Current Pharmaceutical Design - Volume 12, Issue 23, 2006

We are delighted to introduce this Special Issue of Current Pharmaceutical Design. This collection of review articles from leading international experts in the field explores the main aspects of pharmacological modulation of liver ischemia-reperfusion injury (IRI) and confirms this Journal's commitment to publication of high-quality reviews at the interface between life sciences and clinical application. IRI is a phenomenon w Read More

Hepatic ischemia/reperfusion injury is a complication of liver resection surgery, transplantation and hypovolemic shock, leading to local and remote cellular damage and organ dysfunction. This injury is largely a result of an acute inflammatory response characterized by the induction of a cascade of proinflammatory mediators that culminates in the recruitment of leukocytes to the post-ischemic tissue leading to parenchy Read More

Ischemia-reperfusion (IR) injury is a multifactorial process triggered when the liver or other organs are transiently subjected to reduced blood supply followed by reperfusion. It has been shown that "reactive oxygen species" (ROS) are generated during ischemia and reperfusion and may represent pivotal mediators of the ensuing pathological complications. In some cases, however, moderate production of ROS may exert Read More

Thiol-containing compounds have an essential role in many biochemical reactions due to their ability to be easily oxidised and then quickly regenerated. Main representatives are glutathione, lipoic acid and thioredoxin which are synthesised de novo in mammalian cells. N-acetylcysteine and Bucillamine are synthetic thiols which have been administered in experimental and clinical studies for treatment of conditions associ Read More

Oxidative and nitrosative stress triggers DNA strand breakage, which then activates the nuclear enzyme poly(ADP-ribose) polymerase (PARP). One of the key triggers of DNA single strand breakage in pathophysiological conditions is peroxynitrite, a reactive species produced from the reaction of nitric oxide and superoxide. Activation of PARP can dramatically lower the intracellular concentration of its substrate, nicotinamide adeni Read More

This review highlights recent advances in our understanding of intracellular mechanisms underlying programmed cell death in hepatic ischemia / reperfusion injury. A range of molecules have been tested with the intention to block the pathways of programmed cell death at different levels and to thereby enhance viability of the liver in surgical procedures including liver transplantation. Cellular death receptors, the mitochondrial Read More

Liver ischemia-reperfusion injury is characterized by cell necrosis and apoptosis and by profound modifications in the extracellular matrix (ECM). During the complex series of events that take place both during ischemia and when normal blood flow is restored (reperfusion), a concerted regulation of release and activation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) mainly by st Read More

Ischemia reperfusion (IR) of the liver is a multifactorial process that, at least in part, is responsible for the morbidity associated with major liver surgery under occlusion of the portal triad with the Pringle maneuver, total vascular exclusion or after liver transplantation. Surgeons are confronted with IR injury (IRI) more often than they anticipate. Although the human body has its own defense system, understanding the Read More

Glycine is a non-essential amino acid which is cheap, easily available and relatively non-toxic. It is composed of a single carbon attached to an amino and a carboxyl group, with a molecular weight of 75. It is involved in the production of bile, nucleic acids, porphyrins and creatine phosphate. It is part of the normal human diet and is used clinically, as an irrigant solution in urological and gynaecological procedures. Glycine has Read More

Ischemia and reperfusion injury (IRI) is a prime antigen-independent inflammatory factor in the dysfunction of liver transplants. Despite improved allograft preservation and surgical techniques, IRI can still cause up to 10% of early orthotopic liver transplant failure, and can lead to a higher incidence of both acute and chronic graft rejection. Recent advances in gene transfer have resulted in a reduction or inhibition of liver I Read More

It has been shown that capsaicin-sensitive afferent fibers play a crucial role in acute gastroprotection. Release of neurotransmitters such as calcitonin gene-related peptide (CGRP) and the consequent increase in mucosal blood flow have been identified as key factors in the protective effect of the stimulation of these fibers by capsaicin. Conversely the involvement of sensory nerves in the process of tissue repair after Read More

Lithium augmentation refers to the addition of lithium to an antidepressant in the acute treatment phase of patients with depressive episodes who have failed to respond satisfactorily to treatment with antidepressant monotherapy. This article reviews the clinical evidence and hypotheses on the mode of action of lithium augmentation. For this purpose, studies were identified by searching Medline and by scanning the references o Read More