[Withdrawal in a patient with an implantable drug delivery system in spite of continuation of opiate therapy]. / Entzugserscheinungen bei einem Patient mit intrathekaler Schmerzpumpe trotz Fortführung der Opiattherapie.

A male patient with severe chronic pain has been treated with a combined drug therapy scheme of morphine and clonidine. After cessation of clonidine the patient reported opiate-withdrawal symptoms with agitation, polyuria, diarrhea, and hyperalgesia. It is known that the combination of these two substances causes synergistic analgetic effects. The abrupt cessation of clonidine after a combined administration with morphine seems to lead to a relative decrease in opiate effects and furthermore excite opiate-withdrawal symptoms.

Quercinol, an anti-inflammatory chromene from the wood-rotting fungus Daedalea quercina (Oak Mazegill).

The fungus Daedalea quercina (oak mazegill) was examined for its capability of producing antioxidative and anti-inflammatory compounds. Bioactivity guided fractionation of the extract from a mycelial culture led to the isolation of quercinol, which was identified as (-)-(2S)-2-hydroxymethyl-2-methyl-6-hydroxychromene 1 by NMR and X-ray analyses. The cryptic hydroquinone 1 shows a broad anti-inflammatory activity against cyclooxygenase 2 (COX-2), xanthine oxidase (XO), and horseradish peroxidase (HRP) at micromolar concentrations.

[Penicillium expansum, a resident fungal strain of the orbital complex Mir, producing xanthocillin X and questiomycin A]. / Grib Penicillium expansum--shtamm-rezident orbital'nogo komplexa "MIR"--produtsent ksantotsillina X i kvestiomitsina A.

It was demonstrated that the fungus Penicillium expansum 2-7, a resident strain of the orbital complex Mir, which became dominating at the end of a long-term space flight, formed biologically active secondary metabolites (antibiotics). Using physicochemical methods, these metabolites were identified as xanthocyllin X and questiomycin A. Time courses of their biosyntheses during growth and development of the producer culture were studied. Addition of zinc to the culture medium affected both the growth of the culture and the biosyntheses of the antibiotics. The concentrations of zinc in the medium, optimum for xanthocyllin X and questiomycin A production, amount to 0.3 and 3.0 mg/l, respectively.

[Isolation of Penicillium DIERCKX 1901--a producer of diketopiperazine alkaloids rokefortin and 3,12-dihydrokefortin--from permafrost]. / Vydelennye iz vechnoi merzloty griby Penicillium aurantiogriseum DIERCKX 1901--produtsenty diketopiperazinovykh alkaloidov rokefortina i 3/12-digidrorokefortina.

Secondary metabolites of the three strains of Penicillium aurantiogriseum, isolated from permafrost sediments, were identified. It was found that these fungi synthesized diketopiperazine alkaloids roquefortine and 3,12-dihydroroquefortine. The strain VKM FW-766 synthesized alkaloids in in the course of certain growth-related processes. When the strain was grown on a mineral medium, time courses of roquefortine and 3,12-dihydroroquefortine concentrations were characterized by biphasic curves.

[The fungus Penicillium citrinum Thom 1910 VKM FW-800 isolated from ancient permafrost sediments as a producer of the ergot alkaloids agroclavine-1 and epoxyagroclavine-1]. / Grib Penicillium citrinum Thom 1910 VKM FW-800, vydelennyi iz vechnomerzlotnykh drevnikh otlozhenii kak produtsent érgoalkaloidov agroklavina-I i époksiagroklavina-I.

The study of the secondary metabolites of the relict strain Penicillium citrinum VKM FW-800 isolated from ancient Arctic permafrost sediments showed that this fungus produces agroclavine-1 and epoxyagroclavine-1, which are rare ergot alkaloids with the 5R,10S configuration of the tetracyclic ergoline ring system. The production of the alkaloids by the fungus showed a biphasic behavior, being intense in the phase of active growth and slowing down in the adaptive lag phase and in the stationary growth phase. The addition of zinc ions to the incubation medium led to a fivefold increase in the yield of the alkaloids. The alkaloids-producing Penicillium fungi isolated from different regions exhibited the same tendencies of growth and alkaloid production.

Differences in ion-channel formation by ampullosporins B, C, D and semisynthetic desacetyltryptophanyl ampullosporin A.

Peptaibol-type ampullosporins B (2) and D (4) are capable of forming ion-conducting pores in planar lipid bilayer membrane prepared from soybean phosphatidylcholine in a similar manner as it was shown for ampullosporin A (1). However, the isomeric ampullosporin C (3) was required in 20-fold higher concentration to afford a comparable effect. In contrast to 1, 2, 3 and 4, the desacetyltryptophanyl ampullosporin A (5) failed to form ion channels. The results suggest that the sequence of amino acids especially at positions 8-10, the nitrogen-terminal acetyl residues and tryptophane are major factors determining ion-channel formation within bilayer membranes. The differences in membrane activities were comparable to the observed biological activities.

New homoserine lipids from Xerocomus langbianensis.

New diacylglycerotrimethyl homoserine lipids 1 (2 O,3 O-bislinolylglycero-4'-O-(N,N,N-trimethyl)homoserine) and 2 (2 O,3 O-linolyl-palmitylglycero-4'-O-(N,N,N-trimethyl)-homoserine) were isolated from the fruiting body of a Vietnamese species of Xerocomus langbianensis. The chemical structures were settled on the basis of mass spectrometry and NMR spectroscopy.

Synthesis and biological activity of chiral tetrahydrofuranyl amino acids as building moieties of pamamycin analogues.

A new synthetic route to chiral tetrahydrofuranyl amino acids is described starting with D-glucose. The 17-step and a 20-step procedures, respectively, furnished compounds of the general formulas 1 and 2 mimicking the dimethylamino carboxylic acid part of pamamycin (3). In comparison with the absolute stereochemistry of 3 the acyclic compounds 1a-c and 2a-c are enantiomers. Despite of the presence of a dimethylamino function they showed neither antibacterial activity nor protonophoric effects on an artificial bilayer membrane suggesting that the macrodiolide ring of 3 forms an indispensable prerequisite for the known interaction of this antibiotic with biological systems.

Effect of ochratoxin A and ochratoxin C on the monocyte and lymphocyte function.

The effect of practically relevant mycotoxin concentrations on functions of immune cells was studied in in vitro experiments. Porcine mononuclear cells were exposed to a crudeAspergillus-ochraceus toxin containing OTA, a HPLC fraction identical with OTC derived from the crude toxin (RE2), as well as pure OTA and OTC in a concentration range from 0.46 to 3000 ng/ml. The influence of mycotoxin exposure on metabolic activity, mitogen induced proliferation, expression of the activation marker CD25 and the cell cycle of lymphocytes and on the formation of free oxygen radicals as well as the production of the cytokines IL-6 and TNF-α by monocytes was determined. Exposure to high concentrations of all mycotoxin preparations lead to non-specific suppression of the immune cell functions, which was related to cytotoxic effects. Low concentrations caused ambivalent reactions, especially on monocyte function. In general, the HPLC fraction RE2 had an up to 100-fold stronger effect than pure OTA. Ochratoxin-induced suppression of lymphocyte proliferation was not abrogated by phenylalanine or aspartame. The results indicate that immunomodulation can be caused by very low mycotoxin concentrations which are not related to clinical symptoms or loss of performance.