Should we treat soft tissue injuries with Actovegin

Actovegin is a biological drug produced from deproteinised hemodialysate of calf serum with over 50 years of history for its clinical use. There have been many in vitro studies to speculate its potential role and mechanism of action in cells; due to the nature of this drug and serum based culture techniques for most in vitro experiments, presumptuous conclusions and claims from these studies on performance enhancement should be cautiously interpreted. There have been well-designed human in vivo studies suggesting it does not enhance human performance, and has potentially good clinical applications to treat injuries, strokes and diabetes. Recently, evidence has emerged suggesting Actovegin has anti-inflammatory and anti apoptotic effects on injured tissues; further clinical research is needed to define these effects. This article also provides a narrative review of Actovegin summarizing outcomes from recent publications

Regulation of ADAMTS-1, -4 and -5 expression in human macrophages: Differential regulation by key cytokines implicated in atherosclerosis and novel synergism between TL1A and IL-17

Atherosclerosis is an inflammatory disease of the vasculature regulated by cytokines. Macrophages play a crucial role at all stages of this disease, including regulation of foam cell formation, the inflammatory response and stability of atherosclerotic plaques. For example, matrix metalloproteinases produced by macrophages play an important role in modulating plaque stability. More recently, the ADAMTS proteases, which are known to play a key role in the control of cartilage degradation during arthritis, have been found to be expressed in atherosclerotic lesions and suggested to have potentially important functions in the control of plaque stability. Unfortunately, the action of cytokines on the expression of ADAMTS family in macrophages is poorly understood. We have investigated the effect of classical cytokines (IFN-γ and TGF-β) and those that have been recently identified (TL1A and IL-17) on the expression of ADAMTS-1, -4 and -5 in human macrophages. The expression of all three ADAMTS members was induced during differentiation of monocytes into macrophages. TGF-β had a differential action with induction of ADAMTS-1 and -5 expression and attenuation in the levels of ADAMTS-4. In contrast, IFN-γ suppressed the expression of ADAMTS-1 without having an effect on ADAMTS-4 and -5. Although TL-1A or IL-17A alone had little effect on the expression of all the members, they induced their expression synergistically when present together. These studies provide new insight into the regulation of key ADAMTS family members in human macrophages by major cytokines in relation to atherosclerosis