Inflammatory angiogenesis in atherogenesis--a double-edged sword

The adventitia and the outer layers of media of an atherosclerosis-prone arterial wall are vascularized by vasa vasorum. Upon growth of an atherosclerotic lesion in the intima, neovascular sprouts originating from the adventitial vasa vasorum enter the lesion, the local proangiogenic micromilieu in the lesion being created by intramural hypoxia, by increased intramural oxidant stress, and by inflammatory cell infiltration (macrophages, T cells and mast cells). The angiogenic factors present in the lesions include various growth factors, chemokines, cytokines, proteinases, and several other factors possessing direct or indirect angiogenic activities, while the current list of antiangiogenic factors is smaller. An imbalance between endogenous inducers and inhibitors of angiogenesis, with a predominance of the former ones, is essential for the development of neovessels during the progression of the lesion. By providing oxygen and nutrients to the cells of atherosclerotic lesions, neovascularization initially tends to prevent cellular death and so contributes to plaque growth and stabilization. However, the inflammatory cells may induce rupture of the fragile neovessels, and so cause intraplaque hemorrhage and ensuing plaque destabilization. Pharmacological inhibition of angiogenesis in atherosclerotic plaques with ensuing inhibition of lesion progression has been achieved in animal models, but clinical studies aiming at regulation of angiogenesis in the atherosclerotic arterial wall can be designed only after we have reached a firm conclusion about the role of angiogenesis at various stages of lesion development--good or bad.     

Looking after everyone except yourself: the double-edged sword of caring

Caring is, in a broad sense, a basic phenomenon of human life (Benner and Wrubel, 1989; Noddings 1999) and an intrinsic part of what it is to be human. In other words, human beings may not consciously choose to care, but caring is inherent in them: it is an activity encountered beyond the boundaries of nursing, and certainly not unique to nursing or to the overtly 'caring' services, such as palliative care provision in the community, hospitals and hospices.     

Inflammatory response in acute traumatic brain injury: a double-edged sword

Inflammation is an important part of the pathophysiology of traumatic brain injury. Although the central nervous system differs from the other organs because of the almost complete isolation from the blood stream mediated by the blood-brain barrier, the main steps characterizing the immune activation within the brain follow a scenario similar to that in other organs. The key players in these processes are the numerous immune mediators released within minutes of the primary injury. They guide a sequence of events including expression of adhesion molecules, cellular infiltration, and additional secretion of inflammatory molecules and growth factors, resulting in either regeneration or cell death. The question is this: to what extent is inflammation beneficial for the injured brain tissue, and how does it contribute to secondary brain damage and progressive neuronal loss? This review briefly reports recent evidence supporting the dual, the beneficial, or the deleterious role of neuroinflammation after traumatic brain injury.     

Epoxyeicosatrienoic acids: a double-edged sword in cardiovascular diseases and cancer

Epoxyeicosatrienoic acids (EETs) generated from arachidonic acid by cytochrome P450 (CYP) epoxygenases have beneficial effects in certain cardiovascular and kidney diseases. Hence, great efforts have been made to develop drugs targeting the EET pathway. Some of these agents are currently under evaluation in clinical trials for treatment of hypertension and diabetes. In this issue of the JCI, Panigrahy et al. evaluate in a systematic way the role of CYP epoxygenases and the metabolites they generate in cancer progression. Their findings, along with previous studies, raise concerns about using these drugs in humans.     

Prenatal and neonatal testing and screening: a double-edged sword

This article describes some of the more commonly requested prenatal and neonatal screenings and diagnostic tests. Additionally, it outlines the incidence and etiology of specific conditions followed by treatment and counseling options. Finally, issues regarding the ethics involved in testing are discussed. Practical recommendations and responsibilities for the nurse are interwoven throughout the article.