Influence of cyproterone acetate on the activity ofβ-glucuronidase in the hypothalamus and cerebral cortex of the male mouse

Summary Daily s.c. injections of cyproterone acetate greatly decrease the protein content and-glucuronidase activity in the mouse hypothalamus. These effects are reversible and the recovery capacity of the animal seems to be inversely related to the duration of antiandrogenic treatment.Financial aid was given by CNR (finalized project Biologia della Riproduzione) and Ministry of Education. Thanks are also due to Prof. G. Chieffi for suggestions and to Mr R. Auriemma for maintenance of experimental animals.     

Studies on the late-pre-β-lipoprotein of human serum

Summary Very low density lipoprotein (VLDL) isolated from 3 healthy normolipidaemic subjects had a raised VLDL cholesterol to triglyceride ratio. The VLDL fractions gave 2 pre--bands on agarose gel electrophoresis. Family study of the subjects appears to indicate sex linkage of this trait and a possible polygenic type of inheritance.Acknowledgment. This investigation was supported by a grant from University of Nigeria, Nsukka. I am grateful to Prof. Barry Lewis, St. Thomas Hospital Medical School, London, for his advice.     

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.     

The influence of N-methyl-N-β-chloroethyl hydrazines on the mitotic index of Ehrlich ascites tumor cells and the leukopoiesis of the mouse

Summary The cytostatic activity of N-methyl-N--chloroethylbenzaldehyd hydrazone, (B1) is at least equal to that of procarbazine when its effect is tested with the Ehrlich ascites tumor cells of the mouse and the Yoshida sarcoma of the rat. B1 causes a slighter decrease of mitotic cells and no shift from prophase to metaphase. These results suggest that the cytostatic effect of B1 is due to interference with cell metabolism or an effect at the cell membrane and not to an effect on cell proliferation. This assumption is supported by a considerable depression, of lymphocytes and a minor effect on granulopoiesis, which is especially sensitive towards proliferation toxins. All these findings suggest a different mechanism of action of B1 and procarbazine.     

Characterization of 17β-estradiol 3-(β-D-glucopyranoside) and 17-(α-D-glucopyranoside) as the metabolites of 17β-estradiol in the cultured ovaries of the silkworm,Bombyx mori

Summary The structures of the metabolites formed upon incubation of 17-estradiol with the ovaries of silkworm,Bombyx mori, have been determined as 17-estradiol 3-(-D-glucopyranoside) (1) and 17-(-D-glucopyranoside) (2) by spectroscopic means.     

On the mineralocorticoid and hypertensogenic properties of 16β-Hydroxy-Dehydroepiandrosterone

Summary Dosages of either 1 or 2 mg daily of 16-hydroxy-dehydroepiandrosterone, given to mononephretomized, salt-loaded female rats, had no detectable effect upon saline consumption, blood pressure, kallikrein excretion or heart and kidney weight. Its alleged mineralocorticoid properties, as judged by these criteria, were not demonstrable.This study was supported by a grant No. HL 15319 from the United States Public Health Service.     

Periodic acid oxidation of the steroid 11β-hydroxyl group

Zusammenfassung Die 11-Hydroxylgruppe im Steroidmolekül kann selektiv mit Perjodsäure oxydiert werden. Ihre Oxydationsgeschwindigkeit wurde von der Gegenwart substituierender Gruppen im Molekül beeinflusst.     

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.     

Isotrinervi-2β-ol. Structural isomers in the defense secretions of allopatric populations of the termiteTrinervitermes gratiosus

Summary The defense secretions of 3 allopatric populations of the nasute termiteTrinervitermes gratiosus were analyzed. One population afforded a new trinervitene, isotrinervi-2-ol, a missing link in the hypothetical biosynthesis of the trinervitenes. Populations could be readily distinguished on the basis of the chromatographic profiles of their major and minor soldier frontal gland secretions.These studies were initiated (1975–76) with partial financial support by the International Centre of Insect Physiology and Ecology, Nairobi, Kenya and NIH Postdoctoral Fellowship AI-05076. Support by the Department of Chemistry of the State University of New York at Stony Brook and the technical assistance of Mr J. Engstrom allowed completion of this investigation.     

Role of Cys221 and Asn116 in the zinc-binding sites of the Aeromonas hydrophila metallo-β-lactamase

The CphA metallo--lactamase produced by Aeromonas hydrophila exhibits two zinc-binding sites. Maximum activity is obtained upon binding of one zinc ion, whereas binding of the second zinc ion results in a drastic decrease in the hydrolytic activity. In this study, we analyzed the role of Asn116 and Cys221, two residues of the active site. These residues were replaced by site-directed mutagenesis and the different mutants were characterized. The C221S and C221A mutants were seriously impaired in their ability to bind the first, catalytic zinc ion and were nearly completely inactive, indicating a major role for Cys221 in the binding of the catalytic metal ion. By contrast, the binding of the second zinc ion was only slightly affected, at least for the C221S mutant. Mutation of Asn116 did not lead to a drastic decrease in the hydrolytic activity, indicating that this residue does not play a key role in the catalytic mechanism. However, the substitution of Asn116 by a Cys or His residue resulted in an approximately fivefold increase in the affinity for the second, inhibitory zinc ion. Together, these data suggested that the first zinc ion is located in the binding site involving the Cys221 and that the second zinc ion binds in the binding site involving Asn116 and, presumably, His118 and His196.Received 3 March 2003; received after revision 4 August 2003; accepted 25 August 2003     

Heterologous immunoadsorption in the purification of enzymes: N-acetyl-β-glucosaminidase

Summary An immunoadsorbent column was prepared using a specific antibody toN-acetyl--glucosaminidase of human origin. Although no precipitating activity of the antisera was found with mouse or rat liver extracts, enzyme was easily eluted from the column which provided about 50fold, single-step purifications of these heterologous enzymes.     

Molecular function of the novel α7β2 nicotinic receptor

The α7 nicotinic receptor is a promising drug target for neurological and inflammatory disorders. Although it is the homomeric member of the family, a novel α7β2 heteromeric receptor has been discovered. To decipher the functional contribution of the β2 subunit, we generated heteromeric receptors with fixed stoichiometry by two different approaches comprising concatenated and unlinked subunits. Receptors containing up to three β2 subunits are functional. As the number of β2 subunits increases in the pentameric arrangement, the durations of channel openings and activation episodes increase progressively probably due to decreased desensitization. The prolonged activation episodes conform the kinetic signature of α7β2 and may have an impact on neuronal excitability. For activation of α7β2 receptors, an α7/α7 binding-site interface is required, thus indicating that the three β2 subunits are located consecutively in the pentameric arrangement. α7-positive allosteric modulators (PAMs) are emerging as novel therapeutic drugs. The presence of β2 in the pentamer affects neither type II PAM potentiation nor activation by an allosteric agonist whereas it impairs type I PAM potentiation. This first single-channel study provides fundamental basis required to decipher the role and function of the novel α7β2 receptor and opens doors to develop selective therapeutic drugs.     

Butyrate-induced reactivation of the fetal globin genes: A molecular treatment for theβ-hemoglobinophaties

The inherited -hemoglobinopathies (sickle cell disease and thalassemia) are the result of a mutation in the adult () globin gene. The fetal globin chain, encoded by the globin genes, can substitute for the mutated or defective globin chain, but expression of the globin gene is developmentally inactivated prior to birth. Reinducing expression of the normal fetal globin genes is a preferred method of ameliorating sickle cell disease and the thalassemias. Stimulation of as little as 4–8% fetal globin synthesis in the bone marrow can produce >20% fetal hemoglobin in the peripheral circulation, due to enhanced survival of red blood cells containing both sickle and fetal hemoglobin, compared to those containing sickle hemoglobin alone. Butyric acid and butyrate derivatives are generally safe compounds which induce fetal hemoglobin production by stimulating the promoter of the fetal globin genes. An initial trial with the parent compound, delivered as Arginine Butyrate, has demonstrated rapid stimulation of fetal globin expression to levels that have been shown to ameliorate these conditions. Phase 1 trials of an oral butyrate derivative with a long plasma half-life have just begun. These agents now provide a specific new apporach for ameliorating these classic molecular disorders and merit further investigation in larger patient populations.     

Autoradiographic localization of the uptake of3H-β-alanine in rat nervous tissue cultures

Summary Autoradiographic studies on the uptake of³H--alanine have shown that, in spinal cord and brain stem cultures, both neurones and glial cells have accumulated the amino acid. In contrast, in cultures of cerebellum and dorsal root ganglia,³H--alanine was only taken up by glial elements.     

Histochemistry of steroid-3β-ol dehydrogenase in the human adrenal cortex

Zusammenfassung Bericht über histochemische Untersuchungen an menschlichen Nebennieren, die chirurgisch bei Fällen von inoperablem Mammacarcinom (mit oder ohne vorhergehende Stimulation mit exogenen ACTH) sowie bei Fällen von Cushingscher Krankheit entfernt worden waren.Anhand der Verteilung der verschiedenen Enzyme und insbesondere des Steroid-3-ol Dehydrogenase wird auf Fragen der Beziehungen der Morphologie und Funktion der normalen Drüse eingegangen und die Cushingsche Krankheit interpretiert.     

Metabolism in porifera VI. Role of the 5,6 double bond and the fate of the C-4 of cholesterol during the conversion into 3β-hydroxymethyl-A-nor-5α-steranes in the spongeAxinella verrucosa

Summary During the conversion of cholesterol into 3 -hydroxymethyl-A-nor-5-cholestane by the spongeAxinella verrucosa, the carbon-3 of this latter originate from carbon-4 of cholesterol. Cholestanol moreover does not seem an intermediate in this conversion.     

In situ demonstration of the activity of 3β-hydroxysteroid dehydrogenase on steroid hormone secreting cells within the paraaortic lymph nodes of golden hamster

Summary The in situ activity of 3-hydroxysteroid dehydrogenase was detected in clustered cells which showed steroid-producing morphology, within the capsule of the paraaortic lymph node. In light and electron microscopic studies, the positive reaction products were detected on intracapsular cell clusters. This result indicates that these unique cells may have a steroid secreting function within the lymph nodes.     

β-Methyl carboline,a benzodiazepine inverse agonist,attenuates the effect of triazolam on the circadian rhythm of locomotor activity

Summary The benzodiazepine triazolam, the benzodiazepine inverse agonist, -methyl carboline (-CCM) or both, were administered to adult male hamsters under conditions of constant light. When given alone, triazolam induced phase advances in the circadian activity rhythm of about 90 min, while -CCM when given alone, had no effect on phase of the activity rhythm. However, when triazolam and -CCM were given at the same time, the magnitude of the phase advances induced by triazolam were attenuated to about 30 min. These data, in conjunction with previous results, provide pharmacological evidence for a GABAergic system involved in the regulation of a central circadian pacemaker.