BACKGROUND Curcumin exhibits anti-diabetic activities, induces heme-oxygenase-1 (HO-1) and is an inhibitor of transcriptional co-activator p300. A novel water soluble curcumin derivative (NCD) has been developed to overcome low invivo bioavailability of curcumin. We evaluated the effect of the NCD on signaling mechanisms involved in cardiomyocyte hypertrophy and studied whether its action is me...

In aiming to develop a gene therapy approach for hemophilia B, we expressed and characterized human factor IX in rat capillary endothelial cells (CECs). Moloney murine leukemia virus-derived retrovirus vectors that contain human factor IX cDNA linked to heterologous promoters and the neomycin-resistant gene were constructed and employed to prepare recombinant retroviruses. Rat CECs and NIH 3T3 ...

Factor IX Chicago-2 and prothrombin Madrid were purified from patients with hemophilia B and congenital dysprothrombinemia. respectively. Each protein displays defects in zymogen activation secondary to the failure to cleave one of the sessile bonds whose cleavage is necessary for full coagulant activity. These proteins were isolated by immunoaffinity chromatography using conformation-specific ...

Recent evidence suggests that carbonic anhydrase (CA) IX in humans is under the regulatory control of hypoxia-inducible factor and is overexpressed in certain cancers. However, little is known of its presence in nonmammalian vertebrates or its physiological function in any vertebrate. The objective of this study was to examine and characterize the presence, distribution, induction by hypoxia, a...

The velocity of rolling leukocytes is thought to be determined by the expression of adhesion molecules and the prevailing wall shear stress. Here, we investigate whether rapid cleavage of L-selectin may be an additional physiologic regulatory parameter of leukocyte rolling. A unique protease in the membrane of leukocytes cleaves L-selectin after activation, resulting in L-selectin shedding. The...

Clostridium difficile is the major cause of antibiotic-associated colitis, a disease with significant morbidity and mortality. This study investigated the role of the haem oxygenase-1 (HO-1)/carbon monoxide (CO) pathway in C. difficile toxin A-induced enteritis in mice. The HO substrate haemin, zinc protoporphyrin IX (ZnPP IX), a specific HO-1 inhibitor, dimanganese decacarbonyl (DMDC), a CO do...

Human plasma–derived factor IX (pdFIX) concentrates are routinely used to treat patients with hemophilia B, an X-linked bleeding disorder that affects 1 in 30 000 males, but concerns remain regarding transmission of blood-borne pathogens. Therefore, the safety and efficacy of recombinant human factor IX (rFIX) were evaluated. A 20-center international trial was conducted in previously treated p...

Two structurally different forms of activated human Factor IX (Factor IXaa and IXa8) have been previously reported to have essentially identical clotting activity in vitro. Although it has been shown that activated Factor IXChapel Hills an abnormal Factor IX isolated from the plasma of a patient with mild hemophilia B, and normal Factor IXaa are structurally very similar, the clotting activity ...