Pervasive inflammatory activation in patients with deficiency in very-long-chain acyl-coA dehydrogenase (VLCADD).

Objectives: Very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a disorder of fatty acid oxidation. Symptoms are managed by dietary supplementation with medium-chain fatty acids that bypass the metabolic block. However, patients remain vulnerable to hospitalisations because of rhabdomyolysis, suggesting pathologic processes other than energy deficit.

A Review of the Clinical Subgroup Analyses From the RE-LY Trial.

Dabigatran was the first direct-acting oral anticoagulant approved by the US Food and Drug Administration for prevention of stroke and systemic embolism in people with atrial fibrillation, based on data from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. Over 18,000 patients with nonvalvular atrial fibrillation and a moderate-to-high risk of thromboembolic stroke were randomized to warfarin or dabigatran. With respect to the primary endpoints for efficacy and safety, dabigatran was superior to warfarin in the prevention of stroke and thromboembolism and noninferior with respect to major bleeding.

ELR-negative CXC chemokine CXCL11 (IP-9/I-TAC) facilitates dermal and epidermal maturation during wound repair.

In skin wounds, the chemokine CXCR3 receptor appears to play a key role in coordinating the switch from regeneration of the ontogenically distinct mesenchymal and epithelial compartments toward maturation. However, because CXCR3 equivalently binds four different ELR-devoid CXC chemokines (ie, PF4/CXCL4, IP-10/CXCL10, MIG/CXCL9, and IP-9/CXCL11), we sought to identify the ligand that coordinates epidermal coverage with the maturation of the underlying superficial dermis. Because CXCL11 (IP-9 or I-TAC) is produced by redifferentiating keratinocytes late in the regenerative phase when re-epithelialization is completed and matrix maturation ensues, we generated mice in which an antisense construct (IP-9AS) eliminated IP-9 expression during the wound-healing process.

Attraction or repulsion: a matter of individual taste?

Cell migration along the correct paths is critical to normal organogenesis and tissue repair, and goes awry in tumor dissemination. Understanding the molecular cues that control such migration would provide opportunities to control these events. Recent findings in Drosophila highlight the role of the epidermal growth factor receptor (EGFR) in chemotaxis and pathfinding during development.

Celecoxib and rofecoxib potentiate chronic colitis and premalignant changes in interleukin 10 knockout mice.

Nonsteroidal anti-inflammatory drugs decrease sporadic colorectal carcinoma and adenomas in patients with familial adenomatous polyposis and in rodent models of sporadic colon cancer and familial adenomatous polyposis. Similarly, selective cyclooxygenase 2 inhibitors decrease adenomas in humans and rodents. However, their effects on chronic colitis and colitis-associated neoplasia are unknown.

Impairment of gallbladder emptying in diabetes mellitus.

Individuals with diabetes mellitus are reported to have a twofold to threefold increase in the incidence of cholesterol gallstones. A frequently cited but unproven pathophysiologic mechanism for this phenomenon is reduced gallbladder muscle function, which results in stasis and allows for cholesterol gallstone crystal formation and gallstone growth. To date, gallbladder motor function has not been investigated in a well-characterized diabetic population.