In vivo effects of immunostimulating lipopeptides on mouse liver microsomal cytochromes P-450 and on paracetamol-induced toxicity

Summary Immunomodulating lipopeptides lauroyl-L-Ala--D-Glu-LL-A2pmNH2-Gly (RP 44.102) and lauroyl-L-Ala--D-Glu-LL-A2pmNH2 (RP 56.142) were found to protect mice against the hepatotoxicity of paracetamol, which is due to cytochrome P-450 dependent formation of toxic metabolites and radicals. In fact they decreased the amount of hepatic microsomal cytochrome P-450, and the level of CCl₄-induced lipid peroxidation. In contrast lauroyl-L-Ala--D-Glu-DD-A2pmNH2 (RP 53.204), which only differs by the configuration of the two chiral carbons of A2pm (diaminopimelic acid) and is not an immunomodulating agent, failed to protect against poisoning by paracetamol and had no effect on the level of hepatic cytochrome P-450 or the microsomal CCl₄-induced lipid peroxidation. This provides a clear connection between the immunostimulating properties of a compound and its effects on xenobiotic biotransformations.     

Evolutionary and ecological implications of cardenolide sequestration in the monarch butterfly

Summary Monarch butterflies sequester cardenolides from their larval host plants in the milkweed genusAsclepias for use in defense against predation. Of 108Asclepias species in North America, monarchs are known to feed as larvae on 27. Research on 11 of these has shown that monarchs sequester cardenolides most effectively, to an asymptote of approximately 350 g/0.1 g dry butterfly, from plants with intermediate cardenolide contents rather than from those with very high or very low cardenolide contents. SinceAsclepias host plant species are distributed widely in space and time across the continent, monarchs exploit them by migration between breeding and overwintering areas. After overwintering in central Mexico, spring migrants east of the Rocky Mountains exploit three predominantAsclepias species in the southern USA that have moderately high cardenolide contents. Monarchs sequester cardenolides very effectively from these species. First generation butterflies are thus well protected against predators and continue the migration north. Across the northern USA and southern Canada most summer breeding occurs on a fourthAsclepias species and in autumn most of these monarchs migrate back to Mexican overwintering sites. The ecological implications of this cycle of cardenolide sequestration for the evolution of monarch migration are discussed.     

Comments on “aggregation of equivalence relations” by P. C. Fishburn and A. Rubinstein

The theorem of the paper Aggregation of Equivalence Relations, by Fishburn and Rubinstein, states a result already known. This theorem improves a result from Mirkin (1975) and appears as a corollary occurring in Leclerc (1984).

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Resume L'unique théorème de l'article Aggregation of Equivalence Relations de Fishburn et Rubinstein est déja connu. Il améliore, en fait, un résultat de Mirkin (1975) et apparait en tant que corollaire dans Leclerc (1984).

     

The contents of the pygidial gland of the primitive antNothomyrmecia macrops (Hymenoptera:Formicidae)

Summary The principal constituent of the pygidial gland ofNothomyrmecia macrops is 3,7-dimethyloct-6-en-2-one, a substance not previously identified in insects. Also identified were 2,6-dimethylhept-5-enal, 2-nonanone, indole, -dodecalactone, and the hydrocarbons pentadecane, heptadecane, heptadecene and heptadecadiene, all in low nanogram quantities.     

Paranormal health claims

Summary Faith in paranormal cures has always been the last hope of many sufferers from chronic or incurable diseases. Magico-religious rituals of healing are still around, but some have been replaced by pseudo-scientific systems, thinly disguising old superstitions in new obscurantism, more appealing to the half-educated. in medical quackery, inventiveness seems to be limitless, and only the main paranormal healing systems can be reviewed here. The increasing popularity of alternative healing indicates the extent of dissatisfaction with dehumanising aspects of modern, technological medicine and its preoccupation with curing the curable at the expense of caring for the incurable. This leaves the sufferers, and also healthy people labelled with non-existent diseases, bleeding prey for the sharks roving the seas of medical ignorance. Medicine came into the world with a twin brother called Charlatanism — Lavoisier     

Pharmacodynamic profile of CQP 201-403, a novel 8α-amino-ergoline

Summary The profile of action in animals of CQP 201-403, a novel 8-amino-ergoline, is in most aspects that of a very potent dopaminomimetic, both as a prolactin secretion inhibitor, and at the levels of the CNS and the cardiovascular system. Qualitatively CQP 201-403 differs slightly from bromocriptine and apomorphine in its effects on the CNS (no influence on serotonin metabolism in the rat cortex; induction of masculine mounting behavior in rats) and the cardiovascular system of the dog (reflex tachycardia in response to a blood-pressure fall). In man the new compound proved to be highly active in lowering prolactin serum levels and to be more potent than bromocriptine (Parlodel^®).In memory of Dr Annemarie Closse, who died 14 June 1987.     

Changes in erythrocyte membrane lipid composition affect the transient decrease in membrane order which accompanies insulin receptor down-regulation

We have recently demonstrated, using electron paramagnetic resonance (EPR) spectroscopy, that insulin receptor internalization in response to insulin incubation (down-regulation) in human erythrocytes is accompanied by a transient decrease in membrane order, as measured by the 2T order parameter. Since membrane lipids play such an important role in receptor internalization, we investigated the possible effects that an alteration of the normally-occurring lipid profile might have on down-regulation and the concomitant transient decrease in membrane order. Consequently, human erythrocytes enriched with cholesterol and erythrocytes from cirrhotic patients were examined, because both of these groups of cells have a higher cholesterol/phospholipid molar ratio (CH/PL) than controls. The 5-nitroxystearate spin label, which inserts into the lipid bilayer of cell membranes, was used to monitor changes in 2T for a 3-h period at 37°C. We report here that both cholesterol-enriched and cirrhotic erythrocytes do not down-regulate, as demonstrated by binding assays, and that they do not show the typical transient decrease in membrane order observed in controls. The results seem to indicate that a more ordered membrane inhibits internalization of the insulin receptor in erythrocytes, and that an increase in membrane disorder is necessary for insulin receptor down-regulation.     

Proopiomelanocortin expression in the skin during induced hair growth in mice

We demonstrate for the first time a hair cycle-dependent gene and protein expression of proopiomelanocortin in mouse skin in vivo. Northern blot detected POMC mRNA with an apparent size of 0.9 kb in anagen but not telogen skin. Western blot emphasized a specific protein of 30–33 kDa recognized by anti -endorphin in late but not early anagen or telogen skin. By immunocytochemistry, -endorphin antigen was localized in the sebaceous gland in a hair cycle dependent manner.     

Preferential excretion of glycated albumin in C57BL-Ks-J mice: Effects of diabetes

Urinary excretion of glycated albumin was quantitated in genetically hyperglycemic mice (C57BL-Ks-J, db/db mice), a model for non-insulin-dependent diabetes mellitus, and compared with their non-diabetic littermates. The data indicated a preferential excretion of glycated albumin in non-diabetic mice. This phenomenon of editing of glycated albumin is decreased significantly in diabetic mice. Quantitative measurements of overall excretion of glycated albumin suggested that the loss of editing in diabetic mice is due to the dilution of glycated albumin by the unmodified albumin which is excreted in large amounts in diabetic mice. Therefore, the loss of editing observed in this model resembled the one we characterized in insulin-dependent diabetic humans and a streptozotocin-diabetic rat model³.     

C1 inhibitor hinge region mutations produce dysfunction by different mechanisms.

Heterozygosity for a mutant dysfunctional C1 inhibitor protein, a member of the serine proteinase inhibitor (serpin) superfamily, results in type II hereditary angioneurotic oedema. We identified a "hinge" region mutation in C1 inhibitor with a Val to Glu replacement at P14 Val-432. Recombinant C1 inhibitors P10 Ala-->Thr and P14Val-->Glu did not form stable complexes with fluid phase C1s or kallikrein. The P14 Val-->Glu mutant, however, was cleaved to a 96K form by C1s, while the P10 Ala-->Thr mutant was not. The recombinant P10 mutant also did not complex with C1s, kallikrein or beta-factor Xlla-Sepharose. The two mutations, therefore, result in dysfunction by different mechanisms: in one (P14 Val-->Glu), the inhibitor is converted to a substrate, while in the other (P10 Ala-->Thr), interaction with target protease is blocked.