Morphological effects of prostaglandins E1, E2 and F2α on fibroblast-like cultures of human synovial cells

Summary In medium supplemented with serum, PGE₁ and PGE₂ were equally potent in inducing cells with a fenestrated appearance, whereas PGF₂ was comparatively ineffective. In BSA without serum the effects were more persistent and characterized by a high proportion of astrocyte-like cells. The effects were reversed upon removal of the prostaglandins.This work was supported by the National Health and Medical Research Council of Australia.     

Prostaglandin E2 increases mechanically evoked potentials in the peripheral nerve

Summary Subdermal injections of PGE₂ (5 g) in the rat foot lead to increases in the potentials evoked in sensory nerve branches by the mechanical stimulation of the skin. This sensitization of both A and C fibres complements the previously described hyperalgesic effects of prostaglandins of the E series.     

ACTH response induced by interleukin-1 is mediated by CRF secretion stimulated by hypothalamic PGE

Summary We investigated whether hypothalamic prostaglandin E₂ (PGE₂) and corticotropin releasing factor (CRF) are responsible for the development of the adrenocorticotropic hormone (ACTH) response induced by interleukin-1 (IL-1). The present results show that ACTH responses induced by intravenous injection of IL-1 were suppressed by systemic pretreatment with indomethacin and that intrahypothalamic injection of PGE₂ stimulates the secretion of ACTH. Furthermore, systemic pretreatment with anti-CRF antibody significantly suppressed the ACTH response induced by intrahypothalamic injection of PGE₂. These data suggest that the ACTH response induced by IL-1 is mediated by CRF secretion stimulated by hypothalamic PGE₂.     

Influence of prostaglandins E1 and E2 on coagulation of rat blood

Zusammenfassung Die Prostaglandine E₁ (PGE₁) und E₂ (PGE₂) haben keinen Einfluss auf die Gerinnung von Rattenblut. Im Gegensatz zu früheren Postulationen können die Ca-Ionen im Plasma nicht von PGE₁ ersetzt werden. PGE₁ beeinflusst die maximale Amplitude des Thrombelastogramms in vitro nach Zugabe von 0.3–6 g/ml, während PGE₂ diesen Effekt nicht aufweist.     

Prostaglandin E1 induced salivary secretion

Summary PGE₁ but not PGF₂ at 500–1000 g/kg induced a slow and sparse flow from the parotid and no flow at all from submaxillary glands. Composition of PGE₁-induced parotid saliva was quite different from that evoked by any autonomic agonists. The present study suggests that PGE₁ might act directly on parotid acinar cells.Acknowledgment. This work was supported by NIDR grant DE05633. The authors wish to thank Ms Sonya Wynn for her technical assistance.     

Etamsylate as inhibitor of prostaglandin biosynthesis in pregnant human myometrium in vitro

Summary The effects of etamsylate on prostaglandin (PG) biosynthesis in microsomes of pregnant human myometrium in vitro have been determined, and compared with those of indomethacin. Both drugs inhibited PG biosynthesis, indomethacin being the more potent inhibitor of the two. Etamsylate inhibited synthesis of 6-oxo-PGF₁, PGF₂, PGE₂, and thromboxane B₂; increasing the concentration of etamsylate increased the inhibition of synthesis. It is suggested that etamsylate has no anti-cyclo-oxygenase activity, but acts by inhibiting the activity of prostacyclin synthetase, endoperoxide reductase, endoperoxide isomerase, and thromboxane synthetase.     

Calcium dobesilate (Doxium) as a prostaglandin synthetase inhibitor in pregnant human myometrium in vitro

Summary This comparative study on the effect of calcium dobesilate and indomethacin on prostaglandin biosynthesis was performed on microsomal fractions of pregnant human myometrium. Both drugs inhibited prostaglandin synthesis, indomethacin being more potent. Calcium dobesilate inhibited, in a dose-dependent manner, the synthesis of 6-oxo-PGF₁, PGF₂, PGE₂ and TXB₂. Its inhibitory action is comparable to that of etamsylate.     

Effect of ricin,of its subunits and of modeccin on cAMP level in Yoshida ascites cells

Summary The B chain of ricin strongly decreases the PGE₁-enhanced level of cAMP in Yoshida ascites sarcoma cells, whereas the A chain is ineffective. Modeccin does not have any effect.Acknowledgments. We thank E. Lorenzoni for preparing ricin and modeccin. The work was aided by a contract from The Consiglio Nazionale delle Ricerche, Rome, within The Piano Finalizzato Controllo della crescita neoplastica and by Pallotti's legacy for cancer research.     

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.     

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.     

Stimulation of histamine synthesis in rat mast cells by compound 48/80 in vitro

Summary The histamine content of rat peritoneal fluid cells is doubled within 20 min by 0.5 g/ml of compound 48/80. Histamine catabolism inhibitors do not reproduce this effect; cells pre-incubated with -fluoromethylhistidine are unresponsive to compound 48/80 which therefore activates pre-formed histidine decarboxylase rather than inducing it. Non-mast cells showed no change after treatment with compound 48/80.     

Effects of PGE1 on the frog ventricular strip

Résumé Les effets de la PGE₁ ont été étudiés sur les bandelettes ventriculaires isoleés de la grenouille. La PGE₁ augmente la force de contraction de ces préparations. Le propranolol antagonise significantivement les effets de la noradrenaline sans altérer les réponses à la PGE₁. Un bloqueur des récepteurs -adrenergiques, la phénoxybenzamine n'inhibe pas les effets induits par la PGE₁ ou les catécholamines. L'inhibition de la pompe à sodium par l'ouabaine ne modifie pas la réponse du tissu à la PGE₁.

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We should like to thank Prof.D. A. van Dorp (Unilever Research Vlaardingen) for supplying PGE₁.     

Effects of PGE2 and PGF2α on the simulation by noradrenaline and oxytocin of human cervical muscle activity at term

Summary Cervical specimens were obtained by needle biopsy in connection with caesarean section at term pregnancy. The preparations were superfused in an organ chamber and contractions were registered isometrically. Prostaglandin (PG) E₂ and F₂ inhibited spontaneous contractions. The stimulatory action of noradrenaline was not influenced by PGF₂ but was reduced by PGE₂ whereas both PGs abolished the excitatory effect of oxytocin.     

Effects of prostaglandins PGE1 and PGF2α on oxygen consumption,sodium and potassium content of renal tissue

Résumé Chez le rat la prostaglandine E₁ augmente la consommation d'oxygène et la teneur en potassium, tandis qu'elle abaisse la teneur en sodium dans le tissu rénal et hépatique. On y a observé une corrélation entre l'effet et la dose de PGE₁ employée. Cependant dans les coupes du tissu hépathique, la PGE₁ est restée sans action. A même dose la PGF₂ a produit des effets comparables à ceux qu'on obtient avec la PGE₁. Ces résultats indiqueraient que la réponse natriurétique à la PGE₁ ne semble pas due à une inhibition de la pompe de sodium des cellules tubulaires, mais à une élévation du flux sanguin rénal.

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The authors wish to express their sincere thanks to Dr.M. Cereijido for his valuable criticism of this work and to MissL. A. Vargas andMr. G. Jordan for their competent technical assistance.

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This work was supported by a grant from the CONICET and CondesaAna Thyssen de Zichy.     

Versuche zum enzymatischen Abbau der «gebundenen» gibberelline vonPharbitis purpurea

Summary Seeds and fruit walls ofPharbitis purpurea contain in addition to the free gibberellins A₈, A₃, A₅, more polar gibberellin-like substances, so-called bound gibberellins tentatively namedPharbitis and. After purification by thin layer chromatography, these 2 substances were treated with both Ficin and Emulsin in buffered solutions of pH 6.2. After treatment with Emulsin, the free gibberellins A₈ and A₅, after treatment with Ficin the gibberellins A₃ and A₅, were detectable in thin layer chromatograms.     

Biosynthesis of 1-aminocyclopropanecarboxylic acid: Steric course of the reaction at the C-4 position

Summary Under the action of the appropriate synthase from ripe tomatoes a 11 mixture of (3S, 4R)-[3,4-²H₂] and (3R, 4S)-[3,4-²H₂]-(2S)-adenosylmethionine is transformed into a 11 mixture of the two meso forms of [²H₂]-1-aminocyclopropanecarboxylic acid, a result which proves the operation of an inversion mechanism and which is consistent with direct nucleophilic displacement of the leaving group in the substrate.     

Nouvelles données sur la cytogénétique et la spéciation des Leggada (Mammalia-Rodentia-Muridae)

Summary To the 237 pigmy-mice studies in his previous papers, the author brings new data concerning the cytogenetics of 25 Leggada. One first set of 12 mice from Nigeria belongs to the same polymorphic series containing themusculoides from the Ivory Coast and the Central African Republic.A small sample from Ippy (Central African Republic), although the individuals are morphologically all alike and referable tomusculoides, shows an amazing diversity: /259.2N=28, N.F.=36, sex chromosomes of the translocated type (TR). We meet here a new robertsonian combination in the polymorphic series, 34/33/32/31 ... 28/... 22/... 19/18./260.2N=32, N.F.=36, sex chromosomesTR. Both big biarmed autosomes are metacentric — submetacentric with a centromeric index of about 0.25 by the typicalmusculoides having the same diploid number./261.2N=19, N.F.=36, sex chromosomesX/Y ₁ Y ₂. The first occurrence of such sex chromosomes by the Leggada. By themusculoides from Rhodesia we were dealing with the typeX ₁ X ₂ /Y. /262.2N=18, N.F.=36, sex chromosomesX/X. Very likely the female of /261.In the complexminutoides-musculoides, we meet many different caryotypes and it is obvious that the chromosomal mutations play here the part of a primary factor of isolation, previous to the gene mutations which later will allow the taxonomic determination of the species actually in statu nascendi.     

Identification of swelling-activated Cl<Superscript>-</Superscript> current in rabbit cardiac Purkinje cells

The presence and functional role of the swelling-activated Cl^- current (I_Cl(swell)) in rabbit cardiac Purkinje cells was examined using patch-clamp methodology. Extracellular hypotonicity (210 or 135 mOsm) activated an outwardly rectifying, time-independent current with a reversal potential close to the calculated Cl^- equilibrium potential (E_Cl). The magnitude of this current was related to tonicity of the superfusate. The current was blocked by 0.5 mM 4,4-diisothiocyanostilbene-2,2-disulfonic acid (DIDS). These features are comparable to those of I_Cl(swell) found in sinoatrial nodal, atrial, and ventricular myocytes. I_Cl(swell) activation at 210 and 135 mOsm depolarized the resting membrane potential with 6 and 10 mV and shortened the action potential by 18 and 33%, respectively. DIDS partially reversed I_Cl(swell)-induced action potential changes. We conclude that I_Cl(swell) is present in Purkinje cells and its activation leads to action potential shortening and resting membrane potential depolarization, both of which can promote the development of reentrant arrhythmias.Received 20 January 2004; received after revision 17 February 2004; accepted 25 February 2004     

The phytotoxins ofMycosphaerella fijiensis,the causative agent of Black Sigatoka disease of bananas and plantains

Black Sigatoka is the most costly to control disease of bananas and plantains in the world. Currently, a worldwide search is underway either to find or to produce cultivars that are disease-resistant or-tolerant. Phytotoxins isolated from the pathogen might facilitate the discovery of such cultivars. Several aromatic compounds from liquid cultures ofMycosphaerella fijiensis, the causal agent of Black Sigatoka disease of bananas and plantains, have been isolated. The most abundant and phytotoxic of these compounds is 2,4,8-trihydroxytetralone, which induces necrotic lesions at 5 g/5 l in less than 12 h on sensitive cultivars of bananas. This compound exhibits host-selectivity that mimics that of the pathogen. Other phytotoxins isolated from this fungus, in lesser amounts, were juglone, the novel compound 2-carboxy-3-hydroxycinnamic acid, isoochracinic acid and 4-hydroxyscytalone. Some of the phytotoxins isolated are melanin shunt pathway metabolites, which makes this fungus unique among plant pathogens.     

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.