Occurrence and Functions of PACAP in the Placenta

Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide with a widespread distribution both in the nervous system and peripheral organs. The peptide is also present in the female gonadal system, indicating its role in reproductive functions. While a lot of data are known on PACAP-induced effects in oogenesis and in the regulation of gonadotropin secretion at pituitary level, its placental effects are somewhat neglected in spite of the documented implantation deficit in mice lacking endogenous PACAP. The aim of the present review is to give a brief summary on the occurrence and actions of PACAP and its receptors in the placenta. Radioimmunoassay (RIA) measurements revealed increased serum PACAP levels during the third trimester and several changes in placental PACAP content in obstetrical pathological conditions, further supporting the function of PACAP during pregnancy. Both the peptide and its receptors have been shown in different parts of the placenta and the umbilical cord. PACAP influences blood vessel and smooth muscle contractility of the uteroplacental unit and is involved in regulation of local hormone secretion. The effects of PACAP on trophoblast cells have been mainly studied in vitro. Effects of PACAP on cell survival, angiogenesis and invasion/proliferation have been described in different trophoblast cell lines. PACAP increases proliferation and decreases invasion in proliferative extravillous trophoblast cells, but not in primary trophoblast cells, where PACAP decreased the secretion of various angiogenic markers. PACAP pretreatment enhances survival of non-tumorous primary trophoblast cells exposed to oxidative stress, but it does not influence the cell death-inducing effects of methotrexate in proliferative extravillous cytotrophoblast cells. Interestingly, PACAP has pro-apoptotic effect in choriocarcinoma cells suggesting that the effect of PACAP depends on the type of trophoblast cells. These data strongly support that PACAP plays a role in normal and pathological pregnancies and our review provides an overview of currently available experimental data worth to be further investigated to elucidate the exact role of this peptide in the placenta

Extremely high maternal alkaline phosphatase serum concentration with syncytiotrophoblastic origin

An extremely high alkaline phosphatase (AP) concentration (3609 IU/litre) was found in a 20 year old primigravida at 37 week’s gestation, prompting an examination of its histological and cellular origin. Immunohistochemistry and western blots using antibodies against AP, Ki-67, phospho-protein kinase B (Akt), phospho-p44/42 mitogen activated protein kinase/extracellular signal regulated kinase 1/2 (MAPK/Erk1/2), phospho-glycogen synthase kinase-3β (GSK-3β), phospho-stress activated protein kinase/c-Jun N-terminal kinase, total-Akt, total-GSK-3β, and phospho-p38-MAPK were carried out on index and control placental samples of the same gestational age. Compared with controls, staining of the index placenta showed minimal AP labelling of the brush border and remarkable positivity of the intervillous space. Cytotrophoblastic proliferation was 8–10% in the index placenta compared with 1–2% in controls. The index placenta also had raised concentrations of protein kinases with important roles in cell differentiation. The proliferation and differentiation rates of the cytotrophoblasts were found to be five times higher in index samples than in controls. It is hypothesised that loss of syncytial membranes in immature villi led to increased AP concentrations in the maternal circulation and decreased AP staining of the placenta. Loss of the syncytium might also stimulate increased proliferation of villous cytotrophoblasts, which would then fuse and maintain the syncytium

Reviews

Anna T. LITOVKINA–Wolfgang MIEDER: Old Proverbs Never Die, They Just Diversify: A Collection of Anti-Proverbs. Burlington: The University of Vermont–Veszprém: The Pannonian University of Veszprém 2006, 414 pp. Anna T. LITOVKINA–Katalin VARGHA: „Viccében él a nemzet”. Magyar közmondásparódiák [“The Nation Lives in Its Jokes”: Hungarian Proverb Parodies]. Budapest, privately published, 2005, 102 pp; „Éhes diák pakkal álmodik”. Egyetemisták közmondás-elváltoztatásai [“A Hungry Student Dreams about a Parcel”: Twisted Proverbs of Students Variations]. Budapest, privately published, 2005, 94 pp. Anna T. LITOVKINA: Magyar közmondástár. Közmondások értelmező szótára példákkal szemléltetve [Dictionary of Hungarian Proverbs: Definitive Dictionary of Proverbs Supplemented with Examples]. Budapest: Tinta Könyvkiadó 2005, 848 pp. George L. NAGY: Thesaurus of English Idioms. Budapest: Tinta Könyvkiadó 2006, 1249 pp. Erzsébet FORGÁCS: Nyelvi játékok. Kreativitás a viccekben, a reklámnyelvben, a sajtó- nyelvben és irodalmi szövegekben [Language Games: Creativity in the Language of Jokes, Advertising, Press and Literature]. Szeged: SZEK Juhász Gyula Felsőoktatási Kiadó 2005, 290 pp. Хappи ВАЛЬТЕР–Валерий Михайлович МОКИЕНКО: Антипословицы русского народа. Санкт-Петербург: Издательский Дом «Нева» 2005, 576 с. Csaba FÖLDES (ed.): Res humanae proverbiorum et sententiarum. Ad honorem Wolfgangi Mieder. Tübingen: Gunter Narr Verlag 2004, 405 pp. (ISBN 3-8233-6092-2; 58 Euro) Kimberly J. LAU–Peter TOKOFSKY–Stephen D. WINICK (eds.): What Goes Around Comes Around: The Circulation of Proverbs in Contemporary Life [Logan, Utah: Utah State University Press 2004], 190 pp. Chilukuri BHUVANESWAR (ed): Down the Proverb Lane, A Festschrift for Mieder at 62. Vol 1, Su:rya Kamalam Series, The Proverbial Linguistics Group 2006, 88 pp. Gulnas UMUROVA: Was der Volksmund in einem Sprichwort verpackt … Moderne Aspekte des Sprichwortgebrauchs – anhand von Beispielen aus dem Internet. Bern: Peter Lang AG, Europäischer Verlag der Wissenschaften 2005, 362 Seiten. Wolfgang MIEDER: „Andere Zeiten, andere Lehren.“ Sprichwörter zwischen Tradition und Innovation. (Phraseologie und Parömiologie, Bd. 18.) Baltmannsweiler: Schneider Verlag Hohengehren 2006, 312 Seiten. ISBN 3-8340-0030-2 Titinga-Frédéric PACÉRÉ : Pensées africaines – Proverbes, dictons et sagesse des Anciens. (Sociétés africaines et diaspora) Paris: L’Harmattan 2005, 363 p. Stéphane VIELLARD (sous la direction de): Les proverbes en Russie – Trois siècles de parémiographie. Paris: Institut d’études slaves – Centre d’études slaves 2005, p. 180– 400. (Revue des études slaves, tome LXXVI, fascicule 2–3

Quercetin increases the efficacy of glioblastoma treatment compared to standard chemoradiotherapy by the suppression of PI-3-kinase-Akt pathway

The goal of the present study was to compare the efficacy of treatment with irradiation (IR), temozolomide, and quercetin, alone, or in combinations, on 2 glioblastoma cell lines, DBTRG-05 and U-251. Cell viability assay, flow cytometry analysis, colony formation assay, and Western blot analysis were used to compare the effects of treatment on the 2 cell lines. The greatest reduction in cell viability and colony formation was observed when cells were treated with a combination of the agents including quercetin. The treatment of cells with the combination of IR and quercetin was equal to the efficiency of the combination of IR and temozolomide in decreasing cell viability as well as colony formation. Quercetin alone, or in combination with IR, increased the cleavage of caspase-3 and PARP-1 showing an activated apoptosis and significantly reduced the level of phospho-Akt. Moreover, these treatments increased the levels of phospho-ERK, phospho-JNK, phospho-p38, and phospho-RAF1. Our data indicate that the supplementation of standard therapy with quercetin increases efficacy of treatment of experimental glioblastoma through synergism in the induction of apoptosis via the cleavage of caspase-3 and PARP-1 and by the suppression of the actitivation of Akt pathway