Storage of irradiated human blood; a source of error in quantitative chromosome analysis

Summary Human whole blood was irradiated with 2.5 Gy of 220 kVp X-rays and stored before culture with 9.7 M BrdU and 19.4 or 38.7 M BrdU for 0, 24, 48 and 72 h. The frequency of dicentrics and ring chromosomes was determined in cells staining as first division (M1) metaphases with the fluorescence plus Giemsa technique. Storage had no influence on the observed aberration yields in 44 h cultures containing 9.7 M BrdU. In 66 h cultures at 19.4 M BrdU the observed yields after 2 and 3 days' storage were significantly lower as compared to cultures from fresh blood. No storage effect was revealed in 66 h cultures containing 38.7 M BrdU. In cases where cytogenetic radiation dosimetry has to be carried out using blood samples which have been in transit for 2–3 days, the findings are of relevance for a correct determination of the chromosome damage in M1 cells.     

Bromocriptine-induced removal of endoplasmic membranes from prolactinoma cells

Summary Adenomatous prolactin cells lose 39% of their cytoplasm volume within 7 days after the beginning of bromocriptine treatment. A simultaneous reduction of the rough-surfaced endoplasmic reticulum and the Golgi apparatus occurs. Their membranes are removed by rapid transport along the secretory pathway to the cell surface and to lysosomal destruction.We thank Prof. E. del Pozo, Sandoz Ltd, Basle, for the generous gift of injectable bromocriptine, Prof. E.R. Weibel, Dept. of Anatomy, University of Bern, for his technical advice, Dr U. Helfenstein, Institute of Biostatistics, University of Zürich, for his help in the statistical evaluation of the results and the EMDO-Foundation, Zürich, for financial support.     

In vitro amiodarone protein binding and its interaction with warfarin

Summary The binding of amiodarone to human plasma protein and to bovine serum, albumin was studied by three different methods, ultracentrifugation, equilibrium dialysis and fluorescence spectroscopy. The fraction of amiodarone bound to plasma protein amounted to 96.3%. The changes in the binding properties of 1-anilino-naphthalene-8-sulfonate for bovine serum albumin using warfarin and amiodarone as independent inhibitors were analyzed in terms of binding site specificity. The findings indicated that amiodarone and warfarin have two different binding sites on bovine serum albumin, so a noncompetitive inhibition mechanism was indicated. On the basis of our data we cannot exclude other mechanisms of interaction besides direct displacement of one drug by another; nevertheless, metabolite interference between amiodarone and coagulation cofactors may better explain the enhancement of warfarin's pharmacological action in association with amiodarone.This work was partially funded by the CNR (National Research Council, Rome, Italy), Program on Clinical Pharmacology and Rare Diseases. The authors would like to thanks Drs E. Marzi and E. riva for their help.     

Studies on some enzymes of the toad (Bufo melanostictus) testis and their probable role at the time of fertilization

Summary Glycosidases like sialidase,-galactosidase, -L-fucosidase, N-acetyl hexosaminidase and proteases were detected in toad testis. Neuraminic acid aldolase activity was also detected. The enzyme activities were found to vary as production of spermatozoa varied. All enzymes, except N-acetyl glucosaminidase, were shown to decrease after injection of toad pituitary extract and they were also found to be absent from testis containing no spermatozoa. The glycosidases were found to act on toad oviduct jelly and they may therefore be involved in the degradation of the jelly after fertilization, into smaller bits, which may be utilized as nutrients by the fertilized zygote.Acknowledgment. We thank Prof. T.R. Ramaiah, Head of the Department of Biochemistry, University of Mysore, for his help. We also acknowledge the financial assistance of University Grants Commission to one of us (MS) and CSIR through a grant No. 9 (165)83/EMR-II to HSS. Please address all correspondence to H.S. Seshadri.     

Antidiuretic effects of oxytocin in the Brattleboro rat

Summary The antidiuretic activity of oxytocin (OT) was measured in Brattleboro rats with congenital diabetes insipidus. A dose dependent antidiuretic response was found in animals receiving chronic infusions of 0.1 g/h, 1.0 g/h, and 5 g/h of OT. OT infused at the rate of 5 g/h over a 7-day period completely reversed the symptoms of diabetes insipidus. The results support the concept that OT serves as a weak agonist of vasopressin at the level of the kidney and at pharmacological levels exhibits antidiuretic activity.     

Selective protection of cells against X-irradiation. Isoproterenol protects only those cells that possesβ-adrenoreceptors

Summary In mixed culture of Chinese hamster fibroblatst, clone 431, and transformed murine L fibroblasts, clone B-82, isoproterenol was found to protect only 431 cells against ionizing radiation. It was shown that 431 cells, in contrast to B-82 cells, possess-adrenoreceptors, and the radioprotective effect of isoproterenol can be realized only if this agent interacts with-adrenoreceptors coupled with the cAMP system. Since malignization often causes the disappearance of-adrenergic and other hormone receptors, the combined culturing and irradiation of the cells studied can be regarded as a model of the growth of malignant cells (B-82) among normal tissue cells (431 cells) under conditions of radiation therapy. A possibility of selective protection against radiation damage of normal tissue cells, with retention of the former radiosensitivity of tumor cells, is discussed.     

In vitro mutagenicity testing of a potent,new, benzoyl urea insect growth regulator

Summary Bacterial mutagenicity assay to detect potential chronic toxicity of a potent, new, benzoyl urea insect growth regulator (CGA-112913 or IKI-7899, formerly UC-62644) was conducted using 5 histidine auxotrophs ofSalmonella typhimurium. Tests within the concentration range of 0.9–500 g (saturating)/plate of the compound with and without the 5–9 mammalian metabolic activation system showed no mutagenic effects clearing the way for long-term chronic toxicology studies.The authors thank Professor Bruce N. Ames for supplying the tester strains together with all the relevant information for conducting the bioassays and Ms. Norma Charlebois for her meticulous technical assistance.     

Adrenocortical metabolism and plasma corticosterone in soman intoxicated rabbits

Summary The organophosphate neurotoxin soman produced impairments in adrenocortical RNA and protein metabolism. Fasciculate and reticular cell RNA and protein contents were supporessed with sublethal to acutely lethal dosages (20, 30 and 40 g/kg, s.c.) during the acute excitatory phase of intoxication and at 6–8 h post injection. All three dosages produced ca 90% inactivation of plasma cholinesterase. A transient elevation of plasma corticosterone occurred with 20 g/kg soman whereas there was a protracted increase with 30 g/kg. Corticosterone was not significantly elevated with 40 g/kg, but death occurred at 13±4 min. Thus, the magnitude and/or nature of soman-induced metabolic impairments does not appear to prevent adrenal activation.Supported by US Army Medical Research and Development Command Contract DAMD 17-81-C-1202.     

A new semisynthetic ergot peptide alkaloid: DCN 203-922

Summary We report the synthesis, stereochemistry and preliminary pharmacological evaluation of DCN 203-922, a novel ergot alkaloid of the cyclol type, which contains in its peptide moiety the uncommon amino acid L-allo-isoleucine.Part of this paper was reported by this author at the Herbstversammlung der Schweizerischen Chemischen Gesellschaft, Bern, in October 1986.