Ischemia-reperfusion injury of the intestine is a significant problem in abdominal aortic aneurysm surgery, small bowel transplantation, cardiopulmonary bypass, strangulated hernias, and neonatal necrotizing enterocolitis. It can also occur as a consequence of collapse of systemic circulation, as in hypovolemic and septic shock. It is associated with a high morbidity and mortality. This article is a comprehensive review of the current status of the molecular biology and the strategies to prevent ischemia-reperfusion injury of the intestine. Various treatment modalities have successfully been applied to attenuate reperfusion injury in animal models of reperfusion injury of the intestine. Ischemic preconditioning has been found to be the most promising strategy against reperfusion injury during the last few years, appearing to increase the tolerance of the intestine to reperfusion injury. Although ischemic preconditioning has been shown to be beneficial in the human heart and the liver, prospective controlled studies in humans involving ischemic preconditioning of the intestine are lacking. Research focused on the application of novel drugs that can mimic the effects of ischemic preconditioning to manipulate the cellular events during reperfusion injury of the intestine is required.

Oxidative stress is an important factor in many pathological conditions such as inflammation, cancer, ageing and organ response to ischemia-reperfusion. Humans have developed a complex antioxidant system to eliminate or attenuate oxidative stress. Liver ischemia-reperfusion injury occurs in a number of clinical settings, including liver surgery, transplantation, and hemorrhagic shock with subsequent fluid resuscitation, leading to significant morbidity and mortality. It is characterized by significant oxidative stress but accompanied with depletion of endogenous antioxidants. This review has 2 aims: firstly, to highlight the clinical significance of liver ischemia-reperfusion injury, the underlying mechanisms and the main pathways by which the antioxidants function, and secondly, to describe the new developments that are ongoing in antioxidant therapy and to present the experimental and clinical evidence about the role of antioxidants in modulating hepatic ischemia-reperfusion injury. (Liver

Fatty liver or hepatic steatosis, which is the result of the abnormal accumulation of triacylglycerol within the cytoplasm of hepatocytes, is a common histological finding in human liver biopsy specimens that is attributed to the effects of alcohol excess, obesity, diabetes, or drugs. There is a general consensus that fatty liver compromises hepatic microcirculation, the common exchange network upon which hepatic arterial and portal inflows converge, regardless of underlying etiology. A significant reduction in hepatic microcirculation has been observed in human fatty donor livers and in experimental models of hepatic steatosis. There is an inverse correlation between the degree of fat infiltration and both total hepatic blood flow and flow in microcirculation. Fatty accumulation in the cytoplasm of the hepatocytes is associated with an increase in the cell volume that reduces the size of the hepatic sinusoid space by 50% compared with a normal liver and may result in partial or complete obstruction of the hepatic sinusoid space. As a result of impaired hepatic microcirculation, the hepatocytes of the fatty liver have reduced tolerance against ischemia-reperfusion injury, which affects about 25% of the donors for liver transplantation because severe steatosis is associated with a high risk of primary nonfunction after liver transplantation.

No abstract

Insulin-like growth factor binding protein-4 (IGFBP-4) is an important member of the insulin-like growth factor (IGF) system. The IGFBP-4 has three domains of which the N-terminal sequence is important for the binding of IGF. It acts as a transport protein for IGF-I and IGF-II and modulates their biological effects. There is increasing evidence that IGFBP-4 inhibits IGF-induced cellular growth both in vitro and in vivo. IGFBP-4 can also mediate its actions through a mechanism independent of IGFs. IGFBP-4 level and expression in various tissues are influenced by IGFBP protease, nutrition, several growth factors and hormones. Overexpression of IGFBP-4 in transgenic animal models causes reduced growth of organs containing smooth muscle. Most cancers express IGFBP-4 at levels which correlate with their state of differentiation. However, the effects of IGFBP-4 on tumor growth are uncertain. In vitro studies have shown that overexpression of IGFBP-4 inhibit the growth of some colon cancer cells. Overexpression of IGFBP-4 in vivo has been reported to decrease the growth of prostate cancer. The effect of altered expression of IGFBP-4 in vivo in colon and other cancers needs to be explored as locally available IGFs appear to stimulate mitogenesis. Contents 1. Introduction 2. Structure and binding characteristics of IGFBP-4 3. Biological actions of IGFBP-4 4. Factors controlling IGFBP-4 expression 5.

In nature, the self-assembly of sequence-specific biopolymers into hierarchical structures plays an essential role in the construction of functional biomaterials. To develop synthetic materials that can mimic and surpass the function of these natural counterparts, various sequence-defined bio- and biomimetic polymers have been developed and exploited as building blocks for hierarchical self-assembly. This review summarizes the recent advances in the molecular self-assembly of hierarchical nanomaterials based on peptoids (or poly-N-substituted glycines) and other sequence-defined synthetic polymers. Modern techniques to monitor the assembly mechanisms and characterize the physicochemical properties of these self-assembly systems are highlighted. In addition, discussions about their potential applications in biomedical sciences and renewable energy are also included. This review aims to highlight essential features of sequence-defined synthetic polymers (e.g., high stability and protein-like high-information content) and how these unique features enable the construction of robust biomimetic functional materials with high programmability and predictability, with an emphasis on peptoids and their self-assembled nanomaterials.

The main protective effect of NAC becomes apparent 5 h after hepatic ischaemic injury.

Ischemic premnditioning (IPC) may pmtcct the liver fmm ischemia reperfusion injury by nitric oxide formation. This d v has invatinated the dfcct of ischemic Ischemic preconditioning (IPC) is a potential therapeutic strategy, which may increase the tolerance of the liver to ischemic insults ofsurgery and preservation. It refers to the phenomenon of initial brief period of ischemia improving tolerance to subsequent sustained ischemia. An increase in ischemic tissue tolerance could decrease the morbidity and mortality associated with IRI. The existence of hepatic IPC in animal~9.'~ as well as humansll has been demonstrated but the mechanism