Biomaterial Database

Beneficial effects of UK 37248, a thromboxane synthetase inhibitor, in experimental endotoxic shock in the rat. 1983

P V Halushka, and J A Cook, and W C Wise

1 The effects of pretreatment with the thromboxane synthetase inhibitor UK 37248 (dazoxiben) administered 30 min before intravenous endotoxin (S. enteriditis) in the rat was investigated 2 Plasma prostaglandins and thromboxanes were determined via radioimmunoassay. Endotoxaemia was associated with significant elevations above control values (less than 200 pg/ml) in plasma thromboxane B2 (TXB2), prostaglandin E (PGE) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). Within 30 min after endotoxin administration plasma immunoreactive (i) iTXB2 was 875 +/- 90 pg/ml (n = 9), iPGE was 1670 +/- 271 (n = 9) and i6-keto-PGF1 alpha was 1191 +/- 209 pg/ml (n = 10). By 4 h plasma iTXB2 was 1743 +/- 328 pg/ml (n = 5), iPGE was 2589 +/- 494 pg/ml (n = 9) and i6-keto-PGF1 alpha was 4251 +/- 984 pg/ml (n = 10). UK 37248 pretreatment resulted in a significant (P less than 0.001) decrease in plasma iTXB2 at 30 min and 4 h to 193 +/- 28 pg/ml (n = 5) and 421 +/- 57 pg/ml (n = 5), respectively. Unexpectedly UK 37248 also significantly decreased plasma i6-keto PGF1 alpha at 30 min and 4 h to 360 +/- 75 pg/ml (n = 10) (P less than 0.005) and 1920 +/- 513 pg/ml (n = 10) (P less than 0.05), respectively, iPGE plasma levels were not significantly changed in the UK 37248-pretreated rats 30 min (2210 +/- 370 pg/ml (n = 9) or 4 h 3529 +/- 1093 pg/ml (n = 13) after endotoxin compared to the vehicle-treated rats. 3 UK 37248 significantly (P less than 0.05) reduced the endotoxin mortality rate at 24 h from 69% (n = 13) to 30% (n = 13), UK 37248 also reduced splanchnic infarction from 90% (n = 20) to 6% (n = 16). 4 UK 37248 significantly improved the endotoxin-induced thrombocytopaenia, disseminated intravascular coagulation, hypoglycaemia and lysosomal labilization. 5 We conclude that UK 37248 provides significant beneficial effects in experimental endotoxic shock in the rat.

UI	MeSH Term	Description	Entries
D007093	Imidazoles	Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D008264	Macrophages	The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)	Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008297	Male		Males
D010088	Oxidoreductases	The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)	Dehydrogenases,Oxidases,Oxidoreductase,Reductases,Dehydrogenase,Oxidase,Reductase
D010976	Platelet Count	The number of PLATELETS per unit volume in a sample of venous BLOOD.	Blood Platelet Count,Blood Platelet Number,Platelet Number,Blood Platelet Counts,Blood Platelet Numbers,Count, Blood Platelet,Count, Platelet,Counts, Blood Platelet,Counts, Platelet,Number, Blood Platelet,Number, Platelet,Numbers, Blood Platelet,Numbers, Platelet,Platelet Count, Blood,Platelet Counts,Platelet Counts, Blood,Platelet Number, Blood,Platelet Numbers,Platelet Numbers, Blood
D011458	Prostaglandins E	(11 alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid (PGE(1)); (5Z,11 alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid (PGE(2)); and (5Z,11 alpha,13E,15S,17Z)-11,15-dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid (PGE(3)). Three of the six naturally occurring prostaglandins. They are considered primary in that no one is derived from another in living organisms. Originally isolated from sheep seminal fluid and vesicles, they are found in many organs and tissues and play a major role in mediating various physiological activities.	PGE
D011863	Radioimmunoassay	Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation.	Radioimmunoassays
D001786	Blood Glucose	Glucose in blood.	Blood Sugar,Glucose, Blood,Sugar, Blood
D004731	Endotoxins	Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells.	Endotoxin
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia