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A novel amino acid glycoside (-)-N-(1'-deoxy-1'-beta-D-fructopyranosyl)-S-allyl-L-cysteine sulfoxide [1], was isolated from a hydrophilic extract of the leaves of Allium sativum (Alliaceae), together with three known compounds: (+)-S-allyl-L-cysteine sulfoxide [2],(+)-S-methyl-L-cysteine sulfoxide [3], and (+)-S-(trans-1-propenyl)-L-cysteine sulfoxide [4]. The latter two substances were isolated for the first time from garlic. The structure elucidation of 1 was performed by extensive chemical, spectroscopic (ir, fabms, 1D and 2D(1)H- and (13)C-nmr measurements) and chromatographic experiments. For the first time, detailed nmr data and the unambiguous assignment of all (13)C-nmr data for compounds 2-4 were reported. Compound 1, the amino acid glycoside, revealed a significant inhibition of in vitro platelet aggregation induced by ADP and epinephrine, whereas none of the amino acids tested displayed any activity.

ZusammenfassungPhytopharmaka sind galenische Zubereitungen aus Pflanzen, Pflanzenbestandteilen und Pflanzenextrakten und entsprechen der Definition des Arzneimittelgesetzes. Sie unterscheiden sich von synthetischen Monopräparaten durch ihre komplexe Zusammensetzung aus Wirkund Begleitstoffen. Phytopharmaka stellen in ihrer Mehrheit Arzneimittel mit großer therapeutischer Breite dar, die vorwiegend adjuvant eingesetzt werden, wie z. B. die gefäßwirksamen Phytopharmaka. Als antiarteriosklerotisch wirksam haben sich Präparate aus Allium sativum erwiesen, Ginkgoextrakte finden Verwendung bei Hirnleistungsstörungen und peripheren Durchblutungsstörungen. Verbindungen mit thrombozytenaggregationshemmender Wirkung sind in zahlreichen Pflanzen enthalten wie in Knoblauch, Ginkgo, Mariendistel, Weißdorn und Arnika. Im venösen Bereich finden vornehmlich Roßkastanienextrakte, Rutindrogen und Mäusedorn Verwendung.

Epinephrine- and collagen-induced aggregation of platelets was determined under standardized conditions in vitro in 100 healthy normotonic subjects, and the relation between the platelet-parameters and diastolic and systolic blood pressure analysed. A correlation between aggregation and blood pressure could be demonstrated only in the case of epinephrine-induced aggregation. Intensity of epinephrine-induced aggregation correlated well with the simultaneously measured diastolic and systolic blood pressure and with the calculated mean arterial pressure (R = 0.775; p less than 0.001). From the results it can be concluded, that the correlation between epinephrine-induced aggregation and blood pressure depends on endogenous levels of catecholamines.

About 50% of the circulating platelets can be taken from healthy donors by means of the cell separation technique. In order to investigate the effect of cell separation on thrombopoesis bone marrow samples were taken from 12 voluntary donors up to 5 times. The megacaryocytes were analyzed before and after cell separation by morphometric measures and determinations of platelet count and platelet function (adhesion, aggregation, spreading, retraction) were carried out. Removing of large amounts of platelets form the circulation by stimulation of thrombopoesis resulted in an increase of the peripherical platelet count already 48 h after cell separation. Of the platelet functions tested only aggregation induced by collagen was found to be increased after cell separation as compared to that before the procedure.

Inzolen, a combination of the potassium, magnesium, copper, manganese and cobalt salts of aspartic acid, inhibits the second phase of ADP-induced aggregation probably by affecting the membrane-located adenylatecyclase/phosphodiesterase system. Correspondingly inzolen affects the activation of platelet factor 3 (PF3), which is also located in the platelet membrane. Thus spontaneous as well as kaolin-induced platelet factor availability is reduced by inzolen. The significant inhibition of factor 3 availability can be interpreted by a magnesium-mediated activation of phosphoryltransferases.

Studies on the Effect of Cephalexin on Platelet Functions in Diabetics and Healthy Volunteers. The effect of cephalexin (Ceporexin) on platelet functions of diabetics with proliferative retinopathy and of healthy volunteers was studied. Cephalexin, 3 X 1 g for 7 days, reduced epinephrine- and collagen-induced platelet aggregation of the diabetics in a significant, but clinically not relevant manner. Platelet factor-3 availability and retraction remained unaffected by treatment with cephalexin. Cephalexin in vitro in a concentration of 500 mg/l reduced the rate and peak amplitude of platelet aggregation in diabetics and healthy volunteers to the same extent. The in vitro inhibition of epinephrine- and collagen-induced platelet aggregation was lacking clinical relevance. Platelet factor-3 availability was not changed by addition of cephalexin in vitro; the retraction was significantly increased, however, without clinical relevance.

Heavy water (D2O) is able to activate or to inhibit biological systems and thus influences metabolism and functions of tissues and organs. On the basis of results obtained in preservation experiments performed on various organs, the effects of D2O on the functions of human platelets (retraction, spreading, aggregation induced by adrenaline, ADP and collagen) have been investigated. The effects of D2O, involving changes of membrane receptor conformation, binding strength of substances to their specific receptors, pH-values or enzyme activities, resulted in a significant decrease of ADP- and collagen-induced aggregation, while adrenaline-induced aggregation was significantly increased at the same D2O concentration. Retraction in the presence of D2O was significantly inhibited in a dose-related manner, while spreading was diminished, but not fully inhibited even by highest concentrations of D2O (95%).

In recent investigations it was found that ciprofloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7 (1-piperazinyl)-3-fiquinoline-carboxylic acid, Ciprobay) in concentrations similar to maximal levels obtained in the serum of patients with normal renal function after application of therapeutic doses and 4- to 5fold such concentrations does not influence aggregation induced by epinephrine and collagen in platelet rich plasma of healthy subjects. Because in literature there are several reports about disturbances of platelet aggregation in patients with renal failure treated with antibiotics and because renal failure often is accompanied by defect platelet function the effect of ciprofloxacin on epinephrine and collagen induced aggregation was studied in platelet rich plasma of patients with chronic renal failure undergoing dialysis. Compared to platelets from patients with renal failure which had been incubated with saline instead of ciprofloxacin, patients platelets under the influence of ciprofloxacin did not show any significant differences. From this we conclude that the defect which may be present in platelets of patients with chronic renal failure is not further increased by ciprofloxacin.

Concentrations of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid (ciprofloxacin; designated tradename: Ciprobay) similar to maximal levels obtained in the serum of patients with intact renal function after application of therapeutic doses and 4- to 5-fold such concentrations do not influence epinephrine- or collagen-induced aggregation. 100 micrograms/ml ciprofloxacin, corresponding to the 20 fold maximal serum level of patients with intact renal function, does not influence aggregation induced by 2 micrograms/ml collagen as regards degree and kinetics of aggregation, while aggregation induced by 0.2 micrograms/ml collagen is significantly reduce. Aggregation induced by 1, 2 and 4 mumol/l epinephrine is also reduced significantly by 100 micrograms/ml ciprofloxacin. Changes brought about by high doses of ciprofloxacin still occur within the normal range. It is therefore concluded from this study that the hemostatic function of the platelets is not influenced in a clinically relevant manner by ciprofloxacin. Regarding the effect on platelet aggregation ciprofloxacin corresponds to the structurally related pipemidic acid.

Concentrations of pipemidic acid (Deblaston) similar to maximal levels obtained in the serum of patients with intact renal function after application of therapeutic doses do not influence epinephrine (adrenaline)- or collagen-induced aggregation in vitro. With 20 micrograms/ml pipemidic acid, corresponding 4- to 5-fold maximal serum levels epinephrine-induced aggregation is reduced significantly, while aggregation by collagen is not affected. A significant reduction of epinephrine-induced aggregation as well as of collagen-induced aggregation is brought about only with doses of pipemidic acid as high as 100 micrograms/ml. But these changes still occur within the normal range. Therefore we conclude from our study, that platelet aggregation is not affected in a clinically relevant manner by pipemidic acid.