Biological activity of precocene analogues onLocusta migratoria

Summary Structure-optimization studies of C-5-C-8-substituted precocene (P) analogues revealed that 1) compounds disubstituted asymmetrically at C-6, C-7 had an anti-allatal effect only if the C-6 side-group was shorter than that at C-7, 2) in the case of C-5, C-7 disubstitution, activity was enhanced by Me at C-5 whereas MeO caused inactivity. Effects of various other substitutions are also discussed.     

Implication of C-5, C-6 unsaturation as a key structural factor in steroidal alkaloid-induced mammalian teratogenesis

Hamster teratogenicity induced upon oral administration of steroidal alkaloids (solanidanes, spirosolanes and jervanes) appears to relate very closely to the presence or absence of C-5, C-6 unsaturation in the alkaloid, which may be more important than molecular configuration at C-22 and placement of the nitrogen atom with regard to the plane of the steroid.     

The glutathione status of the rat liver.

For the determination of cellular total glutathione, a new method is presented based on a fluorometric procedure. The relation between reduced glutathione, mixed glutathione disulfides and disulfide glutathione will be designated the glutathione status.     

The glutathione status of the rat liver

Summary For the determination of cellular total glutathione, a new method is presented based on a fluorometric procedure. The relation between reduced glutathione, mixed glutathione disulfides and disulfide glutathione will be designated the glutathione status.Supported by DFG (Ha 743/3).     

Inhibition of cytosolic rat hepatic glutathione S-transferase activities by bromosulfophthaleins

Summary The enzymatically catalyzed conjugation of glutathione with 1-chloro-2,4-dinitrobenzene and styrene-7,8-oxide is inhibited by tetrabromosulfophthalein in a non-competetive way, although tetrabromosulfophthalein itself is a substrate for glutathione S-transferases. Dibromosulfophthalein, which is not a substrate for glutathione S-transferases, inhibits the 1-chloro-2,4-dinitrobenzene conjugation competetively and the styrene-7,8-oxide conjugation non-competetively.     

Studies on the interaction of the mistletoe lectin I with carbohydrates

Summary Carbohydrates and modified derivatives of D-galactose have been studied for their capacity to inhibit the hemagglutination of human erythrocytes by mistletoe lectin I. Inhibition data suggest that unmodified hydroxyl groups at the C-2, C-3, and C-4 position of the D-galactopyranosyl ring are essential for binding to the active sites of the lectin.     

Some aspects of the NMR-spectra of aporphine and phenanthrene alkaloids

Summary The C-11 proton of an aprophine possessing a C-1,2 methylenedioxy group falls relatively upfield between 7.47 and 7.86. Additionally, the i.c.s. for the two protons of the methylenedioxy group is large (4–12 Hz). The presence of a methylenedioxy at C-3,4 in a phenanthrene alkaloid also results in an upfield shift ( 8.95–9.00) of the C-5 proton.This project was supported by NIH research grant No. HL-12971, awarded by the National Heart and Lung Institute, PHS/DHEW.     

Role of thiols in human peripheral blood Natural Killer and Killer lymphocyte activities

The thiol reagents, dithiothreitol, diethyldithiocarbamate and reduced glutathione were each found to inhibit Natural Killer and Killer lymphocyte-mediated cytotoxicities. A biphasic aspect to the inhibition with increasing concentration was observed with diethyldithiocarbamate and reduced glutathione. The inhibition observed in response to reduced glutathione, a non-permeant compound, suggests that cell surface thiols may be critical functional groups in the processes of NK and K lymphocyte-mediated cytotoxicities.     

Role of thiols in human peripheral blood natural killer and killer lymphocyte activities

The thiol reagents, dithiothreitol, diethyldithiocarbamate and reduced glutathione were each found to inhibit Natural Killer and Killer lymphocyte-mediated cytotoxicities. A biphasic aspect to the inhibition with increasing concentration was observed with diethyldithiocarbamate and reduced glutathione. The inhibition observed in response to reduced glutathione, a non-permeant compound, suggests that cell surface thiols may be critical functional groups in the processes of NK and K lymphocyte-mediated cytotoxicities.     

Der Einfluss von 2-Deoxy-D-glucose auf die Substratoxydation in Ascites-Tumorzellen

Summary The effect of the glycolytic inhibitor 2-deoxy-D-glucose on the oxidation of¹⁴C-labelled substrates of the tricarboxylic acid cycle was investigated in ascites carcinoma cells of the mouse. In the presence of high concentrations of glucose, deoxyglucose stimulates the oxidation of pyruvate C-2 and C-3 to CO₂, but not the oxidation of succinate C-1,4 to CO₂. While deoxyglucose causes, in the absence of glucose, an inhibition of the oxidation of exogenous palmitate C-1 to CO₂, it causes, in the presence of glucose, a stimulation of the palmitate oxidation. There is a possible correlation between the effect of deoxyglucose on the intracellular ATP metabolism and the effect of deoxyglucose on the palmitate oxidation.     

Changes in the cardiac glutathione status after ischemia and reperfusion

In the isolated and perfused rabbit heart ischemia induced a rapid decline of contractility, associated with a reduction of the content of tissue GSH with no significant changes in GSSG. Reperfusion induced a small recovery of contractility, a substantial release of total glutathione and a further decrease in the content of tissue GSH with a significant increase of tissue GSSG. Glutathione reductase and glutathione peroxidase activities were not affected by ischemia and reperfusion. This study suggests a possible role for glutathione in the determination of functional damage induced by myocardial ischemia and reperfusion.     

Changes in the cardiac glutathione status after ischemia and reperfusion

Summary In the isolated and perfused rabbit heart ischemia induced a rapid decline of contractility, associated with a reduction of the content of tissue GSH with no significant changes in GSSG. Reperfusion induced a small recovery of contractility, a substantial release of total glutathione and a further decrease in the content of tissue GSH with a significant increase of tissue GSSG. Glutathione reductase and glutathione peroxidase activities were not affected by ischemia and reperfusion. This study suggests a possible role for glutathione in the determination of functional damage induced by myocardial ischemia and reperfusion.This study was supported by a grant from Ministero Pubblica Istruzione and CNR Rome (no 8202331.56).     

Zum Mechanismus derβ-Lysin-Mutase-Reaktion

Summary Using tritium labelled substrates it is shown that in the rearrangement of (S) --lysine to 3,5-diaminohexanoic acid catalysed by-lysine mutase a stereospecific hydrogen migration from C-5 to C-6 of the substrate occurs. When the reaction is carried out in the presence of [5-³H]-coenzyme B₁₂, the heavy isotope is transferred both to C-6 of 3, 5-diaminohexanoate and to C-5 of-lysine. In the latter the labelled atom occupies the same diastereotopic position as the H atom that is transferred to C-6 of the product.     

Hemolysis and peroxidation in heavy metal-treated erythrocytes; GSH content and activities of some protecting enzymes

Summary The activities of superoxide dismutase, catalase and glutathione peroxidase, and the level of reduced glutathione, were measured in heavy metal-treated erythrocytes. The hemolytic metals were found to significantly deactivate both catalase and glutathione peroxidase and to decrease the level of reduced glutathione, thus providing suitable conditions for the development of peroxidation.     

1-Hydroxy-N-methylacridon,ein ungewöhnlich substituiertes acridin-alkaloid ausRuta graveolens

Résumé A partir des racines deRuta graveolens, on a isolé un alcaloide acridonique, 1-hydroxy-N-méthyl-acridone, dont la biosynthèse doit comporter une élimination réductive des OH-groups en C-1 et C-3.     

Ceramide mediates growth inhibition of the <Emphasis Type="Italic">Plasmodium falciparum</Emphasis> parasite

In mammalian cells, ceramide mediates death by chemotherapeutic drugs. We analysed, for the first time, the role of ceramide in inhibiting growth of the malaria-causing parasite Plasmodium falciparum. Added exogenously, ceramide significantly decreased the number of parasites, and this effect was abolished by sphingosine-1-phosphate, a biological antagonist of ceramide action. Ceramide can induce death of cancer cells by decreasing glutathione levels, and in our work it induced dose- and time-dependent depletion of glutathione in P. falciparum parasites. N-acetylcysteine, a precursor of glutathione, abrogated the cytotoxic effect of ceramide. Thus, ceramide can mediate growth inhibition of P. falciparum parasites by decreasing glutathione levels. The antimalarial drugs artemisinin and mefloquine induced the death of P. falciparum parasites by sphingomyelinase-generated ceramide and by decreasing parasite glutathione levels. Altogether, ceramide was identified as a signalling molecule capable of inducing growth inhibition of P. falciparum malarial parasites.     

Sul meccanismo di azione della vaccinoterapia nella infezione tifoidea

Summary Having observed before that the blood serum of typhoid patients acquires under the stimulus of the vaccine an evident bacteriolytic action on the typhoid bacillus, we have studied variations brought about by the vaccine stimulus in the blood of the patients as to the redox-potential and to the glutathione in the blood.It has been seen that under vaccine stimulus there is a rapid increase of redox-potential and of the glutathione in the blood: lasting in the cases which tend to recovery, temporary in the cases in which the illness takes its natural course.The values of the total glutathione increase more than those of reduced glutathione, so that an increase of the values of the oxidized glutathione is found.The variations of the values of the redox-potential and of the oxidized glutathione brought about by the vaccine reaction in the blood of the patients leads us to consider the mechanism of the action of vaccine therapy in typhoid infection, on the same principle described by us regarding the action of penicillin.     

Spontaneous morphine withdrawal from the rat spinal cord

A characteristic and reproducible sign of narcotic withdrawal is the naloxone induced increase in arterial pressure. In morphine-dependent rats allowed to undergo spontaneous withdrawal (6-24 h) and then transected at the spinal C-1 level, arterial pressure was maintained at a significantly higher level than either spinal-transected nondependent controls or morphine-dependent, spinal-transected rats pithed from C-1 to L-4. These findings indicate that the morphine-dependent spinal cord, independent of supraspinal influences, is able to exhibit an autonomic component of spontaneous withdrawal.     

Glutathione peroxidase in dried blood spots.

A new procedure utilizing dried blood spots was developed for detecting glutathione peroxidase deficiency. Samples from a known patient with a partial defect and from rats with an induced deficiency were distinguished from respective control groups by their longer defluorescence endpoints. Samples from 100 patients with anemia and 2 phenyl-ketonuric infants on low-protein diets contained glutathione peroxidase activity similar to that in 82 controls, when screened for the enzyme defect by the new procedure.     

Zum Mechanismus der Propandioldehydrase-Reaktion

Summary Investigation of the propanediol dehydrase reaction with¹⁸O-labelled substrates indicates that the conversion of propane-1,2-diol to propionaldehyde involves transfer of the oxygen atom from C-2 to C-1. The dehydration of the so formed propane-1,1-diol is sterically controlled by the enzyme.