Completion of the natural groups of ergot alkaloids: Syntheses and pharmacological profiles ofβ-ergosine andβ-ergoptine

Summary The syntheses and pharmacological potencies of -ergosine and -ergoptine, the missing links in the natural groups of ergot peptide alkaloids are described.86th communication on ergot alkaloids.     

Effects of injury on the concentration ofα 1 andα 2 in the plasmas of male and female rats

Summary The effects of injury on the concentration of ₁-macroglobulin and ₂-macroglobulin in the plasmas of male and female rats has been investigated. At 5 days after injury to the male rats the ₁-macroglobulin concentration increased to 131% of its preinjury value. The ₂-macroglobulin concentration increased more rapidly to a maximum of 86 times its initial value. In the female rats ₂-macroglobulin increased only slightly and ₁-macroglobulin not at all.     

Physiological and pathological properties of α-synuclein

alpha-Synuclein belongs to a small group of natively unfolded proteins that can transiently bind to lipid membranes and acquire a partial alpha-helical conformation. Under certain pathogenic conditions, alpha-synuclein aggregates to form oligomers and insoluble fibrils with increased ss-sheet configuration. Although genetic mutations and multiplications of the gene have been found in familial cases, the mechanism by which this protein aggregates in sporadic cases of Parkinson's disease, dementia with Lewy bodies and multisystem atrophy is not fully understood. Here we review the function of alpha-synuclein and recent insight into the mechanisms by which it aggregates.     

Lagrange’s theory of analytical functions and his ideal of purity of method

We reconstruct essential features of Lagrange’s theory of analytical functions by exhibiting its structure and basic assumptions, as well as its main shortcomings. We explain Lagrange’s notions of function and algebraic quantity, and we concentrate on power-series expansions, on the algorithm for derivative functions, and the remainder theorem—especially on the role this theorem has in solving geometric and mechanical problems. We thus aim to provide a better understanding of Enlightenment mathematics and to show that the foundations of mathematics did not, for Lagrange, concern the solidity of its ultimate bases, but rather purity of method—the generality and internal organization of the discipline.     

α-andβ-activity of O-methylated derivatives of norepinephrine and epinephrine

Summary Metanephrine, iso-metanephrine, normetanephrine and isonormetanephrine were tested for - and -activity on various tissues obtained from rats, guinea-pigs and cats. It was found that methylation of the hydroxyl groups of norepinephrine or epinephrine in either the 3-or 4-position markedly reduces or abolishes -and -activity with the exception of the nictitating membrane of the cat. This receptor seems to show a tissue difference.Acknowledgment. W. H. V. would like to thank the Federal Republik of Germany for the U. S. Senior Scientist Award which enabled him to work at the Department of Pharmacology, University of Mainz, and to conduct part of this work. W. H. V. would also like to thank Prof. Dr E. Muscholl, Mainz, for his hospitality, help and advice during this stay.     

The effects of γ-aminobutyric acid and picrotoxin on the junctional potential and the contraction of crayfish muscle

Résumé L'acide-amino-butyrique et la-alanine reproduisent l'action du transmetteur inhibiteur du système neuromusculaire de l'écrevisse. Ces deux acids aminés diminuent la contraction musculaire. L'acide-amino-butyrique réduit la différence de potentiel et augmente sa décomposition. L'action de ces acides aminés est bloquée par la picrotoxine comme l'est celle du transmetteur inhibiteur.

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The study was supported by Grants B-1089 and B-31 from the National Institute of Neurological Diseases and Blindness, United States Public Health Service. Some of this work was done at the Department of Zoology, Cornell University. We are grateful to Prof.S. C. Wang, Columbia University, for generous assistance.     

The oxidative metabolism ofα-chlorohydrin and the chemical induction of spermatocoeles

Summary -Chlorohydrin (I) is oxidatively metabolized to -chlorolactic acid (III) and oxalic acid (IV). Deposition of calcium oxalate within the renal tubules is responsible for the toxic effects of-chlorohydrin and a similar action on the epididymis or epididymal blood vessels could initiate the formation of spermatocoeles from this and other male antifertility agents.     

The steric course of hydrogenation of Δ4 and Δ5 steroids

Zusammenfassung Bei der katalytischen Hydrierung von Steroiden mit Doppelbindung in 4-Stellung entstehen überwiegend A/B-cis-Verbindungen, während Doppelbindung in 5 vor allem A/B-trans liefert. Dieser Unterschied wird mit Hilfe der Konstellationsanalyse erklärt: die als Zwischenformen angenommenen Komplexe aus Substrat, Wasserstoff und Katalysator weisen unterschiedliche sterische Hinderung auf.

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Based in part on a portion of the Ph. D. Thesis of the author, University of Wisconsin, 1951.     

An immunohistochemical and ultrastructural comparison of the effects of 2-bromo-α-ergocryptine on intrasellar and transplanted rat pituitaries

Summary Following 2 weeks of administration of 2-bromo--ergocryptine, a marked decrease was observed in prolactin immunoreactivity of the grafted pituitaries, whereas no reduction was noted in the intrasellar pituitaries. No evidence of crinophagy was revealed by electron microscopy in prolactin cells of 2-bromo--ergocryptine-treated rats.Acknowledgments. This work was supported in part by the Medical Research Council of Canada (grant MA-6349). The excellent technical assistance of Mrs Cynthia Edwards and secretarial help of Mrs Wanda Wlodarski are gratefully acknowledged.     

The effects of 9α-halohydrocortisones and of aldosterone on survival,growth and sodium-potassium excretion in adrenalectomized rats

Zusammenfassung Die Wirkungen von Aldosteron und 9-Halogenhydrocortison-azetaten auf das Überleben und Wachstum adrenalektomierter Ratten wurden studiert. Im Na/K-Ausscheidungstest zeigten sich 9-Chlor-hydrocortison-azetat bzw. 9-Fluor-hydrocortison-azetat 35-bzw. 10mal wirksamer als DCA und wiesen 1/3 bzw. 1/10 der Wirksamkeit von Aldosteron auf.     

Aluminum-triggered structural modifications and aggregation of β-amyloids

We investigated the structural effects induced by Al³⁺ on different β-amyloid (Aβ) fragments at pH 7.4 and T= 25°C, with particular attention given to the sequences 1–40 and 1–42. Al³⁺ caused peptide enrichment in β sheet structure and formation of solvent-exposed hydrophobic clusters. These intermediates evolved to polymeric aggregates which organized in fibrillar forms in the case of the Al³⁺-Aβ_(1–42) complex. Comparative studies showed that Zn²⁺ and Cu²⁺ were much less efficient than Al³⁺ in stimulating the spontaneous aggregation/fibrillogenesis of Aβs. Studies with liposomes as membrane models showed dramatic changes in the structural properties of the lipid bilayer in the presence of Al³⁺-Aβ complexes, suggesting a major role of Al³⁺ in Aβ-induced cell dysfunction. Al³⁺ effects were abolished by desferrioxamine mesylate (DFO) only in solution. We concluded that, in vivo, DFO may act as a protective agent by preventing or reverting Aβ aggregation in the extracellular spaces.Received 29 March 2005; received after revision 10 May 2005; accepted 25 May 2005     

The application of Hudson's lactone rule toγ- andδ-hydroxyamino acids and the question of the configuration ofδ-hydroxy-l-lysine from collagen

Zusammenfassung Die Anwendung von Hudsons Lakton-Regel auf eine Reihe von Laktonen von- und-Oxyaminosäuren bestätigte die unabhängig auf chemischem Wege bewiesenen Konfigurationen an den- und-Kohlenstoffatomen. Im Falle des erstmalig dargestellten Laktons des,-Dibenzoyl--hydroxy-d-lysins führte die Anwendung der Regel zurerythro-Struktur XV, und folglich für natürliches-Oxylysin aus Collagen zur Formel XIa, deren Beweis auf chemischem Wege noch aussteht.     

Synthesis and some pharmacological properties of α-methyltryptamine and its 5-methoxy derivative

Résumé L'-méthyltryptamine et le 5-méthoxy dérivé ont été synthétisés en utilisant une variante de la méthode d'Abramovitch etShapiro.Des expériencesin vitro ont montré que ces deux amines ne subissent pas de désamination par la monoaminoxydase du cerveau des rats blancs. La 5-méthoxy--methyltryptamine injectée aux souris blanches en dose de 10 mg/kg semble accroître l'activité de la monoaminoxydase du cerveau.     

Occurrence of ‘partially acid-fast’ cells in cultures of genusStaphylococcus and genusMicrococcus

Résumé Lorsqu'on applique aux populations des genresStaphylococcus etMicrococcus une coloration semblable à celle deMachiavello, on obtient des cellules différemment colorées.Ce caractère « partiellement acido-résistant » diffère du caractère tinctorial de l'acido-résistance vraie.

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These studies were done with the aid of the Medical Research Council of Canada. Grant MA-729, 1962.     

Comparison of the effects of lithium,β-phenylethylamine and tyrosine onXenopus embryos

Résumé On a étudié les effets du lithium, de la -phényléthylamine et de la tyrosine sur le développement embryonnaire deXenopus laevis. La tyrosine n'a pas d'effet, mais le lithium ou la -phényléthylamine ont végétalisé les embryons s'ils ont été exposés avant le stade blastula.