Abstract：
:Diabetic retinopathy remains the most common microvascular complication suffered by diabetic patients and is the leading cause of registerable blindness in the working population of developed countries. The clinicopathological lesions of diabetic retinopathy have been well characterised and although a multitude of pathogenic mechanisms have been proposed, the underlying dysfunctional biochemical and molecular pathways that lead to initiation and progression of this complication remain largely unresolved. There is little doubt that the pathogenesis of diabetic retinopathy is highly complex and there is a pressing need to establish new therapeutic regimens that can effectively prevent or limit retinal microvascular cell dysfunction and death which is characteristic of the vasodegenerative stages of diabetic retinopathy. The formation and accumulation of advanced glycation endproducts (AGEs) and/or advanced lipoxidation endproducts (ALEs) are among several pathogenic mechanisms that may contribute to diabetic retinopathy. AGEs/ALEs can form on the amino groups of proteins, lipids and DNA through a number of complex pathways including non-enzymatic glycation by glucose and reaction with metabolic intermediates and reactive dicarbonyl intermediates. These reactions not only modify the structure and function of proteins, but also cause intra-molecular and intermolecular cross-link formation. AGEs/ALEs are known to accumulate in the diabetic retina where they may have important effects on retinal vascular cell function, as determined by a growing number of in vitro and in vivo studies. Evidence now points towards a pathogenic role for advanced glycation/lipoxidation in the initiation and progression of diabetic retinopathy and this review will examine the current state of knowledge of AGE/ALE-related pathology in the diabetic retina at a cellular and molecular level. It will also outline how recent pharmaceutical strategies to inhibit AGE/ALE formation or limit their pathogenic influence during chronic hyperglycaemia may play a significant role in the treatment of diabetic retinopathy.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Stitt AW,Frizzell N,Thorpe SRdoi
10.2174/1381612043383124subject
Has Abstractpub_date
2004-01-01 00:00:00pages
3349-60issue
27eissn
1381-6128issn
1873-4286journal_volume
10pub_type
杂志文章,评审abstract：:The beneficial effect of antihypertensive treatment on the risk of major vascular events is well established. Several trials comparing older and newer drugs in the treatment of primary hypertension suggested that it is the blood pressure achieved, rather than choice of the drug that determines most of the primary outc...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/138161207779313713
更新日期：2007-01-01 00:00:00
abstract：:Prostaglandin (PG) D(2), the major cyclooxygenase metabolite generated from immunologically stimulated mast cells, is thought to contribute to the pathogenesis of allergic diseases due to its various inflammatory effects. However, the lack of PGD(2) (DP) receptor antagonists has limited the study of its essential role...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/1381612043382864
更新日期：2004-01-01 00:00:00
abstract：:A large body of evidence has accumulated indicating involvement of oxidative stress (OS) in the mode of action of various bioactive substances, including those of the immune system. The data for anticancer drugs (main and miscellaneous) are summarized herein. Although diverse origins pertain, reactive oxygen species (...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/1381612003401046
更新日期：2000-02-01 00:00:00
abstract：:Protection of the brain is strengthened by active transport and ABC transporters. P-glycoprotein (P-gp) at the blood-brain barrier (BBB) functions as an active efflux pump by extruding a substrate from the brain, which is important for maintaining loco-regional homeostasis in the brain and protection against toxic com...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/138161211797440122
更新日期：2011-01-01 00:00:00
abstract：:Natural products, or their synthetic derivatives are a treasure trove to find potential candidates for novel drugs for human treatment. The selection of diamonds from the huge pile of worthless stone is a critical--and difficult--stage in the discovery pipeline. Of all the factors to be considered, perhaps the most im...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/1381612821666151002114227
更新日期：2015-01-01 00:00:00
abstract：:Cytokines are known to play a key role in regulation of gastric functions. Interferon-alpha (IFN-α) has been published to impair gastric motility. Aims of this study were to clarify effect of IFN-α on gastric acid secretion (GAS) and determine role of nitric oxide (NO) in the process. Both subcutaneous (1000, 10000, 1...
journal_title：Current pharmaceutical design
pub_type： 杂志文章
doi：10.2174/13816128130104
更新日期：2013-01-01 00:00:00
abstract：:LIM (Lin-11, Isl-1, Mec-3), RING (Really interesting new gene), PHD (Plant homology domain) and MYND (myeloid, Nervy, DEAF-1) domains are all zinc-binding domains that ligate two zinc ions. Unlike the better known classical zinc fingers, these domains do not bind DNA, but instead mediate interactions with other protei...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/138161209789271861
更新日期：2009-01-01 00:00:00
abstract：BACKGROUND:Central serous chorioretinopathy (CSC) is the fourth most frequent retinal disorder in terms of prevalence. It typically occurs in young subjects and affects men more often than women. CSC is characterized by serous retinal detachment (SRD) involving mainly the macular area. The clinical course is usually se...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/1381612825666190123165914
更新日期：2018-01-01 00:00:00
abstract：:Antimicrobial photodynamic therapy (aPDT) is an emerging alternative to antibiotics motivated by growing problems with multi-drug resistant pathogens. aPDT uses non-toxic dyes or photosensitizers (PS) in combination with harmless visible of the correct wavelength to be absorbed by the PS. The excited state PS can form...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/138161211795703735
更新日期：2011-01-01 00:00:00
abstract：:Cardiac arrhythmias remain a major source of morbidity and mortality in developed countries. Antiarrhythmic drug therapy was traditionally the mainstay of cardiac arrhythmia treatment; however, drug therapy of cardiac arrhythmias has been plagued by incomplete efficacy and by potentially serious adverse reactions, of ...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/1381612054021051
更新日期：2005-01-01 00:00:00
abstract：:Current antiretroviral therapy has had a significant impact on HIV associated morbidity and mortality. Despite these positive outcomes current antiretroviral regimens have significant deficiencies which include multiple drug-drug interactions, high pill burdens, and considerable financial expense. Perhaps the greatest...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/138161206776055868
更新日期：2006-01-01 00:00:00
abstract：:Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent causes of hepatic dysfunction and is highly correlated with components of the metabolic syndrome such as obesity, insulin resistance and type 2 diabetes. Among others, nutritional factors, physical inactivity, genetic variants and visceral obesity h...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/138161210791208938
更新日期：2010-06-01 00:00:00
abstract：:The most important glycoproteins of trypanosomatids are anchored by glycoinositolphospholipids (GIPLs) to their plasma membrane. In addition, free GIPLs have been described, for instance the lipopeptidophosphoglycan (LPPG) which is a major component of the surface of T. cruzi epimastigotes. An inositolphosphoceramide ...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/1381612013397519
更新日期：2001-08-01 00:00:00
abstract：:Immune activation not only accompanies inflammation in various disorders including infections, autoimmune syndromes and cancer, but it also represents a characteristic feature of ageing. Immune deviations which are most widely expressed in the elderly include increased neopterin production and tryptophan breakdown. Th...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/1381612820666140317110217
更新日期：2014-01-01 00:00:00
abstract：:While it is well documented that the mitogenic actions of estrogens are critical in the development and progression of human breast and some gynecologic cancers, only latest data demonstrate a crucial involvement of estrogen-signaling in the carcinogenesis of non-classical estrogen target tissues, as colon, prostate, ...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/138161212800626139
更新日期：2012-01-01 00:00:00
abstract：:Diabetic macular edema (DME) represents the most common cause of vision loss in patients affected by diabetes mellitus. Although the pathophysiology of DME is not wholly understood, vascular endothelial growth factor (VEGF) has been identified as a key contributor to the development of DME. In addition, latest informa...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/1381612821666150909095756
更新日期：2015-01-01 00:00:00
abstract：:Cumulative scientific evidence gathered over the past ten years has confirmed the role of platelet GP IIb/IIIa inhibitors in reducing ischemic complications of patients undergoing percutaneous coronary intervention (PCI). Recently, mortality data available on more than 20,000 patients enrolled in randomized clinical t...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/1381612043453306
更新日期：2004-01-01 00:00:00
abstract：:Cardiovascular diseases remain the leading cause of morbidity and mortality among postmenopausal women in western societies. There are still no specific and highly efficient methods of preservation of women's vascular health in modern preventive medicine. For many years physicians have assumed that hormone replacement...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/1381612822666151112150520
更新日期：2016-01-01 00:00:00
abstract：:Infections are the most common inflammatory triggers and acute and chronic infections have been associated with the development and progression of atherosclerotic disease raising interest in the infectious hypothesis of atherosclerosis. Pathogens have been identified in atherosclerotic plaques and large epidemiologica...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：
更新日期：2013-01-01 00:00:00
abstract：:The concept of probiotics has evolved immensely since it was first proposed a century ago. There are numerous potential health benefits attributed to certain probiotic bacteria, from preventing gastrointestinal (GI) infections to stimulating the immune system. Recent evidence is now quite compelling for a role of prob...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/138161208784480234
更新日期：2008-01-01 00:00:00
abstract：:The introduction of highly active anti-retroviral therapy (HAART) for Human Immunodeficiency Virus (HIV) infection has significantly improved the life expectancy of HIV positive patients. Hepatitis C virus (HCV) co-infection is common in HIV infected patients and is now a significant cause of morbidity and mortality. ...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/1381612043384286
更新日期：2004-01-01 00:00:00
abstract：:Inflammatory bowel disease (IBD) is a group of disorders characterized by chronic inflammation within the gastrointestinal tract. It is a multifactorial disease associated with immune-cell mediated oxidative damage to the intestinal mucosa. There is no cure for IBD, but anti-cytokine therapy can limit target inflammat...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/1381612824666180717110236
更新日期：2018-01-01 00:00:00
abstract：:Syncytin-1 is a protein coded by a human endogenous retrovirus (HERV) gene of the HERV-W family (HERVWE1). Syncytin- 1 mediates formation of syncytiotrophoblasts through fusion of cytotrophoblasts, a hallmark of terminal differentiation of placental trophoblast linage. Syncytin-1 also possesses nonfusogenic functions ...
journal_title：Current pharmaceutical design
pub_type： 杂志文章
doi：10.2174/13816128113199990541
更新日期：2014-01-01 00:00:00
abstract：:Chronic smoking is associated with functional and structural vascular changes underlying inflammatory processes responsible for plaque formation and rupture. Cyclooxygenase (COX) is the key enzyme linking smoking action to inflammatory damages: it is responsible for the conversion of arachidonic acid to prostanoids, a...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/138161210792062902
更新日期：2010-01-01 00:00:00
abstract：:The human herpesviruses herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) can cause severe recurrent disease in humans and establish lifelong infection in their hosts. Several antiviral therapies are available to control disease and spread, but these are not completely effective and do not affect latent virus. The ...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/138161207781039760
更新日期：2007-01-01 00:00:00
abstract：:Metal ions that leach into biotherapeutic drug product solution during manufacturing and storage, result in contamination that can cause physico-chemical degradation of the active molecule. In this review, we describe various mechanisms by which metal ion leachates can interact with therapeutic proteins and antibodies...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/13816128113199990063
更新日期：2014-01-01 00:00:00
abstract：:Over the past five decades, the pharmacological treatment of depression has been based on the pathophysiological hypothesis of a deficiency in monoamines, mainly serotonin and noradrenaline. Antidepressant prescribed today, all of them designed to enhance central monoaminergic tone, present several important limitatio...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/138161211795164086
更新日期：2011-01-01 00:00:00
abstract：BACKGROUND:The HERC family contains six members from HERC1 to HERC6 that are featured with the HECT domains that exerts ubiquitin ligase activity and the RCC1-like domains that are involved in cell cycle regulation. Although identified as early as 1990s, their biological functions are extensively studied in recent year...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/1381612824666180528081024
更新日期：2018-01-01 00:00:00
abstract：:Drug discovery is generally considered as a costly affair and it takes approximately 15 years to reach a new chemical entity into the market. Among the recent potent drug molecules with most effective pharmacological properties, very few reached for Phase I clinical trial in humans. Unfortunately, the historical avera...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/1381612825666190618121553
更新日期：2019-01-01 00:00:00
abstract：:The liver acts as a host to many functions hence raising the possibility that any one may be compromised by a single gene defect. Inherited or de novo mutations in these genes may result in relatively mild diseases or be so devastating that death within the first weeks or months of life is inevitable. Some diseases ca...
journal_title：Current pharmaceutical design
pub_type： 杂志文章,评审
doi：10.2174/138161211797247541
更新日期：2011-01-01 00:00:00
