Morpholines

Publication Title: 
Journal of thrombosis and haemostasis: JTH

BACKGROUND: Thromboprophylaxis with rivaroxaban (R) is superior to enoxaparin in patients undergoing major orthopedic surgery (MOS). However, rivaroxaban has never been directly compared with fondaparinux (F), which also shows superior efficacy over enoxaparin. The clinical impact of switching from fondaparinux to rivaroxaban thromboprophylaxis is unclear. OBJECTIVES: To evaluate the efficacy and safety of rivaroxaban or fondaparinux thromboprophylaxis in unselected patients undergoing MOS.

Author(s): 
Beyer-Westendorf, J.
L¸tzner, J.
Donath, L.
Radke, O. C.
Kuhlisch, E.
Hartmann, A.
Weiss, N.
Werth, S.
Publication Title: 
European Journal of Pharmacology

Different effects of moderate to high doses of gamma-hydroxybutyric acid, including sedation/hypnosis, have been found to be blocked by gamma-aminobutyric acidB (GABAB) receptor antagonists. The present study investigated whether the protective effect of GABAB receptor antagonists extends also to gamma-hydroxybutyric acid-induced mortality. To this aim, the present study investigated the effect of the GABAB receptor antagonist, (2S)(+)-5,5-dimethyl-2-morpholineacetic acid (SCH 50911; 100 mg/kg, ip), on mortality induced by gamma-hydroxybutyric acid (1-6 g/kg, ip) in DBA mice.

Author(s): 
Carai, Mauro A. M.
Colombo, Giancarlo
Gessa, Gian Luigi
Publication Title: 
Journal of Pharmacological Sciences

The endogenous brain constituent, gamma-hydroxybutyric acid (GHB), as well as its prodrug, gamma-butyrolactone (GBL), have recently gained interest in the drug addiction field due to their abuse potential and fatalities caused by overdose. It is known that GHB has two sites of actions: the gamma-aminobutyric acid(B) (GABA(B)) receptor and a specific-GHB binding site. The present study was designed to extend to GBL the investigations on the contribution of the GABA(B) receptor and the specific-GHB binding site to its in vivo effects.

Author(s): 
Carai, Mauro A. M.
Lobina, Carla
Maccioni, Paola
Cabras, Claudia
Colombo, Giancarlo
Gessa, Gian Luigi
Publication Title: 
Drug Metabolism and Disposition: The Biological Fate of Chemicals

The challenge of predicting the metabolism or toxicity of a drug in humans has been approached using in vivo animal models, in vitro systems, high throughput genomics and proteomics methods, and, more recently, computational approaches. Understanding the complexity of biological systems requires a broader perspective rather than focusing on just one method in isolation for prediction. Multiple methods may therefore be necessary and combined for a more accurate prediction.

Author(s): 
Ekins, Sean
Andreyev, Sergey
Ryabov, Andy
Kirillov, Eugene
Rakhmatulin, Eugene A.
Sorokina, Svetlana
Bugrim, Andrej
Nikolskaya, Tatiana
Publication Title: 
PloS One

INTRODUCTION: Cerebral malaria (CM) is a potentially fatal cerebrovascular disease of complex pathogenesis caused by Plasmodium falciparum. Hydrogen sulfide (HS) is a physiological gas, similar to nitric oxide and carbon monoxide, involved in cellular metabolism, vascular tension, inflammation, and cell death. HS treatment has shown promising results as a therapy for cardio- and neuro- pathology. This study investigates the effects of fast (NaHS) and slow (GYY4137) HS-releasing drugs on the growth and metabolism of P. falciparum and the development of P. berghei ANKA CM.

Author(s): 
DellaValle, Brian
Staalsoe, Trine
Kurtzhals, Jørgen Anders Lindholm
Hempel, Casper
Publication Title: 
Oncotarget

To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications.

Author(s): 
Kast, Richard E.
Boockvar, John A.
Brüning, Ansgar
Cappello, Francesco
Chang, Wen-Wei
Cvek, Boris
Dou, Q. Ping
Duenas-Gonzalez, Alfonso
Efferth, Thomas
Focosi, Daniele
Ghaffari, Seyed H.
Karpel-Massler, Georg
Ketola, Kirsi
Khoshnevisan, Alireza
Keizman, Daniel
Magné, Nicolas
Marosi, Christine
McDonald, Kerrie
Muñoz, Miguel
Paranjpe, Ameya
Pourgholami, Mohammad H.
Sardi, Iacopo
Sella, Avishay
Srivenugopal, Kalkunte S.
Tuccori, Marco
Wang, Weiguang
Wirtz, Christian R.
Halatsch, Marc-Eric
Publication Title: 
Oncotarget

CUSP9 treatment protocol for recurrent glioblastoma was published one year ago. We now present a slight modification, designated CUSP9*. CUSP9* drugs--aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, sertraline, ritonavir, are all widely approved by regulatory authorities, marketed for non-cancer indications. Each drug inhibits one or more important growth-enhancing pathways used by glioblastoma. By blocking survival paths, the aim is to render temozolomide, the current standard cytotoxic drug used in primary glioblastoma treatment, more effective.

Author(s): 
Kast, Richard E.
Karpel-Massler, Georg
Halatsch, Marc-Eric
Publication Title: 
Journal of Immunology (Baltimore, Md.: 1950)

We examined the effect of modulating phosphoinositide 3-kinase (PI3K) activity in a murine model of cecal ligation and puncture-induced polymicrobial sepsis. Inhibition of PI3K activity with wortmannin increased serum cytokine levels and decreased survival time in septic mice. We have reported that an immunomodulator, glucan phosphate, induces protection in murine polymicrobial sepsis. We observed that glucan stimulated tissue PI3K activity, which positively correlated with increased survival in septic mice.

Author(s): 
Williams, David L.
Li, Chuanfu
Ha, Tuanzhu
Ozment-Skelton, Tammy
Kalbfleisch, John H.
Preiszner, Johanna
Brooks, Lynne
Breuel, Kevin
Schweitzer, John B.
Publication Title: 
American Journal of Respiratory Cell and Molecular Biology

Quercetin (3,3',4',5,7-pentahydroxyflavone), a dietary flavonoid, is an inhibitor of phosphatidylinositol (PI) 3-kinase and potent antioxidant. We hypothesized that quercetin blocks airway epithelial cell chemokine expression via PI 3-kinase-dependent mechanisms. Pretreatment with quercetin and the PI 3-kinase inhibitor LY294002 each reduced TNF-alpha-induced IL-8 and monocyte chemoattractant protein (MCP)-1 (also called CCL2) expression in cultured human airway epithelial cells.

Author(s): 
Nanua, Suparna
Zick, Suzanna M.
Andrade, Juan E.
Sajjan, Umadevi S.
Burgess, John R.
Lukacs, Nicholas W.
Hershenson, Marc B.
Publication Title: 
American Journal of Physiology. Endocrinology and Metabolism

An ethanolic extract of Russian tarragon, Artemisia dracunculus L., with antihyperglycemic activity in animal models was reported to decrease phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression in STZ-induced diabetic rats. A quantitative polymerase chain reaction (qPCR) assay was developed for the bioactivity-guided purification of the compounds within the extract that decrease PEPCK expression. The assay was based on the inhibition of dexamethasone-stimulated PEPCK upregulation in an H4IIE hepatoma cell line.

Author(s): 
Govorko, Dmitry
Logendra, Sithes
Wang, Yanxin
Esposito, Debora
Komarnytsky, Slavko
Ribnicky, David
Poulev, Alexander
Wang, Zhong
Cefalu, William T.
Raskin, Ilya

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