1-(5-Carboxyindol-1-yl)propan-2-one Inhibitors of Human Cytosolic Phospholipase A2α with Reduced Lipophilicity: Synthesis, Biological Activity, Metabolic Stability, Solubility, Bioavailability, And Topical in Vivo Activity

2010 ◽  
Vol 53 (14) ◽  
pp. 5165-5178 ◽  
Author(s):  
Andreas Drews ◽  
Stefanie Bovens ◽  
Kirsten Roebrock ◽  
Cord Sunderkötter ◽  
Dirk Reinhardt ◽  
...  
Keyword(s):  
Biological Activity ◽  
Metabolic Stability ◽  
Cytosolic Phospholipase ◽  
Cytosolic Phospholipase A2α

Inhibitors of cytosolic phospholipase A2α with carbamate structure: synthesis, biological activity, metabolic stability, and bioavailability

2014 ◽  
Vol 23 (12) ◽  
pp. 5250-5262 ◽  
Author(s):  
Julian Schwarzkopf ◽  
Tom Sundermann ◽  
Martina Arnsmann ◽  
Walburga Hanekamp ◽  
Jörg Fabian ◽  
...  
Keyword(s):  
Biological Activity ◽  
Metabolic Stability ◽  
Cytosolic Phospholipase ◽  
Structure Synthesis ◽  
Cytosolic Phospholipase A2α

Investigations on the metabolic stability of cytosolic phospholipase A2α inhibitors with 1-indolylpropan-2-one structure

2013 ◽  
Vol 206 (2) ◽  
pp. 356-363 ◽  
Author(s):  
Jörg Fabian ◽  
Walburga Hanekamp ◽  
Mélanie H. Thomas ◽  
Jean Luc Olivier ◽  
Matthias Lehr
Keyword(s):  
Metabolic Stability ◽  
Cytosolic Phospholipase ◽  
Cytosolic Phospholipase A2α

scholarly journals Cytosolic phospholipase A2α–deficient mice are resistant to experimental autoimmune encephalomyelitis

2005 ◽  
Vol 202 (6) ◽  
pp. 841-851 ◽  
Author(s):  
Suzana Marusic ◽  
Michael W. Leach ◽  
Jeffrey W. Pelker ◽  
Mihai L. Azoitei ◽  
Naonori Uozumi ◽  
...  
Keyword(s):  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Platelet Activating Factor ◽  
Transfer Model ◽  
Induction Phase ◽  
Autoimmune Encephalomyelitis ◽  
Cytosolic Phospholipase ◽  
Cytosolic Phospholipase A2α ◽  
Experimental Autoimmune

Experimental autoimmune encephalomyelitis (EAE), a Th1-mediated inflammatory disease of the central nervous system (CNS), is a model of human multiple sclerosis. Cytosolic phospholipase A2α (cPLA2α), which initiates production of prostaglandins, leukotrienes, and platelet-activating factor, is present in EAE lesions. Using myelin oligodendrocyte glycoprotein (MOG) immunization, as well as an adoptive transfer model, we showed that cPLA2α−/− mice are resistant to EAE. Histologic examination of the CNS from MOG-immunized mice revealed extensive inflammatory lesions in the cPLA2α+/− mice, whereas the lesions in cPLA2α−/− mice were reduced greatly or completely absent. MOG-specific T cells generated from WT mice induced less severe EAE in cPLA2α−/− mice compared with cPLA2α+/− mice, which indicates that cPLA2α plays a role in the effector phase of EAE. Additionally, MOG-specific T cells from cPLA2α−/− mice, transferred into WT mice, induced EAE with delayed onset and lower severity compared with EAE that was induced by control cells; this indicates that cPLA2α also plays a role in the induction phase of EAE. MOG-specific T cells from cPLA2α−/− mice were deficient in production of Th1-type cytokines. Consistent with this deficiency, in vivo administration of IL-12 rendered cPLA2α−/− mice susceptible to EAE. Our data indicate that cPLA2α plays an important role in EAE development and facilitates differentiation of T cells toward the Th1 phenotype.

STUDIES IN CONGENITAL GENERALIZED LIPODYSTROPHY

1973 ◽  
Vol 72 (3) ◽  
pp. 495-505 ◽  
Author(s):  
Oddmund Søvik ◽  
Svein Oseid
Keyword(s):  
Biological Activity ◽  
Insulin Response ◽  
Epididymal Adipose Tissue ◽  
Large Individual ◽  
Immunoreactive Insulin ◽  
List Type ◽  
Glucose Load ◽  
Congenital Generalized Lipodystrophy ◽  
The One

ABSTRACT The biological activity of plasma insulin from 4 cases of congenital generalized lipodystrophy has been studied, using rat diaphragm and epididymal adipose tissue in vivo. The results are compared with previous data on plasma immunoreactive insulin obtained in these patients. 2 of the 4 cases exhibited unusually high biological insulin activities during the fasting state as well as after an intravenous (iv) glucose load. In the fat pad assay activities as high as 10 000 μU insulin per ml were observed. During childhood the biological insulin activities were generally high, although there were large individual variations. However, in the one case studied after the age of puberty, the insulin response to a glucose load was negligible. Taken together, the biological and immunological activities observed strongly suggest the presence of pancreatic insulin in these patients. It appears that the circulating insulin has a fully biological activity. The decreasing insulin activities after cessation of growth are in agreement with the appearance of frank diabetes at this time.

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