Strategies to prevent and reverse liver fibrosis in humans and laboratory animals.

Liver fibrosis results from chronic damage to the liver in conjunction with various pathways and is mediated by a complex microenvironment. Based on clinical observations, it is now evident that fibrosis is a dynamic, bidirectional process with an inherent capacity for recovery and remodeling. The major mechanisms involved in liver fibrosis include the repetitive injury of hepatocytes, the activation of the inflammatory response after injury stimulation, and the activation and proliferation of hepatic stellate cells (HSCs), which represents the major extracellular matrix (ECM)-producing cells, stimulated by hepatocyte injury and inflammation. The microenvironment in the liver is synergistically regulated abnormal ECM deposition, scar formation, angiogenesis, and fibrogenesis. Moreover, recent studies have clarified novel mechanism in fibrosis such as epigenetic regulation of HSCs, the leptin and PPARγ pathways, the coagulation system, and even autophagy. Uncovering the mechanisms of liver fibrogenesis provides a basis to develop potential therapies to reverse and treat the fibrotic response, thereby improving the outcomes of patients with chronic liver disease. Although both scientific and clinical challenges remain, emerging studies attempt to reveal the ideal anti-fibrotic drug that could be easily delivered to the liver with high specificity and low toxicity. This review highlights the mechanisms, including novel pathways underlying fibrogenesis that may be translated into preventive and treatment strategies, reviews both current and novel agents that target specific pathways or multiple targets, and discusses novel drug delivery systems such as nanotechnology that can be applied in the treatment of liver fibrosis. In addition, we also discuss some current treatment strategies that are being applied in animal models and in clinical trials.

Serum S-100 beta protein during coronary artery bypass graft surgery with or without cardiopulmonary bypass.

BACKGROUND: Brain damage is a serious complication of cardiac anesthesia. The purpose of this study was to detect brain damage at different surgical stages during coronary artery bypass graft with or without cardiopulmonary bypass. METHODS: We conducted a prospective, longitudinal study to evaluate serum S-100 beta protein, an early marker of brain injury, in patients electively undergoing off-pump (n = 30) or traditional coronary artery bypass graft (n = 60). Blood was sampled immediately before anesthesia, before and after cardiopulmonary bypass, and on the day after surgery. RESULTS: Serum S-100 beta protein was lowest immediately before induction of anesthesia and significantly increased before and after cardiopulmonary bypass, then declined by the first postoperative day in both groups. Peak values were highest in the traditional group directly after coronary artery bypass graft. On the day after surgery, S-100 beta protein levels were similar between groups, but were higher than baseline within each group. Significant increase in serum S-100 beta protein was also observed even before cardiopulmonary bypass in cardiopulmonary bypass patients, or before manipulation of the heart and aorta in off-pump patients. These reflect the possibility that brain damage may occur before major manipulation (cardiopulmonary bypass or manipulating heart and aorta). Moreover, S-100 beta levels did not return to normal on the day after the operation. CONCLUSIONS: This prospective study has shown that serum S-100 beta protein was not only higher than baseline both after cardiopulmonary bypass and on the day after surgery in both groups of patients but it was also significantly increased before cardiopulmonary bypass or manipulation of the heart or aorta. These findings may have implications for anesthesiologic care during the total course of cardiac surgery.