Release of synthesized lipids by isolated Wistar rat liver perfused by labelled oleic acid and glycerol]

After perfusions with oleic acid (9, 10-3H) and glycerol (1-14C) of isolated livers from wistar Rats, previously subjected to fasting, the study of the TG and PL synthesized by the liver and released in the circulation gives of evidence similar ways of metabolising TG and PL. Two liver pools are present: -- a storage pool, built with slow exchanges of AG of endogenous glycerolipids. In our experiments, the TG: 16 : 0 18 : 1 18: 2 and 16 : 0 18 : 1 18 : 1 and the PL: PE and PC are the glycerolipids of liver constitution: -- a pool of liver secretion. TG and PL are formed according to a rapid de novo synthesis using preferentially the exogenous substrates. They are released in the circulation. In our experiments, the TG secreted are the TG 18 : 1 18 : 1 18 : 1 and 16 : 0 18 : 1 18 : 2, the PL are the PE, AP and LPC.     

Comparison in genetically obese and normal rats of the uptake and incorporation of labelled lauric acid, oleic acid, and glycerol by the isolated perfused liver]

Lauric acid, labelled oleic acid and glycerol are perfused in isolated liver of fafa Rats and Wistar Rats previously subjected to fasting. They synthesize TG and PL de novo, though in long time experiments with the normal Rat, the most important method of synthesis is an exchange of AG of the endogenous glycerolipids. However PL are not synthesized with lauric acid. In the livers of fafa Rats the synthesis of TG with oleic acid and glycerol is higher than in livers of Wistar Rats: 16:0 18 : 1 18: 1, 16:0 18: 1 18: 2, 18 : 1 18 :1 18:1, 16 : 0 16 :0 18 : 1 (this TG is not present in liver of Wistar Rat). The hepatic synthesis of PL by the fafa Rat, is less important after 15 min while it is important with Wistar Rats. The synthesized TG with lauric acid (only the TG 12 : 0 12 : 0 12 : 0 with the fafa Rat) are more rapidly oxidized by liver of obese Rat than by liver of normal Rat.     

Comparison in genetically obese and normal rats in the secretion of lipids synthesized from labeled lauric and oleic acids and glycerol in isolated perfused liver]

(1) Isolated livers of previously fasted fafa and Wistar Rats are perfused with labelled oleic acid and glycerol. Two pools of synthesized lipids are studied: --a pool of liver lipids: labelled TG 16:0, 16:0, 18:1, 16:0, 18:1, 18:1 and 18:1, 18:1, 18:1 are synthesized more by the fafa than by the Wistar Rat liver, The TG 16:0, 18:1, 18:2 appears in the liver of the 2 rat strains. After a 30 min. perfusion, the PL are synthesized less by the fafa than by Wistar Rat liver; --a pool of lipids released in the circulation. The labelled tG 16:0, 18:1, 18:2, are increased in the perfusate of fafa rat. The labelled TG 18:1, 18:1, 18:2 and 18:1, 18:2, 18:2 are in the same amount. (2) The liver synthesis of TG 12:0, 12:0, 12:0 is demonstrated in the fafa Rat by a lauric acid perfusion. This TG is not present in circulation, when a Wistar Rat liver synthesizes and releases with this TG, TG containing 1 or 2 molecules of lauric acid.     

Ethanol and opioid receptor signalling

Ethanol may modulate endogenous opioid systems by disrupting opioid receptor signalling. Low concentrations of ethanol slightly potentiate mu-opioid receptor binding by increasing receptor Bmax, and, in some cases, chronic ethanol exposure decreases the density or affinity of the mu-opioid receptors. By contrast, high concentrations of ethanol acutely decrease delta-opioid receptor binding by decreasing receptor affinity, whereas chronic exposure of animals and neuronal cell lines to lower concentrations of ethanol leads to possibly adaptive increases in the density or affinity of the delta-opioid receptors. In the neuronal cell line NG108-15, ethanol does not up-regulate the delta-opioid receptor by blocking receptor degradation or endocytosis, but protein synthesis is required for this response. Up-regulation of the delta-opioid receptor renders ethanol-treated NG108-15 cells 3.5-fold more sensitive to opioid inhibition of adenylyl cyclase. Long-term treatment with ethanol also increases maximal opioid inhibition in NG108-15 cells, possibly by decreasing levels of G alpha s and its mRNA. Ethanol differentially modulates signal transduction proteins in three additional neuronal cell lines, N18TG2, N4TG1, and N1E-115. Ethanol-treated N18TG2 cells show the least up-regulation of the delta-opioid receptor, little heterologous desensitization of adenylyl cyclase, and no changes in G alpha s or G alpha i. By contrast, ethanol-treated N1E-115 cells show the largest up-regulation of the delta-opioid receptor, the most heterologous desensitization of adenylyl cyclase, and concentration-dependent decreases in G alpha s and increases in G alpha i. Further analysis of these related neuronal cell lines may help to identify the molecular elements that endow some, but not all, neuronal cells with the capacity to adapt to ethanol.     

The effects of time of equilibration with cryoprotectants at 0 degree C prior to freezing on the survival of mouse embryos frozen by the two-step method

Mouse embryos were frozen by the two-step method after equilibration for 0.1-60 min with cryoprotectants at 0 degree C. No survival or a very low survival was obtained after equilibration for only 0.1 min. The morulae showed the highest survival rates when equilibration time was 5-30 min with 2 M DMSO, 20-30 min with 2 M glycerol, 5-10 min with 2 M ethylene glycol and 20-30 min with 2 M propylene glycol, respectively.     

Neuartige Umwandlungen bei den Steroiden

Summary The problem of an efficient partial synthesis of the important corticosteroidal hormone, aldosterone, involves the ability to obtain steroids with functional groups at C-18. Thus, naturally occuring steroid alkaloids, holarrhimine and conessine, were degraded to nitrogen-free 18-hydroxysteroids.In order to find other more efficient methods of synthesis, attempts were made to effect direct functionalization of the unactivated angular methyl group 18 in steroids. This was achieved by known and by novel intramolecular substitution procedures.In the course of these investigations, conessin-type compounds, novel pentacarbocyclic steroids with four-and five-membered E ring as well as novel 18,20-oxido steroids were synthesized from pregnane derivatives. The lead tetraacetate oxidation of 20-hydroxypregnanes, leading to ether formation between C-18 and C-20, ultimately provided the key step for the first partial synthesis ofnat.-aldosterone. The latter work was carried out in close collaboration with the research group of the Pharmaceutical Department of CIBA Ltd., Basle.

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Erweiterte Fassung eines am 6. 5. 59 in der Zürcher Chemischen Gesellschaft sowie am 11. 6. 59 in der CIBA AG., Basel, vom Seniorautor gehaltenen Vortrages.     

Antidepressant drugs elevate rat pineal and plasma melatonin

Summary Acute administration in the mid-light phase of a number of antidepressant drugs of different pharmacological profiles elevated pineal and plasma melatonin (measured by radioimmunoassay). Following chronic treatment with the tricyclic antidepressant clomipramine, the elevation was significantly reduced. This may be an effect of reduced -adrenergic receptor sensitivity after chronic clomipramine administration, analogous to other findings of reduced -adrenergic receptor binding and reduced noradrenaline-sensitive adenylate-cyclase response.These collaborative studies were made possible by a Twinning Grant from the European Training Programme for Brain and Behaviour Research; J.A. was supported by the Medical Research Council of Great Britain. We thank M. Lichtsteiner for excellent technical assistance. This paper was written during a Fellowship of the Swiss Biomedical Research Foundation to A.W.-J. Hofmann-LaRoche AG, Basel kindly provided the 1-5HTP-ester (Ro 11-5940) and Ro 11-2465, CIBA-Geigy AG, Basel, the maprotiline, clomipramine, and imipramine, USV, New York, the desmethylimipramine.     

Yeast as a sensor of factors affecting the accuracy of protein synthesis

The cell monitors and maintains the fidelity of translation during the three stages of protein synthesis: initiation, elongation and termination. Errors can arise by multiple mechanisms, such as altered start site selection, reading frame shifts, misincorporation or nonsense codon suppression. All of these events produce incorrect protein products. Translational accuracy is affected by both cis- and trans-acting elements that insure the proper peptide is synthesized by the protein synthetic machinery. Many cellular components are involved in the accuracy of translation, including RNAs (transfer RNAs, messenger RNAs and ribosomal RNAs) and proteins (ribosomal proteins and translation factors). The yeast Saccharomyces cerevisiae has proven an ideal system to study translational fidelity by integrating genetic approaches with biochemical analysis. This review focuses on the ways studies in yeast have contributed to our understanding of the roles translation factors and the ribosome play in assuring the accuracy of protein synthesis.Received 27 November 2002; received after revision 16 April 2003; accepted 25 April 2003     

ERK activation by Ca2+ ionophores depends on Ca2+ entry in lymphocytes but not in platelets, and does not conduct membrane scrambling

Rapid Ca²⁺-dependent phospholipid (PL) reorganization (scrambling) at the plasma membrane is a mechanism common to hematopoietic cells exposing procoagulant phosphatidylserine (PS). The aim of this research was to determine whether activation of the extracellular signal-regulated kinase (ERK) pathway was required for PL scrambling, based on a single report analyzing both responses induced by Ca²⁺ ionophores in megakaryoblastic HEL cells. Ca²⁺ ionophore-stimulated ERK phosphorylation was induced in platelets without external Ca²⁺, whereas exogenous Ca²⁺ entry was crucial for ERK activation in Jurkat T cells. In both cells, membrane scrambling only occurred following Ca²⁺ entry and was not blocked by inhibiting ERK phosphorylation. Furthermore, ERK proteins are strongly phosphorylated in transformed B lymphoblastic cell lines, which do not expose PS in their resting state. Overall, the data demonstrated that ERK activation and membrane scrambling are independent mechanisms. A. Arachiche, I. Badirou: These authors contributed equally to this work. Received 18 June 2008; received after revision 24 September 2008; accepted 1 October 2008     

Synthese von Solanidin aus Demissidin

Summary The steroidal alkaloid solanidine (solanid-5-ene-3-ol, II) which occurs in the potato plantSolanum tuberosum L. has been synthesized from demissidine (5-solanidane-3-ol, I), an alkaloid from the Mexican wild potatoSolanum demissum Lindl. The synthesis involves the following steps: 5-solanidane-3-one, 2,4-dibromo-5-solanidane-3-one, solanid-4-ene-3-one, 3-acetoxy-solanida-3,5-diene, and solanidine (II).

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Solanum-Alkaloide. XVII. Mitteilung. — XVI. Mitteilung:K. Schreiber undG. Adam, Exper.17, 490 (1961).     

Triacylglycerol hydrolase: role in intracellular lipid metabolism

Recent scientific advances have revealed the identity of several enzymes involved in the synthesis, storage and catabolism of intracellular neutral lipid storage droplets. An enzyme that hydrolyzes stored triacylglycerol (TG), triacylglycerol hydrolase (TGH), was purified from porcine, human and murine liver microsomes. In rodents, TGH is highly expressed in liver as well as heart, kidney, small intestine and adipose tissues, while in humans TGH is mainly expressed in the liver, adipose and small intestine. TGH localizes to the endoplasmic reticulum and lipid droplets. The TGH genes are located within a cluster of carboxylesterase genes on human and mouse chromosomes 16 and 8, respectively. TGH hydrolyzes stored TG, and in the liver, the lipolytic products are made available for VLDL-TG synthesis. Inhibition of TGH activity also inhibits TG and apolipoprotein B secretion by primary hepatocytes. A role for TGH in basal TG lipolysis in adipocytes has been proposed. TGH expression and activity is both developmentally and hormonally regulated. A model for the function of TGH is presented and discussed with respect to tissue specific functions.     

铁银共掺杂TiO2纳米材料的制备及性能

本文采用溶胶一凝胶法制备了Fe^3＋、Ag单掺杂以及Fe^3＋Ag共掺杂的TiO2复合材料,采用XRD、SEM研究分析了样品晶体的结构变化和形貌。以甲基橙为光催化反应模型化合物,考察了掺杂对光催化活性的影响。无论是单掺杂还是共掺杂,掺杂后效果明显提高,性能均优于纯TiO2,特别是共掺杂效果更为明显。根据最后试验共掺杂的最佳比例Fe^3＋0．1％、Ag0．7％,确定了共掺杂降解环境的最佳pH值。     

Ethanol and opioid receptor signalling

Summary Ethanol may modulate endogenous opioid systems by disrupting opioid receptor signalling. Low concentrations of ethanol slightly potentiate -opioid receptor binding by increasing receptor B_max, and, in some cases, chronic ethanol exposure decreases the density or affinity of the -opioid receptors. By contrast, high concentrations of ethanol acutely decrease -opioid receptor binding by decreasing receptor affinity, whereas chronic exposure of animals and neuronal cell lines to lower concentrations of ethanol leads to possibly adaptive increases in the density or affinity of the -opioid receptors. In the neuronal cell line NG108-15, ethanol does not up-regulate the -opioid receptor by blocking receptor degradation or endocytosis, but protein synthesis is required for this response. Up-regulation of the -opioid receptor renders ethanol-treated NG108-15 cells 3.5-fold more sensitive to opioid inhibition of adenylyl cyclase. Long-term treatment with ethanol also increases maximal opioid inhibition in NG108-15 cells, possibly by decreasing levels of G_s and its mRNA. Ethanol differentially modulates signal transduction proteins in three additional neuronal cell lines, N18TG2, N4TG1, and N1E-115. Ethanol-treated N18TG2 cells show the least up-regulation of the -opioid receptor, little heterologous desensitization of adenylyl cyclase, and no changes in G_s or G_i. By contrast, ethanol-treated N1E-115 cells show the largest up-regulation of the -opioid receptor, the most heterologous desensitization of adenylyl cyclase, and concentration-dependent decreases in G_s and increases in G_i. Further analysis of these related neuronal cell lines may help to identify the molecular elements that endow some, but not all, neuronal cells with the capacity to adapt to ethanol.     

Action of ACTH,cAMP and cytochalasin B on steroid production by Y-1 mouse adrenal tumor cells in culture

Summary Continued incubation of Y-1 mouse adrenal tumor cells with adrenocorticotrophic hormone (ACTH) or with dibutyryl-3,5-cyclic adenosine monophosphate (dbcAMP) resulted in an initial increase and a subsequent decrease in steroidogenesis. ACTH-or dbcAMP-stimulated steroidogenesis was inhibited by cytochalasin B (CB) to approximately the same extent during the entire period of incubation; CB inhibition of the ACTH response was reversible.Supported in part by NTSU Faculty Research grant No. 34711, and NIA No. AG01055-02A1.Acknowledgment is made for the assistance of L. Hershberger, J. Youngblood and V. Dang; K. Mrotek, K. Johansson and M. Donahue were editors.     

Effects of isoxazolyl-naphthoquinoneimines on growth and oxygen radical production inTrypanosoma cruzi andCrithidia fasciculata

Several 4-(aminomethylisoxazolyl)-1,2-naphthoquinones inhibited growth and DNA synthesis inTrypanosoma cruzi and stimulated O₂ uptake and generation by the parasite epimastigotes and their mitochondrial and microsomal membranes; these results support the idea that oxygen radicals play a role in quinone toxicity. Maximal effects on respiration and generation were observed with antimycin-inhibited cells. Similar results as well as stimulation of H₂O₂ production were obtained withCrithidia fasciculata despite the presence of catalase in this organism.Acknowledgments. This work was aided by grants from the University of Buenos Aires, the Scientific Office of the American States Organization and CEDIQUIFA (Buenos Aires). S.G.G. and M.P.M.P. are Research Fellows and A.O.M.S. is Career Investigator of CONICET (Argentina). L. T. Viñas and M. G. Gutierrez lent able technical assistance.     

Evidence of major role of the intestine in cholesterol synthesis in the adult male rat.

By an new in vivo method using 1-14-C-acetate, it becomes apparent that the intestine is the main organ concerned in cholesterol synthesis. The liver contributes a mere 13.5% to the total. These results challenge the traditional theory which considers the liver as responsible for producing most of cholesterol synthesized by the rat.     

Un nouveau système polymorphe robertsonien chez une nouvelle espèce de «Leggada» (Mus goundae Petter)

Summary A sample of 6 Leggada from N'Délé (Central African Republic) morphologically different from all these studied up to now, constitue a new species, which will be described by Dr F.Petter asMus goundae Petter. The caryological analysis reveals a new robertsonian polymorphical system. The diploïd numbers are 2N=16, 17, 18 or 19, whereas theN.F. is constant and equal to 30. The 3 first pairs of autosomes, constituted by SM or MC elements are identical in the 4 types, as well as pairs V (MC) and VI (AC) morphologically constant by all individuals. The robertsonian mechanisms, from which polymorphism originates, take place at pairs IV, VII and VIII. The fourth pair, while heterozygote by 2N=19, assembling one MC and two AC elements, is homozygote and MC by 2N=18, 17 and 16; pairs VII and VIII are both constituted by two AC in the cases of 19 and 18 chromosomes; to form caryotypes with 17 and 16 chromosomes these 2 pairs will fusion: by 2N=17 the mutation is heterozygote (1 MC and 2 AC) and it becomes homozygote by 2N=16 giving birth to 2 MC. The sexual chromosomes are from TR Type (X MC andY SM).From these observations arises the problem of low chromosome numbers (16–20) which shall be discussed in a further publication.     

Synthesis of L-[3-2H,18O]glycerol and its incorporation into the 4-methyl-5-hydroxyethyl thiazole moiety of thiamine byEscherichia coli

Summary L-[3-²H,¹⁸O]glycerol was prepared and fed toEscherichia coli in order to determine the origin of the oxygen atom in the biosynthesized thiazole moiety of thiamine. Measurement by GC-MS of the isotope incorporation into the thiazole from this substrate confirmed that the 2 hydrogens and the oxygen on the C-3 carbon of glycerol are incorporated directly into the thiazole.     

Rauwolfia alkaloids XXI. The stereochemistry of reserpine and deserpidine

Zusammenfassung Für Reserpin und Deserpidin wird eine neue stereochemische Formulierung vorgeschlagen, die auf folgenden experimentellen Befunden beruht:1. Reserpin- und Deserpidinderivate epimerisieren als 3-Epialloverbindungen vollständig zu den entsprechenden Isoverbindungen. Im Gegensatz dazu epimerisieren einfachere 3-Epialloyohimbane (ohne Substituenten in 16, 17 und 18-Stellung) zu einer Mischung von normaler und iso-Verbindung. Beide Isomere scheinen in diesem Fall ungefähr gleiche Stabilität zu besitzen.2. Im Gegensatz zu Reserpsäure bildet iso-Reserpsäure kein Lakton.3. Interpretation der Drehungswerte deutet darauf hin, dass das H-Atom in Stellung 3 und die Substituenten in Stellung 16 und 18-Orientierung besitzen.     

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.