Effect of prostaglandins on skin tumorigenesis

Summary Concomitant administration of prostaglandins E₂ (PGE₂) and F₂ a(PGF₂ a) with a carcinogen, 3-methylcholanthrene (MCA) to mice for 2 months markedly enhanced the occurrence of squamous cell carcinomas. Only epidermal cell hyperplasia occurred in mice treated with MCA alone by that time. Radioactivity measurements and electron microscopic autoradiography revealed that prostaglandins stimulate DNA, RNA and protein synthesis in neoplastic cells. These findings indicate that PGE₂ and PGF₂ a can act as cocarcinogens on skin tumorigenesis.     

Erythropoietic effects of PGE2 and 2 endoperoxide analogs

Summary The erythropoietic effects in exhypoxic polycythemic mice of two endoperoxide analogs were assessed and compared with PGE₂. The 9a, 11a epoxymethano analog (U-44069) was found to be a much more potent erythropoietic stimulus than the 11a,9a analog (U-46619) or PGE₂.This work was supported by a Senior Research Grant-in-Aid from the American Heart Association-Louisiana (DMG) and USPHS Grant No. AM 13211 (JWF).     

Alterations in the fraction of oxygen in inspired gas affect rates of renal prostaglandin E2 synthesis in anesthetized dogs

Summary Reductions of oxygen in inspired gas from 20% to 15%, in anesthetized dogs, reduced arterial PO₂ and increased the renal efflux of PGE₂ but not PGF_2a . Renal blood flow, blood pressure, plasma renin activity as well as arterial pH and PCO₂ were unaffected. PGs may mediate the renal hemodynamic or excretory consequences of alterations in PO₂. In addition, minor variations in PO₂ might account, in part, for the variable renal venous PGE₂ concentrations reported under basal conditions.Authentic prostaglandins were supplied by Dr John E. Pike of the Upjohn Company. This work was supported by grants from the Veterans Administration, the Southern Medical Association and U.S. Public Health Service. Dr. Brash is an American Heart Association, Missouri Affiliate Fellow.     

Level of marker enzymes in spermatogenesis on administration of PGF2a in rats

Summary Intrapertioneal administration of PGF_2a in rats significantly increased testicular acid phosphatase (p<0.05), decreased hyaluronidase (p<0.05), whereas the activities of 5-nucleotidase, N-acetyl-B-glucosaminidase, B-galactosidase and uridine diphosphatase remained unaffected.Acknowledgment. We are grateful to Dr D. Sundaresan, for his interest in the study and to Mr B. M. Sharma for technical assistance.     

Activation of the human FP prostanoid receptor disrupts mitosis progression and generates aneuploidy and polyploidy

Studies have shown prostaglandin F_2α to be an endogenous tumor promoter in mouse models of skin carcinogenesis; however, the mechanisms by which PGF_2α affects cell cycle events remain unknown. Here we performed cell cycle analyses on HEK cells stably expressing the human FP receptor and found that treatment with PGF_2α delays mitosis and is associated with an increased expression of cyclin B1 and Cdc2 kinase activity. In addition, multipolar spindles and misaligned chromosomes were observed in a significant proportion of cells treated with PGF_2α. Defective cytokinesis was also observed which resulted in gross aneuploidy and polyploidy. Expression of dominant negative Rho attenuated the cell cycle delay and prevented the generation of micronuclei following treatment with PGF_2α. This suggests that FP receptor activation of Rho signaling by PGF_2α can interfere with nuclear division. Aneuploidy is associated with genomic instability and may underlie the tumor-promoting properties of PGF_2α. Received 7 July 2005; received after revision 22 October 2005; accepted 11 November 2005     

Effect of prostaglandin F2α on the secretion of pancreatic juice induced by secretin and by dopamine

Zusammenfassung Die Wirksamkeit von Prostaglandin F₂ (PGF₂) auf die exokrine Pankreassekretion wurde an einem mit Blut perfundiereten Pankreas-Präparat des Hundes untersucht. PGF₂ (100 g) hemmte die durch Sekretin stimuliete, aber nicht die durch Dopamin stimulierte Sekretion.     

Unit dimensions and space group of Tl2Cl3

Zusammenfassung Die Struktur von Tl₂Cl₃ gehört wahrscheinlich der Raumgruppe D _3d ² an. Die hexagonale Zelle hat die Dimensionena=14·3 k X,c=25·1 k X und enthält 32 Einheiten Tl₂Cl₃.     

Synthesis Ca3Y2Ge3O12

Zusammenfassung Ca₃Y₂Ge₃O₁₂ wurde in chemisch homogener Form auf hydrothermalem Weg hergestellt. Es besitzt eine Garnet-Struktur mit dem Gitterparametera ₀=12,804 Å.     

Specific reaction of aloe extract with serum proteins of various animals

Summary We found that aloe extract contains a lectin-like substance which reacts with serum proteins of various animals. Furthermore, in human serum 2 proteins,a ₂-macroglobulin anda ₁-antitrypsin, were shown to be reactive with aloe extract.     

Alkyl substituents and the cyclisation of esters

Summary K(CdCl₃) has a structure of the E 2₄-type. In comparison with the isotype (NH₄) (CdCl₃) only two of the three lattice constants have noticeably different values. They area andb which show a contraction of about 2%, whereas the constantc is about the same for both salts.     

Application of the linear partial information model to forecasting the Swiss timber market

Most often, statistical analyses only provide partial information about the appropriateness of different models, structures and parameters which may underlie the dynamic process that has generated a time series. Linear partial information (LPI), in particular, consists of linear restrictions such as LPI: p_a> p_b, p_a> p_c where p_a denotes the probability that structure a holds. Fuzzy information of this type can be put to use for decision-making by LPI analysis. In this paper, LPI analysis is applied to answer the question of whether subsidizing price, given an abnormal disturbance on the timber market, would contribute to continuous forest management, a stated goal of Swiss environmental policy.     

Présence d'une α2-globuline lente au cours de la polyarthrite immunologique déterminée par l'adjuvant de Freund

Summary Paper, agar-gel, and starch-gel electrophoretic studies of rat serum show aslow ₂-globulin in adjuvant induced arthritis.     

Differential effects of ethanol on prostaglandin responses of arterial and venous smooth muscle

Summary The present results, using isolated rat aortic strips and portal vein segments, demonstrate that ethanol, depending upon concentration, can either enhance or attenuate the contractile actions of PGF₂ on at least 2 different types of vascular smooth muscle. At the very least, the present findings question the use of ethanol as a solvent when investigating the contractile actions of PG molecules on smooth muscles.Supported by NIH grant No. HL-18015 and NIMH grant No. MH-26236. The authors are indebted to Dr.John E. Pike and Dr.John Babcock of the Upjohn Company for generously providing us with the PGF₂ used in this study.     

Effect of sodium chloride on the respiratory function ofStaphylococcus aureus

Summary Sodium chloride at concentrations below 0.5 M, enhanced the respiratory activity (O₂-consumption) ofStaphylococcus aureus under endogenous and sugar-supported conditions, but did not overcome the inhibitory action of sodium azide. Several sugars, including the glucose analoguea-methylglucoside, and their metabolites enhanced bacterial O₂-consumption, but acetylmethylcarbinol was ineffective.     

The attenuation of prostaglandin-induced luteolysis in decidual tissue-bearing pseudopregnant rats

Summary Decidual tissue (DT)-bearing pseudopregnant (PSP) rats, in contrast to hysterectomized PSP rats, were resistant to a luteolytic regimen of either PGF₂ or PGE₂ when examined for the duration of PSP diestrus. The PG treatments, however, caused a marked fall in the serum progesterone levels on days 10 and 12, although the levels in DT-bearing rats on day 10 were significantly higher than in the hysterectomized rats.Acknowledgment. The authors wish to thank Helen Wilk and Edward Butler for their help in animal care; Ellen O'Laughlin-Phillips for the progesterone assays; Rosa Garnett, Jo Fletcher, and Aileen Svaty for editorial and secretarial help; Dr John E. Pike of the Upjohn Company for the gifts of PGE₂ and PGF₂; and Dr G. N. Niswender for the gift of antiserum GDN-337 used in the RIA for progesterone.Aided in part by NIH Training Grant HD-00024, Ford Foundation Grant 670-0135A, and NIH Program Project HD-07640.     

Age-related differences in the urinary excretion of prostaglandin F2α catabolites in the rat

Summary Tritium-labelled PGF₂ was administered i.v. into rats of varying ages (2, 4, 6 weeks and adult). Urine was collected and assayed for radioactive products by thin-layer-chromatography. Results showed a distinctly different urinary profile between the 2-week-old and the adult rat. While the urinary pattern from the 2-week-old rat gave a single less polar product than PGF₂, the pattern from the adult rat gave products more polar than PGF₂. Urine from the 4- and 6-week-old rats gave a mixture of these types of products. These results indicate that some prostaglandin catabolic pathway (likely the -oxidative system) is activated in vivo within the 4–6-week postnatal period in the rat.Supported by a grant (MT-4181) to C.P.-A. from the Medical Research Council of Canada.This study is in partial fulfillment of the requirements for a Ph.D. degree in the Department of Pharmacology, University of Toronto.     

The metabolism of the soil fumigant 1,2-dibromo-3-chloropropane in the rat

Summary The soil fumigant 1,2-dibromo-3-chloropropane (I) undergoes hydrolysis in the rat to a series of epoxide metabolites. Alkylation of glutathione by these epoxides produces 2 urinary metabolites identified as the mercapturic acids VI (R=COCH₃) and VII (R=COCH₃). Hydrolysis of the epoxides produces the male antifertility agentsa-chlorohydrin (IX, X=Cl) anda-bromohydrin (IX, X=Br) which are oxidatively metabolized to oxalic acid (XII), thus causing renal damage. These metabolic pathways can explain the toxic nature of the fumigant as a carcinogen, a male chemosterilant and as an agent causing kidney damage.This work was supported in part by the National Health and Medical Research Council of Australia.     

Luteolytic potency of 16-phenoxy-derivatives of prostaglandin F2α

Summary The binding of 16-phenoxy derivatives of prostaglandin (PG) F₂ to rat luteal membranes, and also their abortifacient potency in pregnant rats, have been studied. Competitive binding studies with various PG-analogues were performed in ovaries of juvenile rats pretreated with PMSG and HCG, and in parallel studies the abortifacient potency of these substances was tested, in pregnant rats. It was observed that this class of derivatives bound to the PGF₂ receptor as well as, or even better than the parent compound PGF₂. Modifications in the carboxyl group at C-1 yielded derivatives with a higher affinity for the receptor, in decreasing order of effectiveness as follows:-COOR>COOH>OH. The data obtained from the binding studies also compared well with data on the abortifacient potency in pregnant rats. It is concluded that the addition of a phenoxy group to either the lower or upper side chain of PGF₂ may augment the binding to the receptor as well as the biological responses induced by the post receptor effect.     

Dissociation constants of water-insoluble carboxylic acids by13C-NMR. pK as of mesobiliverdin-XIIIα and mesobilirubin-XIIIα

High-field¹³C-NMR of¹³C-enriched compounds in dilute aqueousd ₆-Me₂SO solutions provides a simple, accurate method for measuring pK _as of sparingly soluble carboxylic acids. Using this method, we found the pK _as of mesobilirubin-XIII to be 4.2 and 4.9, much lower values than reported recently for bilirubin, and of mesobiliverdin-XIII to be 3.9 and 5.3.