To observe the correlation between Nε-carboxymethyl-Lysine (CML), the main component of advanced glycation end products and the calcification of the anterior tibial artery plaque in patients with ...diabetic foot post foot amputation.
Sixty patients hospitalized for foot amputation operation due to diabetic foot from June 2012 to June 2016 in the Department of Orthopedics, Affiliated Hospital of Jiangsu University were prospectively recruited.The patients were categorized into mild stenosis (0<stenosis<50%,
=20), moderate stenosis (50%≤stenosis<70%,
=20) and severe stenosis (70%≤stenosis≤100%,
=20) based on the color Doppler ultrasound assessed severity of anterior tibial artery stenosis.The baseline clinical data of patients were collected and anterior tibial artery was isolated.Then, HE staining, O-Cresolphthalein Complexone method, enzymic method and ELASA analysis were then performed to detect the evolution of calcification, arterial calcium content, alkaline phosphatase activity and serum CML concentration,
Chronic kidney disease (CKD) is associated with high morbidity and mortality rates, main causes related with cardiovascular disease (CVD) and bone mineral disorder (CKD-BMD). Uremic toxins, as ...advanced glycation end products (AGEs), are non-traditional cardiovascular risk factor and play a role on development of CKD-BMD in CKD. The measurement of skin autofluorescence (sAF) is a noninvasive method to assess the level of AGEs in tissue, validated in CKD patients.
The aim of this study is analyze AGEs measured by sAF levels (AGEs-sAF) and its relations with CVD and BMD parameters in HD patients.
Twenty prevalent HD patients (HD group) and healthy subjects (Control group, n = 24), performed biochemical tests and measurements of anthropometric parameters and AGEs-sAF. In addition, HD group performed measurement of intact parathormone (iPTH), transthoracic echocardiogram and radiographies of pelvis and hands for vascular calcification score.
AGEs-sAF levels are elevated both in HD and control subjects ranged according to the age, although higher at HD than control group. Single high-flux HD session does not affect AGEs-sAF levels. AGEs-sAF levels were not related to ventricular mass, interventricular septum or vascular calcification in HD group. AGEs-sAF levels were negatively associated with serum iPTH levels.
Our study detected a negative correlation of AGEs-sAF with serum iPTH, suggesting a role of AGEs on the pathophysiology of bone disease in HD prevalent patients. The nature of this relation and the clinical application of this non-invasive methodology for evaluation AGEs deposition must be confirmed and clarified in future studies.
Abstract Background We recently reported that serum levels of pentosidine, one of the well-defined advanced glycation end products (AGE), was an independent prognostic factor for heart failure. ...Receptor for AGEs (RAGE) is expressed in a variety of tissues, and RAGE has a C-truncated secretory isoform of the receptor protein, termed soluble RAGE . In the present study, we measured serum soluble RAGE levels in patients and examined whether serum soluble RAGE predicts prognosis in patients with heart failure. Methods and Results Serum soluble RAGE concentration was measured in 160 patients with heart failure by a competitive enzyme-linked immunosorbent assay. Patients were prospectively followed during a median follow-up period of 872 days with end points of cardiac death or rehospitalization. Serum soluble RAGE level increased with advancing New York Heart Association functional class. Serum soluble RAGE level was also higher in patients with cardiac events than in event free patients. From the receiver operating characteristic curve analysis, the cutoff value of serum soluble RAGE level was determined as 1220 pg/mL. Kaplan-Meier analysis clearly demonstrated that the high soluble RAGE group had a significantly higher incidence of cardiac events than occurred in the low serum soluble RAGE group ( P = .0004). In the multivariate Cox proportional hazard analysis, soluble RAGE and serum pentosidine were independent risk factors for cardiac events (soluble RAGE: HR 1.90, 95% CI 1.16-3.09, P = .010; pentosidine: HR 1.59, 95% CI 1.11-2.29, P = .012). Conclusions Serum soluble RAGE level is an independent prognostic factor for heart failure, and this novel marker may be useful for risk stratification of patients with heart failure.
Background: Advanced glycation end products (AGE) have been found in inflamed gingival tissue and have been shown to interfere with the integrity of extracellular matrix and cell–matrix interactions. ...This study aims to investigate the modulatory effect of aminoguanidine (AG), an AGE inhibitor, in various stages of experimental periodontitis.
Methods: Thirty‐six Sprague‐Dawley rats were used. AG or normal saline (NS) was systemically administered in the induction, progression, and recovery phases of ligature‐induced periodontitis. Dynamic changes of the periodontium were evaluated by microcomputed tomography, histology, and immunohistochemistry of the receptor for AGE (RAGE). Molecular mechanisms were evaluated by myeloperoxidase activity, gene expression of RAGE, and markers associated with tissue repair and homeostasis, including vascular endothelial growth factor (VEGF), type I collagen, fibronectin, and periostin.
Results: AG appeared to inhibit the degradation of the collagen matrix in the induction phase but promoted collagen reorganization in the progression and recovery phases of experimental periodontitis. In the induction sites, periodontal bone loss was significantly reduced (P <0.05), with significantly reduced RAGE (P <0.05) and significantly elevated fibronectin and periostin levels (P <0.01). No significant alterations in the levels of myeloperoxidase, VEGF, and collagen were noted. In the progression and recovery sites, similar trends were observed, with insignificant differences relative to NS‐treated animals.
Conclusions: AG reduced periodontal bone loss during the induction of experimental periodontitis, and the effects appeared to be insignificant in the progression and recovery phases. This modulation was related to the inhibition of the AGE–RAGE axis to resume cell–matrix interactions and maintain tissue integrity.
Flow-mediated remodeling of resistance arteries is essential for revascularization in ischemic diseases, but this is impaired in diabetes. We hypothesized that breaking advanced glycation end product ...(AGE) cross-links could improve remodeling in mesenteric resistance arteries in Zucker diabetic fatty (ZDF) rats compared with lean Zucker (LZ) rats. Arteries, exposed to high (HF) or normal (NF) blood flow after alternate arterial ligation in vivo, were collected after 2 weeks. In LZ rats, HF artery diameter was larger than for NF vessels, but this was not the case in ZDF rats. Endothelium-mediated dilation in ZDF rats, which was lower than in LZ rats, was further decreased in HF arteries. Treatment of rats with the AGE-breaker 4,5-dimethyl-3-phenacylthiazolium chloride (ALT-711) (3 mg/kg/day; 3 weeks) reversed diabetes-induced impairment of HF-dependent remodeling. ALT-711 also improved endothelium nitric oxide-dependent relaxation in mesenteric resistance arteries. Reactive oxygen species reduction restored relaxation in ZDF rats but not in LZ or ALT-711-treated rats. AGEs were reduced in ALT-711-treated ZDF rats compared with ZDF rats. Metalloproteinase activity, necessary for HF-dependent remodeling, was reduced in ZDF rats compared with LZ rats and restored by ALT-711. Thus, targeting AGE cross-links may provide a therapeutic potential for overcoming microvascular complications in ischemic disorders occurring in diabetes.
OBJECTIVE：Accumulation of advanced glycation end products（AGEs） in the body due to the non-enzymatic glycation of proteins and oxidation is associated with aging and diabetes mellitus.In this study ...we wanted to investigate the antiglycation and antioxidation potential of two medicinal plants：Juglans regia and Calendula officinalis.METHODS：In-vitro investigation was carried out to discover the antiglycation and antioxidation potential of J.regia and C.officinalis.Using an Ultraviolet Double-beam Spectrophotometer,we evaluated the antiglycation property of the crude methanolic extracts of J.regia and C.officinalis by assessing their ability to inhibit the Maillard reaction.Employing the same instrument we also measured the antioxidation potential of these plant extracts using the nitric oxide（NO） free radical-scavenging assay.RESULTS：J.regia had greater antiglycation ability,with a minimum inhibitory concentration（MIC 50） of 28 μg/mL as compared with that of C.officinalis（270 μg/mL）.C.officinalis had greater antioxidation potential（26.10,22.07 and 16.06% at 0.5 mg,0.25 mg and 0.125 mg,respectively,as compared with 18.15,16.50 and 16.06% of J.regia,respectively）.CONCLUSION：J.regia and C.officinalis inhibited the Maillard reaction and prevented oxidation in-vitro.Hence,the extracts of these plants could have therapeutic uses in curbing chronic diabetic complications and slowing down aging.
Advanced glycation end products (AGEs) enhance NADPH oxidase, and hence respiratory burst activity, of stimulated neutrophils. They are thus potentially vasculopathic, especially in diabetes, uremia, ...and aging, in which AGEs classically accumulate. We investigated the underlying mechanisms.
Neutrophils prelabeled with 3Harachidonic acid display increased 3Harachidonate release on exposure to AGE-albumin over exposure to albumin alone (by 151+/-16%, P<0.01). Arachidonic acid (AA) itself seems to mediate the AGE-augmented neutrophil respiratory burst (ascertained by chemiluminescence). Inhibitors of the cyclooxygenase pathway (indomethacin) and lipoxygenase pathway (MK-886) do not impair this AGE effect, excluding a contribution from AA metabolites. Cytosolic phospholipase A2 (cPLA2) controls AA generation. Its inhibition by methyl arachidonyl fluorophosphonate abrogates the AGE-enhanced activated neutrophil respiratory burst, and it is demonstrably stimulated in AGE-exposed neutrophils, as evidenced by isoform gel-shift and an increasingly membrane-translocated state in Western blots of neutrophil subfractions. Inhibition of other PLA2 isoforms, secretory PLA2 and calcium-independent PLA2, by manoalide and haloenol-lactone suicide substrate, respectively, does not affect this effect of AGEs relative to inhibitor-treated controls. The thiol antioxidant NAC reduces activation of cPLA2 (assessed by isoform gel-shift and membrane translocation), production of AA in AGE-albumin-exposed neutrophils (H3 release reduced to 104+/-17%, P=0.94 compared with albumin-exposed neutrophils), and the AGE-augmented neutrophil respiratory burst.
AGE augmentation of the activated neutrophil respiratory burst requires AA generation, through which neutrophil NADPH oxidase may be upregulated, enhancing reactive oxygen species output. AA is generated by cPLA2, which may be stimulated through an AGE-activated redox-sensitive pathway.
Aminoguanidine (AMG) was prepared more than 100 years ago. During the last 10 years two important effects of AMG have been discovered which have made this molecule attract a lot of interest. Firstly, ...AMG inhibits, in vitro and in vivo, formation of highly reactive advanced glycosylation end products (AGEs) associated with pathogenesis of secondary complications to diabetes and with cardiovascular changes in aging. AMG ameliorates various complications to diabetes and prevents age related arterial stiffening and cardiac hypertrophy, effects probably dependent on inhibition of AGEs formation. Secondly, AMG inhibits NO synthase particularly the inducible NO synthase isoform making AMG an important pharmacological tool. The inducible NO synthase isoform is associated with production of large quantities of NO synthase in response to e. g. cytokines. When these effects of AMG were disclosed it had already been known for many years that AMG, in nM concentrations, inhibits diamine oxidase. This enzyme catalyzes degradation of biologically active diamines such as histamine and putrescine. Data obtained from studies using AMG should be interpreted with precaution since this substance interferes with several important regulatory systems. In this review these important targets for AMG are addressed.
Renin angiotensin system (RAS) worsens diabetic nephropathy (DN) by increasing oxidative stress. We compared the effect of three different RAS inhibitors: the angiotensin converting enzyme inhibitor ...Ramipril, the vasopeptidase inhibitor AVE7688 and the angiotensin receptor (AT1) antagonist Losartan on the formation of oxidative and carbonyl stress derived protein modifications in kidney from Zucker obese hyperglycemic rats (ZDFn Gm-fa/fa). Gas chromatography–mass spectrometry was used to measure representative markers of several protein oxidative pathways: direct oxidation dinitrophenylhydrazine reactive carbonyls (DNP), glutamic (GSA), and aminoadipic (AASA) semialdehydes, mixed glyco- and lipoxidation Nε-carboxyethyl-lysine (CEL) and Nε-(carboxymethyl)-lysine (CML) and lipoxidation-Nε-(malondialdehyde)-lysine-(MDAL), as well as renal fatty acid composition. Urinary albumin (a marker of DN), DNP, GSA, and MDAL levels, were increased in all obese rats and were dose dependently decreased by AVE7688 whereas Ramipril and Losartan were less efficient. These results show that RAS inhibition improves DN at several levels, independently of its effects on blood pressure and glycemic control, via mechanisms depending of renal oxidative stress.
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