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The isomorphous structures of the hirugen (N-acetylhirudin 53'-64' with sulfato-Tyr63') and hirulog 1 (D-Phe-Pro-Arg-Pro-(Gly)4 desulfato-Tyr63'-hirugen) complexes of human alpha-thrombin have been determined and refined at 2.2 A resolution to crystallographic R-factors of 0.167 and 0.163, respectively. The binding of hirugen to thrombin is similar to that(More)
Platelet 12-lipoxygenase (P-12-LOX) is overexpressed in different types of cancers, including prostate cancer, and the level of expression is correlated with the grade of this cancer. Arachidonic acid is metabolized by 12-LOX to 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE], and this biologically active metabolite is involved in prostate cancer(More)
PUFA metabolites have a profound effect on inflammatory diseases and cancer progression. Blocking their production by inhibiting PUFA metabolizing enzymes (dioxygenases: cyclooxygenases and LOXs) might be a successful way to control and relieve such problems, if we learn to better understand their actions at a molecular level. Compounds with strong(More)
The number of people diagnosed with type 2 diabetes has risen steeply recently exhausting the ability of health care systems to deal with the epidemic. Seventy-five percent of people with diabetes live in low- and middle-income countries. The largest populations of diabetics are in China and India, with many of those(More)
OBJECTIVE To explore the use of photodynamic therapy (PDT) as a minimally invasive form of treatment for organ-confined prostate cancer, for although there are several therapies, ablative treatments are associated with significant morbidity. MATERIALS AND METHODS Using the photosensitizer tin etiopurpurin, dogs were treated with interstitially placed(More)
Soybean lipoxygenase isoenzyme L3 represents a second example (after L1) of the X-ray structure (R = 17% at 2.6 A resolution) for a member of the large family of lipoxygenases. L1 and L3 have different characteristics in catalysis, although they share 72% sequence identity (the changes impact 255 amino acids) and similar folding (average C alpha rms(More)
OBJECTIVE To investigate the potential for the future clinical use of a very long half-life plasminogen activator inhibitor type 1 (VLHL PAI-1) as a haemostatic agent. MATERIALS AND METHODS We developed a VLHL PAI-1 (half-life >700 h) recombinant mutant of PAI-1 and assessed VLHL PAI-1 for its ability to inhibit fibrinolysis in vitro using human, rabbit,(More)
Many lipoxygenase inhibitors including curcumin are currently being studied for their anti-carcinogenic properties. Curcumin is a naturally occurring polyphenolic phytochemical isolated from the powdered rhizome of the plant Curcuma longa that possesses anti-inflammatory properties and inhibits cancer formation in mice. Recently it was shown that the(More)
Fruits, vegetables, spices and a variety of teas are suggested for the prevention of many diseases. They encompass active, non-nutritional ingredients called nutraceuticals which are defined as food products that provide health benefits. Many nutraceuticals have been tested to identify inhibitors of plasminogen activator inhibitor (PAI-1). PAI-1 is the(More)