Idiopathic retroperitoneal fibrosis with particular perirenal and intrarenal extension associated with left renal artery stenosis. The atheromatous periaortitis with retroperitoneal fibrosis suggests a pathogenic relationship between atherosclerosis and fibrosis?

We present a case of idiopathic retroperitoneal fibrosis (RPF) in a female patient of 45 years, obese (BMI = 39 kg/sqm), hypertensive since 2005, with diabetes mellitus treated with diet and diabetes insipidus in whom, during a routine control, the following has been found: serum creatinine 1.74 mg/dl, and an inflammatory syndrome associated with fever. Spiral-CT (Multi-slice-Sensation 64) scan shows retroperitoneal fibrosis in relation with periaortitis that affects the thoracic and abdominal aorta. RPF is extending perirenally and at the level of the renal hilum with subsequent calyceal dilations (hydrocalycosis) associated with left renal artery stenosis. The particularity of the case is represented by the perirenal and intrarenal evolution of fibrosis with left renal artery stenosis with moderate impairment of renal function reversible under treatment with Tamoxifen. This case, with chronic periaortitis subsequent to an extended aortic atherosclerosis with retroperitoneal fibrosis can be representative for the pathogenic relationship between atherosclerosis and fibrosis.     

5例继发性腹膜后纤维化诊治分析

目的继发性腹膜后纤维化(retroperitoneal fibrosis,RPF)发病率低,临床缺乏特征性表现,早期诊断困难,常致误治。通过总结分析后,旨在提高对该病的早期诊断率。方法回顾性分析继发于胃肠道手术后RPF5例患者的诊疗经过进行总结分析。结果继发于恶性肿瘤行肠梗阻转流术3例和乙状结肠造瘘术1例后于3~13周内死亡,继发于外伤性行肠梗阻转流后效果良好。结论遇到患者腹部手术后1~3个月之间,如出现主诉模糊不清和出现不同程度的腹、腰背疼痛或腹部肿块,而临床上又不能用某些疾病进行解释时,应考虑到RPF的可能。B超可以了解肾盂积水情况,CT和MRI检查对RPF的诊断和鉴别诊断有重要价值。非恶性肿瘤的RPF在炎症活动期应内科治疗,晚期出现腹膜后空腔脏器梗阻时则需外科手术治疗,而继发于恶性肿瘤者预后极差。     

Involvement of oxidative stress and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in inflammatory bowel disease

The pathophysiology of inflammatory bowel disease involves excessive immune effects of inflammatory cells against gut microbes. In genetically predisposed individuals, these effects are considered to contribute to the initiation and perpetuation of mucosal injury. Oxidative stress is a fundamental tissue-destructive mechanisms that can occur due to the reactive oxygen species and reactive nitrogen metabolites which are released in abundance from numerous inflammatory cells that have extravasated from lymphatics and blood vessels to the lamina propria. This extravasation is mediated by interactions between adhesion molecules including mucosal addressin cell adhesion molecule-1 and vascular cell adhesion molecule-1 on the surface of lymphocytes or neutrophils and their ligands on endothelial cells. Thus, reactive oxygen species and adhesion molecules play an important role in the development of inflammatory bowel disease. The present review focuses on the involvement of oxidative stress and adhesion molecules, in particular mucosal addressin cell adhesion molecule-1, in inflammatory bowel disease.     

Oncostatin M is a proinflammatory mediator. In vivo effects correlate with endothelial cell expression of inflammatory cytokines and adhesion molecules.

Oncostatin M is a member of the IL-6 family of cytokines that is primarily known for its effects on cell growth. Endothelial cells have an abundance of receptors for oncostatin M, and may be its primary target. We determined if oncostatin M induces a key endothelial cell function, initiation of the inflammatory response. We found that subcutaneous injection of oncostatin M in mice caused an acute inflammatory reaction. Oncostatin M in vitro stimulated: (a) polymorphonuclear leukocyte (PMN) transmigration through confluent monolayers of primary human endothelial cells; (b) biphasic PMN adhesion through rapid P-selectin expression, and delayed adhesion mediated by E-selectin synthesis; (c) intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 accumulation; and (d) the expression of PMN activators IL-6, epithelial neutrophil activating peptide-78, growth-related cytokine alpha and growth-related cytokine beta without concomitant IL-8 synthesis. The nature of the response to oncostatin M varied with concentration, suggesting high and low affinity oncostatin M receptors independently stimulated specific responses. Immunohistochemistry showed that macrophage-like cells infiltrating human aortic aneurysms expressed oncostatin M, so it is present during a chronic inflammatory reaction. Therefore, oncostatin M, but not other IL-6 family members, fulfills Koch's postulates as an inflammatory mediator. Since its effects on endothelial cells differ significantly from established mediators like TNFalpha, it may uniquely contribute to the inflammatory cycle.     

Effect of gold sodium thiomalate and its thiomalate component on the in vitro expression of endothelial cell adhesion molecules.

Endothelial adhesion molecules play an important role in the tissue recruitment of leukocytes in inflammatory conditions such as rheumatoid arthritis. We have investigated the effect of the antirheumatic drug gold sodium thiomalate on adhesion molecule protein and mRNA expression in cultured human endothelial cells. Gold sodium thiomalate inhibited cytokine (TNF, IL-1, IL-4)-stimulated expression of vascular cell adhesion molecule-1 and E-selectin but not intercellular adhesion molecule-1 on endothelial cells. Gold sodium thiomalate also suppressed TNF-stimulated increases in vascular cell adhesion molecule-1 and E-selectin mRNA levels but had no effect on intercellular adhesion molecule-1 mRNA. Thiomalate (mercaptosuccinate), but not gold thioglucose or D-penicillamine, mimics the effect of gold sodium thiomalate at equimolar concentrations. We propose that the inhibition of vascular cell adhesion molecule-1 and E-selectin expression by gold sodium thiomalate is due to its thiomalate and not its gold component. Gold sodium thiomalate has a direct effect on endothelial adhesion molecule expression, and this may contribute to its antiinflammatory activity.     

Retrograde inflammatory signaling from neutrophils to endothelial cells by soluble interleukin-6 receptor alpha.

Endothelial cells initiate the inflammatory response by recruiting and activating leukocytes. IL-6 is not an agonist for this, but we found soluble IL-6 receptor alpha-subunit (IL-6Ralpha), with their constitutive IL-6 synthesis, stimulated endothelial cells to synthesize E-selectin, intracellular adhesion molecule-1, vascular cellular adhesion molecule-1, IL-6, and IL-8, and to bind neutrophils. Neutrophils express significant amounts of IL-6Ralpha and upon stimulation shed it: this material activates endothelial cells through a newly constituted IL-6 receptor. Retrograde signaling from PMN activated in the extravascular compartment to surrounding endothelial cells will recruit more and a wider variety of leukocytes. The limiting signal is a soluble receptor, not a cytokine.     

腹膜后纤维化与肾积水发生关系的临床研究

目的：探讨腹膜后纤维化（RPF）导致肾积水的原因及诊治经验。方法：回顾分析2004年1月—2010年12月24例腹膜后纤维化致肾积水患者的诊治资料。结果：（1）RPF患者常见首发症状为腰背痛或腹痛（69.2%）;（2）红细胞沉降率（ESR）增快和血清IgG4升高最常见。超声检查仅提示上尿路积水。RPF的静脉肾盂造影（IVP）和CT尿路成像（CTU）表现具有特征性。IVP肾盂输尿管显影不良时,CTU能较清晰的显示上尿路影像。CT扫描发现腹膜后软组织肿块9例（37.5%）,优于超声检查;（3）输尿管松解和腹腔化手术治疗22例;行肾切除术1例;行输尿管置双J管术1例。最终确诊为继发性RPF8例,其中4例为术前诊断,3例为术中腹膜后软组织肿块冷冻活检证实,1例为术后病理证实;（4）特发性RPF手术后肾积水均获长期缓解,而继发性RPF的预后取决于原发疾病及其治疗方案。结论：影像学检查是诊断RPF的重要手段,CTU优于超声检查和IVP。输尿管松解和腹腔化手术可以使特发性RPF输尿管梗阻得到长期的缓解,术中对肿块进行冷冻活检有助于鉴别特发性和继发性RPF,及时调整治疗方案。     

腹膜后纤维化16例误诊分析

目的分析腹膜后纤维化(retroperitoneal fibrosis, RPF)误诊原因,提高临床医生对本病的认识。方法回顾分析我院16例RPF误诊病例资料。结果 16例均以腰背部疼痛不适为主要症状,伴恶心、呕吐2例,血尿4例,伴肾区叩击痛11例,触及上腹部包块7例,伴腹胀6例,下肢水肿3例。CT扫描16例均见腹主动脉周围有低密度灶包裹,边界不清,6例累及髂血管,4例累及下腔静脉;8例腹主动脉管壁不规则增厚,正常结构消失,管腔轻度狭窄;10例出现肾积水,4例病变侵犯输尿管,病灶以上段输尿管明显扩张、包埋段输尿管显示不清;7例行增强CT扫描,病灶强化不明显或稍强化。误诊为腹主动脉大动脉炎8例、输尿管肿瘤及腹部包块性质待查各4例。16例均行手术治疗,经术中病理均诊断为RPF,予手术缓解输尿管梗阻及周围组织血管压迫,术后予抗生素、糖皮质激素等治疗后出院,随诊1年均未见复发。结论当临床遇及腰背痛、腹膜后组织肿物或不明原因出现尿路梗阻症状患者,CT检查发现有异常密度灶包绕腹膜后大血管,并伴肾积水、输尿管扩张征象时,应想到本病可能,及时行CT增强扫描,结合患者症状体征及相关检查结果,综合分析病情,仔细鉴别诊断,必要时可行手术病理检查明确诊断。     

Decreased soluble cell adhesion molecules after tirofiban infusion in patients with unstable angina pectoris

Aim  

The inflammatory response, initiated by neutrophil and monocyte adhesion to endothelial cells, is important in the pathogenesis of acute coronary syndromes. Platelets play an important role in inflammatory process by interacting with monocytes and neutrophils. In this study, we investigated the effect of tirofiban on the levels of cell adhesion molecules (soluble intercellular adhesion molecule-1, sICAM-1, and vascular cell adhesion molecule-1, sVCAM-1) in patients with unstable angina pectoris (AP).     

Soluble adhesion molecules as markers for sepsis and the potential pathophysiological discrepancy in neonates,children and adults

Sepsis is a severe and life-threatening systemic inflammatory response to infection that affects all populations and age groups. The pathophysiology of sepsis is associated with aberrant interaction between leukocytes and the vascular endothelium. As inflammation progresses, the adhesion molecules that mediate these interactions become shed from cell surfaces and accumulate in the blood as soluble isoforms that are being explored as potential prognostic disease biomarkers. We critically review the studies that have tested the predictive value of soluble adhesion molecules in sepsis pathophysiology with emphasis on age, as well as the underlying mechanisms and potential roles for inflammatory shedding. Five soluble adhesion molecules are associated with sepsis, specifically, E-selectin, L-selectin and P-selectin, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. While increased levels of these soluble adhesion molecules generally correlate well with the presence of sepsis, their degree of elevation is still poorly predictive of sepsis severity scores, outcome and mortality. Separate analyses of neonates, children and adults demonstrate significant age-dependent discrepancies in both basal and septic levels of circulating soluble adhesion molecules. Additionally, a range of both clinical and experimental studies suggests protective roles for adhesion molecule shedding that raise important questions about whether these should positively or negatively correlate with mortality. In conclusion, while predictive properties of soluble adhesion molecules have been researched intensively, their levels are still poorly predictive of sepsis outcome and mortality. We propose two novel directions for improving clinical utility of soluble adhesion molecules: the combined simultaneous analysis of levels of adhesion molecules and their sheddases; and taking age-related discrepancies into account. Further attention to these issues may provide better understanding of sepsis pathophysiology and increase the usefulness of soluble adhesion molecules as diagnostic and predictive biomarkers.     

Mast cells modulate the pathogenesis of elastase-induced abdominal aortic aneurysms in mice

Abdominal aortic aneurysm (AAA), an inflammatory disease, involves leukocyte recruitment, immune responses, inflammatory cytokine production, vascular remodeling, neovascularization, and vascular cell apoptosis, all of which contribute to aortic dilatation. This study demonstrates that mast cells, key participants in human allergic immunity, participate in AAA pathogenesis in mice. Mast cells were found to accumulate in murine AAA lesions. Mast cell-deficient KitW-sh/KitW-sh mice failed to develop AAA elicited by elastase perfusion or periaortic chemical injury. KitW-sh/KitW-sh mice had reduced aortic expansion and internal elastic lamina degradation; decreased numbers of macrophages, CD3+ T lymphocytes, SMCs, apoptotic cells, and CD31+ microvessels; and decreased levels of aortic tissue IL-6 and IFN-gamma. Activation of mast cells in WT mice via C48/80 injection resulted in enhanced AAA growth while mast cell stabilization with disodium cromoglycate diminished AAA formation. Mechanistic studies demonstrated that mast cells participated in angiogenesis, aortic SMC apoptosis, and matrix-degrading protease expression. Reconstitution of KitW-sh/KitW-sh mice with bone marrow-derived mast cells from WT or TNF-alpha-/- mice, but not from IL-6-/- or IFN-gamma-/- mice, caused susceptibility to AAA formation to be regained. These results demonstrate that mast cells participate in AAA pathogenesis in mice by releasing proinflammatory cytokines IL-6 and IFN-gamma, which may induce aortic SMC apoptosis, matrix-degrading protease expression, and vascular wall remodeling, important hallmarks of arterial aneurysms.     

Chlamydial and human heat shock protein 60s activate human vascular endothelium, smooth muscle cells, and macrophages

Both chlamydial and human heat shock protein 60s (HSP 60), which colocalize in human atheroma, may contribute to inflammation during atherogenesis. We tested the hypothesis that chlamydial or human HSP 60 activates human endothelial cells (ECs), smooth muscle cells (SMCs), and monocyte-derived macrophages. We examined the expression of adhesion molecules such as endothelial-leukocyte adhesion molecule-1 (E-selectin), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), and the production of the proinflammatory cytokine interleukin-6 (IL-6). We also tested whether either HSP 60 induces nuclear factor-kappaB (NF-kappaB), which contributes to the gene expression of these molecules. Either chlamydial or human HSP 60 induced E-selectin, ICAM-1, and VCAM-1 expression on ECs similar to levels induced by Escherichia coli lipopolysaccharide (LPS). Each HSP 60 also significantly induced IL-6 production by ECs, SMCs, and macrophages to an extent similar to that induced by E. coli LPS, as assessed by enzyme-linked immunosorbent assay (ELISA). In ECs, either HSP 60 triggered activation of NF-kappaB complexes containing p65 and p50 Rel proteins. Heat treatment abolished all these effects, but did not alter the ability of E. coli LPS to induce these functions. Chlamydial and human HSP 60s therefore activate human vascular cell functions relevant to atherogenesis and lesional complications. These findings help to elucidate the mechanisms by which a chronic asymptomatic chlamydial infection might contribute to the pathophysiology of atheroma.     

Interleukin (IL) 4 and IL-13 act on human lung fibroblasts. Implication in asthma.

Airway hyperresponsiveness leading to subepithelial fibrosis is mediated by inflammatory cells activated by T helper (Th) 2-derived cytokines such as IL-4 and IL-5. By analyzing the phenotype and response of human lung fibroblasts derived from either fetal (ICIG7) or adult (CCL202) tissue as well as from a Th2-type stromal reaction (FPA) to IL-4 and IL-13, we provide evidence that human lung fibroblasts may behave as inflammatory cells upon activation by IL-4 and IL-13. We show that the three types of fibroblasts constitute different populations that display a distinct pattern in cell surface molecule expression and proinflammatory cytokine and chemokine release. All fibroblasts express functional but different IL-4/IL-13 receptors. Thus, while IL-4 receptor (R) alpha and IL-13Ralpha1 chains are present in all the cells, CCL202 and FPA fibroblasts coexpress the IL-13Ralpha2 and the IL-2Rgamma chain, respectively, suggesting the existence of a heterotrimeric receptor (IL-4Ralpha/IL-13Ralpha/IL-2Rgamma) able to bind IL-4 and IL-13. Stimulation with IL-4 or IL-13 triggers in the fibroblasts a differential signal transduction and upregulation in the expression of beta1 integrin and vascular cell adhesion molecule 1 and in the production of IL-6 and monocyte chemoattractant protein 1, two inflammatory cytokines important in the pathogenesis of allergic inflammation. Our results suggest that when activated by IL-4 and IL-13, different subsets of lung fibroblasts may act as effector cells not only in the pathogenesis of asthma but also in lung remodeling processes. They may also differentially contribute to trigger and maintain the recruitment, homing, and activation of inflammatory cells.     

Adhesion molecules as therapeutic targets for autoimmune diseases and transplant rejection

Inflammatory disorders such as autoimmune diseases and graft rejection are mediated by activated leukocytes, particularly T lymphocytes, which penetrate the inflamed tissue and perpetuate or amplify the immune reaction. In an unstimulated state, leukocytes do not readily adhere to the vascular endothelium. However, inflammatory signals induce the expression of proteins on the endothelial cell surface that promote the adhesion and extravasation of activated immune cells from the circulation into the underlying tissues. Key among these molecules are P- and E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the endothelial cells, and their respective counter receptors, P-selectin glycoprotein ligand-1 (PSGL-1), leukocyte function-associated antigen-1 (LFA-1) and very late antigen-4 (VLA-4), on the leukocytes. In vitro blockade of these molecules inhibits the adhesion of leukocytes. In many cases there is attenuation of leukocyte activation as well. Adhesion blockade in animal models prevents or ameliorates graft rejection and disease severity in autoimmune models. Clinical studies with humanised monoclonal antibodies which interfere with LFA-1/ICAM-1 or VLA-4/VCAM-1 interactions have shown significant efficacy and good safety profiles in autoimmune disease, including psoriasis, multiple sclerosis and inflammatory bowel disease. Thus, adhesion blockade is emerging as a useful therapeutic strategy in several inflammatory settings.     

Keishibukuryogan (gui-zhi-fu-ling-wan), a Kampo formula, decreases disease activity and soluble vascular adhesion molecule-1 in patients with rheumatoid arthritis

An increasing death rate due to cardiovascular disease in patients with rheumatoid arthritis (RA) has been reported. Keishibukuryogan (KBG) is a traditional Chinese/Japanese (Kampo) formula that has been administered to patients with blood stagnation, e.g. thrombotic disease and atherosclerosis. The objective of this study was to evaluate the efficacy of KBG on disease activity and endothelial dysfunction in RA patients. Sixteen RA patients were enrolled and administered KBG (12 g per day) for 12 weeks in addition to continuing other drugs. The disease activity of RA was assessed by modified disease activity scores for 28 joints (DAS(28)). Plasma levels of adhesion molecules, soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were evaluated. C-reactive protein (CRP), inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) and lipid peroxide (LPO) were also evaluated. Fourteen patients completed the study. The disease activity of RA, tender joint count, swollen joint count and DAS(28) decreased significantly. Among adhesion molecules, only sVCAM-1 decreased significantly. LPO also decreased significantly, whereas CRP and inflammatory cytokines remained unchanged. These results suggest that KBG has insufficient anti-inflammatory or immunomodulating effect but does have a beneficial effect on articular symptoms and a protective effect against endothelial dysfunction in RA patients.     

ICAM-1 expression on conjunctival epithelial cells in patients with cystic fibrosis

BACKGROUND: Cystic fibrosis is one of the most common lethal genetic conditions. The defect is due to mutations in a gene on chromosome 7, named the cystic fibrosis transmembrane regulator (CFTR), which functions as a chloride channel in epithelial membranes It is presumed that the disease affects all secretory epithelia including the eye. The objective of this study is to investigate the expression of intercellular adhesion molecule-1 (ICAM-1) by conjunctival epithelial cells of patients with cystic fibrosis and the correlation between of the expression of ICAM-1 and the grade of cystic fibrosis severity. METHODS: Impression cytology specimens were collected in 24 patients with cystic fibrosis. Cells were processed for flow cytometry, by using monoclonal antibodies to ICAM-1. RESULTS: A significant increase of ICAM-1 expression on epithelial cells was found in patients with cystic fibrosis when compared with normal eyes. A positive correlation between the ICAM-1 expression and severe clinical status of CF patients was also observed. CONCLUSIONS: Our findings suggest that the inflammation appears to have a role in the pathogenesis of the ocular surface changes in patients with cystic fibrosis. ICAM-1 expression on conjunctival epithelial cells may be a marker of the inflammatory status in cystic fibrosis patients. The method described here reveal good repeatability and reliability for the analysis of the inflammatory markers on conjunctival epithelial cells and can be a useful tool in evaluating of the ocular findings and treatment interventions in patients with cystic fibrosis.     

A 24-h work shift in intensive care personnel: biological pathways between work stress and ill health

This study evaluated inflammatory, coagulation and microvascular responses to a continuous 24-h work day in 13 healthy intensive care physicians. Inflammatory markers (interleukin [IL]-2, IL-6, IL-10, tumour necrosis factor-α, matrix metalloproteinase [MMP]-9 and adiponectin), adhesion molecules (vascular cellular adhesion molecule-1 and intercellular adhesion molecule-1 [ICAM-1]), coagulation parameters (thrombin-anti thrombin, von Willebrand factor and tissue factor) and sublingual micro circulation were assessed before and after a 24-h work shift. The 24-h work shift had no effect on inflammatory markers and ICAM-1. Direct visualization of micro-circulation did not reveal stress-related perfusion abnormalities. A 24-h work shift in the intensive care unit was associated with significantly increased plasma levels of tissue factor - a potentially important mechanism linking acute job strain, haemostasis and atherosclerosis. The long-term consequences warrant further evaluation.     

Elevated soluble CD40 ligand is related to the endothelial adhesion molecules in patients with acute coronary syndrome

BACKGROUND: Increasing evidence indicates that the CD40-CD40L interaction plays a pivotal role in the inflammatory regulation of atherosclerosis. Adhesion molecules especially the vascular adhesion molecules also play an important role in the pathogenesis of atherosclerosis which act as markers of inflammation. These inflammatory factors render vulnerability to the atherosclerotic plaque by triggering the fissure, rupture, and subsequent thrombosis, leading to the clinical scenario of unstable angina and acute myocardial infarction. METHODS: The difference of sCD40L concentration in different subtype of coronary heart disease and its relationship with vascular adhesion molecules was investigated. Enzyme-linked Immunosorbent Assay (EIA) was used to measure the serum sCD40L, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1). RESULTS: The sCD40L concentration was significantly higher in patients with acute coronary syndrome (ACS) (3.17+/-2.84 ng/ml) than in controls (1.19+/-1.05 ng/ml, p<0.01) and in patients with stable coronary heart disease (1.61+/-1.46 ng/ml, p<0.05). The sCD40L concentration was positively correlated with sICAM-1 (r=0.413, p<0.01), triglycerides (TG) (r=0.23, p<0.05), apoB (r=0.248, p<0.05), and HDL-cholesterol (r=-0.253, p<0.05). CONCLUSIONS: The sCD40L concentration was increased in acute coronary syndrome, suggesting the possible relation of CD40L to the pathogenesis. The serum CD40L concentration was positively correlated with adhesion molecule and was negatively associated with serum high-density lipoprotein cholesterol (HDL-C).     

Time-related effects of cytomegalovirus infection on the development of chronic renal allograft rejection in a rat model

Cytomegalovirus (CMV) infection is a risk factor for chronic allograft rejection. The histological findings of chronic renal allograft rejection include inflammation, vascular intimal thickening, glomerulosclerosis, tubular atrophy and fibrosis. We have developed a rat model of renal transplantation in which transplants, after an early inflammatory episode, end up with chronic rejection within 60 days. During the early phase of the process in this model, CMV increased and prolonged the inflammatory response, the expression of adhesion molecules, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 and their ligands, lymphocyte function antigen-1 and very late antigen-4 in the graft. Simultaneously, the production of various growth factors, such as transforming growth factor beta, platelet-derived growth factor and connective tissue growth factor was upregulated, which induce smooth muscle cell proliferation in the vascular wall and collagen synthesis by fibroblasts. Chronic rejection developed within 20 days in CMV-infected grafts. In summary, CMV infection accelerated and enhanced the early immune response, the induction of growth factors and collagen synthesis, and the development of chronic rejection in renal allografts.     

Vascular cell adhesion molecule‐1: a viable therapeutic target for atherosclerosis?

Atherosclerosis is now well recognised as a chronic inflammatory process which may ultimately lead to myocardial infarction, stroke and peripheral vascular disease. The role of inflammation in the pathogenesis of atherosclerosis has lead to interest in developing therapies that target vascular inflammation. Leucocytes play a key role during atherosclerotic plaque development. Activated vascular endothelium expresses vascular cell adhesion cell molecule-1 (VCAM-1), a member of the adhesion molecule superfamily, to which monocytes and lymphocytes can bind. These inflammatory cells can then move through the endothelium by diapedesis and release cytokines and enzymes, important components in the progression of the lesion. Researchers have demonstrated that the extent of atherosclerotic lesions is significantly reduced in animal models with decreased VCAM-1 expression. VCAM-1 has therefore been identified as a potential anti-inflammatory therapeutic target, the hypothesis being that reduced expression of VCAM-1 will slow the development of atherosclerosis. Succinobucol (AGI-1067), an anti-oxidant compound also capable of inhibiting VCAM-1 gene expression, is an example of such an agent and is currently being investigated in a phase III cardiovascular end-point trial due to report in 2007. If the results are positive, further investigations should derive to what extent blockade of VCAM-1 by succinobucol, rather than its other effects, accounts for the reduction in vascular events.