Rates of Progression in Diabetic Retinopathy During Different Time Periods: A systematic review and meta-analysis

10.2337/dc09-0615Diabetes Care32122307-2313DICA

Protein kinase C in heart failure: a therapeutic target?

Heart failure (HF) afflicts about 5 million people and causes 300 000 deaths a year in the United States alone. An integral part of the pathogenesis of HF is cardiac remodelling, and the signalling events that regulate it are a subject of intense research. Cardiac remodelling is the sum of responses of the heart to causes of HF, such as ischaemia, myocardial infarction, volume and pressure overload, infection, inflammation, and mechanical injury. These responses, including cardiomyocyte hypertrophy, myocardial fibrosis, and inflammation, involve numerous cellular and structural changes and ultimately result in a progressive decline in cardiac performance. Pharmacological and genetic manipulation of cultured heart cells and animal models of HF and the analysis of cardiac samples from patients with HF are all used to identify the molecular and cellular mechanisms leading to the disease. Protein kinase C (PKC) isozymes, a family of serine–threonine protein kinase enzymes, were found to regulate a number of cardiac responses, including those associated with HF. In this review, we describe the PKC isozymes that play critical roles in specific aspects of cardiac remodelling and dysfunction in HF

Ruboxistaurin: Review of Safety and Efficacy in the Treatment of Diabetic Retinopathy

Ruboxistaurin (Eli Lilly, Indianapolis, IN), an orally active inhibitor of the β isoform of protein kinase C (PKC), has been studied as a systemic treatment for diabetic retinopathy. PKC-β appears to be overactivated in response to hyperglycemia. This overactivation associates with various pathological effects within the retinal vascular system, including ischemia, vascular leakage, and angiogenesis. Several randomized clinical trials of ruboxistaurin have been performed. In most trials, the primary outcomes were not achieved. Analysis of secondary outcomes data from these trials has demonstrated some evidence of safety and efficacy in the treatment of diabetic retinopathy. At this time, ruboxistaurin has not received approval from the US Food and Drug Administration