Advanced glycation end-product peptides are associated with impaired renal function, but not with biochemical markers of endothelial dysfunction and inflammation, in non-diabetic individuals.

BACKGROUND: Patients with end-stage renal disease as well as mild renal impairment have an increased risk for the development of cardiovascular disease. It has been suggested that advanced glycation end-products (AGEs) are involved in atherogenesis, possibly through induction of endothelial dysfunction and low-grade inflammation. METHODS: In a cross-sectional, single-centre study, we investigated four groups of 20 non-diabetic subjects with a creatinine clearance ranging from normal (> 90 ml/min/1.73 m2) to < 31 ml/min/1.73 m2. We measured AGE-peptides, markers of endothelial dysfunction (von Willebrand factor, soluble E-selectin, plasminogen activator inhibitor-1, tissue-type plasminogen activator, soluble vascular cell adhesion molecule-1) and markers of inflammatory activity (soluble intercellular adhesion molecule-1, C-reactive protein, secretory phospholipase A2). We constructed composite endothelial dysfunction and inflammatory activity Z-scores using these markers. RESULTS: AGE-peptides were independently related to creatinine clearance (standardized beta -0.55, 95% confidence interval (CI) -0.77 to -0.34, P < 0.001). AGE-peptides were not independently related to the individual markers of endothelial dysfunction and inflammation, nor to the composite endothelial dysfunction Z-score (standardized beta 0.08, 95% CI -0.14 to -0.30, P = 0.48) or the inflammatory activity Z-score (standardized beta -0.05, 95% CI -0.25 to -0.16, P = 0.66). CONCLUSIONS: Plasma concentrations of AGE-peptides are associated with creatinine clearance but not with biochemical markers of endothelial dysfunction and inflammatory activity in non-diabetic patients over a wide range of renal function. This suggests that the atherogenic effects of AGE-peptides in individuals with renal functional impairment are not mediated by endothelial dysfunction or inflammatory activity as estimated by the markers used.     

Prognostic implications of retinopathy and a high plasma von Willebrand factor concentration in type 2 diabetic subjects with microalbuminuria.

BACKGROUND: Microalbuminuria in subjects with type 2 diabetes may be heterogeneous with respect to clinical features, renal histology, and prognosis. There may be at least two types of microalbuminuria in diabetes, namely with and without generalized endothelial dysfunction. We investigated whether, among microalbuminuric subjects with type 2 diabetes, the presence of generalized endothelial dysfunction, as indicated by the presence of retinopathy or a high plasma von Willebrand factor (vWf) level, has prognostic implications. METHODS: In 173 type 2 diabetic subjects of a population-based cohort, we assessed the urinary albumin-to-creatinine ratio, the plasma vWf level, and the presence of retinopathy. The main outcome was cardiovascular mortality. RESULTS: The absolute difference in 7 years' cardiovascular mortality between microalbuminuric (albumin-to-creatinine ratio 2.0-30.0 mg/mmol) and normoalbuminuric subjects was higher in the presence as compared to the absence of retinopathy (55.6 vs 11.1%). The age- and sex-adjusted relative risk (95% confidence interval) of cardiovascular mortality, as compared to normoalbuminuric subjects without retinopathy, was 1.1 (0.1-9.2) for normoalbuminuric subjects with retinopathy, 1.8 (0.5-6.7) for microalbuminuric subjects without retinopathy, and 9.8 (3.1-30.9) for microalbuminuric subjects with retinopathy. The absolute difference in risk of 7 years' cardiovascular mortality between microalbuminuric and normoalbuminuric subjects was higher in the presence as compared to the absence of a high (>1.89 IU/ml) vWf level (49.8 vs 16.4%). The age- and sex-adjusted relative risk of cardiovascular mortality, as compared to normoalbuminuric subjects without a high vWf level, was 1.5 (0.4-5.5) for normoalbuminuric subjects with a high vWf level, 2.6 (0.7-9.6) for microalbuminuric subjects without a high vWf level, and 12.0 (2.9-49.5) for microalbuminuric subjects with a high vWf level. These differences in risk of cardiovascular mortality did not change materially after further adjustment for known duration of diabetes, hypertension, creatinine clearance, level of glycated haemoglobin and high-density lipoprotein cholesterol, and presence of cardiovascular disease. Analysis of all-cause instead of cardiovascular mortality showed a similar difference in risk of mortality between microalbuminuric subjects with or without retinopathy or a high vWf level. CONCLUSIONS: Among type 2 diabetic subjects with microalbuminuria, the presence of retinopathy or a high plasma vWf level affects the risk of cardiovascular death. Although larger studies are necessary, these findings support the concept that microalbuminuria in type 2 diabetes can occur in the absence or the presence of generalized endothelial dysfunction, and that the latter is a much more 'malignant' condition than the former.     

White light interferometry to characterize the hydrogel contact lens surface

Purpose: The aim of this study was to characterize, qualitatively and quantitatively, the surface morphology of four unworn conventional hydrogel contact lenses (Omafilcon, Hioxifilcon‐based, Nefilcon A and Ocufilcon B) by White Light Optical Profiling (WLOP). WLOP is an ideal technique for sampling larger areas as well as for higher measurement speed compared with other topography techniques used in contact lens studies. Methods: Surface roughness was assessed by WLOP in the Vertical Scanning Mode, with a Wyko^® NT1100, which is a non‐contact optical profiling system that provides high vertical resolution. Representative roughness parameters, the Average Roughness (R_a), Root‐mean‐square Roughness (R_ms), and Maximum Roughness (R_max), for areas of 625, 2500, 10829 and 67 646 μm² were calculated. Results: Higher R_a, R_ms and R_max values were obtained for larger areas in all lenses. Daily disposable contact lenses (Nefilcon A and Ocufilcon B) presented the highest R_a, R_ms and R_max values, the larger changes in these parameters becoming apparent with the increase in the measured area. Differences between lenses were less obvious when data from 625 and 2500 μm² area were compared. Conclusions: Daily disposable contact lenses showed the highest roughness surface. Analyzing larger areas might be adequate to detect differences between lenses in terms of surface characteristics, which may not be so obvious if smaller areas are studied.     

Effects of Diet-Induced Weight Loss on Plasma Markers for Cholesterol Absorption and Synthesis: Secondary Analysis of a Randomized Trial in Abdominally Obese Men

Cross-sectional studies have shown that obesity is associated with lower intestinal cholesterol absorption and higher endogenous cholesterol synthesis. These metabolic characteristics have also been observed in patients with type 2 diabetes, metabolic syndrome, steatosis or cholestasis. The number of intervention studies evaluating the effect of weight loss on these metabolic characteristics is, however, limited, while the role of the different fat compartments has not been studied into detail. In a randomized trial, abdominally obese men (N = 54) followed a 6-week very low caloric (VLCD) diet, followed by a 2 week weight-maintenance period. Non-cholesterol sterols were measured at baseline and after 8 weeks, and compared to levels in lean participants (N = 25). After weight loss, total cholesterol (TC)-standardized cholestanol levels increased by 0.18 µmol/mmol (p < 0.001), while those of campesterol and lathosterol decreased by 0.25 µmol/mmol (p < 0.05) and 0.39 µmol/mmol (p < 0.001), respectively. Moreover, after weight loss, TC-standardized lathosterol and cholestanol levels were comparable to those of lean men. Increases in TC-standardized cholestanol after weight loss were significantly associated with changes in waist circumference (p < 0.01), weight (p < 0.001), BMI (p < 0.001) and visceral fat (p < 0.01), but not with subcutaneous and intrahepatic lipids. In addition, cross-sectional analysis showed that visceral fat fully mediated the association between BMI and TC-standardized cholestanol levels. Intrahepatic lipid content was a partial mediator for the association between BMI and TC-standardized lathosterol levels. In conclusion, diet-induced weight loss decreased cholesterol synthesis and increased cholesterol absorption. The increase in TC-standardized cholestanol levels was not only related to weight loss, but also to a decrease in visceral fat volume. Whether these metabolic changes ameliorate other metabolic risk factors needs further study.     

Heterogeneity of the association between plasma homocysteine and atherothrombotic disease: insights from studies of vascular structure and function.

Among individuals with severe hyperhomocysteinaemia, there is a striking heterogeneity in the severity of the clinical features. This observation demonstrates that factors must exist that modulate the relationship between hyperhomocysteinaemia and clinical disease. Investigations of the association between mild-to-moderate hyperhomocysteinaemia and atherothrombotic disease also suggest heterogeneity in the association between plasma homocysteine levels and 1) clinical disease; 2) angiographic and echographic estimates of the extent of atherosclerosis; 3) arterial stiffness; 4) endothelial function; and 5) procoagulant status. The commonly held view that homocysteine is a vasculotoxic substance that promotes atherogenesis by causing endothelial damage is incomplete, because it cannot explain this heterogeneity. I suggest that homocysteine may have both prothrombotic and proatherogenic properties, but that there are strong, as yet unidentified enhancing and protective factors, the prevalence of which may differ among populations. This concept could account for some of the observed heterogeneity. Identifying these factors would be of major clinical importance and would provide crucial mechanistic insights.     

安乃近的流动注射分光光度法分析

A new flow injection spectrophotometric method for the determination of analgin has been developed. The main factors which affect the determination were investigated. The absorption maximum is 650 nm. Under optimum conditions the calibration graph is linear in the range of 0. 2～3 mg/ml, the average recovery is 99. 8% with a relative standard deviation of 0. 5%. The proposed system permits the analysis of about 240 samples per hour and has the advantages of analytical efficiency, sensitivity and accuracy for the determination of analgin.     

Irbesartan treatment reduces biomarkers of inflammatory activity in patients with type 2 diabetes and microalbuminuria: an IRMA 2 substudy

The impact of irbesartan treatment on biomarkers of low-grade inflammation, endothelial dysfunction, growth factors, and advanced glycation end products (AGEs) during the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IRMA 2) study was evaluated. IRMA 2 was a 2-year multicenter, randomized, double-blind trial in patients comparing irbesartan (150 or 300 mg once daily) versus placebo. The primary end point was onset of overt nephropathy. A subgroup (n = 269, 68%) was analyzed for biomarkers at baseline and after 1 and 2 years. High-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, fibrinogen, adhesion molecules, transforming growth factor-beta, and AGE peptides were assessed. Irbesartan treatment yielded significant changes in hs-CRP (based on generalized estimating equation regression coefficient) with a 5.4% decrease per year versus a 10% increase per year in the placebo group (P < 0.001). Fibrinogen decreased 0.059 g/l per year from baseline versus placebo's 0.059 g/l increase per year (P = 0.027). IL-6 showed a 1.8% increase per year compared with placebo's 6.5% increase per year (P = 0.005). Changes in IL-6 were associated with changes in albumin excretion (P = 0.04). There was no treatment effect on the other biomarkers. Irbesartan (300 mg once daily) reduces low-grade inflammation in this high-risk population, and this may reduce the risk of micro- and macrovascular disease.     

Microalbuminuria and risk for cardiovascular disease: Analysis of potential mechanisms

Microalbuminuria is a strong and independent indicator of increased cardiovascular risk among individuals with and without diabetes. Therefore, microalbuminuria can be used for stratification of risk for cardiovascular disease. Once microalbuminuria is present, cardiovascular risk factor reduction should be more "aggressive." The nature of the link between microalbuminuria and cardiovascular risk, however, remains poorly understood. There is no strong evidence that microalbuminuria causes atherothrombosis or that atherothrombosis causes microalbuminuria. Many studies have tested the hypothesis that a common risk factor underlies the association between microalbuminuria and cardiovascular disease but, again, have found no strong evidence in favor of this contention. At present, the most likely possibility is that a common pathophysiologic process, such as endothelial dysfunction, chronic low-grade inflammation, or increased transvascular leakage of macromolecules, underlies the association between microalbuminuria and cardiovascular disease, but more and prospective studies of these hypotheses are needed.