Serum Pentosidine Levels Research Articles

Can serum pentosidine levels predict risk of vertebral fracture in patients with type 2 diabetes mellitus?

Can serum pentosidine levels predict risk of vertebral fracture in patients with type 2 diabetes mellitus?

Serum Pentosidine Levels Are Positively Associated with the Presence of Vertebral Fractures in Postmenopausal Women with Type 2 Diabetes

Although type 2 diabetic patients are at increased risk of fractures, bone mineral density (BMD) may not be useful for assessing the risk. Recent studies have reported that increased bone content of pentosidine (PEN) is associated with its plasma concentration and bone fragility. To examine the association between serum PEN levels and vertebral fractures (VFs) in Japanese type 2 diabetic patients (77 males older than 50 yr and 76 postmenopausal females), we compared parameters including BMD, PEN, serum bone-specific alkaline phosphatase, and urinary levels of N-telopeptide between those with and without VFs. Comparison of diabetic subjects with and without VFs revealed no significant differences in BMD values or bone metabolic markers in either gender. In contrast, PEN levels in women with VFs were significantly higher than in those without VFs (0.0440+/-0.0136 vs. 0.0321+/-0.0118 microg/ml; P<0.001). Multivariate logistic regression analysis adjusted for age, height, weight, hemoglobin A1c, estimated glomerular filtration rate, the presence of diabetic complications, histories of taking insulin or pioglitazone, risk factors for osteoporosis, and lumbar BMD identified PEN levels as a factor associated with the presence of VFs in postmenopausal diabetic women independent of BMD, risk factors for osteoporosis, diabetic status, and renal function (odds ratio 2.50, 95% confidential interval 1.09-5.73 per sd increase; P=0.0302). PEN levels, but not BMD, may be useful for assessing the risk of prevalent VFs in postmenopausal diabetic women and may reflect bone quality in this group.

High Serum Level of Pentosidine, an Advanced Glycation End Product (AGE), is a Risk Factor of Patients with Heart Failure

Pentosidine, one of the advanced glycation end products (AGE), is generated by nonenzymatic glycation and oxidation of proteins. The receptor of AGE (RAGE) is expressed in a variety of tissue, and interaction of AGE with RAGE induces oxidative stress and activation of intracellular signaling, causing production of cytokines and mediators of inflammation. We investigated whether serum pentosidine is a risk factor for heart failure. Serum pentosidine concentration was measured in 141 patients with heart failure and 18 control subjects by a competitive enzyme-linked immunosorbent assay. Patients were prospectively followed during a median follow-up period of 479 days with end points of cardiac death or rehospitalization. Serum concentration of pentosidine was significantly higher in New York Heart Association (NYHA) Class III/IV patients than in NYHA class I/II patients (P < .0001). Serum pentosidine was also higher in patients with cardiac events than in event-free patients (P < .001). In the univariate Cox proportional hazard analysis, age, NYHA class, pentosidine, creatinine, uric acid, B-type natriuretic peptide, left ventricular end-systolic volume, and left ventricular mass were significant risk factors to predict cardiac events. In the multivariate Cox analysis, serum pentosidine concentration was an independent risk factor for cardiac events (hazard ratio 1.88, 95% confidence interval 1.23-2.69, P = .002). The highest 4th quartile of pentosidine was associated with the highest risk of cardiac events (4.52-fold). Serum pentosidine concentration is an independent prognostic factor for heart failure, and this new marker may be useful for risk stratification of patients with heart failure. Patients were divided into 4 groups based on the serum pentosidine levels.

Advanced glycation end product pentosidine is not a relevant marker of disease activity in patients with rheumatoid arthritis

Advanced glycation end-product (AGE) pentosidine has previously been demonstrated in different tissues and body fluids. It was suggested as a novel marker for evaluating the pathologic activity in rheumatoid arthritis (RA). In this study we analyzed the relation between pentosidine and markers of inflammation, cartilage turnover, immune response, and disease status of RA. Using HPLC, we analyzed pentosidine in serum and synovial fluid from 39 patients with RA and in serum from 38 healthy controls. Cartilage oligomeric matrix protein (COMP) and antibodies to CCP (anti-CCP) were measured by ELISA. Clinical disease status was assessed by Disease Activity Score 28 (DAS 28) and functional status by Health Assessment Questionnaire (HAQ). We demonstrated significantly higher serum levels of pentosidine in RA patients in comparison with controls. Pentosidine in serum significantly correlated with pentosidine in synovial fluid. Serum pentosidine levels were associated with erythrocyte sedimentation rate (p<0.03) but not with CRP, COMP, anti-CCP antibodies, DAS 28, or HAQ. In contrast to previous studies, we could not show any correlation of pentosidine levels with inflammatory status, clinical disease activity, markers of immune response, or cartilage breakdown. However, AGEs can be suggested as important players participating in joint destruction rather than markers of disease activity.

Treatment with anti-TNF-α antibody infliximab reduces serum IL-15 levels in patients with rheumatoid arthritis

The aim of this study was to analyze the change of serum cytokines and pentosidine levels in patients with rheumatoid arthritis (RA) by infliximab treatment. Twenty-three patients with RA were studied for 30 weeks on the effects of infliximab treatment. Serum levels of IL-15, IL-16, IL-17, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured with ELISA methods and pentosidine levels were determined using high-performance liquid chromatography, both at baseline and at 14 and 30 weeks after the initial treatment with infliximab. In addition, the patients also underwent physical and routine blood examinations. The higher levels of serum IL-15 in RA patients before treatment with infliximab significantly decreased at 14 and 30 weeks after the initial treatment with infliximab, but serum IL-16, IL-17, GM-CSF, and pentosidine levels did not decrease. The serum IL-17 and GM-CSF levels remained to be a limited detectable level at the pre- and posttreatment with infliximab. Infliximab treatment significantly lowered the serum levels of IL-15 in patients with RA. IL-15 is one of the crucial cytokines affected by infliximab.

Hyaluronic acid levels may have predictive value for the progression of knee osteoarthritis

Study objectives: To study prognostic value of different biochemical markers for morphological progression of early knee osteoarthritis. Design: A total of 89 patients with knee osteoarthritis (OA) were enroled into the study. The follow-up period was 2 years. Radiological OA progression was evaluated by measuring joint space width. Pentosidine was detected using the HPLC method described earlier, cartilage oligomeric matrix protein (COMP) using the method published by our team. MMP-9, tissue inhibitors of metalloproteinases (TIMP), YKL-40 and hyaluronic acid were detected using commercially available kits. Results: In the group of patients suffering from knee OA, higher serum levels of pentosidine ( P=0.04), MMP-9 ( P=0.02), TIMP ( P=0.04) and COMP ( P=0.05) were detected compared with healthy control subjects. Using a correlation analysis method, it has been found that the patients with higher basic serum levels of hyaluronic acid had a faster radiological progression ( r=0.56, P<0.005), as well as the patients with higher basic serum pentosidine levels ( r=0.30, P<0.005). Other biochemical markers had no statistically significant prognostic value. Conclusions: In our study, serum levels of hyaluronic acid and pentosidine had a predictive value for further development of knee OA in that further joint space narrowing was detected in the patients with knee OA in the next 2 years.

Advanced glycation end products and oxidative stress are increased in chronic allograft nephropathy

Background: The histologic picture of chronic allograft nephropathy (CAN) resembles early arteriosclerotic lesion. Oxidative stress and advanced glycation end products (AGES) have been implicated in the pathogenesis of atherosclerosis and progression of renal disease. Methods: The authors serially measured the plasma malonyldialdehyde (MDA), carbonyl protein (CP), pentosidine, and argpyramidine levels in 11 postrenal transplant patients with normal renal function (KPT) and 10 patients with biopsy proven CAN at 1, 3, 6, 9 through 12, and 18 through 24 months posttransplant. Data were also obtained in 16 controls and 13 patients with chronic renal failure (CRF). Results: Although serum creatinine, MDA, CP, pentosidine, and argpyrimidine levels decreased during follow-up in KPT, it progressively increased in patients with CAN. The mean serum creatinine level was higher in patients with CRF (3.3 ± 0.8 mg/dL [291.7 ± 70.7 μmol/L]) and CAN (2.4 ± 1.1 mg/dL [212.1 ± 96.6 μmol/L]) than in controls (1.2 ± 0.3 mg/dL [105.8 ± 26.7 μmol/L]) and KPT patients (1.2 ± 0.2 mg/dL [109.7 ± 17.7 μmol/L]; P < 0.001). Markers of oxidative stress and AGEs measured at 18 to 24 months posttransplant in patients with CAN were higher than in KPT, controls, and CRF patients. MDA (nmol/mL) was significantly higher in patients with CAN (1.30 ± 0.30) compared with controls (0.53 ± 0.12), KPT (0.52 ± 0.15), and CRF (0.74 ± 0.27) groups (P < 0.001). Plasma CP (nmol/mg protein) in patients with CAN (4.3 ± 1.00) was higher than in controls (1.90 ± 0.69) and KPT (2.62 ± 1.00) groups at the same time-point (P < 0.001), but comparable with CRF (2.69 ± 1.20). Plasma pentosidine (pmol/μmol protein) level in patients with CAN (19.69 ± 5.05) was higher compared with controls (2.49 ± 0.86), CRF (13.10 ± 3.68), and KPT (14.32 ± 6.28) groups (P < 0.001). Plasma argpyrimidine (pmol/10 μmol protein) was higher in patients with CAN (123.8 ± 17.9) compared with controls (4.81 ± 1.91), CRF (56.92 ± 29.67), and KPT (31.1 ± 11.1; P < 0.001) groups. Conclusion: Oxidative stress and AGEs are increased in patients with CAN, which cannot be explained by the decline in renal function alone. Oxidative stress and AGEs may be one among the nonimmune mediators of CAN.

Determination of urinary and serum pentosidine and its application to elder patients.

Pentosidine, a fluorescent cross-linking compound, accumulates in extracellular matrix, especially in the collagen, and is formed by the nonenzymatic process of advanced Maillard reaction. We developed a method of determination of pentosidine and tried to examine its level in urine and serum of elder patients. The method, which involves the hydrolysis of samples, pretreatment using a CF-11 cellulose column and HPLC quantification, resulted in a high recovery (94.3%) of pentosidine with low coefficient of variation (8-10%) of total analysis. Serum and urinary levels of pentosidine in control subjects gradually increased with age. Elder patients with cerebral infarction showed higher levels of serum and urinary pentosidine as compared with those with senile dementia and other geriatric disorders. These results suggest that serious damage to systemic vascular tissues has already occurred in these patients due to glycation.

Mechanism of collagen network stabilization in human irreversible granulomatous liver fibrosis

BACKGROUND & AIMS: Cross-linking participates in the increased stability of collagen towards proteolytic degradation. Liver collagen cross-linking by pyridinoline, from the lysyl oxidase pathway, and by pentosidine, issued from glycation, was investigated to determine their respective contribution to collagen stabilization in patients with an irreversible liver fibrosis caused by the parasitic granulomatous disease alveolar echinococcosis. METHODS: Liver pyridinoline and pentosidine were analyzed by high-performance liquid chromatography, and urinary pyridinoline was analyzed by immunoassay. Cross-linked type I collagen was localized by immunohistochemistry with an antibody against the C-terminal part of the molecule, involved in pyridinoline formation, that was measured in serum by radioimmunoassay. RESULTS: In contrast to pyridinoline, pentosidine decreased in fibrotic lesions. Cross-linked I collagen was located predominantly in collagen bundles in the periparasitic granuloma. Serum pentosidine and urinary pyridinoline levels did not differ significantly from controls, but the serum concentration of the C-terminal telopeptide of type I collagen increased significantly. CONCLUSIONS: Lysyl oxidase-mediated cross- linking is the major process contributing to the stabilization of collagen in granulomatous fibrosis, and glycation is not significantly involved in it. The changes induced by alveolar echinococcosis in liver collagen metabolism are associated with an increase in serum C- telopeptide of type I collagen. (Gastroenterology 1996 Jul;111(1):172-82)

Endothelial cell adhesion receptors and their role in angiogenesis

The advanced glycation end products (AGEs)-receptor for AGE (RAGE) axis activity are implicated in diabetic vascular complications. We measured serum AGE, sRAGE and pentosidine levels in Tunisian patients with diabetic retinopathy (DR) and examined whether these biomarkers are related to the severity of DR.We included 30 healthy control subjects and 100 diabetic patients were divided into 2 subgroups: 40 patients with nonproliferative diabetic retinopathy (NPDR), and 60 patients with proliferative diabetic retinopathy (PRD). AGEs, sRAGE and pentosidine were measured in serum by ELISA.Serum levels of AGEs, sRAGE and pentosidine were significantly increased in patients with diabetes mellitus compared to nondiabetic controls (P < .01, P < .001, P < .001 respectively). In diabetic patients, serum AGEs, sRAGE and pentosidine levels were significantly higher in patients who had PDR than in those with NPDR (P = .001, P = .01, P = .005 respectively). Furthermore, in stepwise multivariate regression analysis, the levels of pentosidine and duration of diabetes were independently associated with severity of DR.Serum AGEs, sRAGE, and pentosidine levels are related with the presence of DR. Duration of diabetes and pentosidine were independently correlated with the severity of DR.