulation of Pb from air pollution could be evaluated. Air-pollution inputs and the spatial acidification risk is directly related to altitude. Up to altitudes of 1000 m and 1100 m, SO2 impact and acid depositions, respectively were indicated and elevated ozone doses and Pb inputs were observed in the sensitive sub-alpine areas. These results underline the necessity for increased protection of mountain forest ecosystems, among others through a further reduction of emissions or forest-related strategies.

Air Pollutants↗
PubMed2000

Indeno[1,2-b]pyrazin-2,3-diones: a new class of antagonists at the glycine site of the NMDA receptor with potent in vivo activity.

Indeno¿1,2-bpyrazin-2,3-diones have been identified as a novel series of potent ligands on the glycine site of the NMDA receptor. To improve their in vivo activities, an acetic acid-type side chain was introduced to the 5-position, giving water-soluble compounds when formulated as the sodium salt (>10 mg/mL). Introduction of a chlorine atom in the 8-position led to a dramatic improvement of anticonvulsant activity and this was surprising since this change did not improve binding affinity. A plausible explanation is a reduced recognition by a Na(+),K(+)-ATPase active transport system responsible for the excretion of these compounds from the brain and kidney. This promising new chemical series led to the optically active isomer (-)-10i (RPR 118723), a glycine/NMDA antagonist with nanomolar binding affinity and in vivo activity in animal model of convulsions and electrophysiology at doses in the range of 2-3 mg/kg following iv administration.

Animals↗
PubMed2000

RPR112378 and RPR115781: two representatives of a new family of microtubule assembly inhibitors.

A screening program aimed at the discovery of new antimicrotubule agents yielded RPR112378 and RPR115781, two natural compounds extracted from the Indian plant Ottelia alismoides. We report their isolation, structural determination, and mechanisms of action. RPR112378 is an efficient inhibitor of tubulin polymerization (IC(50) = 1.2 microM) and is able to disassemble preformed microtubules. Regarding tubulin activity, RPR115781 is 5-fold less active than RPR112378. Tubulin-RPR112378 complexes, when isolated by gel filtration, were able to block further tubulin addition to growing microtubules, a mechanism that accounts for the substoichiometric effect of the drug. RPR112378 was found to prevent colchicine binding but not vinblastine binding to tubulin. Although colchicine binding is known to induce an increase of tubulin GTPase activity, no such increase was observed with RPR112378. We show that RPR112378 is a highly cytotoxic compound and that RPR115781 is 10, 000-fold less active as an inhibitor of KB cell growth. Part of the cytotoxicity of RPR112378 is probably caused by a reaction of addition with sulfhydryl groups, an observation that has not been made with RPR115781. In conclusion, these molecules represent a new class of inhibitors of microtubule assembly with potential therapeutic value.

Antineoplastic Agents, Phytogenic↗
PubMed1998

[Dysfunction of the sphincter of Oddi in cholecystectomy patients].

Sphincter of Oddi dysfunction (SOD) is an obstructive syndrome of the papilla not resulting from a stone. It may cause recurrent biliary type pain to cholecystectomized patients. SOD is caused by sphincter dyskinesia or benign stenosis. Diagnosis is usually based on symptoms, serum biochemistry, endoscopic retrograde cholangiopancreatography and Sphincter of Oddi manometry. The latter is the best means of evaluating Sphincter of Oddi dynamics. However, because of the many inconveniences of Sphincter of Oddi manometry and of its high morbidity rate, it is seldom used. Non invasive techniques, such as cholescintigraphy, have been developed to replace Sphincter of Oddi manometry in diagnosing SOD. Patients can be cured by sphincterotomy. Certain drugs could also be effective but few controlled studies have been carried out of date.

Biliary Tract Diseases↗
PubMed1997

Degradation pathways of salmon calcitonin in aqueous solution.

Salmon calcitonin (sCT), a 32-amino-acid peptide, is the active component in many pharmaceuticals used for the management of bone diseases. The degradation pathways of sCT were determined, and the structures of the major degradation products were identified. Aqueous solutions of sCT at pH values of 3, 4, 5, and 6 were degraded, and the major degradation products were detected using reversed phase and size-exclusion high-performance liquid chromatography (HPLC). The degradation rate and pathways of sCT are strongly dependent on pH in the pH range between 3 and 6. The major degradation products were isolated by semipreparative HPLC and identified using a variety of spectroscopic and bioanalytical techniques. The results show that sCT can undergo hydrolyses resulting in cleavage of the 1-2 amide bond and deamidation of the Gln14 and Gln20 residues, sulfide exchange that leads to an unusual trisulfide derivative, and dimerization to reducible and nonreducible dimers. The mechanisms for the pathways can be rationalized from known degradation pathways of peptide and proteins.

Amino Acid Sequence↗
PubMed1994

Solution structure of RP 71955, a new 21 amino acid tricyclic peptide active against HIV-1 virus.

The structure of RP 71955, a new tricyclic 21 amino acid peptide active against human immunodeficiency virus 1, was determined. Its amino acid composition was inferred from the results of fast atom bombardment mass spectrometry, nuclear magnetic resonance, Raman spectroscopy, and amino acid analysis. Its sequence could not be determined classically, using Edman degradation, given the lack of a free terminal NH2. It was deduced from the interpretation of interresidue nuclear Overhauser effects and confirmed by the sequencing of peptides obtained by limited chemical hydrolysis. It was found to be CLGIGSCNDFAGCGYAVVCFW. An internal amide bond between the NH2 of C1 and the gamma-COOH of D9 was observed, as well as two disulfide bridges, one between C1 and C13 and one between C7 and C19. The three-dimensional structure of RP 71955 was determined from nuclear magnetic resonance derived constraints using distance geometry, restrained molecular dynamics, nuclear Overhauser effect back calculation, and an iterative refinement using a full relaxation matrix approach. Analogies between the structure of RP 71955 and some functional domains of gp41, the transmembrane protein of human immunodeficiency virus 1, suggest hypotheses concerning the mode of action of RP 71955.

Amino Acid Sequence↗
PubMed1990

A d(GpG)-platinated decanucleotide duplex is kinked. An extended NMR and molecular mechanics study.

A conformational study of the double-stranded decanucleotide d(GCCG*G*ATCGC).d(GCGATCCGGC), with the G* guanines chelating a cis-Pt(NH3)2 moiety, has been accomplished using 1H and 31P NMR, and molecular mechanics. Correlation of the NMR data with molecular models has disclosed an equilibrium between several kinked conformations and has ruled out an unkinked structure. The deformation is localized at the CG*G*.CCG trinucleotide where the helix is kinked by approximately 60 degrees towards the major groove and unwound by 12-19 degrees. The models revealed an unexpected mobility of the cytosine complementary to the 5'-G*. This cytosine can stack on either branch of the kinked complementary strand. The energy barrier between the two positions has been calculated to be less than or equal to 12 kJ/mol. The NMR data are in support of rapid flip-flopping of this cytosine. An explanation for the strong downfield shift observed in the 31P resonance of the G*pG* phosphate is given.

Base Sequence↗