D.A. Kalbhen

Evidence for the Biogenic Formation of Amphetamine Derivatives from Components of Nutmeg

Myristicin and elemicin are phenylallyl derivatives present in nutmeg. The similarity of their chemical structure to that of mescaline or certain amphetamine derivatives has led to the assumption that

Pharmacological Studies on the Anti-Inflammatory Effect of a Semi-Synthetic Polysaccharide (Pentosan Polysulfate)

Certain biochemical characteristics of pentosan polysulfate (SP 54) indicated possible antiphlogistic properties of this substance. Our extensive investigations with different models of acute inflammatory reactions (rat paw edema induced by hyaluronidase, trypsin, carrageenin or kaolin) have shown that pentosan polysulfate has a pronounced anti-inflammatory and antiphlogistic effect, although it has no analgetic properties. In contrast to other well-known antiphlogistic drugs, such as salicylate, pyrazolone or anthranilic acid derivatives, pentosan polysulfate exerts its strong anti-inflammatory effect on all types of experimental edema. This outstanding antiphlogistic and anti-inflammatory potency of pentosan polysulfate can be explained by a suppression of hyaluronidase, histamine and certain complement factors as well as by its specifically vasotropic and stabilizing effects.

Gas-liquid chromatoographic properties of catecholamines, phenylethylamines and indolalkylamines as their propionyl derivatives

Abstract The gas chromatographic properties of the biogenic amines, catecholamines, phenylethylamines and indolalkylamines as their propionyl derivatives were studied. These derivatives are readily formed in an aqueous medium. Propionylated amines are more stable than their parent compounds and increasingly lipophilic, so that they can be extracted quantitatively into an organic solvent. The propionyl derivatives of the biogenic amines show good gas chromatographic properties. They can be well separated on OV-101 and OV-17 silicones. Care must be taken of certain interactions of the compounds during the chromatographic procedures. Pre-treatment of the column with thionyl chloride inhibits decomposition of β-O-propionylated catecholamines and prevents their interference with other amines. Propionylation is a useful means for the isolation and determination of a wide range of biogenic amines from biological materials by gas chromatography.

Histomorphological Studies on the Effect of Recombinant Human Superoxide Dismutase in Biochemically Induced Osteoarthritis

Enzymatic scavenging of .O-2 radicals by injections of superoxide dismutase has been described to inhibit the free radical reactions resulting in tissue damage. Using a biochemically induced model of osteoarthritis (OA) in the knee joints of hens, we investigated the histomorphological alterations under therapy with recombinant human superoxide dismutase (rH-SOD) in various doses by histological-histochemical grading. Treatment of experimental OA with rH-SOD (0.1 mg/0.1 ml intra-articularly) led to a significant reduction in the intensity of cartilage degradation. The pathomorphological alterations in the osteoarthritic cartilage of hens treated with rH-SOD were quantitatively but not qualitatively different from the placebo-treated group. Our results indicate that rH-SOD exerts an inhibitory effect on the deleterious processes on articular cartilage tissue during the course of OA and may counteract cartilage degradations induced or accelerated by oxygen radicals.

A New Concept and Further Support for the Importance and Occurrence of 3,4-Dimethoxyphenylethylamine (DMPEA) in Urine of Schizophrenic Patients

The biogenic formation of certain methylated derivatives of catecholamines and serotonin have been discussed in causal connection with schizophrenia. Positive and negative results by various research groups in detecting 3,4-dimethoxyphenylethylamine (DMPEA) in urine of schizophrenics have led to contradictory interpretations of the importance of DMPEA in urine as an indicator of schizophrenia. Based on the fact that most hallucinogens rapidly develop tolerance in man, we postulate that in schizophrenics endogenously formed psychotoxins must be produced at greatly altering rates in order to affect the mental state over a given period of time. Accordingly, there must be significant alterations in the excretion of endogenously formed psychotoxins or their metabolites in urine. Our first and preliminary investigations of the daily excretion of DMPEA in urine of schizophrenics over a 10-day period (horizontal study) clearly indicate the altering excretion patterns of DMPEA. These results support our hypothesis and demonstrate the necessity for further and more extensive studies of DMPEA excretion in urine of schizophrenics over a continuous period of 10–30 days.

Gaschromatographische Untersuchungen biogener Amine in Form ihrer Acetyl-, Propionyl-, n-Butyryl-, iso-Butyryl- und Pivaloylderivate

SummaryWe describe a method for derivatisation of biogenic amines of the neurohormone metabolism (catecholamines, phenylethylamines and indolalkylamines). Derivatisation employed the anhydrides of acetic, propionic, n-butyric, iso-butyric and pivalic acid. The procedure can take place in an aqueous medium and results in stable and hydrophobic compounds which are quantitatively extractable by organic solvents. The acyl derivatives of biogenic amines posses good gas chromatographic properties and can be separated and analysed less than 20 minutes. Therefore the derivatisation described proves quite useful for the analytical gas chromatography of such amines.ZusammenfassungZur gaschromatographischen Bestimmung wichtiger biogener Amine aus dem Neurohormonstoffwechsel (Katecholamine, Phenyläthylamine und Indolalkylakine) wird ihre Derivatisierung mit den Anhydriden der Essigsäure, Propionsäure, n-Buttersäure, iso-Buttersäure und Pivalonsäure beschrieben. Die Derivate lassen sich im wäßrigen Medium bilden. Auf diese Weise werden sie stabilisiert und hydrophobiert, so daß sie quantitativ mit Hilfe organischer Lösungsmittel aus der wäßrigen Phase isoliert werden können. Alle Derivate zeigen gute gaschromatographische Eigenschaften mit einer Auftrennung innerhalb von weniger als 20 Minuten.

Effects of tribenoside (Glyvenol) on experimental osteoarthrosis.

An experimental model of chemically induced osteoarthrosis in the knee joint of adult hens was used to investigate the possible anti-arthrotic potency of the D-glucofuranose derivative tribenoside (Glyvenol). Development and intensity of progressing degenerative processes in the articular tissue were controlled and quantitatively determined by radiographic and macroscopic methods. Tribenoside was given in daily oral doses of 50 and 150 mg/kg by cannulation into the crop. Control of the knee joints by X-ray using mammography film as well as joint space measurements were performed at the beginning and 6, 8, 10, and 12 weeks after induction of osteoarthrosis. The results clearly demonstrate that the higher dose (150 mg/kg) of tribenoside had a significant inhibitory influence on the degenerative processes in the knee joints. The obvious anti-arthrotic potency of tribenoside may be explained by the various chondrotropic and vasotropic activities of this drug. The mode of action of tribenoside on connective tissue is discussed in relation and contrast to the inhibitory effect of most anti-inflammatory antirheumatics on anabolic cartilage metabolism.

Effects of the hydroxamic acid derivate Ro 31-4724 on the metabolism and morphology of interleukin-1-treated cartilage explants.

Matrix metalloproteinases (MMPs) belong to the key enzymes of the proteolytic destruction of cartilage matrix during chronic rheumatic diseases. Our work focused on the inhibitory potential of the hydroxamate Ro 31-4724 on the activity of MMP-proteoglycanases as well as on the viability, morphology and proteoglycan metabolism of interleukin-1 (IL-1)-treated bovine articular cartilage explants. The in vitro activity of MMP-proteoglycanases as well as the release of proteoglycans from IL-1-treated cartilage explants were significantly and concentration-dependently inhibited by Ro 31-4724 tested at concentrations ranging from 1 nmol/l to 10 mumol/l. Histopathological evaluation of sections from cartilage explants treated with this drug revealed no microscopically discernible alterations, and did not show any cytotoxic effects of Ro 31-4724. In addition, Ro 31-4724 had no effect on the rate of proteoglycan biosynthesis by IL-1-treated cartilage explants and increased the percentage of newly synthesized proteoglycans to form macromolecular aggregates. In conclusion, Ro 31-4724 displayed MMP-proteoglycanase inhibitory activity both in vitro and ex vivo and proved to be not harmful to the morphology, viability and proteoglycan biosynthesis of bovine articular cartilage explants.