Background-Remnant lipoprotein particles (RLPs), products of lipolytic degradation of triglyceride-rich lipoprotein derived from VLDL, exert atherogenesis. In this study, we observed how RLPs induced cytotoxicity in human umbilical vein endothelial cells (HUVECs) and cilostazol prevented cell death. Methods and Results-RLPs were isolated from the plasma of hyperlipidemic patients by use of an immunoaffinity gel mixture of anti-apolipoprotein A-1 and anti-apolipoprotein B-100 monoclonal antibodies. RLPs (50 g/mL) significantly increased superoxide formation in HUVECs associated with elevated gp91phox mRNA and protein expression and Rac1 translocation, accompanied by increased production of tumor necrosis factor (TNF)-␣ and interleukin-1␤, DNA fragmentation, and cell death. Cilostazol (1 to 100 mol/L) significantly suppressed not only NAD(P)H oxidase-dependent superoxide production but also TNF-␣ and interleukin-1␤ release and restored viability. RLPs activated a lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), which was not inhibited by cilostazol. Treatment of HUVECs with monoclonal antibody for LOX-1 attenuated RLP-mediated production of superoxide, TNF-␣, and interleukin-1␤ and DNA fragmentation. Conclusions-RLPs stimulated NAD(P)H oxidase-dependent superoxide formation and induction of cytokines inHUVECs via activation of LOX-1, consequently leading to reduction in cell viability with DNA fragmentation, and cilostazol exerts a cell-protective effect by suppressing these variables.

OBJECTIVEThe aim of this study was to evaluate the association of urinary cystatin C, a tubular damage marker, with the progression of type 2 diabetic nephropathy.RESERCH DESIGN AND METHODSThe baseline values of serum and urinary cystatin C were measured as primary parameters and those of urinary nonalbumin protein (NAP) were measured as secondary parameters. In this prospective observational study, a total of 237 type 2 diabetic patients were followed up for 29 months (13–44 months).RESULTSBoth the urinary cystatin C-to-creatinine ratio (CCR) and NAP-to-creatinine ratio (NAPCR) were significantly different according to the degree of albuminuria. Both markers had strongly positive correlations at baseline. After adjusting for several clinical factors, both urinary CCR and NAPCR had significant associations with the decline of the estimated glomerular filtration rate (eGFR) (r = 0.160, P = 0.021; r = 0.412, P < 0.001, respectively). Urinary CCR had positive correlations with the decline of eGFR in the subpopulation of patients with eGFR ≥60 mL/min/1.73 m2. In patients with eGFR ≥60 mL/min/1.73 m2 and normoalbuminuria, only urinary NAPCR showed a significant association with the decline of eGFR; urinary CCR did not. In multivariate regression analysis, the number of patients who progressed to chronic kidney disease stage 3 or greater was higher in those in the upper tertiles of both the urinary levels of cystatin C and NAP than in those in the lower tertiles.CONCLUSIONSThe results of this study suggest that urinary cystatin C and NAP may be predictors of the progression of type 2 diabetic nephropathy.

This study was done to evaluate clinical usefulness of cystatin C levels of serum and urine in predicting renal impairment in normoalbuminuric patients with type 2 diabetes and to evaluate the association between albuminuria and serum/urine cystatin C. Type 2 diabetic patients (n = 332) with normoalbuminuria (n = 210), microalbuminuria (n = 83) and macroalbuminuria (n = 42) were enrolled. Creatinine, urinary albumin levels, serum/urine cystatin C and estimated glomerular filtration rate (eGFR by MDRD [Modification of Diet in Renal Disease] and CKD-EPI [Chronic Kidney Disease Epidemiology Collaboration] equations) were determined. The cystatin C levels of serum and urine increased with increasing degree of albuminuria, reaching higher levels in macroalbuminuric patients (P < 0.001). In multiple regression analysis, serum cystatin C was affected by C-reactive protein (CRP), sex, albumin-creatinine ratio (ACR) and eGFR. Urine cystatin C was affected by triglyceride, age, eGFR and ACR. In multivariate logistic analysis, cystatin C levels of serum and urine were identified as independent factors associated with eGFR < 60 mL/min/1.73 m2 estimated by MDRD equation in patients with normoalbuminuria. On the other hand, eGFR < 60 mL/min/1.73 m2 estimated by CKD-EPI equation was independently associated with low level of high-density lipoprotein in normoalbuminuric patients. The cystatin C levels of serum and urine could be useful markers for renal dysfunction in type 2 diabetic patients with normoalbuminuria.

In the agIng population, osteoporosis is an important public health problem worldwide due to its high morbidity and mortality. Also, metabolic syndrome (MS) is another very common medical problem of epidemic importance, and the number of patients with MS is rapidly increasing in industrialized countries.There have been many studies about the relationship between MS and bone metabolism, but their results are inconsistent. A population-based US study has shown that bone mineral density (BMD) of the femoral neck Association between bone mineral density and metabolic syndrome in pre-and postmenopausal women We measured BMD at the lumbar spine and femoral neck. MS was defined according to the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) criteria. The prevalence of MS was 5.5% in the premenopausal group and 13.5% in the postmenopausal group. In the postmenopausal group, C-reactive protein (CRP) was significantly higher in subjects with MS than those without MS, but it was not in the premenopausal group. In the postmenopausal group, women with MS had a lower BMD at the lumbar spine and femoral neck before or after adjustment. In the premenopausal group, women with MS had a lower BMD at the lumbar spine, but not at the femoral neck. In stepwise linear regression analysis, predictive variables for BMD of the lumbar spine were systolic blood pressure in the premenopausal group and HDL-cholesterol and diastolic blood pressure (DBP) in the postmenopausal group. The predictive variables for BMD of the femoral neck were DBP and waist circumference in the premenopausal group and CRP and DBP in the postmenopausal group. Inflammation might have a more important role in BMD than obesity in the postmenopausal women.Key words: Bone mineral density, Metabolic syndrome, Menopause increases with increasing components of MS [1]. On the other hand, men with MS had a lower BMD after adjustment for body mass index (BMI) in the Rancho Bernardo Study [2] and women with MS also have a lower BMD in a recent study [3]. A prospective study has also demonstrated that men with MS had a lower BMD at the hip, whole body and distal forearm [4]. MS is characterized by abdominal obesity, impaired glucose tolerance, hypertension and dyslipidemia [5]. MS is a cluster of conditions with detrimental effects on cardiovascular health and has a strong association with low grade inflammation [6]. Obesity or high BMI is known to be a protecting factor against excessive bone loss in aging [7][8][9][10]. However, inflammation is more severe in subjects with high insulin resistance than in those with low insulin resistance [11,12], even-

BackgroundSeveral inflammatory biomarkers, especially a high preoperative neutrophil-to-lymphocyte count ratio (NLR) and platelet-to-lymphocyte count ratio (PLR), are known to be indicator of poor prognosis in several cancers. However, very few studies have evaluated the significance of the NLR and PLR in papillary thyroid cancer (PTC). We evaluated the association of the preoperative NLR and PLR with clinicopathological characteristics in patients with PTC.MethodsThis study included 1,066 female patients who underwent total thyroidectomy for PTC. Patients were stratified into 4 quartiles by preoperative NLR and PLR. And the combination of preoperative NLR and PLR was calculated on the basis of data obtained value of tertile as follows: patients with both an elevated PLR and an elevated NLR were allocated a score of 2, and patients showing one or neither were allocated a score of 1 or 0, respectively.ResultsThe preoperative NLR and PLR were significantly lower in patients aged ≥45 years and in patients with Hashimoto's thyroiditis. The PLR was significantly higher in patients with tumor size >1 cm (P=0.021).When the patients were categorized into the aforementioned four groups, the group with the higher preoperative PLR was found to have a significantly increased incidence of lateral lymph node metastasis (LNM) (P=0.018). However, there are no significant association between the combination of preoperative NLR and PLR and prognostic factors in PTC patients.ConclusionThese results suggest that a preoperative high PLR were significant associated with lateral LNM in female patients with PTC.

This study investigated the chemical characteristics and microbial population during incubation of four kinds of aerated compost teas based on oriental medicinal herbs compost, vermicompost, rice straw compost, and mixtures of three composts (MOVR). It aimed to determine the effects of the aerated compost tea (ACT) based on MOVR on the growth promotion of red leaf lettuce, soybean and sweet corn. Findings showed that the pH level and EC of the compost tea slightly increased based on the incubation time except for rice straw compost tea. All compost teas except for oriental medicinal herbs and rice straw compost tea contained more NO−3-N than NH+4-N. Plate counts of bacteria and fungi were significantly higher than the initial compost in ACT. Microbial communities of all ACT were predominantly bacteria. The dominant bacterial genera were analyzed as Bacillus (63.0%), Ochrobactrum (13.0%), Spingomonas (6.0%) and uncultured bacterium (4.0%) by 16S rDNA analysis. The effect of four concentrations, 0.1%, 0.2%, 0.4% and 0.8% MOVR on the growth of red leaf lettuce, soybean and sweet corn was also studied in the greenhouse. The red leaf lettuce with 0.4% MOVR had the most effective concentration on growth parameters in foliage part. However, 0.8% MOVR significantly promoted the growth of root and shoot of both soybean and sweet corn. The soybean treated with higher MOVR concentration was more effective in increasing the root nodule formation by 7.25 times than in the lower MOVR concentrations Results indicated that ACT could be used as liquid nutrient fertilizer with active microorganisms for culture of variable crops under organic farming condition.

This study shows cilostazol effect to prevent remnant lipoprotein particle (RLP)-induced monocyte adhesion to human umbilical vein endothelial cells (HUVECs). Upon incubation of HUVECs with RLP (50 g/ml), adherent monocytes significantly increased by 3.3-fold with increased cell surface expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1, E-selectin, and monocyte chemoattractant protein-1 (MCP-1). Cilostazol (ϳ1-100 M) concentration dependently repressed these variables as did (E)3-[(4-t-butylphenyl)sulfonyl]-2-propenenitrile (BAY 11-7085) (10 M), a specific nuclear factor-B (NF-B) inhibitor. Cilostazol effects were significantly antagonized by iberiotoxin (1 M), a maxi-K channel blocker. RLP significantly increased expression of lectin-like receptor for oxidized low-density lipoprotein (LDL) (LOX-1) receptor protein. Upon transfection with antisense LOX-1 oligodeoxynucleotide (As-LOX-1), LOX-1 receptor expression was reduced, whereas HUVECs with sense LOX-1 oligodeoxynucleotide did express high LOX-1 receptor. RLP-stimulated superoxide and tumor necrosis factor-␣ levels were significantly lowered with decreased expression of VCAM-1 and MCP-1 by transfection with As-LOX-1 as did polyinosinic acid (10 g/ml, a LOX-1 receptor inhibitor). RLP significantly degraded inhibitory B␣ in the cytoplasm and activated nuclear factor-B (NF-B) p65 in the nucleus of HUVECs with increased luciferase activity of NF-B, all of which were reversed by cilostazol (10 M), BAY 11-7085, and polyinosinic acid. Together, cilostazol suppresses RLP-stimulated increased monocyte adhesion to HUVECs by suppression of LOX-1 receptorcoupled NF-B-dependent nuclear transcription via mediation of the maxi-K channel opening.Atherosclerosis is known as chronic inflammatory processes resulting from interaction between oxidized low-density lipoprotein (Ox-LDL), macrophages, lymphocytes, and other cellular elements of the arterial wall (Ross, 1999). Recent clinical evidence has suggested that endothelial dysfunction elicited by Ox-LDL is critically important in the pathogenesis of atherosclerosis, in that inflammation plays a central role in its development (Ross, 1999;Blake and Ridker, 2001). Since Nakajima et al. (1993) have developed a simple and rapid assay method for determination of remnant lipoprotein particles (RLP)-cholesterol, i.e., chylomicron and VLDL remnants, a number of reports have focused on the role of RLP, derived from VLDL and chylomicrons, as an atherogenic factor (Hodis, 1999). It has been shown that RLP elicit endothelial vasomotor dysfunction in human coronary arteries and in isolated rabbit aorta . Endothelium-derived reactive oxygen species initiate and propagate free radical chain reactions in polyunsaturated fatty acid in RLP (Doi et al., 2000). Ox-LDL elicits endothelial dysfunction by enhancing expresArticle, publication date, and citation information can be found at http://jpet.aspetjournals.org. doi:10.1124/jpet.104.077826. ABBREVIATIONS:Ox-LDL, oxidized low-density lipoprot...

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