2-Amino-6-[(1'R,2'S)-1',2'-dihydroxypropyl]-3-methyl-pterin-4-one,a biologically active metabolite from the anthozoanAstroides calycularis Pallas

Summary 2-Amino-6-[(1'R,2'S)-1',2'-dihydroxypropyl]-3-methyl-pterin-4-one (1) has been isolated from the marine anthozoanAstroides calycularis; its structure was illustrated by spectral analyses including 2D-NMR and by partial synthesis.1 appears to possess cell-growth inhibiting activity.29 December 1986Work supported by C.N.R. (Progetto Finalizzato Chimica Fine e Secondaria) and by Ministero Pubblica Istruzione Italy. — Acknowledgments. Mass spectral data were provided by Servizio di Spettrometria di massa del C.N.R. e dell'Università di Napoli. The assistance of the staff is gratefully appreciated. Finally we would like to thank Prof. C. Pietropaolo for supplying chick embryo fibroblasts.     

Ethanol diminishes the toxicity of the mushroomAmanita phalloides

Summary Survival of mice after lethal doses of a lyophilizate fromAmanita phalloides (death cap) was markedly increased by single doses of ethanol applied 30 min before or 5 min after the mushroom. Hepatic histopathological damage (confluent necrosis) was largley prevented. Acute, but not chronic, consumption of ethanol may thus influence favorably the outcome of death cap poisoning and should be taken into consideration in the evaluation of therapeutic measures.     

Eicosapentaenoic acid in tissue lipids ofPieris brassicae

Summary Larvae of the cabbage white butterfly,Pieris brassicae, have a dietary requirement for linolenic acid (C183n3) and were found to accumulate two other members of the n-3 family, C203n3 and C205n3 (eicosapentaenoic acid) especially in testicular phospholipids. Arachidonic acid was observed in trace amounts only. During diapause the relative titer of eicosapentaenoic acid increased in testicular phospholipids to about 4.2% of the fatty acids. Eicosapentaenoic acid is a possible precursor of prostaglandins, suggesting that prostaglandins of the 3-series predominate in this insect.     

Modulation of 3-hydroxy-3-methyl glutaryl CoA reductase by 2,3-diphosphoglyceric acid

Rat liver microsomal 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase was activated by 50% at a concentration of 0.4 mM 2,3-diphosphoglyceric acid (DPG) and by 11-fold at 10 mM DPG. DPG also prevented the inactivation of HMG-CoA reductase by ATP and Mg++. Rat liver microsomal HMG-CoA reductase prepared in the presence of 1 mM DPG was significantly more active than when prepared in the absence of DPG. Activation of the enzyme by DPG and protection of the enzyme against inhibition by ATP and Mg++ by DPG were also observed with solubilized HMG-CoA reductase.     

The potential therapeutic role of statins in central nervous system autoimmune disorders

3-Hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins are widely used oral cholesterol-lowering drugs. Statins competitively inhibit HMG-CoA reductase, the enzyme that catalyzes conversion of HMG-CoA to L-mevalonate, a key intermediate in cholesterol synthesis. Certain metabolites of mevalonate are also involved in posttranslational modification of specific proteins involved in cell proliferation and differentiation. Thus, statins have important biologic effects that may be independent of their cholesterol-reducing properties. Recent studies indicate that statins have antiinflammatory and neuroprotective properties which may be beneficial in the treatment of multiple sclerosis as well as other central nervous system (CNS) neurodegenerative diseases. This article will outline current experimental evidence that may suggest potential clinical benefits for patients with CNS autoimmune disorders. Ultimately, clinical trials will have to determine the safety and efficacy of statins in this patient population.Received 17 April 2003; received after revision 21 May 2003; accepted 22 May 2003     

Modulation of 3-hydroxy-3-methyl glutaryl CoA reductase by 2,3-diphosphoglyceric acid

Summary Rat liver microsomal 3-hydroxy-3-methylgularyl CoA (HMG-CoA) reductase was activated by 50% at a concentration of 0.4 mM 2,3-diphosphoglyceric acid (DPG) and by 11-fold at 10 mM DPG. DPG also prevented the inactivation of HMG-CoA reductase by ATP and Mg⁺⁺. Rat liver microsomal HMG-CoA reductase prepared in the presence of 1 mM DPG was significantly more active than when prepared in the absence of DPG. Activation of the enzyme by DPG and protection of the enzyme against inhibition by ATP and Mg⁺⁺ by DPG were also observed with solubilized HMG-CoA reductase.This work was supported by Research Award # 697 G2-1 from the American Heart Association, Greater Los Angeles Affiliate, and by grant # 1R01 HL22672 from the National Institutes of Health. We thank M. Brun and M. Curtis for their excellent technical assistance.     

Powerful hepatoprotective and hepatotoxic plant oligostilbenes,isolated from the Oriental medicinal plantVitis coignetiae (Vitaceae)

The methanol extract of the Oriental medicinal plantVitis coignetiae (Vitaceae) showed hepatoprotective activity in the in vitro assay method using primary cultured rat hepatocytes. Activity-guided fractionation of the extract afforded -viniferin as an active principle. The protective effect of -viniferin against mice carbon tetrachloride-induced hepatic injury in mice was shown by serum enzyme assay as well as by pathological examination. In addition to -viniferin, plant oligostilbenes, ampelopsins A, C, F and the mixture of vitisin A andcis-vitisin A were also present in the extract. Among them, ampelopsin C and the mixture of vitisin A andcis-vitisin A were found to be powerful hepatotoxins.     

(E)-3-tridecen-2-one,an antibiotic from the interdigital glands of black-tailed deerOdocoileus hemionus columbianus

(E)-3-tridecen-2-one, the major volatile component of interdigital gland extracts from the black-tailed deer,Odocoileus hemionus columbianus, inhibited the growth of gram-positive bacteria and fungi. The bacteria,Propionibacterium acnes, and the fungi,Trichophyton mentagrophytes had a minimum inhibitory concentration (MIC) of 12.5 g/mL and 25 g/mL, respectively.     

The sensitive period for yellow phenocopy induction inDrosophila melanogaster

Summary Yellow phenocopies ofDrosophila melanogaster were produced by raising larvae on -DMT contaminated media. Using a survivorship test, the sensitive period for phenocopy induction was found to occur during the third larval instar of development, with increased survivorship at 1% -DMT compared with lower concentrations. It was also found that treatment with -DMT significantly slowed development. These findings are related to the relevant morphological and behavioral developmental pathways and to phenocopy induction.Publication No. 35 from the Evolutionary Genetics Laboratory, University of Auckland.Acknowledgments. We thank the New Zealand Entomology Society for a grant from their Anniversary Fund to R. D. Newcomb and the University Grants Committee, Research Grant No. 394.597 to D.M. Lambert.     

Persistence of added retinoids in organ culture media during induction of mucous metaplasia and glandular morphogenesis in hamster cheek pouches

Summary The retinoid concentration (determined colorimetrically) did not change significantly in retinyl acetatesupplemented (6 g/ml) Eagle's Minimal Essential Medium containing 10% fetal calf serum when stored at –20 or 4°C over 7 days. After the medium was incubated at 37°C for 48 h, 37–49% of the retinoid remained, whether or not tissue (neonatal Syrian hamster cheek pouch) was present, and irrespective of explant age. The normal retinoid level in the tissue was approximately 0.25 g per gram. Therefore, neonatal hamster cheek pouches, incubated in medium with the addition of 6 g of retinyl acetate per ml of medium and undergoing mucous metaplasia and some mucous gland morphogenesis, were continually being exposed to retinoid levels which, though gradually decreasing, remained well above their normal physiological level.     

A new antiandrogen. 6α-Bromo-17β-hydroxy-17α-methyl-4-oxa-5α-androstan-3-one

Zusammenfassung Es wird gezeigt, dass 6-Brom-17-hydroxy-17-methyl-4-oxa-5-androstan-3-one beträchtliche antiandrogene Wirkung besitzt. Isomere dieser Verbindung mit verschiedener Konfiguration an C-5 und C-6 wurden als inaktiv befunden.     

Action duCorynebacterium parvum sur les taux de lysozyme (muramidase) sérique

Summary An i.v. injection of 548 g of killedCorynebacterium parvum into C57B1 mice leads to significant changes in serum lysozyme (muramidase) levels. After an initial fall at 24 h, the activity of the enzyme increased progressively, reached a peak on the 9th day and returned to control range after the 15th day.     

Plasma and hepatic antioxidant control and vitamin A nutritional status

Twenty-seven rats were divided into three groups and fed on diets containing 0.3, 6 or 60 RE (retinol equivalent) retinyl palmitate/g food. After 7 weeks, hepatic vitamin A uptake was found to be more efficient in vitamin A-deficient rats than in rats given adequate vitamin A. We showed that during the metabolic adaptation of the animals to the level of vitamin A in the diet, extensive modifications occur in the antioxidant defences of the organism. In parallel with the increase in the level of vitamin A, the decrease in the level of -tocopherol in the plasma can bring about a greater susceptibility of the lipoproteins to oxidative stress. Similarly, the decrease in the hepatic -tocopherol level and in glutathione peroxidase activity leads to the weakening of the liver's antioxidant defences.     

Polymorphisme des lipoprotéines et des glycoprotéines sériques chez la Truite

Summary It is shown that there are important differences among the serum proteins of 3 different species of trout. We stress that these genetic variations concern the lipoproteins as well as the glycoproteins. Furthermore, 3 serum proteins ofEsox lucius have antigenic determinants common with the serum proteins ofS. gairdneri; they are an ₂-lipoprotein, an ₂-glycoprotein and a -globulin.     

Juvenile hormone and reproduction in the cricket. II. Effect of rearing temperature on corpus allatum activity (in vitro) in adult females

Summary In the Mediterranean field cricket,Gryllus bimaculatus, reproduction is controlled by temperature and the corpus allatum (CA) hormone JH III. In CA of females reared at 24°12°C(168 h) (high reproduction rate) a first peak in JH III synthesis is reached about 4 days earlier than in those of 20°C females (low reproduction rate). Furthermore, in 20°C animals CA activity is low during the entire oviposition period, whereas at 24°12°C high CA activity is found during this period of adult life. The results indicate a stimulation of CA activity and reproduction by thermoperiods around a constant low temperature.Supported by the DFG (SFB 87 A 4).     

A method for the fluorimetric determination of 4-(2-Hydroxy-3-isopropylaminopropoxy)-indole (LB 46), aβ-blocking agent,in plasma and urine

Zusammenfassung Eine empfindliche fluorimetrische Methode zur Bestimmung von 4-(2-Hydroxy-3-isopropylaminopropoxy)-indol, dem-Blocker LB 46, in Plasma (Erfassungsgrenze 0,02 g) und in Urin (Erfassungsgrenze 0,05 g) wird beschrieben. Die mit dieser Methode gemessene biologische Halbwertszeit im Plasma beträgt nach peroraler Verabreichung beim Menschen 3 h und bei der Ratte etwa 30 min.     

Sex pheromone of the pine sawflyDiprion pini (Hymenoptera: Diprionidae): Chemical identification,synthesis and biological activity

The main component of the sex pheromone secretion of femaleDiprion pini L. (Hymenoptera: Diprionidae) from insects collected both in Finland and in France has been identified as athreo-3,7-dimethyl-2-tridecanol (8 ng per female) stereoisomer by GC-MS and synthesis. The secretion also contains lower and higher homologues in small amounts (1–4% of the main component). Combined gas chromatographic-electroantennographic detection showed activity in both natural and esterified extracts (acetates and propionates); the esters of the main component gave the largest responses. The acetates and propionates of the eight stereoisomers of 3,7-dimethyl-2-tridecanol were synthesized from enantiomerically highly enriched (>99% ee) building blocks. The stereochemistry of the main component was established to be (2S,3R,7R)-3,7-dimethyl-2-tridecanol by GC analysis of the natural material. It was purified by liquid chromatography prior to the GC analysis of both its pentafluorobenzoates and its isopropylcarbamates on a non-chiral polar column (ECD) and a chiral column (NPD), respectively. Field tests demonstrated that both the acetate and propionate of the main component (100 g of each applied on cotton roll dispensers) were active in attracting males, with or without the presence of several of the minor compounds. Experiments with smaller amounts of the acetate and the propionate (1 g in France and 50 g in Finland) demonstrated that the propionate was more active than the acetate, and that it also caught more males than a blend of the two compounds.     

Methoxymercuration-demercuration and mass spectrometry in the identification of the sex pheromones ofPanolis flammea,the pine beauty moth

Summary The major components of the sex pheromone system ofPanolis flammea, pine beauty moth have been identified as (Z)-9-tetradecenyl acetate, (Z)-11-hexadecenyl acetate and (Z)-11-tetradecenyl acetate in the ratio 10051; the double bond position of these derivatives was established by microscale application of a methoxymercuration-demercuration technique and GC-MS followed by multiple ion monitoring.We thank the Science Research Council and Forestry Commission for financial support. We are grateful for the collaboration of Messrs Stoakley and Bevan, Dr C. Longhurst and Mrs J. Edwards.     

Inhibition of respiratory oxidation of reduced sulfur compounds by intact cells ofThiobacillus denitrificans (strain RT) grown on thiosulfate

Thiobacillus denitrificans strain RT, an obligate sulfur-oxidizing chemolithoautotroph, was grown under microaerophilic conditions with thiosulfate as the only energy source. The rates of tetrathionate, thiosulfate, elemental sulfur (S^o) and sulfite oxidation were measured respirometrically with an oxygen electrode, using actively growing cells. Cells oxidized thiosulfate, elemental sulfur (S^o) and sulfite, but not tetrathionate. The thiosulfateoxidizing activity and elemental sulfur-oxidizing activity (SOA) were almost totally inhibited by 50 M myxothiazol (>80%), an inhibitor of the quinone-cytochrome b region, and by 10 M of the uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) (>82%). Sulfite-oxidizing activity was also significantly inhibited (>60%) by 50 M myxothiazol and 10 M CCCP. 1 mM KCN totally inhibited (>90%) all respiratory activities. This study confirms that a sulfur-oxidizing activity appears during microaerophilic growth ofThiobacillus denitrificans strain RT on thiosulfate. The SOA is linked to the respiratory chain, probably releasing electrons in the quinone-cytochrome b region.To whom correspondence should be addressed. Submitted by R. Bachofen.