Effect of Plasmodium berghei infection on benzoic acid metabolism in mice

The metabolism of benzoic acid was studied in Plasmodium berghei infected mice both in vitro and in vivo. Results of in vitro studies showed a considerable decrease in the ability of the infected liver to detoxify benzoic acid by hippuric acid formation. The in vivo study showed that hippuric acid formation decreases with increasing parasitemia and the emergence of benzoyl-glucuronide. This new pathway stops operating with further increase in parasitemia.     

Mean cytoplasmic protein concentration of host erythrocytes and the reticulocyte response inPlasmodium berghei infected mice

Summary the decreasing mean cytoplasmic protein concentration (MPC) ofP. berghei host cells is paralled by an increasing parasitemia and percent reticulocyte response. The reticulocyte response parallels the percent parasitemia except during a period of accelerated reticulocytosis noted during the midpoint of the infection at which time the percent reticulocytes increases at a rate more than double the rate of increase of percent parasitemia. Although the reticulocyte population and the host cell population are usually equivalent, the disparity noted suggests the existence of unique characteristics in the reticulocyte response ofP. berghei infected mice.     

The course ofPlasmodium berghei infection in mice latently infected withToxoplasma gondii

Summary The course of infection with 2 different virulent strains ofPlasmodium berghei was investigated in mice latently infected withToxoplasma gondii. When given the highly virulent ANKA strain ofP. berghei all Toxoplasma-infected mice died but the survival time was prolonged. After infection with the less virulent strain K 173 mice could survive the subsequent infection. In these cases levels of parasitemia depended upon the duration of theT. gondii infection. Mice infected for about 6 weeks withT. gondii showed maximum protection. These studies were conducted in the Institut für Medizinische Parasitologie der Universit?t Bonn (D-5300 Bonn, Federal Republic of Germany).     

Increased susceptibility ofTrypanosoma lewisi infected,or decomplemented rats toSalmonella typhimurium

Summary Rats infected withTrypanosoma lewisi or decomplemented by injection of cobra venom factor or complement activating factor of trypanosomes were found to be more susceptible to infection withSalmonella typhimurium. Decomplemented rats subsequently infected withT. lewisi developed higher blood parasitemia than did normalT. lewisi infected rats.This project is supported by the National Research Council of Canada grant A 0068 and a grant from the International Development Research Center.     

Occurrence and biosynthesis of 11 (R)-hydroxy-eicosatetraenoic acid (11-R-HETE) in the Caribbean soft coralPlexaurella dichotoma

Gorgonian soft corals from the Caribbean Sea are known to contain prostaglandin-like compounds as well as other products of arachidonic acid lipoxygenation, and the formation of the latter has been suggested to represent the first step in prostaglandin biosynthesis. Here we present evidence for the presence of 11-R-hydroxy-5Z, 8Z, 12E, 14Z-eicosatetraenoic acid (11-R-HETE), as well as of the enzyme responsible for its biosynthesis, in the Caribbean gorgonianPlexaurella dichotoma. Lipid extracts fromP. dichotoma were purified by conventional SiO₂ column chromatography followed by reversed phase high-pressure liquid chromatography (HPLC). These yielded a component having chromatographic and spectroscopic properties identical to synthetic 11-HETE. Electron impact mass spectrometric analysis of the acetoxy-, methyl ester derivative of the compound confirmed its identity as 11-HETE, while chiral phase HPLC of the methyl ester derivative showed that the stereochemistry of the alcoholic carbon atom wasR. Enzymatically active homogenates fromP. dichotoma were able to convert both unlabelled and [³H] arachidonic acid into 11-HETE. In vitro biosynthesis of the latter metabolite was also observed with homogenates of the Mediterranean gorgonianParamuricea clavata, another non-prostaglandin-containing soft coral, thus suggesting that 11-R-HETE production is not necessarily accompanied by prostaglandin formation in gorgonian corals.     

Ein chemisch und pharmakologisch neuartiger Antagonist von pathophysiologisch bedeutsamen Aminen,Kininen und kininbildenden Faktoren

Summary CIBA 21 401-Ba, a glucofuranoside derivative (ethyl-3,5,6-O-benzyl-d-glucofuranoside), antagonizes in vitro the smooth-muscle action of a large number of biogenic amines and polypeptides, the accelerated migration of leucocytes induced by endotoxin, and the Schultz-Dale phenomenon. In vivo, the compound shows anti-inflammatory and anti-allergic effects and improves the survival rate of infected mice treated with suboptimal doses of a sulphonamide.     

Nosiheptide,a sulfur-containing peptide antibiotic isolated fromStreptomyces actuosus 40037

Summary Nosiheptide (9671 R.P.) isolated fromStreptomyces actuosus 40037 (NRRL 2954) is a sulfur-containing polypeptidic antibiotic, quite different from all the other members of this family. Very active in vitro against gram-positive bacteria, it is inactive in vivo in experimentally infected mice. Not toxic, even at high dose, it may be used as a feed additive for chickens and pigs and it shows a favourable effect on the growth and conversion index.     

Mean cytoplasmic protein concentration of host erythrocytes and the reticulocyte response in Plasmodium berghei infected mice.

The decreasing mean cytoplasmic protein concentration (MPC) of P. berghei host cells is paralled by an increasing parasitemia and percent reticulocyte response. The reticulocyte response parallels the percent parasitemia except during a period of accelerated reticulocytosis noted during the midpoint of the infection at which time the percent reticulocytes increases at a rate more than double the rate of increase of percent parasitemia. Although the reticulocyte population and the host cell population are usually equivalent, the disparity noted suggests the existence of unique characteristics in the reticulocyte response of P. berghei infected mice.     

Presence of benzodiazepine binding sites (receptors) and amplification thereof by imprinting inTetrahymena

Summary LiveTetrahymena cells bound³H-diazepam specifically, as demonstrated by autoradiographic evidence of displacement of about 25% of labeled diazepam in the presence of a 1000-fold amount of cold diazepam. The³H-diazepam bound to membrane preparations isolated from untreated (control) cells was not displaced by cold diazepam, whereas cells involved in primary interaction (imprinting) with diazepam showed amplification and specificity of diazepam binding in both in vivo (cell suspension) and in vitro (pellicle) systems, as well as displacement of bound label in the presence of 1000-fold cold diazepam. It appears that diazepam induced imprinting and, consequently, also the formation of specific receptors inTetrahymena.     

Intorno alle attività biochimiche deiFlavobacterium

Summary A fewFlavobacterium, among themFlav. dehydrogenans, present oxidative activities upon sterins from the serie of sexual hormons, acting in a selective manner. These microorganisms have a scarce fermentative capacity against carbohydrates and an eminent oxidative action upon hydrocarbures and their derivatives as toluol, xylol, paraphine, benzoic acid, salicylic acid, phenol.The pigment ofFlav. dehydrogenans, which is exclusively elaborated at diffusive light, is straightly fixed at oxidative processes determined by the bacterium.     

Leonurine,an improved synthesis

Summary Leonurine (1) is the uterotonic principle ofLeonurus artemisia. We have developed a simple, high-yield synthetic procedure of1 that is adaptable to large scale preparation. The synthesis involves the condensation of syringic acid and 4-guanidino-1-butanol hydrochloride in the presence of DDC using 11 HMPT-ether as solvent. The synthetic leonurine showed uterotonic activity in vivo and in vitro.Acknowledgment. This work was partly supported by World Health Organization, Geneva, Switzerland.     

The role of cysteine in the detoxification of an herbicide]

The methyl 2-chloro-3 (4-chlorophenyl) propionate is quickly hydrolysed through coleoptiles of wheat (coleoptile test). Then, depending on the concentration of the compounds, one observes mainly a further degradation (at 0,01 mM) of the acid or conjugation (at 0,1 mM) of it with cystein in vivo. This second type of physiological neutralisation appears to be more efficient than the catabolism which give derivatives of benzoic acid.     

The effect of oxine-5-sulphonic acid on the hepatic drug metabolism in the rat

Summary Oxine-5-sulphonic acid inhibits the metabolism of aminopyrine in the rat liver in vitro. The characteristics of this inhibition vary according to whether the oxidativeN-demethylation of the substrate is determined by the formation of the metabolite 4-aminoantipyrine or by the production of formaldehyde.     

Aragusterol C: A novel halogenated marine steroid from an Okinawan sponge,Xestospongia sp., possessing potent antitumor activity

A novel chlorinated steroid, aragusterol C, was isolated from an Okinawan marine sponge of the genusXestospongia. The compound strongly inhibited the proliferation of KB cells in vitro, and also showed potent in vivo antitumor activity against L1210 cells in mice. The complete structure of aragusterol C was determined by spectroscopic analysis and X-ray crystallographic analysis.     

Sexual dimorphism in the defensive secretion of a carabid beetle

Summary The defensive secretions of male and femaleOodes americanus display striking qualitative differences. Altogether 13 carboxylic acids were identified in the secretions of the two sexes. Methacrylic, crotonic, and tiglic acids are produced exclusively by the female; the male lacks these unsaturated components, but produces their saturated analogs. 2-Methylbutyric acid is a major component produced by both sexes. Shared components also include hexanoic, (E)-2-hexenoic, benzoic, and (E)-2-octenoic acid, of which the latter two had not previously been reported from carabid beetles.Paper no. 98 in the series Defense Mechanisms of Arthropods; no. 97 is by Smedley et al., J. Lepid. Soc., in press.     

Evaluation of models for the mechanism of action of 4-hydroxyphenylpyruvate dioxygenase

Summary 4-Hydroxyphenylpyruvic acid was oxygenated with various complexes of oxygen with Fe²⁺, superoxide ion, hydroperoxide anion, triplet and singlet oxygen. Oxidation occurred giving varying amounts of the 4-hydroxy derivatives of benzaldehyde, benzoic acid, phenol, phenylacetic acid and 4-carboxymethylquinone, but no homogentisic acid. 4-Hydroxyphenylperacetic acid was prepared and shown not to undergo self-oxidation. Its ferrous salt decomposed to 4-hydroxybenzyl alcohol. It is concluded that thea-keto carboxylic function is the site of oxygenation in the enzyme process and that a trioxalanone rather than a peracid intermediate may be implicated.Acknowledgments. We thank a referee for drawing our attention to the work of Hawkinsin and we are indebted to the Swiss National Science Foundation for the support of this work (grant No 2.418.0.79).     

Cerebral ischemia revisited: New insights as revealed using in vitro brain slice preparations

Summary The elucidation of the pathophysiological mechanisms of cerebral ischemia/hypoxia dictates the use of experimental models which mimic this disabling brain condition. In vivo experimental models have been available for many decades and are responsible for the bulk of, though incomplete, knowledge we have about these mechanisms. Since study in isolation of each postulated mechanism is impossible in vivo, the need for an in vitro experimental model has intensified in recent years. Consequently, rat and guinea pig hippocampal slice preparations have emerged as the models of choice. This review attempts to highlight some of the results obtained using brain slices in the study of cerebral ischemia/hypoxia and compare them to those obtained in vivo. Both the biochemical and the physiological correlates of energy metabolism, ion homeostasis, neurotransmission and neuromodulation of this brain condition are reviewed. The agreements, and especially the disagreements, between the in vivo and in vitro findings are emphasized. Details are given of the possible roles of both lactic acid, Ca²⁺ and excitotoxins in the neuronal damage inflicted by cerebral ischemia/hypoxia. Recent attempts to protect brain slices against experimental cerebral ischemic/hypoxic damage are also reviewed here briefly.     

Novel diterpenoid diacylglycerols from marine molluscs: potent morphogens and protein kinase C activators

Five novel 1,2-sn-diacylglycerols with diterpenoid acyl moieties in thesn-1 position were isolated and characterized, together with the corresponding 1,3-sn-diacylglycerols, from three species of dorid nudibranchs molluscs. Their potent activity as morphogens in vivo in theHydra tentacle regeneration assay and their parallel activity as activators of rat brain protein kinase C (PKC) in vitro are reported here. Our findings promote the use of these compounds as useful molecular probes for both in vivo and in vitro studies on the participation of PKC in cell development.     

Lysozyme activates Enterococcus faecium to induce necrotic cell death in macrophages

Enterococci are commensal organisms in the alimentary tract. However, they can cause a variety of life-threatening infections, especially in nosocomial settings. We hypothesized that induction of cell death might enable these facultative pathogenic bacteria to evade the innate immune response and to cause infections of their host. We demonstrate that E. faecium when exposed to lysozyme induces cell death in macrophages in vitro and in vivo. Flow cytometric analyses of J774A.1 macrophages infected with E. faecium revealed loss of cell membrane integrity indicated by uptake of propidium iodide and decrease of the inner mitochondrial transmembrane potential ΔΨ_m. Inhibition of caspases, treatment of macrophages with cytochalasin D, or rifampicin did not prevent cells from dying, suggesting cell death mechanisms that are independent of caspase activation, bacterial uptake, and intracellular bacterial replication. Characteristics of necrotic cell death were demonstrated by both lack of procaspase 3 activation and cell shrinkage, electron microscopy, and release of lactate dehydrogenase. Pretreatment of E. faecium with lysozyme and subsequently with broad spectrum protease considerably reduced cell death, suggesting that a bacterial surface protein is causative for cell death induction. Moreover, in a mouse peritonitis model we demonstrated that E. faecium induces cell death of peritoneal macrophages in vivo. Altogether, our results show that enterococci, under specific conditions such as exposure to lysozyme, induce necrotic cell death in macrophages, which might contribute to disseminated infections by these facultative pathogenic bacteria.     

Activation and specificity of alkaline phosphatase of a mineralizing collagen-rich system

Summary Alkaline phosphatase from tibia tendon ofMeleagris gallopavo L. was highly purified. The enzyme activation by different ions was measured. Mg²⁺ showed a high activation with a broader spectrum of phosphomonoester hydrolization. The in vivo Mg²⁺ concentration was an optimum for in vitro activation.Dedicated to Prof. Dr. G. Pfefferkorn on the occasion of his 65^th birthday.We thank Deutsche Forschungsgemeinschaft for support.