Prognostic value of Geriatric Nutritional Risk Index and systemic immune-inflammatory index in elderly patients with acute coronary syndromes.

The objective of this study was to evaluate the predictive value of the Geriatric Nutritional Risk Index (GNRI) combined with the Systemic Immunoinflammatory Index (SII) for the risk of major adverse cardiovascular events (MACE) following percutaneous coronary intervention in elderly patients with acute coronary syndrome (ACS). We retrospectively reviewed the medical records of 1202 elderly patients with acute coronary syndromes divided into MACE and non-MACE groups according to whether they had a MACE. The sensitivity analysis utilized advanced machine learning algorithms to preliminarily identify the critical role of GNRI versus SII in predicting MACE risk. We conducted a detailed analysis using a restricted cubic spline approach to investigate the nonlinear relationship between GNRI, SII, and MACE risk further. We constructed a clinical prediction model based on three key factors: GNRI, SII, and Age. To validate the accuracy and usefulness of this model, we compared it to the widely used GRACE score using subject work and recall curves. Additionally, we compared the predictive value of models and GRACE scores in assessing the risk of MACE using the Integrated Discriminant Improvement Index (IDI) and the Net Reclassification Index (NRI). This study included 827 patients. The GNRI scores were lower in the MACE group than in the non-MACE group, while the SII scores were higher in the MACE group (P < 0.001). The multifactorial analysis revealed a low GNRI (OR = 2.863, 95% CI: 2.026-4.047, P = 0.001), High SII (OR = 3.102, 95% CI: 2.213-4.348, P = 0.001). The area under the curve (AUC) for the predictive model was 0.778 (95% CI: 0.744-0.813, P = 0.001), while the AUC for the GRACE score was 0.744 (95% CI: 0.708-0.779, P = 0.001). NRI was calculated to be 0.5569, with NRI + at 0.1860 and NRI- at 0.3708. The IDI was found to be 0.0571, with a P-value of less than 0.001. These results suggest that the newly developed prediction model is more suitable for use with the population in this study than the GRACE score. The model constructed using GNRI and SII demonstrated good standardization and clinical impact, as evidenced by the standard, DCA, and clinical impact curves. The study shows that combining GNRI and SII can be a simple, cost-effective, and valuable way to predict the risk of MACE within one year in elderly acute coronary syndromes.

Comparative analysis of four nutritional scores predicting the incidence of MACE in older adults with acute coronary syndromes after PCI.

To determine the most appropriate nutritional assessment tool for predicting the occurrence of major adverse cardiovascular events (MACE) within 1 year in elderly ACS patients undergoing PCI from four nutritional assessment tools including PNI, GNRI, CONUT, and BMI. Consecutive cases diagnosed with acute coronary syndrome (ACS) and underwent percutaneous coronary intervention (PCI) in the Department of Cardiovascular Medicine of the Air force characteristic medical center from 1 January 2020 to 1 April 2022 were retrospectively collected. The basic clinical characteristics and relevant test and examination indexes were collected uniformly, and the cases were divided into the MACE group (174 cases) and the non-MACE group (372 cases) according to whether a major adverse cardiovascular event (MACE) had occurred within 1 year. Predictive models were constructed to assess the nutritional status of patients with the Prognostic Nutritional Index (PNI), Geriatric Nutritional Risk Index (GNRI), Controlling nutritional status (CONUT) scores, and Body Mass Index (BMI), respectively, and to analyze their relationship with prognosis. The incremental value of the four nutritional assessment tools in predicting risk was compared using the Integrated Discriminant Improvement (IDI) and the net reclassification improvement (NRI). The predictive effect of each model on the occurrence of major adverse cardiovascular events (MACE) within 1 year in elderly ACS patients undergoing PCI was assessed using area under the ROC curve (AUC), calibration curves, decision analysis curves, and clinical impact curves; comparative analyses were performed. Among the four nutritional assessment tools, the area under the curve (AUC) was significantly higher for the PNI (AUC: 0.798, 95%CI 0.755-0.840 P < 0.001) and GNRI (AUC: 0.760, 95%CI 0.715-0.804 P < 0.001) than for the CONUT (AUC: 0.719,95%CI 0.673-0.765 P < 0.001) and BMI (AUC: 0.576, 95%CI 0.522-0.630 P < 0.001). The positive predictive value (PPV) of PNI: 67.67% was better than GNRI, CONUT, and BMI, and the negative predictive value (NPV): of 83.90% was better than CONUT and BMI and similar to the NPV of GNRI. The PNI, GNRI, and CONUT were compared with BMI, respectively. The PNI had the most significant improvement in the Integrated Discriminant Improvement Index (IDI) (IDI: 0.1732, P < 0.001); the PNI also had the most significant improvement in the Net Reclassification Index (NRI) (NRI: 0.8185, P < 0.001). In addition, of the four nutritional assessment tools used in this study, the PNI was more appropriate for predicting the occurrence of major adverse cardiovascular events (MACE) within 1 year in elderly ACS patients undergoing PCI.

Advanced oxidation protein products in predicting acute kidney injury following cardiac surgery.

To test the hypothesis whether serum advanced oxidation protein products (AOPP) are associated with increased acute kidney injury (AKI) after cardiopulmonary bypass (CPB) and could serve as a biomarker in this aspect, we performed a prospective cohort study. Thirty-five (22.3%) patients developed AKI, and 32 age- and gender-matched patients without AKI were selected as control. Serum AOPP 1 h after CPB were significantly higher among AKI patients compared with non-AKI patients (81.8 ± 18.6 versus 67.4 ± 12.5 µmol/L, p < 0.001), with an area under the receiver-operating characteristic (ROC) curve of 0.714. An optimal serum AOPP 1 h after CPB cutoff of 69.9 µmol/L had a sensitivity of 74%, specificity of 63% and a positive predictive value of 68% for predicting AKI. These results demonstrated that serum AOPP might be an early biomarker for AKI after CPB.

Increased plasma advanced oxidation protein products is an early marker of endothelial dysfunction in type 2 diabetes patients without albuminuria 2.

BACKGROUND: Endothelial dysfunction is an early event of cardiovascular disease in type 2 diabetes (T2D) and can occur before albuminuria. Oxidative stress has been found to play a key role in the development of endothelial dysfunction. Therefore, we hypothesized that increases in plasma advanced oxidized protein products (AOPPs), a family of oxidized, dityrosine-containing protein compounds generated during oxidative stress, could serve as an early marker of endothelial dysfunction in T2D patients without albuminuria. METHODS: We conducted a cross-sectional investigation of 147 newly diagnosed T2D patients (112 without albuminuria and 35 with albuminuria) and 49 age-matched healthy control subjects. Flow-mediated vasodilation (FMD) was used to assess endothelium-dependent vasodilator function, and plasma soluble intercellular adhesion molecule-1 (sICAM-1) concentrations were determined to evaluate vascular injury. Plasma AOPPs concentrations were measured using a modified spectrophotometric assay. RESULTS: Plasma AOPPs concentrations were significantly elevated in normoalbuminuric patients with T2D compared with healthy controls. Plasma AOPPs concentrations were correlated with FMD and plasma sICAM-1 concentrations in this population. Multivariate regression analysis demonstrated that increased plasma AOPPs was the strongest risk factor for impaired endothelial vasodilation and increased sICAM-1 in these patients. Similar results were observed in T2D patients with albuminuria. CONCLUSIONS: Increased plasma AOPPs concentrations were an independent risk factor for endothelial dysfunction, and therefore may be an early marker of vasculopathy in individuals at an early stage of diabetes.

Higher plasma AOPP is associated with increased proteinuria excretion and decreased glomerular filtration rate in pre-eclamptic women.

BACKGROUND: Advanced oxidation protein products (AOPP) as a novel biomarker of oxidative stress has been demonstrated in chronic kidney disease (CKD) patients. The research was to investigate the plasma AOPP level in pre-eclamptic pregnant women and its correlation with 24-h proteinuria collection, cystatin C(CC), uric acid(UA) and creatinine(Cr). METHODS: Fifty pre-eclamptic women, including 22 mild and 28 severe preeclampsia were enrolled. Twentyfive healthy singleton pregnant women were selected as control. Blood samples were obtained from all groups to measure the levels of AOPP, CC, UA, Cr and other biochemical parameters at admission. Total protein in the 24h urine collection was measured. Pearson correlation was performed to evaluate the associations between plasma AOPP level and 24-h proteinuria collection, plasma cystatin C, uric acid and creatinine. RESULTS: The means of AOPP levels were significantly different among severe, mild pre-eclampsia and normotensive pregnant women (88.6±10.0µmmol/L, 72.1±11.1µmmol/L and 48.7±11.3µmmol/L). The means of cystatin C levels were significantly different among severe, mild pre-eclampsia and normotensive pregnant women (1.8±0.6µmmol/L, 1.2±0.3µmmol/L and 1.0±0.2µmmol/L). Mild, severe pre-eclampsia and control groups did not differ significantly from each other with respect to uric acid and creatinine. Significant positive correlation between AOPP and 24-h proteinuria excretion in preeclamptic pregnant women was found in mild and severe preeclamptic pregnant women (r=0.792). Significant positive correlation between AOPP and cystatin C was found in normal and preeclamptic pregnant women (r=0.521). CONCLUSION: Plasma AOPP level had a significant positive correlation with 24-h proteinuria excretion and cystatin C. Further research about the relevance between the level of AOPP and the onset of preeclampsia was needed in order to have a profound prospective in oxidative stress and preeclampsia.

Current pattern of Chinese dialysis units: a cohort study in a representative sample of units.

BACKGROUND: Understanding the characteristics of Chinese dialysis patients and the current practice trends is the first step to evaluate the association between practice pattern and outcome in these populations. In the present study, we evaluated the status of medical treatment and characteristic features of chronic dialysis patients in China. METHODS: Through a clustering sampling, we selected 9 centers from the largest dialysis facilities in 6 cities around China. All adult undergoing dialysis in the selected units were screened. A total of 2388 (1775 on hemodialysis (HD) and 613 on peritoneal dialysis (PD)) patients were finally enrolled. All data were collected at enrollment on the bases of review of medical records. RESULTS: In this cohort, 1313 (55.0%) were male. The mean age was 54 years old. The median time for dialysis was 26 months (12 - 51 months). Seventy-five percent of patients were on HD and 25.0% on PD. Among PD patients, about 21% patients did not receive dialysis adequacy. For HD patients, about 14.0% of them did not achieve dialysis adequacy when the target of kt/V was set as 1.2. Only 44.7% of patients achieved blood pressure target of 140/90 mmHg. About 60% of patients did not reach the hemoglobin target of 110 g/L even though 85.0% of them were treated with erythropoietin. In addition, 48.5% of the patients had uncontrolled mineral metabolism revealed by the high calcium-phosphate product. Compared with HD patients, higher level of serum glucose, triglyceride, and total and low density lipoprotein cholesterol were more common in PD patients. CONCLUSIONS: This observational study suggests that many Chinese dialysis patients did not achieve the therapeutic target, particularly in blood pressure control, anemia correction, and mineral balance. PD patients were more likely to suffer metabolic disturbance.

[Effect of the ethanol extract of Picrorhiza scrophulariiflora on the progression of chronic kidney disease in a rat remnant kidney model].

OBJECTIVE: To investigate the effect of the ethanol extract of Picrorhiza scrophulariiflora (EPS) on renal function and tissue damage in a rat remnant kidney model. METHODS: Rat models of chronic kidney disease induced by 5/6 nephrectomy (5/6 Nx) were randomly assigned into two groups for treatment with a gavage of either EPS or vehicle for 9 weeks. The rats in the control group received only sham operation. RESULTS: Compared with vehicle-treated 5/6 Nx rats, the EPS-treated rats displayed significantly decreased urinary excretion of malondialdehyde, serum levels of AGEs and AOPPs, and increased serum SeGSHPx activities. These changes were associated with attenuated urinary protein excretion, glomerular sclerosis and interstitial fibrosis. CONCLUSION: EPS can obviously improve the renal functions and renal pathologies in rats with chronic kidney disease probably by inhibiting the oxidative stress.

[Genetic analysis of epistatic effects between ApoB and UCP on abdominal fat trait in chicken].

It has been found that epistasis for selective response plays an indispensible role in animal genetics and breeding. In this study, the polymorphisms of T123G in apoliprotein B (ApoB) and C1197A in uncoupling protein (UCP) among individuals from the 8th to the 10th generation populations of the Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHFL) were detected, and genetic analysis of the epistatic effects between the two SNPs on abdominal fat percentage (AFP) was performed using Natural and Orthogonal InterActions (NOIA) model. According to these assays, we concluded that at least one out of four epistatic components between these two SNPs was significantly associated with AFP (Plt;0.05) in fat lines from the 8th to the 10th generations of NEAUHFL; on the contrary, none was significantly associated with AFP (P>0.05) in lean lines. Our results suggested that epistatic interactions among QTLs and functional SNPs in candidate genes affecting fat traits might lead to differences in growth patterns of fat traits between lean and fat chicken lines.

Accumulation of advanced oxidation protein products induces podocyte apoptosis and deletion through NADPH-dependent mechanisms.

The accumulation of plasma advanced oxidation protein products (AOPPs) is prevalent in diverse disorders such as diabetes, metabolic syndromes, and chronic kidney disease. To study whether accumulated AOPPs have an important role in the progression of proteinuria and glomerulosclerosis, we chronically treated normal Sprague-Dawley rats with AOPP-modified rat serum albumin. Podocyte apoptosis was significantly increased coincident with the onset of albuminuria and preceded significant losses of glomerular podocytes. Increasing the amount of AOPPs in the media of conditionally immortalized podocytes rapidly triggered the production of intracellular superoxide by activation of NADPH oxidase and this, in turn, led to an upregulation of p53, Bax, caspase 3 activity, and apoptosis. Chronic inhibition of NADPH oxidase by apocynin prevented podocyte apoptosis, ameliorated podocyte depletion, and decreased albuminuria in AOPP-challenged rats. Our study demonstrates that accumulation of AOPPs promotes NADPH oxidase-dependent podocyte depletion by a p53-Bax apoptotic pathway both in vivo and in vitro.

[Advanced glycation end products induce expression of PAI-1 in cultured human proximal tubular epithelial cells through NADPH oxidase dependent pathway].

AIM: 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. METHODS: 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). RESULTS: 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. CONCLUSION: AGES-HSA stimulate tubular epithelial cells to produce PAI-1 through activation of NADPH oxidase.

[Relationship between protein oxidation levels in the follicular fluid and the outcome parameters of in vitro fertilization-embryo transplantation].

OBJECTIVE: To explore the relationship between protein oxidation levels in the follicular fluid and the outcome parameters of in vitro fertilization-embryo transplantation (IVF-ET). METHODS: The levels of advanced oxidation protein products (AOPP) in the follicular fluid were measured in 64 women with tubal infertility undergoing IVF-ET. The relationship between the AOPP levels and IVF-ET outcome parameters was analyzed. RESULTS: AOPP levels showed significant inverse correlations between the proportion of mature oocytes (r=-0.401, P=0.001), fertilization rate (r=-0.257, P=0.045), cleavage rate (r=-0.290, P=0.024) and good embryo rate (r=-0.520, P=0.000). AOPP levels differed significantly between the groups with different retrieved oocyte numbers (F=3.851, P=0.027), being the lowest in women with 8 to 15 retrieved oocytes and the highest in those with retrieved oocytes below 8. The AOPP level in the non-pregnant women was significantly higher than that in the pregnant women (t=3.665, P=0.001). The AOPP levels also differed significantly with age (F=15.919, P=0.000), and the women >35 years of age had the highest level and those below 30 years had the lowest level. CONCLUSION: Protein oxidative stress is present in the follicular fluid of women on IVF-ET cycles. High level of AOPP may have adverse effects on the oocytes and early embryonic development and may affect the outcome of IVF-ET.

Picrorhiza scrophulariiflora improves accelerated atherosclerosis through inhibition of redox-sensitive inflammation.

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-alpha, 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.

Advanced oxidation protein products activate vascular endothelial cells via a RAGE-mediated signaling pathway.

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.

Advanced oxidation protein products promote inflammation in diabetic kidney through activation of renal nicotinamide adenine dinucleotide phosphate oxidase.

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-beta1. 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 p47(phox) and gp91(phox). 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.

[Effects of ultrapure water on the levels of oxidative stress and inflammation parameters in maintenance hemodialysis patients].

OBJECTIVE: To evaluate the effects of ultrapure water on the levels of oxidative stress and inflammation parameters in maintenance hemodialysis patients. METHODS: Thirty-six stable maintenance hemodialysis patients were involved in this study, who were free of acute infection, vasculitis or disease activity and on hemodialysis therapy for at least 3 months before using ultrapure water. The parameters including serum advanced oxidation protein products (AOPP), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), myeloperoxidase (MPO), albumin (Alb), C-reactive protein (CRP), neopterin , tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 were measured before and 6, 12 months after use of ultrapure water, respectively. RESULTS: After modification of the water management system, the microbial counts and endotoxin concentration decreased significantly (P<0.01). During the study period, the levels of the measured parameters gradually improved, showing significant difference between the time points of measurement (P<0.05). Use of ultrapure water for 6 months significantly improved serum AOPP, MDA, GSH-Px, MPO, Alb, CRP, neopterin, and TNF-alpha levels (P<0.05), and the level of IL-6 was further reduced after 12 months (P<0.05). Serum MPO activity was closely correlated with AOPP (r=0.335, P<0.05) and CRP (r=0.369 or 0.347, P<0.05) before or after use of ultrapure water. CONCLUSIONS: Ultrapure water can improve the status of oxidative stress and inflammation in maintenance hemodialysis patients. Serum MPO activity may help estimate the levels of oxidative stress and inflammation.

Advanced oxidation protein products accelerate renal fibrosis in a remnant kidney model.

Accumulation of plasma advanced oxidation protein products (AOPP) has been found in patients with chronic kidney disease. However, the biologic consequences of AOPP consumption on progression of renal disease still are unclear. For testing of the hypothesis that AOPP accelerate progression of chronic kidney disease, Sprague-Dawley rats were subjected to five-sixths nephrectomy (5/6 Nx) or to sham operation. Rats in each group were randomly assigned in three subgroups (n = 30 in each group) and treated with repeated intravenous injections of AOPP-modified rat serum albumin (RSA), unmodified RSA, or vehicle for indicated period. Compared with RSA- or vehicle-treated 5/6 Nx rats, AOPP RSA-treated 5/6 Nx rats displayed greater proteinuria, higher serum creatinine, and lower creatinine clearance. AOPP challenge resulted in more renal hypertrophy, higher macrophage influx, and greater renal fibrosis in the remnant kidney. Chronic administration of AOPP in sham-operated rats increased urinary protein excretion and renal macrophage infiltration, but histologic renal fibrosis was not observed during the study period. AOPP treatment enhanced AOPP level in renal tissue. This was associated with marked increase of thiobarbituric acid reactive substances, decrease of glutathione peroxidase activity, and upregulated expression of monocyte chemoattractant protein-1 and TGF-beta1 in renal cortex. These data indicate that AOPP might be a new and potentially important mediator of renal fibrosis in the remnant kidney. Chronic accumulation of AOPP promotes renal fibrosis probably via a redox-sensitive inflammatory pathway.

[Advanced oxidation protein products-induced tumor necrosis factor alpha secretion in monocytes via reactive oxygen species generation].

OBJECTIVE: To investigate the effect of advanced oxidation protein products (AOPP) on the secretion of tumor necrosis factor alpha eTNFalphae in monocytes and its possible mechanism. METHOD: Human monocyte cell line THP-1 and peripheral blood monocytes were incubated with AOPP-bovine serum albumin(BSA) prepared by incubation of BSA with hypochlorous acid. TNFalpha in the supernatant of the culture medium of THP-1 cells was measured by enzyme-linked immunosorbent assay and the production of reactive oxygen species (ROS) evaluated by measuring the fluorescent product from the oxidation of an oxidant-sensitive 2,7-dichlorefluorescin using Wallac 1420 multilabel counter. The intracellular signal was observed by pre-treatment of the cells with antioxidant pyrrolidine dithiocarbamate, NADPH oxidase inhibitor apocynin or p38 phosphorylation inhibitor SB203580. RESULTS: AOPP-BSA induced TNF-alpha secretion and ROS production in monocytes. Pretreatment of the cells with pyrrolidine dithiocarbamate scavenged most of ROS and almost completely blocked TNF-alpha secretion induced by AOPP-BSA. Inhibition of NADPH oxidase by apocynin and p38 phosphorylation by SB203580 could both effectively block AOPP-BSA-induced TNF-alpha secretion. CONCLUSION: AOPP-BSA induced TNF-alpha secretion in monocytes, and the intracellular signaling involves ROS produced by activated NADPH oxidase and subsequent p38 phosphorylation.

[Advanced oxidation protein products induce reactive oxygen species production in endothelial cells].

OBJECTIVE: To investigate the effect of advanced oxidation protein products (AOPP) on production of reactive oxygen species (ROS) in endothelial cells. METHODS: Human umbilical vein endothelial cell line ECV304 were stimulated with AOPP-modified bovine serum albumin (AOPP-BSA) prepared by oxidation of BSA with HOCl in vitro. ROS production in the cells was evaluated by kinetic measurement of dichlorofluoroscein (DCF) fluorescence produced by oxidation of an oxidant-sensitive dye 2,7-dichlorefluorescin (DCFH) using VICTOR 1420 multilabel counter. RESULTS: AOPP-BSA could induce ROS production in ECV304 cells time- and dose-dependently, and the quantity of ROS increased with the oxidation degree of BSA. Pretreatment of cells with a small-molecular-mass glutathione peroxidase mimic ebselen or NADPH oxidase inhibitor apocynin inhibited ROS production by 65% and 29% respectively. CONCLUSION: AOPP-BSA induces ROS production in endothelial cells, partially mediated by NADPH oxidase activation.

[Arginine vasopressin-induced nitric oxide content changes in cultured cardiac fibroblasts and its relation to nuclear factor-kappaB].

To investigate the changes in the nitric oxide (NO) contents, nitric oxide synthase (NOS) activity and inducible nitric oxide (iNOS) mRNA expression in arginine vasopressin (AVP)-induced cardiac fibroblasts (CFs) in vitro and its relation to nuclear factor-kappaB (NF-kappaB), CFs were isolated by trypsin digestion method. Nitric acid reductase method, spectrophotometry, reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence-interactive laser cytometer techniques and Western blotting were used respectively to detect NO contents, NOS activity, iNOS mRNA expression and the activation of NF-kappaB in CFs. AVP increased NO contents, NOS activity and iNOS mRNA expressions in a concentration-dependent manner; NF-kappaB was activated and mobilized from cytoplasm to nucleus in AVP-induced CFs; PDTC, one of the inhibitors of NF-kappaB, could inhibit aforementioned increments. It is suggested that the increases in NO contents, elevation of NOS activity and increment of iNOS mRNA expression may be mediated through NF-kappaB activation pathway in cultured CFs induced by AVP, and that NF-kappaB is involved in the occurrence and development of myocardial fibrosis.

[Inflammatory status in patients with end-stage renal disease: role of monocyte activation].

OBJECTIVE: To study the association of monocyte activation and the inflammatory status in patients with end-stage renal disease (ESRD). METHODS: A total of 166 ESRD patients were recruited in the study, including 63 patients with pre-dialysis chronic renal failure (CRF), 16 undergoing continuous ambulatory peritoneal dialysis (CAPD) and 87 stable hemodialysis (HD) patients. Monocyte activation markers including plasma neopterin, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and plasma levels of acute phase proteins (APP) such as C-reactive protein (CRP) and serum amyloid A (SAA) were monitored using enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: The levels of neopterin, TNF-alpha, IL-1beta, CRP and SAA significantly increased in ESRD patients as compared with the normal controls (P<0.05 ). CRP and SAA in HD patients were higher than those in non-dialysis patients (P<0.05). The levels of CRP was closely correlated with neopterin, TNF-alpha and IL-1beta(r=0.287, 0.314, 0.262, P<0.05, respectively), and SAA with neopterin (r=0.306, P<0.05). These correlations remained significant after the values were adjusted for creatinine clearance in non-dialysis patients. Plasma contents of TNF-alpha, IL-1beta, CRP and SAA were significantly elevated after a single hemodialysis session (P<0.05). CONCLUSION: Chronic inflammation occurs in patients with ESRD, which might be aggravated by hemodialysis. Activation of the monocytes might be involved in the pathogenesis of inflammation in uremia.