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The operation behavior of the supply chain at all stages and the supply chain relationship based on input-output relationship were clarified through analysis of the three-stage supply chain network structure and the operation mode of each stage. In order to measure the efficiency of three-stage dairy supply chain, the network DEA model was constructed, and the supply chain of 29 Chinese dairy enterprises was studied. The total efficiency of three-stage dairy supply chain under DEA model was calculated. The relationship between the total efficiency and the efficiency of each fraction was introduced. By using the envelope model, the frontier was obtained and the corresponding measures were put forward to improve the efficiency of the three-stage dairy supply chain.

Background Accumulation of advanced glycation end products (AGEs) or advanced oxidation protein products (AOPPs) has been identified as a risk factor for accelerated atherosclerosis seen in diabetes and chronic kidney disease. However, little is known about the intervention for atherogenesis associated with these oxidized proteins. The rhizome of Picrorhiza scrophulariiflora (PS) has long been used to treat inflammatory diseases as a traditional medication. The study was performed to test the hypothesis that ethanol extraction of PS (EPS) may improve AGEs- or AOPPs-induced accelerated atherosclerosis in vivo . Methods and results Hypercholesterolemic or normal rabbits were randomly assigned to 8 groups treated with intravenous injection of AGEs- or AOPPs-modified rabbit serum albumin (AGEs-RSA or AOPPs-RSA), unmodified RSA or vehicle in the presence or absence of EPS (10 mg/kg/2 days) gavage for 10 weeks. Compared with hypercholesterolemic rabbits without EPS treatment, EPS administration significantly decreased the aortic plaque volume and oxidized low density lipoprotein (Ox-LDL) deposition in hypercholesterolemic animals. This was accompanied by significant histological improvement including decrease of intimal and smooth muscle cell proliferation and macrophage influx in affected areas. EPS administration almost completely abolished the accelerated atherosclerosis induced by chronic treatment of AGEs- or AOPPs-RSA in both hypercholesterolemic and normal rabbits. EPS administration significantly restored the AGEs- or AOPPs-induced redox imbalance and inflammation, evidenced by decrease of plasma Ox-LDL, thiobarbituric acid reactive substances and TNF-α, and increase of glutathione peroxidase activity. Conclusion These data suggested that EPS may improve atherosclerosis, particularly that induced by AGEs or AOPPs, through inhibition of redox-sensitive inflammation.

There is evidence that inflammatory processes are involved in the development and/or progression of diabetic nephropathy. However, effective treatment for inflammation in the kidneys of diabetic is practically unknown. The rhizomes of Picrorhiza scrophulariiflora (PS) are a traditional medication long used to treat inflammatory diseases. The aim of the present study was to test the hypothesis that the ethanol extract of PS (EPS) may reduce inflammation in patients with diabetic kidneys. Streptozotocin-induced diabetic rats were randomly assigned to two groups treated with a gavage of either EPS or vehicle. A group of non-diabetic control rats was treated concurrently. Compared with vehicle-treated diabetic rats, EPS-treated animals displayed a significant decrease in renal macrophage infiltration and overexpression of chemokine (C-C motif) ligand 2 (CCL2) and TGFB1. This was associated with attenuation of the structural and functional abnormalities of early diabetic nephropathy, such as glomerular hypertrophy, mesangial expansion, and albuminuria. Administration of EPS significantly reduced NADPH oxidase-dependent superoxide generation and decreased expression of malondialdehyde and advanced oxidation protein products in diabetic kidney. These data suggest that EPS might improve diabetic nephropathy, probably through inhibition of redox-sensitive inflammation.

The accumulation of advanced oxidation protein products (AOPPs) has been linked to vascular lesions in diabetes, chronic renal insufficiency, and atherosclerosis. However, the signaling pathway involved in AOPPs-induced endothelial cells (ECs) perturbation is unknown and was investigated. AOPPs modified human serum albumin (AOPPs-HSA) bound to the receptor for advanced glycation end products (RAGE) in a dose-dependent and saturable manner. AOPPs-HSA competitively inhibited the binding of soluble RAGE (sRAGE) with its preferential ligands advanced glycation end products (AGEs). Incubation of AOPPs, either prepared in vitro or isolated from uremic serum, with human umbilical vein ECs induced superoxide generation, activation of NAD(P)H oxidase, ERK 1/2 and p38, and nuclear translocation of NF-kappaB. Activation of signaling pathway by AOPPs-ECs interaction resulted in overexpression of VCAM-1 and ICAM-1 at both gene and protein levels. This AOPPs-triggered biochemical cascade in ECs was prevented by blocking RAGE with either anti-RAGE IgG or excess sRAGE, but was not affected by the neutralizing anti-AGEs IgG. These data suggested that AOPPs might be new ligands of endothelial RAGE. AOPPs-HSA activates vascular ECs via RAGE-mediated signals.

Yifuning is a traditional Chinese medicine recipe that has been used for many years in China for its effects on treating climacteric syndrome in women. The present study aimed to demonstrate the effects and underlying molecular mechanism of Yifuning on the ovaries of aging rats. Selected aging rats were administered different doses of Yifuning (1.0 or 2.0 g/kg by lavage), and after 6 weeks the rats were sacrificed. The activit of indicators of oxidative stress in the serum were measured. The expression levels of 8-oxo-2'-deoxyguanosine (8-OHDG) and p53 in the ovaries were examined using immunohistochemistry. The expression levels of the corresponding genes and proteins were detected by reverse transcription‑quantitative polymerase chain reaction and western blotting analyses, respectively. The results indicated that Yifuning significantly prevented ovarian failure, as indicated by improvements in estrous cycling, reproductive organ weights and sex hormone serum levels. Yifuning significantly increased the levels of superoxide dismutase, glutathione peroxidase, catalase and reduced malondialdehyde and hydrogen peroxide levels. Yifuning reduced DNA damage in the ovaries by reducing the expression of 8‑OHDG and p53. Treatment with Yifuning significantly reduced the age‑induced p19, p53, p21 and Rb activity in the ovaries. The present study demonstrates that Yifuning prevents ovarian failure and the mechanism involved is partly associated with antioxidants and suppression of the Rb/p53 signal transduction pathway.

In this study the chemical constituents of the higher polar sustances from Desmodium caudatum were investigated.The compounds were isolated by using column chromatographies over silicagel, polyamide, ODS, Sephadex LH-20, and preparative HPLC. The structures of these compounds were identified on the basis of NMR and MS spectra. Thirteen compounds were obtained and their structures were identified as vanillin(1), loliolide(2), indole-3-carboxaldehyde(3), salicylic acid(4), swertisin(5), saccharumoside C(6), isosinensin (7), kaempferol 3-O-β-D-glucopyranoside-7-O-α-L-rhamnopyranoside (8), isovitexin (9), vitexin (10), nothofagin(11), resveratroloside (12), and 2"-α-rhamnopyranosyl-7-O-methylvitexin (13). Except for compound 5, the remaining compounds were isolated from D. caudatum for the first time. Compounds 2, 3, 6-8, 11-13 were separated from the genus Desmodium for the first time.

We describe a modified Z-scan technique for the case when nonlinear refraction is accompanied by nonlinear absorption to separately evaluate the nonlinear refraction and the nonlinear absorption by performing straightforward measurements with the aperture removed. We divide the closed aperture (S < 1) normalized Z-scan by a scan with an open aperture (S = 1). With nanosecond scale at a 532 nm wavelength, we first measured the nonlinear optical absorption and refraction coefficients of a solution of Ni(Ac)2[N-(8-quinolyl) pyridine-2-carboxamide] · 4H2O by using the modified Z-scan technique. The nonlinear absorption originates from the near resonant two-photon absorption while the mechanism of the nonlinear refraction is the near resonant two-photon absorption transition enhancement. The linear increasing dependences of the optical nonlinearities on the incident irradiance arise from the population redistribution due to the near resonant two-photon absorption.

To study the chemical constituents of Elephantopus tomentosus.The compounds were isolated by repeated HP20 macro porous adsorption resin column combined with Sephadex LH-20, ODS and silica gel chromatographies. The structures were identified on the basis of extensive spectroscopic data analysis and by comparison of their spectral data reported.Eighteen compounds were identified as 2-deethoxy-2beta-hydroxyphantomolin (1), 2beta-hydroxy-2-deethoxy-8-O-deacylphantomolin-8-O-tiglinate (2), 2beta-methoxy-2-deethoxyphantomolin (3), 2beta-methoxy-2-deethoxy-8-O-deacylphantomolin-8-O-tiglinate (4), molephantin (5), molephantinin (6), tricin (7), luteolin (8), quercetin (9), 3beta-friedelinol (10), 3beta-hydroxyolean-12-en-28-oic acid (11), 3, 5-di-O-caffeoyl quinic acid (12), 3,4-di-O-caffeoyl quinic acid (13), syringaresinol-4-beta-D-glucopyranoside (14), xylogranatinin (15), byzantionoside B (16), 2'-hydroxycinnamaldehyde (17), and caffeic acid ethyl ester (18).Compounds 9, 11, 14-18 were separated from Elephantopus for the first time.

OBJECTIVE To study chemical constituents contained in Desmodium caudatum. METHOD The chemical compounds were separated by using such chromatographic methods as macroporous resin, Sephadex LH-20, ODS and normal phase silicagel column, and their structures were identified by spectroscopic data analysis. RESULT Fifteen compounds were separated and identified as stigmasterol (1), beta-sitosterol (2), citrusinol (3), hibiscone A (4), yukovanol (5), kenusanone I (6), neophellamuretin (7), desmodol (8), erythrotriol (9), hibiscone D (10), kaempferol (11), 8-prenylquercetin (12), leachianone G (13), 5,7,4'-trihydroxy-dihydroflavonol (14), and 4H-1-benzopyran-4-one, 2-(3,4-dihydroxyphenyl) -2, 3-dihydro-3,5,7-trihydroxy-8-( 3-methyl-2-butenyl) -, (2R-trans)-(9CI) (15). CONCLUSION All of the compounds were separated from D. caudatum for the first time except compound 8.

To construct chimerical DNA vaccine plasmid of human papillomavirus type 11 (HPV11) L1-E7, and to evaluate its immunogenicity.Molecular cloning techniques were used to construct recombinant plasmid pcDNA3 L1-E7 as a DNA vaccine. BALB/c mice were vaccinated with DNA recombinants through muscle injection.IL-2 and gamma-INF secreted by immunized spleens lymphocyte and HPV 11 L1 or E7 specific antibodies were assayed by ELISA method. Spleens lymphocyte proliferation was measured by MTT assay.The chimerical DNA plasmid of pcDNA3 L1-E7 was constructed correctly. Specific anti-HPV11 E7 and L1 antibodies, specific lymphocyte proliferation and secretions of IL-2 and gamma-INF were detected in vaccinated mice.Specific immune response, including cellular immunity and humoral immunity, could been detected in mice vaccinated with chimerical DNA vaccine of pcDNA3 L1-E7.

To investigate the effects of advanced glycation end products (AGES) on secretion of plasminogen activator inhibitor-1(PAI-1)by human proximal tubular epithelial cells and its NADPH oxidase dependent pathway.Human proximal tubular epithelial cells were cultured in vitro with indicated concentration of AGES modified human serum albumin (AGES-HSA). NADPH oxidase activity were detected by lucigenin-enhanced chemiluminescence. The production of PAI-1 was evaluated by enzyme-linked immunoadsorbent assay (ELISA). The PAI-1 mRNA expression was assayed by reverse transcription polymerase chain reaction (RT-PCR).AGES-HSA were associated with enhanced oxidative stress and NADPH oxidase activity. AGES-HSA upregulated the expression of PAI-1 mRNA and protein with dose and time dependent fashion. AGES-HSA-induced PAI-1 expression were significantly suppressed by the NAD(P)H oxidase inhibitors DPI, apocynin or O2- scavenger SOD.AGES-HSA stimulate tubular epithelial cells to produce PAI-1 through activation of NADPH oxidase.

Several studies have shown that coronary stenting reduces the frequency of clinical and angiographic restenosis in patients with mild to moderate renal insufficiency. However, less is known about the long-term benefits of stent use in this population. This study was aimed to determine the impact of coronary stenting on extended (5 years) long-term outcomes of patients with chronic renal insufficiency.The study included 602 consecutive patients who underwent successful percutaneous coronary intervention with stenting. Renal insufficiency was defined as an estimated glomerular filtration rate60 ml x min(-1) x 1.73 m(-2). The major adverse cardiac events were compared for patients with (n = 160) and without (n = 442) renal insufficiency.After the third year of follow-up, nonfatal myocardial infarction and revascularization rates were significantly increased in patients with renal insufficiency compared with those without renal dysfunction (16.9% vs 7.7%, P = 0.001; 29.4% vs 15.8%, P0.001). In patients who had recurrent cardiovascular events, a significantly higher rate of de novo stenosis revascularization was found in patients with renal insufficiency than without renal insufficiency (57.7% vs 22.7%, P0.001), while there was no significant difference in target lesion revascularization between the groups (51.9% vs 43.6%, P = 0.323). Multivariate analysis demonstrated an independent impact of the presence of renal insufficiency on the major adverse cardiac events (hazard ratio: 1.488, 95% confidence interval: 1.051 - 2.106, P = 0.025) and de novo stenosis (hazard ratio: 5.505, 95% confidence interval: 2.151 - 14.090, P0.001).The late major adverse cardiac events, after successful coronary stenting, is increased in patients with an estimated glomerular filtration rate60 ml x min(-1) x 1.73 m(-2). This might be associated with increased risk of de novo stenosis in this population.

Background Epidemiological evidence has indicated that vitamin D deficiency increased the risk of insulin resistance in metabolic syndrome. The present study was conducted to test the hypothesis that 1,25-dihydroxyvitamin D may improve the free fatty-acid (FFA)-induced insulin resistance in muscle cells. Method The insulin resistance of muscle cell model was established by treatment of FFA in differentiated C2C12 cells. Glucose uptake of C2C12 myotubes was analysed by the 3H-labelled 2-deoxyglucose uptake assay. The diameter of myotubes was measured under the condition of glutaraldehyde-induced autofluorescense. Tyrosine phosphorylated insulin receptor substrate 1 (IRS-1) was measured by immunoprecipitation. Serine phosphorylated IRS-1 and protein kinase B (Akt), extracellular signal-related kinase (ERK), c-Jun amino-terminal kinases (JNK) as well as their phosphorylated form were analysed by Western blots. Results Compared with a vehicle-treated group, FFA treatment in myotubes was associated with 70.6% reduction in insulin-mediated uptake of glucose, a five-fold increase in serine phosphorylation of IRS-1, 76.9% decrease in tyrosine phosphorylation of IRS-1 and 81.8% decrease in phosphorylation of Akt. Supplement of 1,25-dihydroxyvitamin D improved the FFA-induced inhibition of glucose uptake in a dose- dependent (p < 0.001) and time-dependent manner (p < 0.01). This was accompanied by increase in tyrosine phosphorylation of IRS-1 and phosphorylated Akt and decrease in serine phosphorylation of IRS-1 (p < 0.001). 1,25-Dihydroxyvitamin D also inhibited the FFA-induced reduction in myotube diameter by 35.3% (p < 0.001). JNK phosphorylation was reduced by 126.7% with treatment of 1,25-dihydroxyvitamin D (p < 0.001). 1,25-Dihydroxyvitamin D had no effect on FFA-induced ERK phosphorylation (p = 0.84). Conclusion 1,25-Dihydroxyvitamin D improved the FFA-induced insulin resistance in muscle cells. Copyright © 2008 John Wiley & Sons, Ltd.

The involvement of inflammatory processes has been recognized in development and/or progression of diabetic nephropathy. However, the mechanisms involved in the pathogenesis of renal inflammation have not been completely understood. In this study, we tested the hypothesis that accumulation of advanced oxidation protein products (AOPPs), which occurs in diabetes, may promote inflammatory responses in diabetic kidney. Streptozotocin-induced diabetic rats were randomized to iv injection of vehicle, native rat serum albumin (RSA), and AOPPs-modified RSA (AOPPs-RSA) in the presence or absence of oral administration of apocynin. A control group was followed concurrently. Compared with RSA- or vehicle-treated diabetic rats, AOPPs-RSA-treated animals displayed significant increase in renal macrophage infiltration and overexpression of monocyte chemoattractant protein-1 and TGF-β1. This was associated with deteriorated structural and functional abnormalities of diabetic kidney, such as glomerular hypertrophy, fibronectin accumulation, and albuminuria. AOPP challenge significantly increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent superoxide generation in renal homogenates and up-regulated membrane expression of renal NADPH oxidase subunits p47phox and gp91phox. All these AOPPs-induced perturbations in diabetic kidney could be prevented by the NADPH oxidase inhibitor apocynin. These data suggest that chronic accumulation of AOPPs may promote renal inflammation in diabetes probably through activation of renal NADPH oxidase.

The Renoprotection of Optimal Antiproteinuric Doses (ROAD) study was performed to determine whether titration of benazepril or losartan to optimal antiproteinuric doses would safely improve the renal outcome in chronic renal insufficiency. A total of 360 patients who did not have diabetes and had proteinuria and chronic renal insufficiency were randomly assigned to four groups. Patients received open-label treatment with a conventional dosage of benazepril (10 mg/d), individual uptitration of benazepril (median 20 mg/d; range 10 to 40), a conventional dosage of losartan (50 mg/d), or individual uptitration of losartan (median 100 mg/d; range 50 to 200). Uptitration was performed to optimal antiproteinuric and tolerated dosages, and then these dosages were maintained. Median follow-up was 3.7 yr. The primary end point was time to the composite of a doubling of the serum creatinine, ESRD, or death. Secondary end points included changes in the level of proteinuria and the rate of progression of renal disease. Compared with the conventional dosages, optimal antiproteinuric dosages of benazepril and losartan that were achieved through uptitration were associated with a 51 and 53% reduction in the risk for the primary end point (P = 0.028 and 0.022, respectively). Optimal antiproteinuric dosages of benazepril and losartan, at comparable BP control, achieved a greater reduction in both proteinuria and the rate of decline in renal function compared with their conventional dosages. There was no significant difference for the overall incidence of major adverse events between groups that were given conventional and optimal dosages in both arms. It is concluded that uptitration of benazepril or losartan against proteinuria conferred further benefit on renal outcome in patients who did not have diabetes and had proteinuria and renal insufficiency.

Objective—Increased level of plasma advanced oxidation protein products (AOPPs) has been found in patients with uremia and nonuremic subjects with coronary artery disease. This study was conducted to test the hypothesis that AOPPs play a causal role in atherosclerosis.Methods and Results—Hypercholesterolemic (0.5% wt/wt diet) or normal rabbits received either repeated intravenous injections of AOPPs modified rabbit serum albumin (AOPPs-RSA) or unmodified RSA for 8 weeks. Compared with RSA- or vehicle-treated hypercholesterolemic rabbits, AOPPs-RSA–treated animals displayed increased atherosclerotic plaque area oxidized low-density lipoprotein (oxLDL) deposition, macrophage infiltration, and smooth muscle cell proliferation. Aortic sections from AOPPs-RSA–treated normal rabbits showed significant focal intima proliferation and mild Oil-Red-O staining lipid deposition in the affected areas, a phenomenon not observed in the RSA- or vehicle-treated controls. Plasma AOPPs levels in AOPPs-treated groups significantly increased in both hypercholesterolemic and normal rabbits compared with their relevant controls. Close correlations were found between plasma levels of AOPPs and the parameters of oxidative stress, eg, oxLDL and thiobarbituric acid reactive substances levels, or glutathione peroxidase activity. A highly significant correlation was also observed between plasma AOPPs and tumor necrosis factor (TNF)-α levels.Conclusions—This study provides in vivo evidence for a causal relationship between chronic AOPPs accumulation and atherosclerosis.

To investigate the expression of receptor for advanced glycation end products (RAGE) in chronic renal failure (CRF) and its role in monocyte-mediated inflammation associated with chronic renal failure (CRF).Peripheral monocytes (PMC) were isolated from 96 non-diabetic patients with varying severity of CRF. RAGE expression on monocytes was quantitated by flow cytometry. The binding capacity of monocytes with advanced glycation end products (AGE) was determined by 125I-AGEs-HSA binding assay. The plasma level of pentosidine, a marker of AGE, was determined by competitive ELISA. Commercially available kits were used for measuring the plasma levels of neopterin, TNF-alpha and C-reactive protein (CRP), a systemic acute phase reactant.Flow cytometry showed that the RAGE expression at the PMC surface of CRF patients was 8.02 +/- 0.43, significantly higher than that of the normal controls (P0.001). The number of functional sites to bind 125I-AGEs-HSA at the surface of PMC of CRF patients was increased in comparison with the normal control group. The biding capacity (Ka) at the surface of PMC of CRF patients was 2 times that of normal control group. Stimulated by AGEs-HAS, the TNF-alpha level in the supernatant of PMC increased dose-dependently in both the normal control and CRF patients, especially in the latter (P0.01). After pretreatment of anti-RAGE or non-immune rabbit IgG and then by AGEs-HAS the levels of TNF-alpha in the PMC supernatants of CRF patients and normal controls decreased form 90.52 pg/(10(5) cell) +/- 2.82 pg/(10(5) cell) to 17.86 pg/(10(5) cell) +/- 1.05 pg/(10(5) cell) and from 26.38 pg/(10(5) cell) +/- 1.54 pg/(10(5) cell) to 6.76 pg/(10(5) cell) +/- 0.20 pg/(10(5) cell). HAS not modified by AGEs and non-immune rabbit IgG showed no influence on the secretion of TNF-alpha. The plasma levels of TNF-alpha, neopterin, and CRP increased along with the worsening of renal function. The RAGE expression and pentosidine level at the surface of PMC in CPR patients without hemodialysis were positively correlated with plasma neopterin, TNF-alpha, and CRP levels, even after correction of creatine clearance rate (r = 0.53, P0.001; r = 0.58, P0.001; r = 0.40, P = 0.001). The expression of RAGE in CRF patients with hemodialysis was positively correlated with the plasma TNF-alpha level (r = 0.33, P = 0.029, n = 36), however, not correlated with neopterin or CRP.Enhanced RAGE may trigger a positive feed back loop of AGEs-induced monocyte perturbation, and may contribute to the monocyte-mediated systemic inflammation in CRF.

To investigate the effect of advanced glycation end products (AGE) on atheromatous plaque formation and its possible mechanisms.Fifty rabbits were randomly divided into five groups of 10 rabbits: group A, fed with hypercholesterolemic diet and injected intravenously with AGE modified rabbit serum albumin (AGE-RSA); group B, fed with hypercholesterolemic diet and injected with unmodified RSA; group C, fed with hypercholesterolemic diet; group D, fed with normal diet alone: and group E, fed with normal diet and injected with AGE-RSA. Ten weeks after the rabbits were killed. Their aortas were taken out and stained with Sudan red IV. The extent of atheromatous plaques in the aortas en face was evaluated by computer-assisted morphometry and by histologic examination. Photoshop system was used to measure the percentage of atheromatous plaques in the area of tunica intima. The depositions of AGE, malondialdehyde modified low-density lipoprotein (MDA-LDL), oxidized low-density lipoprotein (ox-LDL) and expression of receptor of AGE (RAGE) in aortic tissue were detected by using immunohistological staining. The circulating AGE, blood lipids, serum selenium glutathione peroxydase (SeGSHPx) activity, malonyldialdehyde (MDA), and oxidized LDL (ox-LDL) were detected before the experiment and after the rabbits were killed.(1) The relative plaque area was significantly increased in group A (50% +/- 8%) compared with in group B (21% +/- 7%) and group C (29% +/- 6%). No plaque could be found in animals fed with normal diet (group D) even in those receiving repeated injections of AGE-RSA (group E). Depositions of ox-LDL, MDA-LDL and AGE in atherosclerotic lesions increased and RAGE expression were upregulated in the rabbits fed with hypercholesterolemic diet and injected with AGE-RSA (group A) compared with the other four groups. (2) All hypercholesterolemic rabbits showed comparable serum levels of triglyceride and cholesterol. However, the serum levels of AGE, ox-LDL and MDA were significantly higher and the serum level of SeGSHPx was relatively lower in group A compared with those in the other four groups. (3) The serum level of AGE was directly correlated with the serum ox-LDL (r = 0.459, P0.01) or serum MDA concentration (r = 0.423, P0.05), and inversely correlated with the serum level of SeGSHPx (r = - 0.448, P0.01). A close correlation was found between the serum level of AGE and endothelium RAGE expression (r = 0.384, P0.05) and deposition area of AGE (r = 0.468, P0.05) in aorta.AGE accelerates the atheromatous plaque formation through induction of oxidative stress and upregulation of RAGE.

Inappropriate chronic inflammation associated with progressive, chronic kidney disease (CKD) reflects sustained activation of immunocompetent cells, like monocytes/macrophages. Advanced glycation end products (AGE) accumulate in CKD, but it is unclear if they stimulate monocytes by binding with the receptor for AGE (RAGE). Posited was the notion that RAGE plays a contributory role to monocyte-mediated systemic inflammation of progressive CKD. Peripheral blood monocytes were isolated from 102 patients without diabetes with varying severity of CKD. RAGE expression on peripheral blood monocytes increased with worsening CKD (r2 = 0.73) and was strongly correlated with plasma levels of pentosidine, a marker for AGE (r = 0.71). Strongly positive statistical correlations were observed in patients with CKD between monocyte RAGE and plasma levels of tumor necrosis factor alpha (TNF-alpha) (r = 0.61), the monocyte activation marker, neopterin (r = 0.65), and the systemic acute phase reactant, C-reactive protein (r = 0.44). Monocytes obtained from patients with CKD showed a monotonic increase in the number and affinity of specific AGE binding sites and increased production of TNF-alpha under stimulation of AGE. All these upregulatory responses in uremic monocytes could be largely blocked by an anti-RAGE antibody. It was concluded that RAGE expression was upregulated on monocytes from patients with CKD. Enhanced RAGE may amplify AGE-induced monocytes perturbation and contribute to monocyte-mediated systemic inflammation in progressive CKD.

To investigate whether advanced glycation end products (AGE) or advanced oxidative protein products (AOPP) contributes to atherogenesis in experimental hypercholesterolemic rabbits.Hypercholesterolemic (0.5% wt/wt diet) rabbits received repeated intravenous injections of either AGE modified rabbit serum albumin (AGE-RSA) or AOPP modified RSA (AOPP-RSA) for 10 weeks. Three control groups were set as follows: a group fed with high cholesterol diet alone, a group fed with high cholesterol diet and injected with normal RSA, and a group fed with normal diet. The animals were sacrificed and aortas were dissected and stained with Sudan red IV. Atheromatous plaques in the aortas en face were evaluated by computer-assisted morphometry and by histologic examination. Hematological parameters (triglyceride, cholesterol, AGE and AOPP) were also tested.(1) The relative plaque area in rabbits receiving repeated injections of AGE or AOPP was 50.1%+/-7.4% and 62.4%+/-8.8% respectively, both were significantly larger than either that of hypercholesterolemic rabbits (29.8%+/-6.3%, P0.05) or that of hypercholesterolemic rabbits injected with unmodified RSA (20.9%+/-6.4%, P0.05). In aortic arch, thoracic aorta and abdominal aorta, atherosclerotic lesions in AGE group and AOPP group were more severe than in any of the control groups. (2)The average thickness of the plaques on thoracic aortas in AGE group [(138.1+/-13.0) microm] and in AOPP group [(147.7+/-13.1) microm ] were significantly thicker than either of that in the group treated with hypercholesterolemic diet alone [(85.7+/-15.0) microm] or that in the group treated with non modified RSA [(95.5+/-15.7) microm]. (3) Glyceride and cholesterol levels in all animals on hypercholesterolemic diet were similar. AGE and AOPP serum levels in groups injected with AGE or AOPP were significantly higher than that in any of the control groups. AGE serum concentrations were positively correlated with the atheromatous plaque area(r=0.408, P=0.005), so were the AOPP serum concentrations (r=0.595, P=0.000).AGE or AOPP modified proteins accelerate the formation of atherosclerosis and may contribute to the accelerated atherosclerosis in end stage renal diseases.

To investigate the effects of advanced glycation end products (AGE) on secretion of monocyte chemoattractant protein-1 (MCP-1) by human endothelial cells and its signal transduction pathway.Human umbilical vein endothelial cells (HUVECs) and HUVEC-derived cell line (ECV304) were cultured in vitro with indicated concentration of AGE modified human serum albumin (AGE-HSA) or AGE modified bovine serum albumin (AGE-BSA). The production of MCP-1 was evaluated by Western blotting and enzyme-linked immunoadsorbent assay (ELISA). The MCP-1 mRNA expression was assayed by reverse-transcription polymerase chain reaction (RT-PCR). Intracellular oxidative stress was detected by flow cytometry. The phosphorylation activity of cellular p38 mitogen-activated protein kinase (p38-MAPK) was analyzed by Western blotting using a phospho-specific antibody.AGE-HSA and AGE-BSA, but not their unmodified form, upregulated the expression of MCP-1 mRNA and protein dose- and time-dependently. The MCP-1 concentration in the supernatant of HUVECs incubated with 50 micro g/ml AGE-HSA for 12 hours increased from 48.3 pg/ micro g +/- 0.6 pg/ micro g protein to 148.1 pg/ micro g +/- 12.6 pg/ micro g protein (P0.01). AGE modified proteins were associated with enhanced oxidative stress and p38-MAPK phosphorylation activity. Incubation of HUVECs with 50 micro g/ml AGE-HSA for 30 minutes resulted in increase of p38-MAPK phosphorylation activity by 91% +/- 14% (P0.01). Antioxidant or SB 203580, a specific inhibitor of p38, could block the over-expression of MCP-1.AGE modified proteins stimulate endothelial cells to produce MCP-1 through activation of the p38 signal pathway. This effect may contribute to the pathogenesis of atherosclerosis seen in AGE-associated diseases.

We use the strong field approximation with a time window function controlling the release time of electrons to study the intra-cycle and inter-cycle interferences in few-cycle intense laser pulses impinging on He. The diffraction fringes, i.e., the vertical stripe-like structure, observed in the experimental two-dimensional photoelectron momentum distributions of Gopal et al. (2009 Phys. Rev. Lett. 103 053001) have been attributed to the interplay of the intra- and inter-cycle interferences. The pure numerical calculations by solving the time-dependent Schrodinger equation are also performed and the results are compared with the experimental measurements directly. It has been found that the position of the stripe-like structure can be used to determine the duration of the laser pulses used in experiments.

BACKGROUND Several studies have shown that coronary stenting reduces the frequency of clinical and angiographic restenosis in patients with mild to moderate renal insufficiency. However, less is known about the long-term benefits of stent use in this population. This study was aimed to determine the impact of coronary stenting on extended (5 years) long-term outcomes of patients with chronic renal insufficiency. METHODS The study included 602 consecutive patients who underwent successful percutaneous coronary intervention with stenting. Renal insufficiency was defined as an estimated glomerular filtration rate < 60 ml x min(-1) x 1.73 m(-2). The major adverse cardiac events were compared for patients with (n = 160) and without (n = 442) renal insufficiency. RESULTS After the third year of follow-up, nonfatal myocardial infarction and revascularization rates were significantly increased in patients with renal insufficiency compared with those without renal dysfunction (16.9% vs 7.7%, P = 0.001; 29.4% vs 15.8%, P < 0.001). In patients who had recurrent cardiovascular events, a significantly higher rate of de novo stenosis revascularization was found in patients with renal insufficiency than without renal insufficiency (57.7% vs 22.7%, P < 0.001), while there was no significant difference in target lesion revascularization between the groups (51.9% vs 43.6%, P = 0.323). Multivariate analysis demonstrated an independent impact of the presence of renal insufficiency on the major adverse cardiac events (hazard ratio: 1.488, 95% confidence interval: 1.051 - 2.106, P = 0.025) and de novo stenosis (hazard ratio: 5.505, 95% confidence interval: 2.151 - 14.090, P < 0.001). CONCLUSIONS The late major adverse cardiac events, after successful coronary stenting, is increased in patients with an estimated glomerular filtration rate < 60 ml x min(-1) x 1.73 m(-2). This might be associated with increased risk of de novo stenosis in this population.