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Sample records for high serum resistin

  1. Serum resistin levels in children with primary snoring.

    PubMed

    Zicari, A M; Cutrera, R; Occasi, F; Carbone, M P; Cesoni Marcelli, A; De Castro, G; Indinnimeo, L; Tancredi, G; Galandrini, R; Giuffrida, A; Duse, M

    2014-01-01

    Primary Snoring (PS) has been positioned at the milder end of the Sleep-Disordered Breathing severity continuum characterized by snoring and it is usually underestimated. PS is defined as snoring without apnea, frequent arousals, or gas exchange abnormalities and recent studies demonstrated that children with PS have increased blood pressure and reduced arterial distensibility. The association between adipokines and SDB has been recently investigated, though most of the studies were focused on OSAS where intermittent hypoxia characterizing the disease may lead to an inflammatory cascade and to the release of several adipokines, contributing to oxidative stress. Resistin, initially described s an adipokine increasing insulin resistance, has been recently identified as a novel important member of the cytokine family involved in the regulation of inflammation. The aim of our study was to investigate circulating resistin levels in normal weight children with PS. Sixty-five children of normal weight aged between 4 and 14 years of age were selected for habitual snoring. Children with positive polysomnography were excluded from the study. Serum resistin levels were detected in all children with PS. Thirty-three healthy non-snorer children with similar age, sex and BMI were selected as a control group. A significantly higher level of resistin was observed in patients with PS compared to the control group (4.67±1.91 ng/ml vs 3.98±1.58 ng/ml; p<0.01). Patients with inconclusive pulse oximetry showed significantly higher resistin levels than those with negative recordings recordings (5.29±1.91 ng/ml vs 4.20±1.93 ng/ml; p<0.008). Moreover, there was a significant increasing trend between sieric adipokine level and the frequency of snoring (p<0.006). Our results suggest that systemic inflammation and oxidative stress may also play a significant role in the pathophysiology of PS. PMID:25280038

  2. Serum resistin is associated with the severity of microangiopathies in type 2 diabetes

    SciTech Connect

    Osawa, Haruhiko . E-mail: harosawa@m.ehime-u.ac.jp; Ochi, Masaaki; Kato, Kenichi; Yamauchi, Junko; Nishida, Wataru; Takata, Yasunori; Kawamura, Ryoichi; Onuma, Hiroshi; Takasuka, Tomomi; Shimizu, Ikki; Fujii, Yasuhisa; Ohashi, Jun; Makino, Hideichi

    2007-04-06

    Resistin, secreted from adipocytes, causes insulin resistance and diabetes in rodents. To determine the relation between serum resistin and diabetic microangiopathies in humans, we analyzed 238 Japanese T2DM subjects. Mean serum resistin was higher in subjects with either advanced retinopathy (preproliferative or proliferative) (P = 0.0130), advanced nephropathy (stage III or IV) (P = 0.0151), or neuropathy (P = 0.0013). Simple regression analysis showed that serum resistin was positively correlated with retinopathy stage (P = 0.0212), nephropathy stage (P = 0.0052), and neuropathy (P = 0.0013). Multiple regression analysis adjusted for age, gender, and BMI, revealed that serum resistin was correlated with retinopathy stage (P = 0.0144), nephropathy stage (P = 0.0111), and neuropathy (P = 0.0053). Serum resistin was positively correlated with the number of advanced microangiopathies, independent of age, gender, BMI, and either the duration of T2DM (P = 0.0318) or serum creatinine (P = 0.0092). Therefore, serum resistin was positively correlated with the severity of microangiopathies in T2DM.

  3. Association between serum resistin level and outcomes in kidney transplant recipients.

    PubMed

    Nagy, Kristof; Ujszaszi, Akos; Czira, Maria E; Remport, Adam; Kovesdy, Csaba P; Mathe, Zoltan; Rhee, Connie M; Mucsi, Istvan; Molnar, Miklos Z

    2016-03-01

    Resistin is an adipocytokine that is associated with inflammation, coronary artery disease, and other types of cardiovascular disease among patients with normal kidney function. However, little is known about the association of resistin with outcomes in kidney transplant recipients. We collected socio-demographic and clinical parameters, medical and transplant history, and laboratory data from 988 prevalent kidney transplant recipients enrolled in the Malnutrition-Inflammation in Transplant-Hungary Study (MINIT-HU study). Serum resistin levels were measured at baseline. Associations between serum resistin level and death with a functioning graft over a 6-year follow-up period were examined in unadjusted and adjusted models. The mean±SD age of the study population was 51 ± 13 years, among whom 57% were men and 21% were diabetics. Median serum resistin concentrations were significantly higher in patients who died with a functioning graft as compared to those who did not die during the follow-up period (median [IQR]: 22[15-26] vs. 19[14-22] ng/ml, respectively; P < 0.001). Higher serum resistin level was associated with higher mortality risk in both unadjusted and fully adjusted models: HRs (95% CI): 1.33(1.16-1.54) and 1.21(1.01-1.46), respectively. In prevalent kidney transplant recipients, serum resistin was an independent predictor of death with a functioning graft. PMID:26639524

  4. Relevance and clinical significance of serum resistin level in obese T2DM rhesus monkey models.

    PubMed

    Qi, S-D; He, Z-L; Chen, Y; Ma, J; Yu, W-H; Li, Y-Y; Yang, F-M; Wang, J-B; Chen, L-X; Zhao, Y; Lu, S-Y

    2015-09-01

    Resistin is a type of hormone-like adipocytokines, which is secreted specifically by adipocytes. It may be a key factor in the development of type 2 diabetes mellitus (T2DM) from obesity- associated insulin resistance due to results that show that it has a close relationship with insulin resistance in rodents. We utilized the rhesus monkeys as study objects to preliminarily test the association with glucose metabolism and to conduct a correlation analysis for clinical parameters and serum resistin levels in obese rhesus monkey models of T2DM. The results suggested that resistin was significantly increased in T2DM monkeys (P <0.01), and that resistin had a positive correlation respectively with total cholesterol (TC), low-density lipoprotein (LDL-C), fasting plasma glucose (FPG), fasting insulin (FPI) and glycated hemoglobin (HbA1c), Insulin resistance index (HOA-IR), but a negative correlation with islet β-cell function (HOMA-β). In the course of glucose metabolism, reverse release change of resistin and insulin in T2DM monkeys occurred, but the phenomenon that was not observed in the control group, these findings indicated that resistin negatively regulated and interfered with carbohydrate metabolism in T2DM monkey models. The character of the releasing change of resistin might be a unique process in T2DM. Therefore, all of the results could provide references for clinical diagnostic criteria for human cases of T2DM, and could have clinical significance for obese T2DM diagnosis and degree of insulin resistance. PMID:26069076

  5. Serum Resistin and Insulin-Like Growth Factor-1 Levels in Patients with Hypothyroidism and Hyperthyroidism

    PubMed Central

    Eke Koyuncu, Ceren; Turkmen Yildirmak, Sembol; Temizel, Mustafa; Ozpacaci, Tevfik; Gunel, Pinar; Cakmak, Mustafa; Ozbanazi, Yüksel Gülen

    2013-01-01

    Introduction. The aim of this study was to evaluate the serum levels of resistin and insulin-like growth factor-1 (IGF-1) and and also the potential relationship between thyroid function and levels of resistin and IGF-1 in hypothyroid and hyperthyroid patients. Methods. Fifteen cases of hypothyroid (HT), 16 of subclinically hypothyroid (SCHT), 15 of hyperthyroid (HrT), 15 of subclinically hyperthyroid (SCHrT), and 17 healthy individuals have been included in the study. Serum resistin levels were measured using enzyme-linked immunosorbent assay and IGF-1 and thyroid stimulating hormone (TSH) levels by chemiluminescence method. Results. Resistin levels in total HT group were significantly higher than in controls (12.66 ± 6.04 and 8.45 ± 2.90 ng/mL, resp.). In SCHrT subgroup resistin levels were significantly higher than those of controls (14.88 ± 7.73 and 8.45 ± 2.90 ng/mL, resp.). IGF-1 levels were significantly lower in total HT than in total HrT and control groups (117.22 ± 52.03, 155.17 ± 51.67, and 184.00 ± 49.73 ng/mL, resp.). Furthermore IGF-1 levels in HT subgroup were significantly lower compared to controls (123.70 ± 44.03 and 184 ± 49.73 ng/mL, resp.). In SCHT subgroup IGF-1 levels were significantly lower than those of control and SCHrT groups (111.11 ± 59.35, 184.00 ± 49.73, and 166.60 ± 47.87 ng/mL, resp.). There were significant correlations between IGF-1 and TSH in HT subgroup and between resistin and TSH in total HrT group. Conclusion. It was concluded that increased resistin levels are directly related to thyroid dysfunction, and GH/IGF-1 axis is influenced in clinically or subclinically hypothyroidism patients. PMID:23533949

  6. Long-time alcohol intake modifies resistin secretion and expression of resistin gene in adipose tissue.

    PubMed

    Pravdová, E; Macho, L; Hlavácová, N; Ficková, M

    2007-09-01

    Elevated serum resistin is implicated in insulin resistance associated with obesity and type 2 diabetes mellitus. Alcohol consumption interferes with the nutritional status, metabolic and hormonal activity of the drinker. Impact of ethanol intake on resistin level and resistin metabolic effects is unknown. Effect of long-time (28 days) ad libitum moderate alcohol (6% ethanol solution) intake on serum resistin and resistin mRNA level in adipose tissue of rats (A) was compared to control (C) and pair-fed (PF) animals. PF rats were fed the same caloric amount as A rats on previous day. Alcohol consumption resulted in reduction of food and energy intake, decreased body mass gain, epididymal fat pads mass and smaller adipocytes (vs. C rats). Alcohol intake significantly increased serum resistin and glucose, insulinemia remained unchanged. Systemic insulin resistance was not proved by HOMA, QUICKI and McAuley indexes, but impaired insulin effect on glucose transport in isolated adipocytes was present. Elevated serum resistin was positively correlated with glycemia (r = 0.88, p < 0.01) and negatively with fat cell size (r = -0.73, p < 0.05). High resistin level as the consequence of long-time alcohol intake could contribute to smaller adipocytes, higher glycemia, attenuation of insulin-stimulated glucose transport in adipocytes. Diminished resistin gene expression in adipose tissue of A and PF rats was present. PMID:18063850

  7. Relationship of serum adiponectin and resistin to glucose intolerance and fat topography in south-Asians

    PubMed Central

    Wasim, Hanif; Al-Daghri, Nasser M; Chetty, Raja; McTernan, Phillip G; Barnett, A H; Kumar, Sudhesh

    2006-01-01

    Objectives South-Asians have lower adiponectin levels compared to Caucasians. It was not clear however, if this intrinsic feature is related to aspects of glucose metabolism. This study aims to determine the relationship between body fat distribution and adipocytokine in South-Asian subjects by measuring serum adipocytokines, adiposity, insulinemia, and glucose tolerance levels. Methods In this cross-sectional study, 150 South-Asians (80 males, 70 females) were included, 60 had NGT (Control group, Age 51.33 ± 11.5, BMI 27 ± 2.3), 60 had IGT (Age 57.7 ± 12.5, BMI 27.2 ± 2.7), 30 had type 2 DM (Age 49.5 ± 10.9, BMI 28 ± 1.7). Measures of adiposity, adipocytokines and other metabolic parameters were determined. Parameters were measured using the following: a) Plasma glucose by glucose oxidase method b) CRP by immunoturbidimetric method (Roche/Hitachi analyser) c) insulin by Medgenix INS-ELISA immunoenzymetric assay by Biosource (Belgium) d) Leptin, Adiponectin by radioimmunoassay kits by Linco Research (St. Charles MO) e) Resistin by immunoassay kits by Phoenix Pharmaceuticals INC (530 Harbor Boulevard, Belmont CA 94002, USA). Results Adiponectin concentrations were highest in NGT, decreased in IGT and lowest in DMT2, (both p < 0.01). Leptin was significantly higher in DMT2 than IGT and NGT p = 0.02 and 0.04 respectively. There was a significant positive relationships between log adiponectin and 2-hr insulin values, p = 0.028 and history of hypertensions and a ischemic heart disease p = 0.008 with R = 0.65. There was a significant inverse correlation between log adiponectin and resistin, p < 0.01. Conclusion Resistin levels had an inverse correlation with adiponectin levels, indicating an inverse relationship between pro-inflammatory cytokines and adiponectin. Adiponectin levels were related to glucose tolerance. PMID:16669997

  8. Resistin gene polymorphisms are associated with acne and serum lipid levels, providing a potential nexus between lipid metabolism and inflammation.

    PubMed

    Younis, Sidra; Blumenberg, Miroslav; Javed, Qamar

    2016-05-01

    Acne vu lgaris is a multifactorial inflammatory skin disease causing social stigma and psychological effect on patients. We hypothesized that the genes that can affect both lipid metabolism and inflammation may be central for acne formation and present targets for treatment. Pro-inflammatory adipokine resistin, one such likely target, activates NFkB and JNK pathways inducing TLR-2, IL-1, IL-6, and TNFα genes. The polymorphisms in promoter and intron region of the resistin gene affect its expression levels. Therefore, we explored the association of resistin polymorphisms (RETN +299G > A and -420C > G) with pathogenesis of acne vulgaris. We used PCR-RFLP method to genotype at the two single nucleotide polymorphisms at RETN promoter in 530 acne patients vs. 550 age- and sex-matched control subjects. We also measured serum lipid levels in acne patients and associated these with RETN genotypes. We found that the RETN gene polymorphisms are strongly associated with acne vulgaris and the severity of acne symptoms. In females the variant allele frequencies of both SNPs are statistically higher in patients than in controls; in males frequency distribution does not reach significance. The haplotype containing both variant alleles is significantly more common in patients than in controls. We find no association of RETN SNPs with the acne types. Importantly, we found that the levels of HDL-C were significantly decreased in variant genotype of RETN. Our results show that the RETN polymorphisms expected to boost resistin expression increase the risk of developing acne. We suggest that resistin may provide an attractive target for treatment. PMID:26858108

  9. Resistin in idiopathic inflammatory myopathies

    PubMed Central

    2012-01-01

    Introduction The purpose of this study was to evaluate and compare the serum levels and local expression of resistin in patients with idiopathic inflammatory myopathies to controls, and to determine the relationship between resistin levels, inflammation and disease activity. Methods Serum resistin levels were determined in 42 patients with inflammatory myopathies and 27 healthy controls. The association among resistin levels, inflammation, global disease activity and muscle strength was examined. The expression of resistin in muscle tissues from patients with inflammatory myopathies and healthy controls was evaluated. Gene expression and protein release from resistin-stimulated muscle and mononuclear cells were assessed. Results In patients with inflammatory myopathies, the serum levels of resistin were significantly higher than those observed in controls (8.53 ± 6.84 vs. 4.54 ± 1.08 ng/ml, P < 0.0001) and correlated with C-reactive protein (CRP) levels (r = 0.328, P = 0.044) and myositis disease activity assessment visual analogue scales (MYOACT) (r = 0.382, P = 0.026). Stronger association was observed between the levels of serum resistin and CRP levels (r = 0.717, P = 0.037) as well as MYOACT (r = 0.798, P = 0.007), and there was a trend towards correlation between serum resistin and myoglobin levels (r = 0.650, P = 0.067) in anti-Jo-1 positive patients. Furthermore, in patients with dermatomyositis, serum resistin levels significantly correlated with MYOACT (r = 0.667, P = 0.001), creatine kinase (r = 0.739, P = 0.001) and myoglobin levels (r = 0.791, P = 0.0003) and showed a trend towards correlation with CRP levels (r = 0.447, P = 0.067). Resistin expression in muscle tissue was significantly higher in patients with inflammatory myopathies compared to controls, and resistin induced the expression of interleukins (IL)-1β and IL-6 and monocyte chemoattractant protein (MCP)-1 in mononuclear cells but not in myocytes. Conclusions The results of this study

  10. Serum Resistin Levels Are Associated with Adiposity and Insulin Sensitivity in Obese Hispanic Subjects

    PubMed Central

    Nieva-Vazquez, Adriana; Torres-Rasgado, Enrique; López-López, José G.; Romero, Jose R.

    2014-01-01

    Abstract Background and Aims: Resistin is involved in the development of obesity and insulin resistance (IR) in mice and may play a similar role in humans through mechanisms that remain unresolved. The objective of this study was to characterize the relationship between resistin levels in obese subjects with and without IR among Hispanic subjects. Material and Methods: A cross-sectional study was performed on 117 nondiabetic Hispanic subjects of both genders that were allocated into three study groups: A control group (n=47) of otherwise healthy individuals in metabolic balance, a group with obesity (OB) (n=36), and a group with obesity and IR (OB-IR) (n=34). Anthropometric and clinical characterization was carried out, and resistin levels were determined by enzyme-linked immunosorbent assay (ELISA). Results: We found that resistin levels were higher in OB and OB-IR groups when compared to the control group (1331.79±142.15 pg/mL, 1266.28±165.97 pg/mL vs. 959.21±171.43 pg/mL; P<0.05), an effect that was not confounded by age (control, 34.04±10.00 years; OB, 37.30±10.78 years; and OB-IR, 35.67±10.15 years). In addition, we observed a significant correlation (P<0.001) between resistin levels and higher adiposity and insulin sensitivity (IS) in our cohort. Conclusions: Our results suggest that higher resistin levels are associated with higher adiposity and lower IS among obese Hispanic subjects. PMID:24266722

  11. Cloning and characterization of porcine resistin gene.

    PubMed

    Dai, M H; Xia, T; Chen, X D; Gan, L; Feng, S Q; Qiu, H; Peng, Y; Yang, Z Q

    2006-02-01

    Resistin is a member of resistin-like molecules (RELMs) and a hormone secreted from mature adipocytes in rodents and leukocytes in human. We now report the cloning and characterization of the full-length porcine resistin cDNA and gene. Sequence analysis indicated that the pig resistin cDNA sequence had an open reading frame of 330 bp encoding a 12 kDa protein of 109 amino acids. The deduced amino acid sequence showed 75.2% identity to the human resistin. The porcine resistin gene was composed of four exons and had exactly the same exon structure as the human resistin gene. The tissue distribution of porcine resistin mRNA was assessed by semi-quantitative RT-PCR. Resistin gene expression was the highest in porcine leukocytes and low in adipose tissue. Resistin protein could be detected in porcine serum by western blotting and it circulated in serum as dimers and trimers. We provided the first evidence that resistin was abundantly expressed in porcine leukocytes and had an expression pattern similar to that in human resistin mRNA and protein. This suggests that the pig may be a suitable animal model for studying the function of resistin in human insulin resistance. PMID:16023825

  12. Novel Adipokines, High Molecular Weight Adiponectin and Resistin, are Associated with Outcomes following Lower Extremity Revascularization with Autogenous Vein

    PubMed Central

    Owens, Christopher D.; Kim, Ji Min; Hevelone, Nathanael; Hamdan, Allen; Raffetto, Joseph D.; Creager, Mark A.; Conte, Michael S.

    2010-01-01

    Objective A significant portion of patients undergoing lower extremity bypass surgery (LEB) for peripheral arterial disease (PAD) will have cardiovascular or graft-related events. It has been previously demonstrated that systemic inflammation is associated with PAD and its clinical outcomes. We hypothesized that serum biomarkers of insulin resistance and inflammation would identify a sub-group at elevated risk for graft failure, limb loss, and mortality. Methods This was a prospective longitudinal study of patients (N=225) undergoing LEB using autogenous vein. Baseline blood samples were obtained prior to surgery in the fasting state. High-sensitivity C-reactive protein (hsCRP) and the adipokines resistin and high-molecular weight adiponectin (HMWA) were measured by ELISA. Median follow-up was 893 days. The major endpoints of primary patency (PP) and amputation free survival (AFS) were examined using multivariable methods. Endpoints were screened against biomarkers and patient characteristics for univariate associations. Promising explanatory variables (P < 0.1) were included in multivariable Cox proportional hazard models. Results The mean age of subjects was 67.6 years; 71.6% were male and 87.1% were Caucasian. One-hundred and thirty-three (59.1%) subjects underwent bypass for critical limb ischemia (CLI) and 73 (32.4%) had tissue loss. Patients with CLI and diabetes demonstrated elevated resistin and hsCRP levels. HMWA levels correlated with CLI and with a measure of insulin resistance (HOMA-IR) but not with clinical diabetes. Baseline biomarkers were higher in those presenting with tissue loss and in patients with post-operative events (mortality, limb loss). After multivariable analysis (including CLI, diabetes, age, estimated glomerular filtration rate (eGFR), adiponectin, resistin, and CRP), resistin (HR 1.75, 95% CI 1.07 to 2.85, P=0.025) and CRP (HR 2.39, 95% CI 1.30 to 4.39, P=0.005) were independently predictive of reduced AFS. However, only resistin

  13. Resistin impairs glucose permeability in EA.hy926 cells by down-regulating GLUT1 expression.

    PubMed

    Li, Qiang; Cai, Yuxi; Huang, Jing; Yu, Xiaolan; Sun, Jun; Yang, Zaiqing; Zhou, Lei

    2016-10-15

    Type 2 diabetes mellitus (T2DM) is a chronic disease which is now affecting the health of more and more people in the world. Resistin, discovered in 2001, is considered to be closely related to metabolic dysfunction and obesity. Previous study showed that hyperglycemia is always accompanied by a high serum resistin concentration. We therefore investigated whether resistin can mediate glucose transfer across the blood-tissue barrier. Here, we employed a transwell system to analyze glucose permeability in EA.hy926 human endothelial cells treated without or with human resistin. In EA.hy926 cells treated with resistin, the permeability to glucose was heavily impaired. This was due to the down-regulation of GLUT1 expression as a result of the treatment, rather than regulation of tight junctions. In addition, overexpression of GLUT1 in EA.hy926 cells was able to recover the blocking effect of resistin on glucose permeability. We further found that resistin could inhibit the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and consequently impede the transcription of GLUT1. The results of the present study suggested that resistin could cause glucose retention in serum and thus result in hyperglycemia. This provides a novel explanation for hyperglycemia and a potential new way of treating type 2 diabetes mellitus. PMID:27353463

  14. The effects of acute exercise on serum adiponectin and resistin levels and their relation to insulin sensitivity in overweight males.

    PubMed

    Jamurtas, A Z; Theocharis, V; Koukoulis, G; Stakias, N; Fatouros, I G; Kouretas, D; Koutedakis, Y

    2006-05-01

    The purpose of this study was to investigate the effects of a submaximal aerobic exercise bout on adiponectin and resistin levels as well as insulin sensitivity, until 48 h post-exercise in healthy overweight males. Nine subjects performed an exercise bout at an intensity corresponding to approximately 65% of their maximal oxygen consumption for 45 min. Adiponectin, resistin, cortisol, insulin, glucose and insulin sensitivity were measured prior to exercise, immediately after exercise as well as 24 and 48 h after exercise. Data were analyzed using repeated measures ANOVA while Pearson's correlations were performed to identify possible relationship among the assessed variables. There were no significant differences for adiponectin (microg ml(-1)) [pre, 3.61(0.73); post, 3.15(0.43); 24 h, 3.15(0.81); 48 h, 3.37(0.76)] or resistin (ng ml(-1)) [pre, 0.19(0.03); post, 0.13(0.03); 24 h, 0.23(0.04); 48 h, 0.23(0.03)] across time. Insulin sensitivity increased and insulin concentration decreased significantly only immediately after exercise. Furthermore, no significant correlations were observed among the variables assessed except for the expected between insulin level and insulin sensitivity. These results indicate that a submaximal aerobic workout does not result in significant changes in adiponectin and resistin up to 48 h post-exercise. Furthermore, it appears that adiponectin or resistin is not associated with insulin sensitivity. PMID:16525810

  15. Relationship of resistin levels with endometrial cancer risk.

    PubMed

    Hlavna, M; Kohut, L; Lipkova, J; Bienertova-Vasku, J; Dostalova, Z; Chovanec, J; Vasku, A

    2011-01-01

    Cancer of endometrium (CAE) is the most common gynecologic malignancy in industrialized nations. Increased resistin levels, an adipocytokine produced by adipose tissue and macrophages, have been considered as a risk factor in gastric, colon and breast cancer, recently. No studies associating resistin levels with endometrial cancer have been done so far. The purpose of this case-control study was to determine the relationship between serum circulating resistin levels and resistin gene -420C>G (rs3219175) variant in endometrial cancer patients. 37 Caucasian female patients and 39 healthy controls were enrolled in this study. Difference in resistin levels between age and BMI matched patients group (mean 24.2 ng/ml) and control subjects (mean 10.1 ng/ml) were statistically significant (p <001). We also determined single nucleotide polymorphism -420C>G (rs3219175) within resistin gene and no significant association between resistin levels and investigated polymorphism was found. Furthermore, no significant association between higher resistin levels and diabetes mellitus 2, body mass index, smoking or age have been observed within studied groups. To our knowledge, this is the first study examining the relationship between serum resistin levels and endometrial cancer and our results show, that patients with endometrial cancer have significantly increased circulating levels of resistin compared to control subjects. PMID:21275461

  16. Circulating resistin protein and mRNA concentrations and clinical severity of coronary artery disease

    PubMed Central

    Sopic, Miron; Spasojevic-Kalimanovska, Vesna; Kalimanovska-Ostric, Dimitra; Andjelkovic, Kristina; Jelic-Ivanovic, Zorana

    2015-01-01

    Introduction Previous studies have implicated a strong link between circulating plasma resistin and coronary artery disease (CAD). The aim of this study was to evaluate the differences in peripheral blood mononuclear cells (PBMC) resistin mRNA and its plasma protein concentrations between the patients with CAD of different clinical severity. Material and methods This study included 33 healthy subjects as the control group (CG) and 77 patients requiring coronary angiography. Of the latter 30 was CAD negative whereas 47 were CAD positive [18 with stable angina pectoris (SAP) and 29 with acute coronary syndrome (ACS)]. Circulating resistin was measured by ELISA; PBMC resistin mRNA was determined by real-time PCR. Results Resistin protein was significantly higher in the ACS group compared to the CG (P = 0.001) and the CAD negative group (P = 0.018). Resistin mRNA expression did not vary across the study groups, despite the positive correlation seen with plasma resistin (ρ = 0.305, P = 0.008). In patients, plasma resistin and PBMC resistin mRNA negatively correlated with HDL-C (ρ = -0.404, P < 0.001 and ρ = -0.257, P = 0.032, respectively). Furthermore, the highest plasma resistin tertile showed the lowest HDL-C (P = 0.006). Plasma resistin was positively associated with serum creatinine (ρ = 0.353, P = 0.002). Conclusion Significant increase of plasma resistin in patients with ACS compared to CG and CAD negative patients was observed. Despite no change in PBMC resistin mRNA in different disease conditions a positive association between resistin mRNA and resistin plasma protein was evident. Both plasma resistin and PBMC resistin mRNA were negatively associated with plasma HDL-C, and plasma resistin positively with serum creatinine. PMID:26110037

  17. Association of Resistin with Insulin Resistance and Factors of Metabolic Syndrome in North Indians.

    PubMed

    Singh, Arun Kumar; Tiwari, Sunita; Gupta, Abhishek; Shukla, Kamla Kant; Chhabra, Kumar Gaurav; Pandey, Achileshwar; Pant, Aditya Bhushan

    2015-07-01

    Metabolic syndrome (MetS) is a cluster of interrelated common clinical disorders. The role of resistin in insulin sensitivity and MetS is controversial till date. So, the aim of the present study was to investigate the relationship of plasma resistin levels with markers of the MetS in Indian subjects. In a case control study, total 528 subjects were selected for the study. 265 (194 male and 71 female) were cases (with MetS) and 263 (164 male and 99 female) were controls (without MetS). Required anthropometric measurements and calculations were carried out accordingly. All the Biochemical estimations were carried out according to standard protocol. Resistin level was measured by the standard protocol (By ELISA i.e. enzyme linked immunosorbent assay) as illustrated in the kit. Insulin level was also measured by the standard protocol as illustrated in the kit and insulin resistance was calculated by the standard procedures. Plasma resistin levels were significantly higher in cases compared with controls (male = 13.05 ± 4.31 vs. 7.04 ± 2.09 ng/ml; p ≤ 0.001 and female = 13.53 ± 4.14 vs. 7.42 ± 2.30 ng/ml; p ≤ 0.001). Plasma resistin levels were well correlated with waist circumference, glucose, triglycerides, waist/hip ratio, systolic and diastolic blood pressure, high density lipoprotein, total cholesterol, serum low density lipoprotein, serum very low density lipoprotein, insulin and insulin resistance. Plasma resistin levels were elevated in presence of the MetS and were associated with increased metabolic risk factors. PMID:26089609

  18. Resistin, Visfatin, Adiponectin, and Leptin: Risk of Breast Cancer in Pre- and Postmenopausal Saudi Females and Their Possible Diagnostic and Predictive Implications as Novel Biomarkers

    PubMed Central

    Assiri, Adel M. A.; Kamel, Hala F. M.; Hassanien, Mohamed F. R.

    2015-01-01

    The mechanisms of obesity-induced breast carcinogenesis are not clear. One hypothesis is that high levels of adipokines could promote breast cancer (BC) development. The aim of this study was to investigate the correlation of resistin, visfatin, adiponectin, and leptin with BC risk in pre- and postmenopausal females. A total of 82 BC newly diagnosed and histologically confirmed patients and 68 age and BMI matched healthy controls were enrolled. Both groups were subdivided into post- and premenopausal subgroups. Resistin, visfatin, adiponectin, and leptin were measured by ELISA. There were significantly higher levels of leptin, resistin, and visfatin in postmenopausal BC patients than their respective controls. Only in postmenopausal subgroups, leptin, resistin, and visfatin levels were positively correlated with TNM staging, tumor size, lymph node (LN) metastasis, and histological grading. In postmenopausal females, multivariate logistic regression analysis revealed that adiponectin, leptin, visfatin, and resistin were risk factors for BC. Our results suggested that serum resistin, leptin, adiponectin, and visfatin levels as risk factors for postmenopausal BC may provide a potential link with clinicopathological features and are promising to be novel biomarkers for postmenopausal BC. PMID:25838618

  19. Resistin as an Intrahepatic Cytokine

    PubMed Central

    Bertolani, Cristiana; Sancho-Bru, Pau; Failli, Paola; Bataller, Ramon; Aleffi, Sara; DeFranco, Raffaella; Mazzinghi, Benedetta; Romagnani, Paola; Milani, Stefano; Ginés, Pere; Colmenero, Jordi; Parola, Maurizio; Gelmini, Stefania; Tarquini, Roberto; Laffi, Giacomo; Pinzani, Massimo; Marra, Fabio

    2006-01-01

    Obesity and insulin resistance accelerate the progression of fibrosis during chronic liver disease. Resistin antagonizes insulin action in rodents, but its role in humans is still controversial. The aims of this study were to investigate resistin expression in human liver and to evaluate whether resistin may affect the biology of activated human hepatic stellate cells (HSCs), key modulators of hepatic fibrogenesis. Resistin gene expression was low in normal human liver but was increased in conditions of severe fibrosis. Up-regulation of resistin during chronic liver damage was confirmed by immunohistochemistry. In a group of patients with alcoholic hepatitis, resistin expression correlated with inflammation and fibrosis, suggesting a possible action on HSCs. Exposure of cultured HSCs to recombinant resistin resulted in increased expression of the proinflammatory chemokines monocyte chemoattractant protein-1 and interleukin-8, through activation of nuclear factor (NF)-κB. Resistin induced a rapid increase in intracellular calcium concentration, mainly through calcium release from intracellular inositol triphosphate-sensitive pools. The intracellular calcium chelator BAPTA-AM blocked resistin-induced NF-κB activation and monocyte chemoattractant protein-1 expression. In conclusion, this study shows a role for resistin as an intrahepatic cytokine exerting proinflammatory actions in HSCs, via a Ca2+/NF-κB-dependent pathway and suggests involvement of this adipokine in the pathophysiology of liver fibrosis. PMID:17148667

  20. Elevated Resistin Gene Expression in African American Estrogen and Progesterone Receptor Negative Breast Cancer

    PubMed Central

    Vallega, Karin A.; Liu, NingNing; Myers, Jennifer S.; Yu, Kaixian; Sang, Qing-Xiang Amy

    2016-01-01

    Introduction African American (AA) women diagnosed with breast cancer are more likely to have aggressive subtypes. Investigating differentially expressed genes between patient populations may help explain racial health disparities. Resistin, one such gene, is linked to inflammation, obesity, and breast cancer risk. Previous studies indicated that resistin expression is higher in serum and tissue of AA breast cancer patients compared to Caucasian American (CA) patients. However, resistin expression levels have not been compared between AA and CA patients in a stage- and subtype-specific context. Breast cancer prognosis and treatments vary by subtype. This work investigates differential resistin gene expression in human breast cancer tissues of specific stages, receptor subtypes, and menopause statuses in AA and CA women. Methods Differential gene expression analysis was performed using human breast cancer gene expression data from The Cancer Genome Atlas. We performed inter-race resistin gene expression level comparisons looking at receptor status and stage-specific data between AA and CA samples. DESeq was run to test for differentially expressed resistin values. Results Resistin RNA was higher in AA women overall, with highest values in receptor negative subtypes. Estrogen-, progesterone-, and human epidermal growth factor receptor 2- negative groups showed statistically significant elevated resistin levels in Stage I and II AA women compared to CA women. In inter-racial comparisons, AA women had significantly higher levels of resistin regardless of menopause status. In whole population comparisons, resistin expression was higher among Stage I and III estrogen receptor negative cases. In comparisons of molecular subtypes, resistin levels were significant higher in triple negative than in luminal A breast cancer. Conclusion Resistin gene expression levels were significantly higher in receptor negative subtypes, especially estrogen receptor negative cases in AA

  1. Resistin: a potential biomarker for periodontitis influenced diabetes mellitus and diabetes induced periodontitis.

    PubMed

    Devanoorkar, Archana; Kathariya, Rahul; Guttiganur, Nagappa; Gopalakrishnan, D; Bagchi, Paulami

    2014-01-01

    Biomarkers are highly specific and sensitive indicators of disease activity. Resistin is a recently discovered adipocytokine, having a potent biomarker quality. Initially resistin was thought to be produced by adipocytes alone; however, emerging evidence suggests that it is also produced in abundance by various cells of the immunoinflammatory system, indicating its role in various chronic inflammatory diseases. Data suggests that resistin plays a role in obesity, insulin resistance, cardiovascular diseases, and periodontitis. Resistin derived its name from the original observation that it induced insulin resistance (resist-in: resist insulin) in mice and is downregulated in mature murine adipocytes cultured in the presence of insulin sensitizing drugs like thiazolidinediones. It is well recognized that obesity, is associated with insulin resistance and diabetes. A three-way relationship has been established between diabetes, obesity and periodontitis. Recent evidence also suggests an association between obesity and increased risk for periodontitis. Our previous research showed incremental elevation of resistin with periodontal disease activity and a reduced level of resistin, after periodontal therapy. Thus resistin would be one of the molecular links connecting obesity, periodontitis, and diabetes and may serve as a marker that links periodontal disease with other systemic diseases. A Medline/PubMed search was carried out for keywords "Diabetes Mellitus," "Periodontitis," and "Resistin," and all relevant research papers from 1990 in English were shortlisted and finalized based on their importance. This review provides an insight into the biological action of resistin and its possible role in periodontitis influenced diabetes mellitus and diabetes induced periodontitis. PMID:24692844

  2. Neutrophil-derived resistin release induced by Aggregatibacter actinomycetemcomitans.

    PubMed

    Furugen, Reiko; Hayashida, Hideaki; Yoshii, Yumiko; Saito, Toshiyuki

    2011-08-01

    Resistin is an adipokine that induces insulin resistance in mice. In humans, resistin is not produced in adipocytes, but in various leukocytes instead, and it acts as a proinflammatory molecule. The present investigation demonstrated high levels of resistin in culture supernatants of neutrophils that are stimulated by a highly leukotoxic strain of Aggregatibacter actinomycetemcomitans. In contrast, the level of resistin was remarkably low when neutrophils were exposed to two other strains that produce minimal levels of leukotoxin and a further isogenic mutant strain incapable of producing leukotoxin. Pretreatment of neutrophils with a monoclonal antibody to CD18, β chain of lymphocyte function-associated molecule 1 (LFA-1), or an Src family tyrosine kinase inhibitor before incubation with the highly leukotoxic strain inhibited the release of resistin. These results show that A. actinomycetemcomitans-expressed leukotoxin induces extracellular release of human neutrophil-derived resistin by interacting with LFA-1 on the surface of neutrophils and, consequently, activating Src family tyrosine kinases. PMID:21658109

  3. Human resistin stimulates the pro-inflammatory cytokines TNF-{alpha} and IL-12 in macrophages by NF-{kappa}B-dependent pathway

    SciTech Connect

    Silswal, Nirupama; Singh, Anil K.; Aruna, Battu; Mukhopadhyay, Sangita; Ghosh, Sudip; Ehtesham, Nasreen Z. . E-mail: nas_ehtesham@yahoo.com

    2005-09-09

    Resistin, a recently discovered 92 amino acid protein involved in the development of insulin resistance, has been associated with obesity and type 2 diabetes. The elevated serum resistin in human diabetes is often associated with a pro-inflammatory milieu. However, the role of resistin in the development of inflammation is not well understood. Addition of recombinant human resistin protein (hResistin) to macrophages (both murine and human) resulted in enhanced secretion of pro-inflammatory cytokines, TNF-{alpha} and IL-12, similar to that obtained using 5 {mu}g/ml lipopolysaccharide. Both oligomeric and dimeric forms of hResistin were able to activate these cytokines suggesting that the inflammatory action of resistin is independent of its conformation. Heat denatured hResistin abrogated cytokine induction while treatment of recombinant resistin with polymyxin B agarose beads had no effect thereby ruling out the role of endotoxin in the recombinant hResistin mediated cytokine induction. The pro-inflammatory nature of hResistin was further evident from the ability of this protein to induce the nuclear translocation of NF-{kappa}B transcription factor as seen from electrophoretic mobility shift assays. Induction of TNF-{alpha} in U937 cells by hResistin was markedly reduced in the presence of either dominant negative I{kappa}B{alpha} plasmid or PDTC, a pharmacological inhibitor of NF-{kappa}B. A protein involved in conferring insulin resistance is also a pro-inflammatory molecule that has important implications.

  4. Resistin modulates glucose uptake and glucose transporter-1 (GLUT-1) expression in trophoblast cells

    PubMed Central

    Di Simone, Nicoletta; Di Nicuolo, Fiorella; Marzioni, Daniela; Castellucci, Mario; Sanguinetti, Maurizio; D’lppolito, Silvia; Caruso, Alessandro

    2009-01-01

    Abstract The adipocytokine resistin impairs glucose tolerance and insulin sensitivity. Here, we examine the effect of resistin on glucose uptake in human trophoblast cells and we demonstrate that transplacental glucose transport is mediated by glucose transporter (GLUT)-1. Furthermore, we evaluate the type of signal transduction induced by resistin in GLUT-1 regulation. BeWo choriocarcinoma cells and primary cytotrophoblast cells were cultured with increasing resistin concentrations for 24 hrs. The main outcome measures include glucose transport assay using [3H]-2-deoxy glucose, GLUT-1 protein expression by Western blot analysis and GLUT-1 mRNA detection by quantitative real-time RT-PCR. Quantitative determination of phospho(p)-ERK1/2 in cell lysates was performed by an Enzyme Immunometric Assay and Western blot analysis. Our data demonstrate a direct effect of resistin on normal cytotrophoblastic and on BeWo cells: resistin modulates glucose uptake, GLUT-1 messenger ribonucleic acid (mRNA) and protein expression in placental cells. We suggest that ERK1/2 phosphorylation is involved in the GLUT-1 regulation induced by resistin. In conclusion, resistin causes activation of both the ERK1 and 2 pathway in trophoblast cells. ERK1 and 2 activation stimulated GLUT-1 synthesis and resulted in increase of placental glucose uptake. High resistin levels (50–100 ng/ml) seem able to affect glucose-uptake, presumably by decreasing the cell surface glucose transporter. PMID:18410529

  5. Resistin as a potential marker of renal disease in lupus nephritis.

    PubMed

    Hutcheson, J; Ye, Y; Han, J; Arriens, C; Saxena, R; Li, Q-Z; Mohan, C; Wu, T

    2015-03-01

    Systemic lupus erythematosus (SLE) and lupus nephritis (LN) have strong concomitance with cardiovascular disease that cannot be explained fully by typical risk factors. We examined the possibility that serum or urine expression of adipokines may act as biomarkers for LN, as these proteins have been associated previously with cardiovascular disease as well as SLE. Antibody arrays were performed on serum and urine from lupus patients and matched controls using a cross-sectional study design. From the initial array-based screening data of 15 adipokines, adiponectin, leptin and resistin were selected for validation by enzyme-linked immunosorbent assay (ELISA). Correlations were determined between adipokine expression levels and measures of disease activity or lupus nephritis. The expression of adiponectin and resistin was increased in both sera and urine from LN patients, while leptin was increased in LN patient sera, compared to matched controls. Serum resistin, but not urine resistin, was correlated with measures of renal dysfunction in LN. Serum resistin expression may be useful as a marker of renal dysfunction in patients with LN, although longitudinal studies are warranted. Further studies are necessary to determine if resistin has functional consequences in LN. PMID:25345756

  6. Resistin as a potential marker of renal disease in lupus nephritis

    PubMed Central

    Hutcheson, J; Ye, Y; Han, J; Arriens, C; Saxena, R; Li, Q-Z; Mohan, C; Wu, T

    2015-01-01

    Systemic lupus erythematosus (SLE) and lupus nephritis (LN) have strong concomitance with cardiovascular disease that cannot be explained fully by typical risk factors. We examined the possibility that serum or urine expression of adipokines may act as biomarkers for LN, as these proteins have been associated previously with cardiovascular disease as well as SLE. Antibody arrays were performed on serum and urine from lupus patients and matched controls using a cross-sectional study design. From the initial array-based screening data of 15 adipokines, adiponectin, leptin and resistin were selected for validation by enzyme-linked immunosorbent assay (ELISA). Correlations were determined between adipokine expression levels and measures of disease activity or lupus nephritis. The expression of adiponectin and resistin was increased in both sera and urine from LN patients, while leptin was increased in LN patient sera, compared to matched controls. Serum resistin, but not urine resistin, was correlated with measures of renal dysfunction in LN. Serum resistin expression may be useful as a marker of renal dysfunction in patients with LN, although longitudinal studies are warranted. Further studies are necessary to determine if resistin has functional consequences in LN. PMID:25345756

  7. Resistin-like molecule α decreases glucose tolerance during intestinal inflammation1

    PubMed Central

    Munitz, Ariel; Seidu, Luqman; Cole, Eric T; Ahrens, Richard; S, Simon P Hogan; Rothenberg, Marc E

    2008-01-01

    Resistin-like molecule α (Relm-α), is a secreted cysteine-rich protein belonging to a newly defined family of proteins including resistin, Relm-β and Relm-γ. Resistin was initially defined based on its insulin resistance activity, but the family members are highly upregulated in various inflammatory states, especially those involving intestinal inflammation. Herein, we report the role of Relm-α at baseline and following an experimental model of colitis. Relm-α was readily detected in the serum at baseline (4−5 ng/ml) and its level was regulated by energy uptake. Retnla−/− mice had decreased baseline circulating leptin levels but displayed normal glucose, glucose clearance and insulin levels. Following exposure to the oral innate trigger dextran sodium sulfate (DSS), a non-redundant pro-inflammatory role for Relm-α was uncovered as Retnla−/− mice were markedly protected from DSS-induced disease activity and histopathological features. Relm-α regulated eosinophil-directed cytokines (e.g. IL-5, CCL11/eotaxin-1 and CCL5/RANTES) ex vivo. Consistently, DSS-treated Retnla−/− mice displayed substantially decreased eosinophil accumulation and decreased phosphorylation of NFκB, ERK1/2 and p38 in macrophages and eosinophils. Following DSS exposure, serum level of Relm-α was upregulated and DSS-treated Retnla−/− mice were markedly protected from hyperglycemia induced by glucose injection independent of changes in insulin levels. Retnla−/− mice were protected from increases in gut hormone serum levels of gastric inhibitory polypeptide and peptide YY that were induced following DSS-treatment. These findings demonstrate a central pro-inflammatory role for Relm-α in the regulation of colonic inflammation and a novel link between colonic injury, glucose tolerance and energy intake. PMID:19201890

  8. Elevated resistin levels in chronic kidney disease are associated with decreased glomerular filtration rate and inflammation, but not with insulin resistance.

    PubMed

    Axelsson, J; Bergsten, A; Qureshi, A R; Heimbürger, O; Bárány, P; Lönnqvist, F; Lindholm, B; Nordfors, L; Alvestrand, A; Stenvinkel, P

    2006-02-01

    In the present study, we explore the role of decreased renal function and a genetic polymorphism on the recently discovered protein resistin, apparently able to inhibit hepatic insulin action in mice. We also investigate possible links with inflammation and the insulin resistance present in patients with chronic kidney disease (CKD). This is a post hoc, cross-sectional study comparing 239 prevalent CKD patients with varying degrees of renal function impairment with an age- and gender-matched randomly selected control group of 25 individuals. Glomerular filtration rate (GFR) was estimated by the mean of urea and creatinine clearance (24-h urine samples) (n=204) or by iohexol clearance (n=60). Plasma analysis of blood lipids, insulin, glucose, inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha, vascular cellular adhesion molecule, intercellular adhesion molecule) and resistin (kit from LINCO Research, St Charles, MS) was performed using commercially available assays or routine methods. Insulin resistance was estimated by quantitative insulin-sensitivity check index (QUICKI) and homeostasis model assessment for insulin resistance (HOMA-IR) and body composition by dual-energy X-ray absorptiometry. Genotyping of a C/G promoter single nucleotide polymorphism (n=168) at position -180 of the resistin gene was performed by PyroSequencing. Serum levels of resistin were markedly elevated in the CKD patients with both advanced (39.9+/-1.3 ng/ml) and mild to moderate (23.2+/-1.0 ng/ml) renal function impairment, as compared to controls (8.5+/-0.7 ng/ml; P<0.001). In a multiple linear regression model in patients (adjusted r(2)=0.60), only GFR (beta=3.4; P<0.0001), lean body mass (beta=2.2; P<0.001) and the inflammatory markers were independently associated with circulating resistin levels. There was a weak but significant impact of -180 C/G genotype on plasma levels of resistin (median 43.0+/-2.4 ng/ml in CC, 37.5+/-2.0 ng

  9. Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.

    PubMed

    Jang, Jessica C; Chen, Gang; Wang, Spencer H; Barnes, Mark A; Chung, Josiah I; Camberis, Mali; Le Gros, Graham; Cooper, Philip J; Steel, Cathy; Nutman, Thomas B; Lazar, Mitchell A; Nair, Meera G

    2015-01-01

    Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated

  10. Macrophage-Derived Human Resistin Is Induced in Multiple Helminth Infections and Promotes Inflammatory Monocytes and Increased Parasite Burden

    PubMed Central

    Jang, Jessica C.; Chen, Gang; Wang, Spencer H.; Barnes, Mark A.; Chung, Josiah I.; Camberis, Mali; Le Gros, Graham; Cooper, Philip J.; Steel, Cathy; Nutman, Thomas B.; Lazar, Mitchell A.; Nair, Meera G.

    2015-01-01

    Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg− mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated

  11. Evolution of the Vertebrate Resistin Gene Family

    PubMed Central

    Hu, Qingda; Tan, Huanran; Irwin, David M.

    2015-01-01

    Resistin (encoded by Retn) was previously identified in rodents as a hormone associated with diabetes; however human resistin is instead linked to inflammation. Resistin is a member of a small gene family that includes the resistin-like peptides (encoded by Retnl genes) in mammals. Genomic searches of available genome sequences of diverse vertebrates and phylogenetic analyses were conducted to determine the size and origin of the resistin-like gene family. Genes encoding peptides similar to resistin were found in Mammalia, Sauria, Amphibia, and Actinistia (coelacanth, a lobe-finned fish), but not in Aves or fish from Actinopterygii, Chondrichthyes, or Agnatha. Retnl originated by duplication and transposition from Retn on the early mammalian lineage after divergence of the platypus, but before the placental and marsupial mammal divergence. The resistin-like gene family illustrates an instance where the locus of origin of duplicated genes can be identified, with Retn continuing to reside at this location. Mammalian species typically have a single copy Retn gene, but are much more variable in their numbers of Retnl genes, ranging from 0 to 9. Since Retn is located at the locus of origin, thus likely retained the ancestral expression pattern, largely maintained its copy number, and did not display accelerated evolution, we suggest that it is more likely to have maintained an ancestral function, while Retnl, which transposed to a new location, displays accelerated evolution, and shows greater variability in gene number, including gene loss, likely evolved new, but potentially lineage-specific, functions. PMID:26076481

  12. Evolution of the Vertebrate Resistin Gene Family.

    PubMed

    Hu, Qingda; Tan, Huanran; Irwin, David M

    2015-01-01

    Resistin (encoded by Retn) was previously identified in rodents as a hormone associated with diabetes; however human resistin is instead linked to inflammation. Resistin is a member of a small gene family that includes the resistin-like peptides (encoded by Retnl genes) in mammals. Genomic searches of available genome sequences of diverse vertebrates and phylogenetic analyses were conducted to determine the size and origin of the resistin-like gene family. Genes encoding peptides similar to resistin were found in Mammalia, Sauria, Amphibia, and Actinistia (coelacanth, a lobe-finned fish), but not in Aves or fish from Actinopterygii, Chondrichthyes, or Agnatha. Retnl originated by duplication and transposition from Retn on the early mammalian lineage after divergence of the platypus, but before the placental and marsupial mammal divergence. The resistin-like gene family illustrates an instance where the locus of origin of duplicated genes can be identified, with Retn continuing to reside at this location. Mammalian species typically have a single copy Retn gene, but are much more variable in their numbers of Retnl genes, ranging from 0 to 9. Since Retn is located at the locus of origin, thus likely retained the ancestral expression pattern, largely maintained its copy number, and did not display accelerated evolution, we suggest that it is more likely to have maintained an ancestral function, while Retnl, which transposed to a new location, displays accelerated evolution, and shows greater variability in gene number, including gene loss, likely evolved new, but potentially lineage-specific, functions. PMID:26076481

  13. Polymorphisms of the resistin gene and their association with obesity and resistin levels in Malaysian Malays.

    PubMed

    Apalasamy, Yamunah Devi; Rampal, Sanjay; Salim, Agus; Moy, Foong Ming; Su, Tin Tin; Majid, Hazreen Abdul; Bulgiba, Awang; Mohamed, Zahurin

    2015-06-01

    Single nucleotide polymorphisms (SNP) in the resistin gene (RETN) are linked to obesity and resistin levels in various populations. However, results have been inconsistent. This study aimed to investigate association between polymorphisms in the resistin gene with obesity in a homogenous Malaysian Malay population. This study is also aimed to determine association between resistin levels with certain SNPs and haplotypes of RETN. A total of 631 Malaysian Malay subjects were included in this study and genotyping was carried out using Sequenom MassARRAY. There was no significant difference found in both allelic and genotype frequencies of each of the RETN SNPs between the obese and non-obese groups after Bonferroni correction. RETN rs34861192 and rs3219175 SNPs were significantly associated with log-resistin levels. The GG genotype carriers are found to have higher levels of log-resistin compared to A allele carriers. The RETN haplotypes (CAG, CGA and GA) were significantly associated with resistin levels. However, the haplotypes of the RETN gene were not associated with obesity. Resistin levels were not correlated to metabolic parameters such as body weight, waist circumference, body mass index, and lipid parameters. RETN SNPs and haplotypes are of apparent functional importance in the regulation of resistin levels but are not correlated with obesity and related markers. PMID:25991560

  14. Correlation between Resistin, Tuberculosis and Khat Addiction: A Study from South Western Province of Saudi Arabia.

    PubMed

    Alvi, Ayesha; Fatima, Nuzhath; Jerah, Ahmed Ali; Rizwan, Mohammed; Hobani, Yahya Hasan; Sunosi, Rashad Al; Taha, Manal Mohamed El Hassan; Habiballah, Eldaw Mohamed; Agarwal, Pradeep Kumar; Abdulwahab, Siddig Ibrahim

    2015-01-01

    Tuberculosis(TB) is a disease of global significance, which accounts for a death in every 15 seconds. Recent studies shows TB is rising in certain parts of the world, and Saudi Arabia is one of them. Several factor contribute in predisposing the subjects for infection including but not limited to addiction to various compounds which have immune modulation properties, such as amphetamines and Heroin etc. Khat a plant whose leaves are chewed for its euphoric effect in east Africa and Arabian Peninsula including Saudi Arabia, is considered as mildly addictive, and its principle compound, Cathinone shares structural and functional similarity with amphetamine a known immunomodulator. Tuberculosis being a disease of immune modulation has a varied spectrum of complex interplay of proinflammatory molecules, resistin is one of them. In the present study, we try to explore the trinity of khat addiction, serum resistin level and tuberculosis by correlating the serum resistin level in non khat addicted healthy subjects, khat addicted healthy subjects, and in patients, both khat addicted and non khat addicted, with active tuberculosis. We observed significantly higher resistin level among the apparently healthy khat addicted subjects as compared to non addicted healthy controls. Thereafter, when we compare the resistin levels between khat addicted and non khat addicted TB patients we did not found significant difference between the two groups. However bacillary load was observe to be significantly higher among the khat addicted TB patient as compare to non addicted one. Validation of above results in animal model revealed dose dependant increase in bacillary growth in the Wistar rats treated with khat. Taken together these results suggest the role of khat in immune modulation albeit in the limited frame of resistin level. PMID:26448186

  15. Correlation between Resistin, Tuberculosis and Khat Addiction: A Study from South Western Province of Saudi Arabia

    PubMed Central

    Alvi, Ayesha; Fatima, Nuzhath; Jerah, Ahmed Ali; Rizwan, Mohammed; Hobani, Yahya Hasan; Sunosi, Rashad Al; Taha, Manal Mohamed El Hassan; Habiballah, Eldaw Mohamed; Agarwal, Pradeep Kumar; Abdulwahab, Siddig Ibrahim

    2015-01-01

    Tuberculosis(TB) is a disease of global significance, which accounts for a death in every 15 seconds. Recent studies shows TB is rising in certain parts of the world, and Saudi Arabia is one of them. Several factor contribute in predisposing the subjects for infection including but not limited to addiction to various compounds which have immune modulation properties, such as amphetamines and Heroin etc. Khat a plant whose leaves are chewed for its euphoric effect in east Africa and Arabian Peninsula including Saudi Arabia, is considered as mildly addictive, and its principle compound, Cathinone shares structural and functional similarity with amphetamine a known immunomodulator. Tuberculosis being a disease of immune modulation has a varied spectrum of complex interplay of proinflammatory molecules, resistin is one of them. In the present study, we try to explore the trinity of khat addiction, serum resistin level and tuberculosis by correlating the serum resistin level in non khat addicted healthy subjects, khat addicted healthy subjects, and in patients, both khat addicted and non khat addicted, with active tuberculosis. We observed significantly higher resistin level among the apparently healthy khat addicted subjects as compared to non addicted healthy controls. Thereafter, when we compare the resistin levels between khat addicted and non khat addicted TB patients we did not found significant difference between the two groups. However bacillary load was observe to be significantly higher among the khat addicted TB patient as compare to non addicted one. Validation of above results in animal model revealed dose dependant increase in bacillary growth in the Wistar rats treated with khat. Taken together these results suggest the role of khat in immune modulation albeit in the limited frame of resistin level. PMID:26448186

  16. Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer patients, display molecular association and promote growth and aggressiveness of tumor cells through STAT3 activation

    PubMed Central

    Bhardwaj, Arun; Singh, Ajay P.; Tyagi, Nikhil; Marimuthu, Saravanakumar; Dyess, Donna L.; Zotto, Valeria Dal; Carter, James E.; Singh, Seema

    2015-01-01

    African-American (AA) women with breast cancer (BC) are diagnosed with more aggressive disease, have higher risk of recurrence and poorer prognosis as compared to Caucasian American (CA) women. Therefore, it is imperative to define the factors associated with such disparities to reduce the unequal burden of cancer. Emerging data suggest that inherent differences exist in the tumor microenvironment of AA and CA BC patients, however, its molecular bases and functional impact have remained poorly understood. Here, we conducted cytokine profiling in serum samples from AA and CA BC patients and identified resistin and IL-6 to be the most differentially-expressed cytokines with relative greater expression in AA patients. Resistin and IL-6 exhibited positive correlation in serum levels and treatment of BC cells with resistin led to enhanced production of IL-6. Moreover, resistin also enhanced the expression and phosphorylation of STAT3, and treatment of BC cells with IL-6-neutralizing antibody prior to resistin stimulation abolished STAT3 phosphorylation. In addition, resistin promoted growth and aggressiveness of BC cells, and these effects were mediated through STAT3 activation. Together, these findings suggest a crucial role of resistin, IL-6 and STAT3 in BC racial disparity. PMID:25868978

  17. Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer patients, display molecular association and promote growth and aggressiveness of tumor cells through STAT3 activation.

    PubMed

    Deshmukh, Sachin K; Srivastava, Sanjeev K; Bhardwaj, Arun; Singh, Ajay P; Tyagi, Nikhil; Marimuthu, Saravanakumar; Dyess, Donna L; Dal Zotto, Valeria; Carter, James E; Singh, Seema

    2015-05-10

    African-American (AA) women with breast cancer (BC) are diagnosed with more aggressive disease, have higher risk of recurrence and poorer prognosis as compared to Caucasian American (CA) women. Therefore, it is imperative to define the factors associated with such disparities to reduce the unequal burden of cancer. Emerging data suggest that inherent differences exist in the tumor microenvironment of AA and CA BC patients, however, its molecular bases and functional impact have remained poorly understood. Here, we conducted cytokine profiling in serum samples from AA and CA BC patients and identified resistin and IL-6 to be the most differentially-expressed cytokines with relative greater expression in AA patients. Resistin and IL-6 exhibited positive correlation in serum levels and treatment of BC cells with resistin led to enhanced production of IL-6. Moreover, resistin also enhanced the expression and phosphorylation of STAT3, and treatment of BC cells with IL-6-neutralizing antibody prior to resistin stimulation abolished STAT3 phosphorylation. In addition, resistin promoted growth and aggressiveness of BC cells, and these effects were mediated through STAT3 activation. Together, these findings suggest a crucial role of resistin, IL-6 and STAT3 in BC racial disparity. PMID:25868978

  18. Association of resistin with visceral fat and muscle insulin resistance.

    PubMed

    Borst, Stephen E; Conover, Christine F; Bagby, Gregory J

    2005-10-01

    Maturing Sprague-Dawley (S-D) rats develop obesity and skeletal muscle insulin resistance. To investigate the relationship between fat mass and insulin responses, we performed surgical removal of the epididymal and retroperitoneal depots of visceral adipose tissue (VF) or sham surgery (SHAM) in male rats aged 4 months. At sacrifice, 30 days later, the mass of visceral fat was 48% lower (p<0.05) in VF- compared to SHAM, while subcutaneous fat was essentially unchanged. VF- animals displayed increased insulin responses in isolated strips of skeletal muscle. Insulin-stimulated glucose transport was increased 28% in soleus muscle (p<0.05), with a trend toward a 31% increase in extensor digitorum longus muscle (p=0.058). Glucose tolerance was not significantly affected by surgical fat removal. In VF- animals, serum resistin was reduced 26% (p<0.05) and serum adiponectin was reduced 30% (p<0.05), with trends for reductions in IL-4 (58% reduction, p=0.084) and IL-6 (56% reduction, p=0.123). TNF-alpha, leptin and free fatty acids (NEFAs) were unchanged. We conclude that in maturing S-D rats, increased visceral adiposity leads to an increase in systemic release in resistin and possibly interleukins. Elevation of circulating cytokines may play a role in the development of muscle insulin resistance. PMID:16154759

  19. Beneficial effect of combination therapy using an angiotensin-converting enzyme inhibitor plus verapamil on circulating resistin levels in hypertensive patients with type 2 diabetes

    PubMed Central

    Rubio-Guerra, Alberto F; Vargas-Robles, Hilda; Lozano Nuevo, Jose J; Elizalde-Barrera, Cesar I; Huerta-Ramirez, Saul; Escalante-Acosta, Bruno A

    2012-01-01

    BACKGROUND: Resistin levels are strongly correlated with insulin resistance and vascular inflammation. Type 2 diabetic and hypertensive patients have higher circulating levels of resistin, which is associated with endothelial dysfunction. OBJECTIVE: To compare the effect of trandolapril (T) and its fixed-dose combination with verapamil (FDTV) on resistin levels in hypertensive, type-2 diabetic patients. METHODS: Forty type-2 diabetic patients with never-treated hypertension were randomly assigned to two groups. One group received FDTV 2 mg/180 mg once per day; the other group received T 2 mg once per day. Study drugs were administered for three months in both groups. Resistin levels were measured using ELISA at the beginning of the study and at study end. Patients were evaluated monthly for blood pressure, fasting serum glucose levels and adverse events. Statistical analysis was performed using ANOVA. RESULTS: All patients experienced a significant reduction in blood pressure. Both therapeutic regimens reduced resistin levels; however, FDTV treatment resulted in a greater decrease in resistin levels (mean [± SD] 25.5±13 ng/mL to 17.2±10 ng/mL) when compared with T treatment (22.4±12 ng/mL to 18.5±8 ng/mL) (P<0.05). None of the patients experienced an adverse event. CONCLUSION: Results showed that FDTV resulted in a greater reduction in resistin levels than T treatment alone. PMID:23592936

  20. Resistin increases monolayer permeability of human coronary artery endothelial cells.

    PubMed

    Jamaluddin, Md Saha; Yan, Shaoyu; Lü, Jianming; Liang, Zhengdong; Yao, Qizhi; Chen, Changyi

    2013-01-01

    Resistin has been linked to obesity, insulin resistance, atherosclerosis, and the development of cardiovascular disease. Nevertheless, the effects and the molecular mechanisms of resistin on endothelial permeability, a key event in the development of atherosclerosis, inflammation, and vascular disease, are largely unknown. In order to determine the effect of resistin on endothelial permeability, human coronary artery endothelial cells (HCAECs) were treated with clinically relevant concentrations of resistin and the endothelial permeability was measured using the Transwell system with a Texas-Red-labeled dextran tracer. The permeability of HCAEC monolayers treated with resistin (80 ng/mL) was 51% higher than the permeability of control monolayers (P<0.05). The mRNA levels of tight junction proteins zonula occludens-1 (ZO-1) and occludin in resistin-treated cells were 37% and 42% lower, respectively, than the corresponding levels in untreated cells. The protein levels of these molecules in resistin-treated cells were significantly reduced by 35% and 37%, respectively (P<0.05), as shown by flow cytometry and Western blot analysis. Superoxide dismutase (SOD) mimetic MnTBAP effectively blocked the resistin-mediated reduction of ZO-1 and occludin levels in HCAECs. In addition, superoxide anion production was increased from 21% (untreated cells) to 55% (cells treated with 40 ng/mL resistin), and 64% (resistin, 80 mg/mL) (P<0.05). The natural antioxidant Ginkgolide A effectively inhibited resistin-induced increase in permeability and the increase in superoxide anion production in HCAECs. Furthermore, resistin treatment significantly activated p38 MAPK, but not ERK1/2. Pretreatment of HCAECs with a p38 inhibitor effectively blocked resistin-induced permeability. These results provide new evidence that resistin may contribute to the vascular lesion formation via increasing endothelial permeability through the mechanism of oxidative stress and the activation of p38 MAPK. PMID

  1. Resistin Increases Monolayer Permeability of Human Coronary Artery Endothelial Cells

    PubMed Central

    Jamaluddin, Md Saha; Yan, Shaoyu; Lü, Jianming; Liang, Zhengdong; Yao, Qizhi; Chen, Changyi

    2013-01-01

    Resistin has been linked to obesity, insulin resistance, atherosclerosis, and the development of cardiovascular disease. Nevertheless, the effects and the molecular mechanisms of resistin on endothelial permeability, a key event in the development of atherosclerosis, inflammation, and vascular disease, are largely unknown. In order to determine the effect of resistin on endothelial permeability, human coronary artery endothelial cells (HCAECs) were treated with clinically relevant concentrations of resistin and the endothelial permeability was measured using the Transwell system with a Texas-Red-labeled dextran tracer. The permeability of HCAEC monolayers treated with resistin (80 ng/mL) was 51% higher than the permeability of control monolayers (P<0.05). The mRNA levels of tight junction proteins zonula occludens-1 (ZO-1) and occludin in resistin-treated cells were 37% and 42% lower, respectively, than the corresponding levels in untreated cells. The protein levels of these molecules in resistin-treated cells were significantly reduced by 35% and 37%, respectively (P<0.05), as shown by flow cytometry and Western blot analysis. Superoxide dismutase (SOD) mimetic MnTBAP effectively blocked the resistin-mediated reduction of ZO-1 and occludin levels in HCAECs. In addition, superoxide anion production was increased from 21% (untreated cells) to 55% (cells treated with 40 ng/mL resistin), and 64% (resistin, 80 mg/mL) (P<0.05). The natural antioxidant Ginkgolide A effectively inhibited resistin-induced increase in permeability and the increase in superoxide anion production in HCAECs. Furthermore, resistin treatment significantly activated p38 MAPK, but not ERK1/2. Pretreatment of HCAECs with a p38 inhibitor effectively blocked resistin-induced permeability. These results provide new evidence that resistin may contribute to the vascular lesion formation via increasing endothelial permeability through the mechanism of oxidative stress and the activation of p38 MAPK. PMID

  2. Endothelin-1 stimulates resistin gene expression.

    PubMed

    Tang, Ya-Chu; Liu, Chi-Wei; Chang, Hsin-Huei; Juan, Chi-Chang; Kuo, Yow-Chii; Kao, Chung-Cheng; Huang, Yao-Ming; Kao, Yung-Hsi

    2014-03-01

    Resistin and endothelin (ET)-1 have been reported to inhibit adipogenesis and regulate adipocyte insulin resistance, respectively. Although both hormones interact with each other, the exact signaling pathway of ET-1 to act on resistin gene expression is still unknown. Using 3T3-L1 adipocytes, we investigated the signaling pathways involved in ET-1-stimulated resistin gene expression. The up-regulation of resistin mRNA expression by ET-1 depends on concentration and timing. The concentration of ET-1 that increased resistin mRNA levels by 100%-250% was approximately 100 nM for a range of 0.25-12 hours of treatment. Treatment with actinomycin D blocked ET-1-increased resistin mRNA levels, suggesting that the effect of ET-1 requires new mRNA synthesis. Treatment with an inhibitor of the ET type-A receptor, such as N-[1-Formyl-N-[N-[(hexahydro-1H-azepin-1-yl)carbonyl]-L-leucyl]-D-tryptophyl]-D-tryptophan (BQ610), but not with the ET type-B receptor antagonist N-[(cis-2,6-Dimethyl-1-piperidinyl)carbonyl]-4-methyl-L-leucyl-1-(methoxycarbonyl)-D-tryptophyl-D-norleucine (BQ788), blocked ET-1, increased the levels of resistin mRNA, and phosphorylated levels of downstream signaling molecules, such as ERK1/2, c-Jun N-terminal kinases (JNKs), protein kinase B (AKT), and signal transducer and activator of transcription 3 (STAT3). Moreover, pretreatment of specific inhibitors of either ERK1/2 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene [U0126] and 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one [PD98059], two inhibitors of MEK1), JNKs (SP600125), phosphatidylinositol 3-kinase/AKT (LY294002 and Wortmannin), or Janus kinase 2 (JAK2)/STAT3 ((E)-2-Cyano-3-(3,4-dihydrophenyl)-N-(phenylmethyl)-2-propenamide, AG490) prevented ET-1-increased levels of resistin mRNA and reduced the ET-1-stimulated phosphorylation of ERK1/2, JNKs, AKT, and STAT3, respectively. However, the p38 kinase antagonist 4-[5-(4-Fluorophenyl)-2-[4-(methylsulfonyl)phenyl]-1H-imidazol-4-yl

  3. Circulating levels of adiponectin, resistin, and visfatin after mud-bath therapy in patients with bilateral knee osteoarthritis

    NASA Astrophysics Data System (ADS)

    Fioravanti, Antonella; Giannitti, Chiara; Cheleschi, Sara; Simpatico, Antonella; Pascarelli, Nicola Antonio; Galeazzi, Mauro

    2015-11-01

    Adipocytokines, including adiponectin, resistin, and visfatin may play an important role in the pathophysiology of osteoarthritis (OA). Spa therapy is one of the most commonly used non-pharmacological approaches for OA, but its mechanisms of action are not completely known. The aim of the present study was to assess whether a cycle of mud-bath therapy (MBT) influences the serum levels of adiponectin, resistin, and visfatin in patients with knee OA. As part of a prospective randomized, single blind-controlled trial evaluating the efficacy of MBT in knee OA, we included in this study 95 outpatients. One group ( n = 49) received a cycle of MBT at the spa center of Chianciano Terme (Italy) in addition to the usual treatment, and one group (control group; n = 46) continued their regular care routine alone. Patients were assessed at basal time and at the end of the study (15 days) for clinical and biochemical parameters. Clinical assessments included spontaneous pain on a visual analog scale (VAS) score and the Western Ontario and McMaster Universities index (WOMAC) subscores for knee OA evaluated as total pain score (W-TPS), total stiffness score (W-TSS), and total physical function score (W-TPFS). Adiponectin, resistin and visfatin serum levels were assessed by enzyme immunoassay methods. At the end of the mud-bath therapy, serum adiponectin levels showed a significant decrease ( p < 0.001), while no significant modifications were found in the control group at day 15. Serum resistin showed a significant decrease ( p < 0.0001) in the MBT group at the end of the study and a significant increase in the control patients ( p < 0.001). No significant modifications of visfatin were found in MBT. Furthermore, we tested the relationships between demographic and clinical parameters and adipocytokine concentrations measured in the MBT group at basal and at the end of the study. In conclusion, the present study shows that a cycle of MBT can modify serum levels of adiponectin and

  4. Resistin is a survival factor for porcine ovarian follicular cells.

    PubMed

    Rak, Agnieszka; Drwal, Eliza; Wróbel, Anna; Gregoraszczuk, Ewa Łucja

    2015-10-01

    Previously, we demonstrated the expression of resistin in the porcine ovary, the regulation of its expression and its direct effect on ovarian steroidogenesis. The objective of this study was to examine the effect of resistin on cell proliferation and apoptosis in a co-culture model of porcine granulosa and theca cells. First, we analysed the effect of resistin at 1 and 10  ng/ml alone or in combination with FSH- and IGF1 on ovarian cell proliferation with an alamarBlue assay and protein expression of cyclins A and B using western blot. Next, the mRNA and protein expression of selected pro-apoptotic and pro-survival regulators of cell apoptosis, caspase-9, -8 and -3 activity and DNA fragmentation using real time PCR, western blot, fluorescent assay and an ELISA kit, respectively, were analysed after resistin treatment. Furthermore, we determined the effect of resistin on the protein expression of ERK1/2, Stat and Akt kinase. Using specific inhibitors of these kinases, we also checked caspase-3 activity and protein expression. We found that resistin, at both doses, has no effect on cell proliferation. The results showed that resistin decreased pro-apoptotic genes, which was confirmed on protein expression of selected factors. We demonstrate an inhibitory effect of resistin on caspase activity and DNA fragmentation. Finally, resistin stimulated phosphorylation of the ERK1/2, Stat and Akt and kinases inhibitors reversed resistin action on caspase-3 activity and protein expression to control. All of these results showed that resistin has an inhibitory effect on porcine ovarian cell apoptosis by activation of the MAPK/ERK, JAK/Stat and Akt/PI3 kinase signalling pathways. PMID:26159832

  5. Resistin: functional roles and therapeutic considerations for cardiovascular disease

    PubMed Central

    Jamaluddin, Md S; Weakley, Sarah M; Yao, Qizhi; Chen, Changyi

    2012-01-01

    Resistin, originally described as an adipocyte-specific hormone, has been suggested to be an important link between obesity, insulin resistance and diabetes. Although its expression was initially defined in adipocytes, significant levels of resistin expression in humans are mainly found in mononuclear leukocytes, macrophages, spleen and bone marrow cells. Increasing evidence indicates that resistin plays important regulatory roles apart from its role in insulin resistance and diabetes in a variety of biological processes: atherosclerosis and cardiovascular disease (CVD), non-alcoholic fatty liver disease, autoimmune disease, malignancy, asthma, inflammatory bowel disease and chronic kidney disease. As CVD accounts for a significant amount of morbidity and mortality in patients with diabetes and without diabetes, it is important to understand the role that adipokines such as resistin play in the cardiovascular system. Evidence suggests that resistin is involved in pathological processes leading to CVD including inflammation, endothelial dysfunction, thrombosis, angiogenesis and smooth muscle cell dysfunction. The modes of action and signalling pathways whereby resistin interacts with its target cells are beginning to be understood. In this review, the current knowledge about the functions and pathophysiological implications of resistin in CVD development is summarized; clinical translations, therapeutic considerations and future directions in the field of resistin research are discussed. LINKED ARTICLES This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3 PMID:21545576

  6. Longitudinal changes in adipose tissue of dairy cows from late pregnancy to lactation. Part 1: The adipokines apelin and resistin and their relationship to receptors linked with lipolysis.

    PubMed

    Weber, M; Locher, L; Huber, K; Kenéz, Á; Rehage, J; Tienken, R; Meyer, U; Dänicke, S; Sauerwein, H; Mielenz, M

    2016-02-01

    The transition from pregnancy to lactation is characterized by major changes in glucose and adipose tissue metabolism. Anti- and prolipolytic pathways mediated via the hydroxycarboxylic acid receptors 1 (HCAR1) and 2 (HCAR2) and tumor necrosis factor-α receptor 1 (TNFR1), as well as the adipokines apelin and resistin, are likely involved in regulating these processes. This study aimed to determine the mRNA abundance of the aforementioned receptors in both subcutaneous and visceral adipose tissue, to characterize the adipokine concentrations in serum, and to test the effects of feeding diets with either high or low portions of concentrate and a concomitant niacin supplementation from late gestation to early lactation. Twenty pluriparous German Holstein cows were all kept on the same silage-based diet until d 42 antepartum, when they were allocated to 2 feeding groups: until d 1 antepartum, 10 animals each were assigned to either a high-concentrate (60:40 concentrate-to-roughage ratio) or a low-concentrate diet (30:70). Both groups were further subdivided into a control and a niacin group, the latter receiving 24 g/d of nicotinic acid from d -42 until 24. From d 1 to 24 postpartum, the concentrate portion was increased from 30 to 50% for all cows. Biopsies of subcutaneous (SCAT) and retroperitoneal adipose tissue (RPAT) were taken at d -42, 1, 21, and 100 relative to parturition. Blood samples were drawn along with the biopsies and on d -14, 3, 7, 14, and 42. The concentrations of the adipokines apelin and resistin in serum were measured via ELISA. The mRNA of the 3 receptors in AT was quantified as well as the protein abundance of HCAR2 by Western blot. The feeding regimen did not affect the variables examined. The concentrations of apelin remained fairly constant during the observation period, whereas the resistin concentrations increased toward parturition and decreased to precalving levels within 1 wk after calving. The mRNA abundance of HCAR1, HCAR2, and TNFR1

  7. Body fat mass and macronutrient intake in relation to circulating soluble leptin receptor, free leptin index, adiponectin, and resistin concentrations in healthy humans.

    PubMed

    Yannakoulia, Mary; Yiannakouris, Nikos; Blüher, Susann; Matalas, Antonia-Leda; Klimis-Zacas, Dorothy; Mantzoros, Christos S

    2003-04-01

    The adipocyte-derived hormones leptin [which circulates in a free form and bound to a soluble leptin receptor (sOB-R)], adiponectin, and resistin play a key role in regulating energy homeostasis and metabolism. We assessed the association between body composition, total energy, and macronutrient intake and serum leptin, sOB-R, free leptin index, adiponectin, and resistin concentrations in 61 female and 53 male consecutively enrolled healthy Greek students. In this cross-sectional study, total energy and macronutrient intake were determined using 3-d food records. Body composition was assessed by bioelectrical impedance analysis; fasting blood samples were taken for the measurement of total leptin, sOB-R, adiponectin, and resistin; and the ratio leptin/sOB-R was used as an index of free leptin. Serum sOB-R concentrations were lower in the female subjects compared with the males (27.24 +/- 29.06 vs. 50.14 +/- 39.74 ng/ml, P < 0.001), whereas leptin, adiponectin, and resistin concentrations were significantly higher in females (leptin: 9.93 +/- 6.01 vs. 3.27 +/- 2.54 ng/ml, P < 0.001; adiponectin: 11.40 +/- 6.73 micro g/ml vs. 4.90 +/- 2.79 micro g/ml; P < 0.001; resistin: 16.86 +/- 5.39 ng/ml in females vs. 14.00 +/- 7.16 ng/ml in males, P < 0.02). Simple regression analysis showed that, in both genders, leptin, free leptin index, adiponectin, and resistin correlated positively with body fat mass and negatively with waist to hip ratio. sOB-R correlated negatively with body fat mass and positively with waist to hip ratio. Multiple regression analysis models controlling for gender, body fat, and total energy intake demonstrated that sOB-R is positively associated with energy intake from carbohydrates and negatively with energy intake from dietary fat, whereas free leptin index is negatively associated with energy intake from carbohydrates and positively with energy intake from dietary fat. No statistically significant correlations were observed between serum

  8. The effect of Morus alba leaves extract and powder on resistin levels and liver transaminase enzymes activities in diabetes.

    PubMed

    Salemi, Z; Barzin Tond, S; Fallah, S; Shojaii, A; Seifi, M

    2016-01-01

    The current study was designed to investigate the changes of the resistin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels of diabetic rats after treatment with Morus alba leaves flavonoid extract (MLE) and Morus alba leaves powder (MLP). Thirty male wistar rats in five groups including control and diabetic groups were included. Diabetic groups consisted of diabetic control, sham and treated group with MLE and MLP. Type 2 diabetes was induced in rats by administration of streptozotocin (STZ) and - nicotinamide. The serum concentrations of resistin and insulin in the study groups were identified by ELISA. ALT and AST activities were assayed by spectrophotometer. For the first time, it was shown that the uptake of MLE and MLP by diabetic rats could significantly decrease the serum fasting blood sugar (FBS), resistin levels and enzymes activity of ALT and AST and increases the concentration of serum insulin significantly (P<0.05). in comparison with the sham group and diabetic control. The results showed that there was no significant difference between the anti-diabetic and inflammatory properties of MLE and MLP. In this study, the possible protective effect of MLE and MLP administration was evaluated against destructive effect of STZ on liver and pancreas function in diabetic rats. The results showed that these effects may play an important role in the regulating of adipokines secretion such as resistin and insulin secretion which are involved in the control of diabetes and obesity. MLE and MLP treatment could be useful agents in combination with other therapies in diabetes improvement. PMID:27262814

  9. Heparanase Interacts with Resistin and Augments Its Activity

    PubMed Central

    Novick, Daniela; Barak, Sara; Ilan, Neta; Vlodavsky, Israel

    2014-01-01

    In an attempt to isolate a heparanase receptor, postulated to mediate non-enzymatic functions of the heparanase protein, we utilized human urine collected from healthy volunteers. Affinity chromatography of this rich protein source on immobilized heparanase revealed resistin as a heparanase binding protein. Co-immunoprecipitation and ELISA further confirmed the interaction between heparanase and resistin. Importantly, we found that heparanase potentiates the bioactivity of resistin in its standard bioassay in which monocytic human leukemia cell line, THP1, differentiates into adherent macrophage-like foam cells. It is thus conceivable that this newly identified complex of heparanase and resistin exerts a stimulatory effect also in various inflammatory conditions known to be affected by the two proteins. PMID:24465803

  10. Autocrine effects of transgenic resistin reduce palmitate and glucose oxidation in brown adipose tissue.

    PubMed

    Pravenec, Michal; Mlejnek, Petr; Zídek, Václav; Landa, Vladimír; Šimáková, Miroslava; Šilhavý, Jan; Strnad, Hynek; Eigner, Sebastian; Eigner Henke, Kateřina; Škop, Vojtěch; Malínská, Hana; Trnovská, Jaroslava; Kazdová, Ludmila; Drahota, Zdeněk; Mráček, Tomáš; Houštěk, Josef

    2016-06-01

    Resistin has been originally identified as an adipokine that links obesity to insulin resistance in mice. In our previous studies in spontaneously hypertensive rats (SHR) expressing a nonsecreted form of mouse resistin (Retn) transgene specifically in adipose tissue (SHR-Retn), we have observed an increased lipolysis and serum free fatty acids, ectopic fat accumulation in muscles, and insulin resistance. Recently, brown adipose tissue (BAT) has been suggested to play an important role in the pathogenesis of metabolic disturbances. In the current study, we have analyzed autocrine effects of transgenic resistin on BAT glucose and lipid metabolism and mitochondrial function in the SHR-Retn vs. nontransgenic SHR controls. We observed that interscapular BAT isolated from SHR-Retn transgenic rats compared with SHR controls showed a lower relative weight (0.71 ± 0.05 vs. 0.91 ± 0.08 g/100 g body wt, P < 0.05), significantly reduced both basal and insulin stimulated incorporation of palmitate into BAT lipids (658 ± 50 vs. 856 ± 45 and 864 ± 47 vs. 1,086 ± 35 nmol/g/2 h, P ≤ 0.01, respectively), and significantly decreased palmitate oxidation (37.6 ± 4.5 vs. 57 ± 4.1 nmol/g/2 h, P = 0.007) and glucose oxidation (277 ± 34 vs. 458 ± 38 nmol/g/2 h, P = 0.001). In addition, in vivo microPET imaging revealed significantly reduced (18)F-FDG uptake in BAT induced by exposure to cold in SHR-Retn vs. control SHR (232 ± 19 vs. 334 ± 22 kBq/ml, P < 0.05). Gene expression profiles in BAT identified differentially expressed genes involved in skeletal muscle and connective tissue development, inflammation and MAPK and insulin signaling. These results provide evidence that autocrine effects of resistin attenuate differentiation and activity of BAT and thus may play a role in the pathogenesis of insulin resistance in the rat. PMID:27113533

  11. Recombinant human FIZZ3/resistin stimulates lipolysis in cultured human adipocytes, mouse adipose explants, and normal mice.

    PubMed

    Ort, Tatiana; Arjona, Anibal A; MacDougall, John R; Nelson, Pam J; Rothenberg, Mark E; Wu, Frank; Eisen, Andrew; Halvorsen, Yuan-Di C

    2005-05-01

    Human FIZZ3 (hFIZZ3) was identified as an ortholog of mouse resistin (mResistin), an adipocyte-specific secreted factor linked to insulin resistance in rodents. Unlike mResistin, hFIZZ3 is expressed in macrophages and monocytes, but is undetectable in adipose tissue. The profound macrophage infiltration of adipose that occurs during obesity suggests that hFIZZ3 may play an important role in adipocyte biology. Using a recombinant protein produced in Escherichia coli, we report here that chronic treatment of cultured human adipocytes with hFIZZ3 results in hypotropic cells with smaller lipid droplets. Recombinant hFIZZ3 facilitates preadipocyte proliferation and stimulates adipocyte triglyceride lipolysis, whereas recombinant mResistin inhibits adipocyte differentiation, with no detectable effect on proliferation or lipolysis. In addition, insulin-stimulated glucose uptake and Akt phosphorylation are not altered in hFIZZ3-treated adipocytes, indicating an intact insulin response. In mouse adipose explants, hFIZZ3 accelerates simultaneously triglyceride lipolysis and fatty acid reesterification, as assessed by measurement of glycerol and fatty acid release. Consistent with the in vitro findings, acute administration of recombinant hFIZZ3 into normal mice caused a significant increase in serum glycerol concentration with no elevation in free fatty acid at 45 min post injection. Taken together, the data suggest that recombinant hFIZZ3 can influence adipose metabolism by regulating preadipocyte cell number, adipocyte lipid content, and energy expenditure via accelerating the fatty acid/triglyceride futile cycle. PMID:15705777

  12. Adiponectin, resistin and IL-6 plasma levels in subjects with diabetic foot and possible correlations with clinical variables and cardiovascular co-morbidity

    PubMed Central

    2010-01-01

    Introduction It is very suggestive that diabetic foot is characterized by a pronounced inflammatory reaction and the pathogenic significance of this inflammation has received little attention. On this basis the aim of our study was to evaluate plasma levels of adiponectin, resistin and IL-6 in subjects with diabetic foot in comparison with subjects without foot complications. Materials and methods We recruited 34 subjects with type 2 diabetes mellitus and foot ulceration hospitalized for every condition related to diabetic disease, but not for new vascular events (group A). As controls we recruited 37 patients with type 2 diabetes mellitus without foot ulceration (group B) hospitalized for every condition related to diabetic disease, but not for new vascular events. Adiponectin, Resistin and IL-6 serum levels were evaluated. Results Subjects of group A showed lower median plasma levels of adiponectin [7.7450 (4.47-12.17) μg/ml vs 8.480 (5.15-12.87) μg/ml], higher median plasma levels of IL-6 [3.21 (1.23-5.34) pg/ml vs 2.73 (1.24-3.97 pg/ml)] and of resistin [3.860 (2.96-6.29 ng/ml) vs 3.690 (2.,37-6.5 ng/ml)]. Conclusion Our study demonstrated that diabetic subjects with diabetic foot showed in comparison with diabetics without diabetic foot higher IL-6 and resistin plasma levels, lower adiponectin plasma levels. PMID:20836881

  13. [Adipokines: adiponectin, leptin, resistin and coronary heart disease risk].

    PubMed

    Kopff, Barbara; Jegier, Anna

    2005-01-01

    Visceral obesity is among the known risk factors of atherosclerotic cardiovascular diseases. As long as adipose tissue was considered only an inert store of excess energy, accumulated in triglycerides, explanation of the mechanisms causing increased cardiovascular risk in obesity was difficult. Finding that the adipose tissue is an active endocrine organ and that the adipokines secreted in it influence several metabolic processes, allowed better understanding of this correlation. Several disturbances in secretion, function and balance of adipokines occur in the course of obesity. Changes of adiponectin, leptin and resistin concentrations are among the reasons of accelerated atherosclerosis occurring in the visceral adiposity. Adiponectin concentrations are decreased in visceral adiposity. Adiponectin is adipokine possessing antiatherogenic properties. It's effects exerted though the specific receptors in skeletal muscles and liver include decreased insulin resistance and improved plasma lipid profile. Acting directly in the vessel wall adiponectin prevents development of atheromatic lesions by inhibiting production of adhesive molecules and formation of foam cells. It has been found that decreased adiponectin concentrations are connected not only with increased coronary risk but also with progression of atherosclerosis in coronary vessels. Moreover it was found that adiponectin plasma concentration is significantly decreased in acute coronary incidences. Leptin regulates energy metabolism and balance. The concentrations of this adipokine are increased in obesity and correlate with insulin resistance. Hiperleptinemia has been also recognized as cardiovascular diseases risk factor. Resistin is considered to be a substance increasing insulin resistance, however the exact mechanisms are not known. Resistin plasma concentrations are increased in obese subjects and correlate with the inflammatory state that underlies the initiation and progression of atherosclerotic

  14. Interaction between resistin and adiponectin in the proliferation of rat vascular smooth muscle cells.

    PubMed

    Hirai, Hiroyuki; Satoh, Hiroaki; Kudoh, Akihiro; Watanabe, Tsuyoshi

    2013-02-01

    We investigated the effect between resistin and adiponectin on the proliferation of vascular smooth muscle cells (VSMCs). We confirmed that resistin significantly increases the number of rat VSMCs as well as thymidine incorporation with them, whereas adiponectin diminishes resistin-induced cell proliferation. Resistin significantly increased p42/44 mitogen-activated protein kinase (MAPK) phosphorylation within rat VSMCs, whereas adiponectin inhibited resistin-induced MAPK phosphorylation. Moreover, resistin significantly increased c-fos expression, whereas adiponectin suppressed resistin-induced c-fos expression. Cell cycle progression is a tightly controlled event that is negatively regulated by cyclin-dependent kinases inhibitors (CDKIs) such as p53, p21, and p27. Resistin significantly decreased the expression of these CDKIs, whereas adiponectin restored the resistin-induced decrease in CDKIs expression. These effects were abolished in the MAPK inhibitors. In conclusion, resistin plays a role in the development of atherosclerosis, whereas adiponectin may be an important in its prevention in insulin-resistant patients. PMID:23267839

  15. Effect of conjugated linoleic acid on body fat, tumor necrosis factor alpha and resistin secretion in spontaneously hypertensive rats.

    PubMed

    Hernández-Díaz, Guillermo; Alexander-Aguilera, Alfonso; Arzaba-Villalba, Agustin; Soto-Rodríguez, Ida; García, Hugo S

    2010-01-01

    Conjugated linoleic acid (CLA) is a naturally occurring group of dienoic derivaties of linoleic acid found mainly in beef and dairy products. CLA has been reported to reduce body fat, as well as to possess anticarcinogenic, antiatherogenic and procatabolic activities in animals. The objective of this study was to evaluate the effect of CLA supplementation to spontaneously hypertensive rats (SHR) on body fat, biochemical parameters of serum related tumor necrosis factor alpha (TNF-alpha) and resistin secretion. Thirty rats were divided in three groups, the first group of spontaneously hypertensive rats received a standard diet (V-SHR group, n=10), a second group of SHR was fed 1.5% of conjugated linoleic acid (CLA-SHR group, n=10) and the third was the control, non-hypertensive group (KW, n=10) also on a standard diet including 7.5% of sunflower oil during eight weeks. After CLA diet administration, spontaneously hypertensive rats showed a significant reduction in blood pressure, serum glucose, cholesterol and triacylglycerols, together with reduction of index of body fat, pericardic, abdominal and epididymal adipose tissue. These effects were accompanied by a decrease in the secretion of TNF-alpha and resistin. PMID:20074923

  16. Adiponectin and resistin in acute and chronic graft-vs-host disease patients undergoing allogeneic hematopoietic stem cell transplantation

    PubMed Central

    Robak, Oliver; Kuzmina, Zoya; Winkler, Andreas; Kalhs, Peter; Rabitsch, Werner; Greinix, Hildegard

    2016-01-01

    Aim To investigate the association of adiponectin and resistin levels in patients undergoing hematopoietic stem cell transplantation (HSCT) with the clinical outcome, including the occurrence of acute and chronic graft-vs-host disease (GVHD), non-relapse mortality, and overall survival. Methods We prospectively collected serum samples from 40 patients undergoing either autologous (n = 12; 10 male) or allogeneic (n = 28; 11 male) HSCT for up to 12 months post HSCT and determined adiponectin and resistin serum concentrations using enzyme-linked immunosorbent assay. Results There were no significant differences in adiponectin levels (18.5 vs 9.3 µg/mL, P = 0.071) and adiponectin/BMI ratio (0.82 vs 0.39, P = 0.068) between patients with acute GVHD grades 2-4 and autologous controls. However, resistin values were significantly lower in patients with acute GVHD grades 2-4 than in autologous controls (4.6 vs 7.3 ng/mL, P = 0.030). Adiponectin levels were higher in patients with chronic GVHD (n = 17) than in autologous controls (13.5 vs 7.6 µg/mL, P = 0.051), but the difference was not significant. Adiponectin/BMI ratio was significantly higher in patients with chronic GVHD than in autologous controls (0.59 vs 0.25, P = 0.006). Patients dying from relapse also had significantly lower adiponectin levels (8.2 µg/mL) and adiponectin/BMI ratio (0.3) on admission than surviving allogeneic (15.8 µg/mL, P = 0.030 and 0.7, P = 0.004) and surviving autologous patients (19.2 µg/mL, P = 0.031 and 0.7, P = 0.021). Conclusion Adiponectin and resistin levels were altered in patients with acute and chronic GVHD compared to autologous controls and were associated with overall survival and relapse mortality in patients undergoing allogeneic HSCT. PMID:27374827

  17. Resistin, a fat-derived secretory factor, promotes metastasis of MDA-MB-231 human breast cancer cells through ERM activation

    PubMed Central

    Lee, Jung Ok; Kim, Nami; Lee, Hye Jeong; Lee, Yong Woo; Kim, Su Jin; Park, Sun Hwa; Kim, Hyeon Soo

    2016-01-01

    Resistin, an adipocyte-secreted factor, is known to be elevated in breast cancer patients. However, the molecular mechanism by which resistin acts is not fully understood. The aim of this study was to investigate whether resistin could stimulate invasion and migration of breast cancer cells. Here, we report that resistin stimulated invasion and migration of breast cancer cells as well as phosphorylation of c-Src. Inhibition of c-Src blocked resistin-induced breast cancer cell invasion. Resistin increased intracellular calcium concentration, and chelation of intracellular calcium blocked resistin-mediated activation of Src. Resistin also induced phosphorylation of protein phosphatase 2A (PP2A). Inhibition of c-Src blocked resistin-mediated PP2A phosphorylation. In addition, resistin increased phosphorylation of PKCα. Inhibition of PP2A enhanced resistin-induced PKCα phosphorylation, demonstrating that PP2A activity is critical for PKCα phosphorylation. Resistin also increased phosphorylation of ezrin, radixin, and moesin (ERM). Additionally, ezrin interacted with PKCα, and resistin promoted co-localization of ezrin and PKCα. Either inhibition of c-Src and PKCα or knock-down of ezrin blocked resistin-induced breast cancer cells invasion. Moreover, resistin increased expression of vimentin, a key molecule for cancer cell invasion. Knock-down of ezrin abrogated resistin-induced vimentin expression. These results suggest that resistin play as a critical regulator of breast cancer metastasis. PMID:26729407

  18. Novel adiponectin-resistin (AR) and insulin resistance (IRAR) indexes are useful integrated diagnostic biomarkers for insulin resistance, type 2 diabetes and metabolic syndrome: a case control study

    PubMed Central

    2011-01-01

    Background Adiponectin and resistin are adipokines which modulate insulin action, energy, glucose and lipid homeostasis. Meta-analyses showed that hypoadiponectinemia and hyperresistinemia are strongly associated with increased risk of insulin resistance, type 2 diabetes (T2DM), metabolic syndrome (MS) and cardiovascular disease. The aim of this study was to propose a novel adiponectin-resistin (AR) index by taking into account both adiponectin and resistin levels to povide a better indicator of the metabolic homeostasis and metabolic disorders. In addition, a novel insulin resistance (IRAR) index was proposed by integration of the AR index into an existing insulin resistance index to provide an improved diagnostic biomarker of insulin sensitivity. Methods In this case control study, anthropometric clinical and metabolic parameters including fasting serum total adiponectin and resistin levels were determined in 809 Malaysian men (208 controls, 174 MS without T2DM, 171 T2DM without MS, 256 T2DM with MS) whose ages ranged between 40-70 years old. Significant differences in continuous variables among subject groups were confirmed by ANCOVA or MANCOVA test using 1,000 stratified bootstrap samples with bias corrected and accelerated (BCa) 95% CI. Spearman's rho rank correlation test was used to test the correlation between two variables. Results The AR index was formulated as 1+log10(R0)-log10(A0). The AR index was more strongly associated with increased risk of T2DM and MS than hypoadiponectinemia and hyperresistinemia alone. The AR index was more strongly correlated with the insulin resistance indexes and key metabolic endpoints of T2DM and MS than adiponectin and resistin levels alone. The AR index was also correlated with a higher number of MS components than adiponectin and resistin levels alone. The IRAR index was formulated as log10(I0G0)+log10(I0G0)log10(R0/A0). The normal reference range of the IRAR index for insulin sensitive individuals was between 3.265 and

  19. Human resistin promotes neutrophil proinflammatory activation and neutrophil extracellular trap formation and increases severity of acute lung injury.

    PubMed

    Jiang, Shaoning; Park, Dae Won; Tadie, Jean-Marc; Gregoire, Murielle; Deshane, Jessy; Pittet, Jean Francois; Abraham, Edward; Zmijewski, Jaroslaw W

    2014-05-15

    Although resistin was recently found to modulate insulin resistance in preclinical models of type II diabetes and obesity, recent studies also suggested that resistin has proinflammatory properties. We examined whether the human-specific variant of resistin affects neutrophil activation and the severity of LPS-induced acute lung injury. Because human and mouse resistin have distinct patterns of tissue distribution, experiments were performed using humanized resistin mice that exclusively express human resistin (hRTN(+/-)(/-)) but are deficient in mouse resistin. Enhanced production of TNF-α or MIP-2 was found in LPS-treated hRtn(+/-/-) neutrophils compared with control Rtn(-/-/-) neutrophils. Expression of human resistin inhibited the activation of AMP-activated protein kinase, a major sensor and regulator of cellular bioenergetics that also is implicated in inhibiting inflammatory activity of neutrophils and macrophages. In addition to the ability of resistin to sensitize neutrophils to LPS stimulation, human resistin enhanced neutrophil extracellular trap formation. In LPS-induced acute lung injury, humanized resistin mice demonstrated enhanced production of proinflammatory cytokines, more severe pulmonary edema, increased neutrophil extracellular trap formation, and elevated concentration of the alarmins HMGB1 and histone 3 in the lungs. Our results suggest that human resistin may play an important contributory role in enhancing TLR4-induced inflammatory responses, and it may be a target for future therapies aimed at reducing the severity of acute lung injury and other inflammatory situations in which neutrophils play a major role. PMID:24719460

  20. Elevated resistin levels induce central leptin resistance and increased atherosclerotic progression in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Resistin was originally identified as an adipocyte-derived factor upregulated during obesity and as a contributor to obesity-associated insulin resistance. Clinically, resistin has also been implicated in cardiovascular disease in a number of different patient populations. Our aim was to simultaneou...

  1. Resistin Induces Hypertension and Insulin Resistance in Mice via a TLR4-Dependent Pathway

    PubMed Central

    Jiang, Yun; Lu, Linfang; Hu, Youtao; Li, Qiang; An, Chaoqiang; Yu, Xiaolan; Shu, Le; Chen, Ao; Niu, Congcong; Zhou, Lei; Yang, Zaiqing

    2016-01-01

    Resistin, an adipokine involved in insulin resistance (IR) and diabetes, has recently been reported to play a role in cardiovascular events. However, its effect on blood pressure (BP) and the underlying mechanisms remain unclear. In the present study, we showed that resistin induces hypertension and IR in wild type (WT) mice, but not in tlr4−/− mice. Resistin upregulated angiotensinogen (Agt) expression in WT mice, whereas it had no effect on tlr4−/− mice, or in mice treated with the angiotensin-converting enzyme inhibitor perindopril. Real-time PCR and chromatin immunoprecipitation further confirmed that resistin activates the renin-angiotensin system (RAS) via the TLR4/P65/Agt pathway. This finding suggested an essential role of resistin in linking IR and hypertension, which may offer a novel target in clinic on the study of the association between diabetes and hypertension. PMID:26917360

  2. Resistin Induces Hypertension and Insulin Resistance in Mice via a TLR4-Dependent Pathway.

    PubMed

    Jiang, Yun; Lu, Linfang; Hu, Youtao; Li, Qiang; An, Chaoqiang; Yu, Xiaolan; Shu, Le; Chen, Ao; Niu, Congcong; Zhou, Lei; Yang, Zaiqing

    2016-01-01

    Resistin, an adipokine involved in insulin resistance (IR) and diabetes, has recently been reported to play a role in cardiovascular events. However, its effect on blood pressure (BP) and the underlying mechanisms remain unclear. In the present study, we showed that resistin induces hypertension and IR in wild type (WT) mice, but not in tlr4(-/-) mice. Resistin upregulated angiotensinogen (Agt) expression in WT mice, whereas it had no effect on tlr4(-/-) mice, or in mice treated with the angiotensin-converting enzyme inhibitor perindopril. Real-time PCR and chromatin immunoprecipitation further confirmed that resistin activates the renin-angiotensin system (RAS) via the TLR4/P65/Agt pathway. This finding suggested an essential role of resistin in linking IR and hypertension, which may offer a novel target in clinic on the study of the association between diabetes and hypertension. PMID:26917360

  3. Resistin deficiency in mice has no effect on pulmonary responses induced by acute ozone exposure.

    PubMed

    Razvi, Shehla S; Richards, Jeremy B; Malik, Farhan; Cromar, Kevin R; Price, Roger E; Bell, Cynthia S; Weng, Tingting; Atkins, Constance L; Spencer, Chantal Y; Cockerill, Katherine J; Alexander, Amy L; Blackburn, Michael R; Alcorn, Joseph L; Haque, Ikram U; Johnston, Richard A

    2015-11-15

    Acute exposure to ozone (O3), an air pollutant, causes pulmonary inflammation, airway epithelial desquamation, and airway hyperresponsiveness (AHR). Pro-inflammatory cytokines-including IL-6 and ligands of chemokine (C-X-C motif) receptor 2 [keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-2], TNF receptor 1 and 2 (TNF), and type I IL-1 receptor (IL-1α and IL-1β)-promote these sequelae. Human resistin, a pleiotropic hormone and cytokine, induces expression of IL-1α, IL-1β, IL-6, IL-8 (the human ortholog of murine KC and MIP-2), and TNF. Functional differences exist between human and murine resistin; yet given the aforementioned observations, we hypothesized that murine resistin promotes O3-induced lung pathology by inducing expression of the same inflammatory cytokines as human resistin. Consequently, we examined indexes of O3-induced lung pathology in wild-type and resistin-deficient mice following acute exposure to either filtered room air or O3. In wild-type mice, O3 increased bronchoalveolar lavage fluid (BALF) resistin. Furthermore, O3 increased lung tissue or BALF IL-1α, IL-6, KC, TNF, macrophages, neutrophils, and epithelial cells in wild-type and resistin-deficient mice. With the exception of KC, which was significantly greater in resistin-deficient compared with wild-type mice, no genotype-related differences in the other indexes existed following O3 exposure. O3 caused AHR to acetyl-β-methylcholine chloride (methacholine) in wild-type and resistin-deficient mice. However, genotype-related differences in airway responsiveness to methacholine were nonexistent subsequent to O3 exposure. Taken together, these data demonstrate that murine resistin is increased in the lungs of wild-type mice following acute O3 exposure but does not promote O3-induced lung pathology. PMID:26386120

  4. Highly sensitive bovine serum albumin biosensor based on liquid crystal

    NASA Astrophysics Data System (ADS)

    Sharma, Vikash; Kumar, Ajay; Ganguly, Prasun; Biradar, A. M.

    2014-01-01

    A highly sensitive liquid crystal (LC) based bovine serum albumin (BSA) protein biosensor is designed. A uniform homeotropic alignment of nematic LC was observed in BSA free substrate which changed into homogeneous in presence of BSA. The change in the LC orientation is found to depend strongly on BSA concentration. This change in the LC alignment is attributed to the modification in the surface conditions which is verified by contact angle measurements. We have detected an ultra low concentration (0.5 μg/ml) of BSA. The present study demonstrates the utilization of LC in the realization of high sensitivity biosensors.

  5. Comparative Analysis of GCF Resistin Levels in Obese Subjects with and without Periodontal Disease

    PubMed Central

    Mahendra, Jaideep; Singh, Gurdeep; Pradeep, AR; Sundaravikram; Sekar, Himanshu

    2016-01-01

    Introduction Resistin is an adipocyte derived hormone that has been shown to play a substantial role in the development of insulin resistance. Resistin acts as a pro-inflammatory molecule and stimulates the synthesis and secretion of pro-inflammatory cytokines. Recent studies have reported the association of Gingival Crevicular Fluid (GCF) resistin levels with periodontal condition. Aim The aim of this study was to assess and compare the GCF resistin levels in obese subjects with periodontal health and disease and to correlate the disease severity with GCF resistin levels. Materials and Methods Ninety subjects of both the sexes with age between 20–45 years were selected for the study and were categorized into four groups: 25 obese or overweight subjects with generalized chronic periodontitis (Group-I), 25 obese or overweight subjects with healthy periodontium (Group-II), 25 non-obese subjects with generalized chronic periodontitis (Group-III) and 15 non obese subjects with healthy periodontium (Group-IV). The demographic variables like age, Body Mass Index (BMI), Waist Circumference (WC) were recorded and the clinical periodontal parameters such as Plaque Index (PI), Gingival Index (GI), and Clinical Attachment Level (CAL) were also assessed in all the groups. GCF was collected and assessed for resistin levels. Results The mean GCF resistin levels in Groups I, II, III & IV were 15.14, 9.06, 12.74 and 5.41 ng/dl respectively and the difference in mean GCF resistin level was statistically significant with the p-value<0.001. The mean GCF resistin levels in Group-I was higher compared to Group II and III and the differences in mean GCF resistin levels were statistically significant. GCF resistin levels were positively correlated with BMI, WC and CAL in Group I and CAL correlated with GCF resistin in Group III and this correlation was statistically significant. Conclusion From our study we report that obese subjects with periodontitis have more GCF resistin levels

  6. Sp1 mediates repression of the resistin gene by PPAR{gamma} agonists in 3T3-L1 adipocytes

    SciTech Connect

    Chung, S.S.; Choi, H.H.; Cho, Y.M.; Lee, H.K.; Park, K.S. . E-mail: kspark@snu.ac.kr

    2006-09-15

    Resistin is an adipokine related to obesity and insulin resistance. Expression of the resistin gene is repressed by the treatment of peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) agonists, thiazolidinediones (TZDs). In this study, we investigated the mechanism by which TZDs inhibit the resistin gene expression. Resistin gene expression was decreased by TZD in fully differentiated 3T3-L1 adipocytes, which was abolished after treatment of cycloheximide (a protein synthesis inhibitor). TZD could not repress the expression of the resistin gene in the presence of mithramycin A (an Sp1 binding inhibitor). Sp1 binding site of the resistin promoter (-122/-114 bp) was necessary for the repression. Further investigation of the effect of TZDs on the modification of Sp1 showed that the level of O-glycosylation of Sp1 was decreased in this process. These results suggest that PPAR{gamma} activation represses the expression of the resistin gene by modulating Sp1 activity.

  7. Effect of high fluoride and high fat on serum lipid levels and oxidative stress in rabbits.

    PubMed

    Sun, Liyan; Gao, Yanhui; Zhang, Wei; Liu, Hui; Sun, Dianjun

    2014-11-01

    The purpose of this study was to explore the effects of high fluoride and high fat on triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total antioxidant capacity (T-AOC), lipid peroxide (LPO) and malondialdehyde (MDA) in rabbits. A factorial experimental design was used, with two factors (fluoride and fat) and three levels. Seventy-two male rabbits were randomly assigned into nine groups according to initial weight and serum lipid levels. The rabbits were fed with basic feed, moderate fat feed or high fat feed and drank tap water, fluoridated water at levels of 50 and 100mgfluorion/L freely. Biological materials were collected after 5 months, and serum lipid, T-AOC, LPO, and MDA levels were then measured. Using these data, the separate and interactive effects of high fluoride and high fat were analyzed. High fluoride and high fat both increased serum levels of TC, HDL-C and LDL-C significantly (P<0.05), and there was also a synergistic effect between high fluoride and high fat (P<0.05). High fluoride and high fat had different effects on TG levels: high fat significantly increased TG levels (P<0.01) whereas high fluoride had nothing to do with TG levels (P>0.05). High fat significantly elevated LPO and MDA levels and lowered T-AOC levels in serum (P<0.05). Similarly, high fluoride significantly increased LPO and MDA levels in serum (P<0.05). However, there was no interactive effect between high fat and high fluoride on these indexes. In summary, high fluoride and high fat increased serum TC and LDL-C levels individually and synergistically, and this would cause and aggravate hypercholesterolemia in rabbits. At the same time, high fluoride and high fat both made the accumulation of product of oxidative stress in experimental animals. PMID:25461561

  8. Resistin impairs SIRT1 function and induces senescence-associated phenotype in hepatocytes.

    PubMed

    Yu, An; Zheng, Yu; Zhang, Rongrong; Huang, Jianfeng; Zhu, Zhoujie; Zhou, Ronghua; Jin, Dan; Yang, Zaiqing

    2013-09-01

    Resistin is a cysteine-rich secreted protein which significantly inhibits phosphorylation of AMP-activated protein kinase in both human and mouse hepatocytes. It has been demonstrated that resistin plays an important role in inducing hepatic insulin resistance. However, whether resistin has other unknown influences on hepatocytes still remains poorly studied. Here, we show that recombinant resistin protein significantly reduces expression of SIRT1, attenuates the interaction between SIRT1 and PPARα as well as PGC-1α, and increases PGC-1α acetyl-lysine levels in HepG2 cells. In line with this, resistin treatment weakens the association between SIRT1 and major satellite repeats and alters the transcription level of SIRT1 target genes in mouse primary hepatocytes. Resistin treatment also significantly increases senescence-associated β-galactosidase activity in mouse primary hepatocytes and this effect can be eliminated by co-treatment with the SIRT1 agonists resveratrol and nicotinamide mononucleotide. Our findings suggest that resistin is a negative regulator of SIRT1 in both human hepatoma cell line HepG2 and mouse hepatocytes and that it might also play an important role in the development of senescence-associated liver diseases. PMID:23827175

  9. N-3 Polyunsaturated fatty acid therapy improves endothelial function and affects adiponectin and resistin balance in the first month after myocardial infarction

    PubMed Central

    Mizia-Stec, Katarzyna; Haberka, Maciej; Mizia, Magdalena; Chmiel, Artur; Gieszczyk, Klaudia; Lasota, Bartosz; Janowska, Joanna; Zahorska-Markiewicz, Barbara; Gąsior, Zbigniew

    2011-01-01

    Introduction N-3 Polyunsaturated fatty acids (n-3 PUFA) exert clinical beneficial effects in patients after acute myocardial infarction (AMI). However, their exact mechanisms of action are not well recognized yet. Our aim was to evaluate effects of early introduced n-3 PUFA supplementation on endothelial function and serum adipokine concentrations in patients with AMI. Material and methods Thirty-eight patients with AMI and successful coronary stent implantation were randomized to the study group (PUFA group: n = 19; standard therapy + PUFA 1 g daily) and the control group (control group: n = 19; standard therapy). The study group patients were given n-3 PUFA (Omacor 1 g daily) starting from the 3rd day of AMI. Ultrasound vascular indexes (flow-mediated dilatation [FMD], nitroglycerine-mediated dilation [NMD]) and serum concentrations of adiponectin and resistin (ELISA) were evaluated before and after 30 days of pharmacotherapy. Results Comparison of the mean delta values (baseline/after 30 days of therapy) between groups revealed significant differences for delta FMD (PUFA 7.6 ±12.4% vs. control –1.7 ±10.5%, p = 0.019) and delta resistin concentrations (PUFA 1.0 ±3.8pg/ml vs. control –1.6 ±2.9pg/ml, p = 0.028). Multiple linear regression analysis for all subjects revealed the n-3 PUFA supplementation (r = 10.933, p = 0.004) and waist circumference (r = –0.467, p = 0.01) as independent factors associated with delta FMD values (R-adjusted 0.29; p = 0.002). Conclusions Early and short-term n-3 PUFA supplementation in AMI with successful primary PCI and optimal pharmacotherapy improves endothelial function. However, increased resistin serum levels observed after 1-month n-3 PUFA supplementation merits further investigations. PMID:22291823

  10. Effect of oncological treatment on serum adipocytokine levels in patients with stage II–III breast cancer

    PubMed Central

    COSKUN, TEOMAN; KOSOVA, FUNDA; ARI, ZEKI; SAKARYA, ASLAN; KAYA, YAVUZ

    2016-01-01

    Adipose tissue-derived hormones (adipocytokines), such as adiponectin, leptin, resistin and visfatin, and the pancreatic hormone insulin, have been suggested to play a role in carcinogenesis. we therefore hypothesized that the oncological treatment of breast cancer may alter the serum levels of these adipocytokines and insulin. In this study, we aimed to compare the serum levels of adipocytokines and insulin between the pre- and post-treatment period in patients with breast cancer. In this prospective study, 20 consecutive patients with stage II and III breast cancer underwent breast-conserving surgery or total mastectomy and/or axillary dissection. The patients received adjuvant chemotherapy and radiotherapy, if necessary. Blood samples were obtained during the preoperative period and postoperatively after completion of the adjuvant therapy. There was no statistically significant difference between the pre- and post-treatment levels of visfatin, adiponectin and leptin. However, the serum insulin and resistin levels and insulin resistance were found to be statistically significantly increased following treatment (P<0.05). Post-treatment resistin levels were positively correlated with insulin resistance (r=0.45, P<0.05). Therefore, oncological treatment of stage II and III breast cancer did not affect visfatin, adiponectin and leptin levels, but statistically significantly increased resistin levels and insulin resistance. In addition, the post-treatment resistin levels were positively correlated with insulin resistance, suggesting that resistin may be involved in the development of insulin resistance in breast cancer patients following treatment. PMID:27123303

  11. Effects of resistin on porcine ovarian follicle steroidogenesis in prepubertal animals: an in vitro study

    PubMed Central

    2013-01-01

    Background Resistin was first reported to be an adipocyte-specific hormone, but recent studies have indicated a connection between resistin and reproductive function. However, it is not yet known if resistin is expressed by the ovary and if it can affect steroidogenesis in ovarian follicles from prepubertal pigs. Methods In this study, using real time PCR, immunoblotting, and ELISA, we quantified resistin expression and concentration in maturing ovarian follicles (small, 3–4 mm; medium, 4–5 mm; large, 6–7 mm) collected from prepubertal pigs. In addition, the dose-responsive effects of recombinant human resistin (0.1, 1, 10, and 100 ng/ml) on steroid hormone (i.e., progesterone [P4], androstendione [A4], testosterone [T], and estradiol [E2]) secretion in culture medium and steroidogenic enzyme (i.e., CYP11A1, 3betaHSD, CYP17A1, 17betaHSD, and CYP19A1) expression in ovarian follicles were determined. Results We observed that resistin gene and protein expression increased significantly (P < 0.05) during follicular growth, with large follicles expressing the highest level of this adipokine. Recombinant resistin also increased P4, A4, and T secretion by up-regulating the steady state levels of CYP11A1, 3betaHSD, CYP17A1, and 17betaHSD. Recombinant resistin had no effects on E2 secretion and CYP19A1 expression in ovarian follicles. Conclusion Our results show resistin expression in ovarian follicles from prepubertal pigs for the first time. We also show that recombinant resistin stimulates steroidogenesis in ovarian follicles by increasing the expression of CYP11A1, 3betaHSD, CYP17A1, and 17betaHSD. The presence of resistin in the porcine ovary and its direct effects on steroidogenesis suggest that resistin is a new regulator of ovary function in prepubertal animals. PMID:23680257

  12. On-Statin Resistin, Leptin, and Risk of Recurrent Coronary Events After Hospitalization for an Acute Coronary Syndrome (from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Study).

    PubMed

    Khera, Amit V; Qamar, Arman; Murphy, Sabina A; Cannon, Christopher P; Sabatine, Marc S; Rader, Daniel J

    2015-09-01

    Resistin is an adipokine secreted by macrophages and inflammatory cells linked to insulin resistance and inflammation. Leptin is an adipokine regulator of appetite and obesity. Although circulating levels of both have been associated with atherosclerosis, few data have reported their relation to coronary events in the context of statin therapy. This study measured on-statin levels of both resistin and leptin through enzyme-linked immunosorbent assay in a nested case-control cohort (n = 176 cases with coronary death, myocardial infarction, or unstable angina pectoris observed in follow-up matched 1:1 to 176 controls) derived from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 study, a randomized controlled trial of atorvastatin 80 mg/day versus pravastatin 40 mg/day in patients with a recent acute coronary syndrome. Resistin demonstrated a moderate association with high-sensitivity C-reactive protein (hsCRP; Spearman rho = 0.25, p <0.0001). On-statin resistin levels were linked to recurrent coronary events in conditional logistic regression analysis adjusted for additional risk factors including hsCRP and history of diabetes (tertile 3 vs 1 adjusted odds ratio 2.08; 95% confidence interval [CI] 1.04 to 4.19). An additive risk was noted when patients were stratified by resistin and glycated hemoglobin levels. In contrast, leptin levels were associated with obesity, diabetes, triglycerides, and hsCRP (p <0.001 for each) but demonstrated no association with recurrent coronary events (tertile 3 vs 1 adjusted odds ratio 0.72; 95% CI 0.28 to 1.83). In conclusion, on-statin resistin, but not leptin, is an independent marker of residual risk for recurrent coronary events in patients after hospitalization for an acute coronary syndrome. PMID:26119654

  13. Resistin reinforces interferon λ-3 to eliminate hepatitis C virus with fine-tuning from RETN single-nucleotide polymorphisms

    PubMed Central

    Chang, Ming-Ling; Liang, Kung-Hao; Ku, Cheng-Lung; Lo, Chia-Chi; Cheng, Ya-Ting; Hsu, Chen-Ming; Yeh, Chau-Ting; Chiu, Cheng-Tang

    2016-01-01

    The effect of resistin (RETN) on the response to anti-HCV therapy remains unclear. A prospective cohort study was performed using 655 consecutive HCV patients, of whom 513 had completed a course of interferon-based therapy. Multivariate and GEE analyses revealed four RETN single-nucleotide polymorphisms (SNPs), rs34861192, rs3219175, rs3745367 and rs1423096, to be synergistically associated with resistin levels. After adjusting for co-factors such as interferon λ-3 (IFNL3)-rs12979860, the resistin level and the hyper-resistinemic genotype at the 4 RETN SNPs were positively and negatively associated with a sustained virological response (SVR), respectively. RETN-rs3745367 was in linkage disequilibrium with IFNL3-rs12979860. Compared to non-SVR patients, SVR patients had higher levels of pre-therapy resistin, primarily originating from intrahepatic lymphocytes, stellate cells, Kupffer cells, hepatic progenitor cells and hepatocytes. This difference diminished over the course of therapy, as only SVR patients exhibited a 24-week post-therapy decrease in resistin. Both resistin and IFNL3 mRNAs were upregulated, but only resistin mRNA was upregulated by recombinant resistin in peripheral blood mononuclear cells with and without hyper-resistinemic genotypes of the 4 RETN SNPs, respectively. Fine-tuned by RETN SNPs, intrahepatic, multi-cellular resistin reinforced IFNL3 in eliminating HCV via immunomodulation to counteract pro-inflammation. These results encourage the development of novel resistin-targeted anti-viral agents. PMID:27477870

  14. High Serum SHBG Predicts Incident Vertebral Fractures in Elderly Men

    PubMed Central

    Vandenput, Liesbeth; Mellström, Dan; Kindmark, Andreas; Johansson, Helena; Lorentzon, Mattias; Leung, Jason; Redlund‐Johnell, Inga; Rosengren, Björn E; Karlsson, Magnus K; Wang, Yi‐Xiang; Kwok, Timothy

    2016-01-01

    ABSTRACT Previous prospective cohort studies have shown that serum levels of sex steroids and sex hormone‐binding globulin (SHBG) associate with nonvertebral fracture risk in men. The predictive value of sex hormones and SHBG for vertebral fracture risk specifically is, however, less studied. Elderly men (aged ≥65 years) from Sweden and Hong Kong participating in the Osteoporotic Fractures in Men (MrOS) study had baseline estradiol and testosterone analyzed by gas chromatography–mass spectrometry (GC‐MS) and SHBG by immunoradiometric assay (IRMA). Incident clinical vertebral fractures (n = 242 cases) were evaluated in 4324 men during an average follow‐up of 9.1 years. In a subsample of these men (n = 2256), spine X‐rays were obtained at baseline and after an average follow‐up of 4.3 years to identify incident radiographic vertebral fractures (n = 157 cases). The likelihood of incident clinical and radiographic vertebral fractures was estimated by Cox proportional hazards models and logistic regression models, respectively. Neither serum estradiol (hazard ratio [HR] per SD increase = 0.93, 95% confidence interval [CI] 0.80–1.08) nor testosterone (1.05, 0.91–1.21) predicted incident clinical vertebral fractures in age‐adjusted models in the combined data set. High serum SHBG, however, associated with increased clinical vertebral fracture risk (1.24, 1.12–1.37). This association remained significant after further adjustment for FRAX with or without bone mineral density (BMD). SHBG also associated with increased incident radiographic vertebral fracture risk (combined data set; odds ratio [OR] per SD increase = 1.23, 95% CI 1.05–1.44). This association remained significant after adjustment for FRAX with or without BMD. In conclusion, high SHBG predicts incident clinical and radiographic vertebral fractures in elderly men and adds moderate information beyond FRAX with BMD for vertebral fracture risk prediction. © 2015 The

  15. Does high serum uric acid level cause aspirin resistance?

    PubMed

    Yildiz, Bekir S; Ozkan, Emel; Esin, Fatma; Alihanoglu, Yusuf I; Ozkan, Hayrettin; Bilgin, Murat; Kilic, Ismail D; Ergin, Ahmet; Kaftan, Havane A; Evrengul, Harun

    2016-06-01

    In patients with coronary artery disease (CAD), though aspirin inhibits platelet activation and reduces atherothrombotic complications, it does not always sufficiently inhibit platelet function, thereby causing a clinical situation known as aspirin resistance. As hyperuricemia activates platelet turnover, aspirin resistance may be specifically induced by increased serum uric acid (SUA) levels. In this study, we thus investigated the association between SUA level and aspirin resistance in patients with CAD. We analyzed 245 consecutive patients with stable angina pectoris (SAP) who in coronary angiography showed more than 50% occlusion in a major coronary artery. According to aspirin resistance, two groups were formed: the aspirin resistance group (Group 1) and the aspirin-sensitive group (Group 2). Compared with those of Group 2, patients with aspirin resistance exhibited significantly higher white blood cell counts, neutrophil counts, neutrophil-to-lymphocyte ratios, SUA levels, high-sensitivity C-reactive protein levels, and fasting blood glucose levels. After multivariate analysis, a high level of SUA emerged as an independent predictor of aspirin resistance. The receiver-operating characteristic analysis provided a cutoff value of 6.45 mg/dl for SUA to predict aspirin resistance with 79% sensitivity and 65% specificity. Hyperuricemia may cause aspirin resistance in patients with CAD and high SUA levels may indicate aspirin-resistant patients. Such levels should thus recommend avoiding heart attack and stroke by adjusting aspirin dosage. PMID:26656902

  16. High serum circulating telopeptide type I in multinodular goiter.

    PubMed

    Loviselli, A; Rizzolo, E; Mastinu, R; Velluzzi, F; Secci, G; Taberlet, A; Mariotti, S

    2003-06-01

    Recently, concentrations of serum carboxy-terminal-1-telopeptide (ICTP), a marker of bone collagen resorption, were found to be more sensitive than sex hormone-binding globulin (SHBG) in identifying peripheral overexposure to thyroid hormones in exogenous subclinical hyperthyroidism. The aim of the present study was to assess serum ICTP and SHBG in multinodular goiter with (pretoxic goiter) or without biochemical evidence of endogenous subclinical hyperthyroidism. Forty-five women affected by multinodular goiter were enrolled in this study. They were subdivided into two groups: group 1, consisting of 27 patients affected by pretoxic goiter; group 2, consisting of 18 patients affected by non toxic goiter; group 3, consisting of thirty-six euthyroid women matched with the other groups for age and lifestyle. In group 1, serum ICTP (mean +/- SD: 5.8 +/- 2.9 microg/l) concentrations were significantly higher when compared either to group 2 (3.6 +/- 1.2 microg/l; p < 0.02) or controls (2.7 +/- 0.7 microg/l; p < 0.0001); serum ICTP concentrations were also slightly but significantly higher in patients of group 2 compared to controls (p < 0.003). In contrast, mean serum SHBG concentrations did not show any difference among the three groups. No significant correlation was found between serum TSH and ICTP concentrations, while a weak positive correlation (p < 0.05) was only found between serum FT 3 and ICTP concentrations when data from the two patient groups were analyzed together. Moreover, when we subdivided patients into pre- and postmenopausal patients, we observed that SHBG but not ICTP serum concentrations were influenced by estrogenic status. In summary, the measurement of serum ICTP seems to be more suitable than SHBG for identifying those with a higher degree of peripheral thyroid hormone exposure in women affected by endogenous subclinical hyperthyroidism. PMID:12920662

  17. A high-capacity hydrophobic adsorbent for human serum albumin.

    PubMed

    Belew, M; Peterson, E A; Porath, J

    1985-12-01

    A simple method, based on salting out hydrophobic interaction chromatography, for the efficient removal of trace amounts of serum albumin from partially purified protein preparations is described. The method is also successfully applied for the purification of albumin from Cohn fraction IV, a by-product obtained from the commercial fractionation of human serum proteins by the ethanol precipitation procedure. About 70% of the adsorbed albumin can be eluted by buffer of low ionic strength and can thus be lyophilized directly, if required. The adsorbent can be used for several cycles of adsorption and desorption without affecting its selectivity or capacity. Its adsorption properties and capacity for serum albumin are compared with those of the commercially available adsorbent Blue Sepharose CL-6B. PMID:3879424

  18. 13C metabolic flux analysis shows that resistin impairs the metabolic response to insulin in L6E9 myotubes

    PubMed Central

    2014-01-01

    Background It has been suggested that the adipokine resistin links obesity and insulin resistance, although how resistin acts on muscle metabolism is controversial. We aimed to quantitatively analyse the effects of resistin on the glucose metabolic flux profile and on insulin response in L6E9 myotubes at the metabolic level using a tracer-based metabolomic approach and our in-house developed software, Isodyn. Results Resistin significantly increased glucose uptake and glycolysis, altering pyruvate utilisation by the cell. In the presence of resistin, insulin only slightly increased glucose uptake and glycolysis, and did not alter the flux profile around pyruvate induced by resistin. Resistin prevented the increase in gene expression in pyruvate dehydrogenase-E1 and the sharp decrease in gene expression in cytosolic phosphoenolpyruvate carboxykinase-1 induced by insulin. Conclusions These data suggest that resistin impairs the metabolic activation of insulin. This impairment cannot be explained by the activity of a single enzyme, but instead due to reorganisation of the whole metabolic flux distribution. PMID:25217974

  19. Cefaclor pharmacokinetic parameters: serum concentrations determined by a new high-performance liquid chromatographic technique.

    PubMed

    Rotschafer, J C; Crossley, K B; Lesar, T S; Zaske, D; Miller, K

    1982-01-01

    Pharmacokinetic parameters of cefaclor were studied in eight patients after an oral dose of 250 mg. Serum samples were obtained before and on 19 occasions after oral administration. Cefaclor serum concentrations were determined by a new high-performance liquid chromatographic technique. PMID:7081972

  20. High-Flux Hemodialysis and High-Volume Hemodiafiltration Improve Serum Calcification Propensity

    PubMed Central

    Dekker, Marijke; Pasch, Andreas; van der Sande, Frank; Konings, Constantijn; Bachtler, Matthias; Dionisi, Mauro; Meier, Matthias; Kooman, Jeroen; Canaud, Bernard

    2016-01-01

    Background Calciprotein particles (CPPs) may play an important role in the calcification process. The calcification propensity of serum (T50) is highly predictive of all-cause mortality in chronic kidney disease patients. Whether T50 is therapeutically improvable, by high-flux hemodialysis (HD) or hemodiafiltration (HDF), has not been studied yet. Methods We designed a cross-sectional single center study, and included stable prevalent in-center dialysis patients on HD or HDF. Patients were divided into two groups based on dialysis modality, were on a thrice-weekly schedule, had a dialysis vintage of > 3 months and vascular access providing a blood flow rate > 300 ml/min. Calcification propensity of serum was measured by the time of transformation from primary to secondary CPP (T50 test), by time-resolved nephelometry. Results We included 64 patients, mean convective volume was 21.7L (SD 3.3L). In the pooled analysis, T50 levels increased in both the HD and HDF group with pre- and post-dialysis (mean (SD)) of 244(64) - 301(57) and 253(55) - 304(61) min respectively (P = 0.43(HD vs. HDF)). The mean increase in T50 was 26.29% for HD and 21.97% for HDF patients (P = 0.61 (HD vs. HDF)). The delta values (Δ) of calcium, phosphate and serum albumin were equal in both groups. Baseline T50 was negatively correlated with phosphate, and positively correlated with serum magnesium and fetuin-A. The ΔT50 was mostly influenced by Δ phosphate (r = -0.342; P = 0.002 HD and r = -0.396; P<0.001 HDF) in both groups. Conclusions HD and HDF patients present with same baseline T50 calcification propensity values pre-dialysis. Calcification propensity is significantly improved during both HD and HDF sessions without significant differences between both modalities. PMID:27064679

  1. Association between Serum Interleukin-17A Level and High-Altitude Deacclimatization Syndrome

    PubMed Central

    He, Binfeng; Li, Hongli; Hu, Mingdong; Dong, Weijie; Wei, Zhenghua; Li, Jin; Yao, Wei; Guo, Xiaolan

    2016-01-01

    High-altitude deacclimatization syndrome (HADAS) is emerging as a severe public health issue that threatens the quality of life of individuals who return to lower altitude from high altitude. In this study, we measured serum levels of SOD, MDA, IL-17A, IL-10, TNF-α, and HADAS score in HADAS subjects at baseline and 50th and 100th days and to evaluate the relationship between interleukins, including IL-17A, and HADAS. Our data showed that and the serum IL-17A levels and HADAS score decreased over time in the HADAS group, and serum IL-17A levels were significantly higher in the HADAS group at baseline and 50th day compared with controls (p < 0.05). Furthermore, baseline serum levels of MDA and TNF-α were significantly higher, while SOD and IL-10 levels were lower in HADAS subjects compared with controls (p < 0.05). It is interesting that serum levels of IL-17A were clearly interrelated with HADAS incidence and severity (p < 0.05). ROC curve analysis showed that combined serum IL-17A and IL-10 levels were a better predictor of HADAS incidence than serum levels of IL-17A or IL-10 alone. These data suggest that serum levels of IL-17A are a novel predictive index of HADAS. PMID:27190491

  2. Neuropeptide B and W regulate leptin and resistin secretion, and stimulate lipolysis in isolated rat adipocytes.

    PubMed

    Skrzypski, Marek; Pruszyńska-Oszmałek, Ewa; Ruciński, Marcin; Szczepankiewicz, Dawid; Sassek, Maciej; Wojciechowicz, Tatiana; Kaczmarek, Przemysław; Kołodziejski, Paweł A; Strowski, Mathias Z; Malendowicz, Ludwik K; Nowak, Krzysztof W

    2012-06-10

    Neuropeptide B (NPB) and W (NPW) regulate food intake and energy homeostasis in humans via two G-protein-coupled receptor subtypes, termed as GPR7 and GPR8. Rodents express GPR7 only. In animals, NPW decreases insulin and leptin levels, whereas the deletion of either NPB or GPR7 leads to obesity and hyperphagia. Metabolic and endocrine in vitro activities of NPW/NPB in adipocytes are unknown. We therefore characterize the effects of NPB and NPW on the secretion and expression of leptin and resistin, and on lipolysis, using rat adipocytes. Isolated rat adipocytes express GPR7 mRNA. NPB and NPW are expressed in macrophages and preadipocytes but are absent in mature adipocytes. Both, NPB and NPW reduce the secretion and expression of leptin from isolated rat adipocytes. NPB stimulates the secretion and expression of resistin, whereas both, NPB and NPW increase lipolysis. Our study demonstrates for the first time that NPB and NPW regulate the expression and secretion of leptin and resistin, and increase lipolysis in isolated rat adipocytes. These effects are presumably mediated via GPR7. The increase of resistin secretion, stimulation of lipolysis and the decrease of leptin secretion may represent mechanisms, through which NPB and NPW can affect glucose and lipid homeostasis, and food intake in rodents. PMID:22484289

  3. High serum creatinine nonlinearity: a renal vital sign?

    PubMed

    Palant, Carlos E; Chawla, Lakhmir S; Faselis, Charles; Li, Ping; Pallone, Thomas L; Kimmel, Paul L; Amdur, Richard L

    2016-08-01

    Patients with chronic kidney disease (CKD) may have nonlinear serum creatinine concentration (SC) trajectories, especially as CKD progresses. Variability in SC is associated with renal failure and death. However, present methods for measuring SC variability are unsatisfactory because they blend information about SC slope and variance. We propose an improved method for defining and calculating a patient's SC slope and variance so that they are mathematically distinct, and we test these methods in a large sample of US veterans, examining the correlation of SC slope and SC nonlinearity (SCNL) and the association of SCNL with time to stage 4 CKD (CKD4) and death. We found a strong correlation between SCNL and rate of CKD progression, time to CKD4, and time to death, even in patients with normal renal function. We therefore argue that SCNL may be a measure of renal autoregulatory dysfunction that provides an early warning sign for CKD progression. PMID:27194712

  4. Identification of novel serum peptide biomarkers for high-altitude adaptation: a comparative approach.

    PubMed

    Yang, Juan; Li, Wenhua; Liu, Siyuan; Yuan, Dongya; Guo, Yijiao; Jia, Cheng; Song, Tusheng; Huang, Chen

    2016-01-01

    We aimed to identify serum biomarkers for screening individuals who could adapt to high-altitude hypoxia at sea level. HHA (high-altitude hypoxia acclimated; n = 48) and HHI (high-altitude hypoxia illness; n = 48) groups were distinguished at high altitude, routine blood tests were performed for both groups at high altitude and at sea level. Serum biomarkers were identified by comparing serum peptidome profiling between HHI and HHA groups collected at sea level. Routine blood tests revealed the concentration of hemoglobin and red blood cells were significantly higher in HHI than in HHA at high altitude. Serum peptidome profiling showed that ten significantly differentially expressed peaks between HHA and HHI at sea level. Three potential serum peptide peaks (m/z values: 1061.91, 1088.33, 4057.63) were further sequence identified as regions of the inter-α trypsin inhibitor heavy chain H4 fragment (ITIH4 347-356), regions of the inter-α trypsin inhibitor heavy chain H1 fragment (ITIH1 205-214), and isoform 1 of fibrinogen α chain precursor (FGA 588-624). Expression of their full proteins was also tested by ELISA in HHA and HHI samples collected at sea level. Our study provided a novel approach for identifying potential biomarkers for screening people at sea level who can adapt to high altitudes. PMID:27150491

  5. Identification of novel serum peptide biomarkers for high-altitude adaptation: a comparative approach

    NASA Astrophysics Data System (ADS)

    Yang, Juan; Li, Wenhua; Liu, Siyuan; Yuan, Dongya; Guo, Yijiao; Jia, Cheng; Song, Tusheng; Huang, Chen

    2016-05-01

    We aimed to identify serum biomarkers for screening individuals who could adapt to high-altitude hypoxia at sea level. HHA (high-altitude hypoxia acclimated; n = 48) and HHI (high-altitude hypoxia illness; n = 48) groups were distinguished at high altitude, routine blood tests were performed for both groups at high altitude and at sea level. Serum biomarkers were identified by comparing serum peptidome profiling between HHI and HHA groups collected at sea level. Routine blood tests revealed the concentration of hemoglobin and red blood cells were significantly higher in HHI than in HHA at high altitude. Serum peptidome profiling showed that ten significantly differentially expressed peaks between HHA and HHI at sea level. Three potential serum peptide peaks (m/z values: 1061.91, 1088.33, 4057.63) were further sequence identified as regions of the inter-α trypsin inhibitor heavy chain H4 fragment (ITIH4 347–356), regions of the inter-α trypsin inhibitor heavy chain H1 fragment (ITIH1 205–214), and isoform 1 of fibrinogen α chain precursor (FGA 588–624). Expression of their full proteins was also tested by ELISA in HHA and HHI samples collected at sea level. Our study provided a novel approach for identifying potential biomarkers for screening people at sea level who can adapt to high altitudes.

  6. Identification of novel serum peptide biomarkers for high-altitude adaptation: a comparative approach

    PubMed Central

    Yang, Juan; Li, Wenhua; Liu, Siyuan; Yuan, Dongya; Guo, Yijiao; Jia, Cheng; Song, Tusheng; Huang, Chen

    2016-01-01

    We aimed to identify serum biomarkers for screening individuals who could adapt to high-altitude hypoxia at sea level. HHA (high-altitude hypoxia acclimated; n = 48) and HHI (high-altitude hypoxia illness; n = 48) groups were distinguished at high altitude, routine blood tests were performed for both groups at high altitude and at sea level. Serum biomarkers were identified by comparing serum peptidome profiling between HHI and HHA groups collected at sea level. Routine blood tests revealed the concentration of hemoglobin and red blood cells were significantly higher in HHI than in HHA at high altitude. Serum peptidome profiling showed that ten significantly differentially expressed peaks between HHA and HHI at sea level. Three potential serum peptide peaks (m/z values: 1061.91, 1088.33, 4057.63) were further sequence identified as regions of the inter-α trypsin inhibitor heavy chain H4 fragment (ITIH4 347–356), regions of the inter-α trypsin inhibitor heavy chain H1 fragment (ITIH1 205–214), and isoform 1 of fibrinogen α chain precursor (FGA 588–624). Expression of their full proteins was also tested by ELISA in HHA and HHI samples collected at sea level. Our study provided a novel approach for identifying potential biomarkers for screening people at sea level who can adapt to high altitudes. PMID:27150491

  7. Sitagliptin decreases ventricular arrhythmias by attenuated glucose-dependent insulinotropic polypeptide (GIP)-dependent resistin signalling in infarcted rats.

    PubMed

    Lee, Tsung-Ming; Chen, Wei-Ting; Chang, Nen-Chung

    2016-01-01

    Myocardial infarction (MI) was associated with insulin resistance, in which resistin acts as a critical mediator. We aimed to determine whether sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, can attenuate arrhythmias by regulating resistin-dependent nerve growth factor (NGF) expression in postinfarcted rats. Normoglycaemic male Wistar rats after ligating coronary artery were randomized to either vehicle or sitagliptin for 4 weeks starting 24 h after operation. Post-infarction was associated with increased myocardial noradrenaline [norepinephrine (NE)] levels and sympathetic hyperinnervation. Compared with vehicle, sympathetic innervation was blunted after administering sitagliptin, as assessed by immunofluorescent analysis of tyrosine hydroxylase, growth-associated factor 43 and neurofilament and western blotting and real-time quantitative RT-PCR of NGF. Arrhythmic scores in the sitagliptin-treated infarcted rats were significantly lower than those in vehicle. Furthermore, sitagliptin was associated with reduced resistin expression and increased Akt activity. Ex vivo studies showed that glucose-dependent insulinotropic polypeptide (GIP) infusion, but not glucagon-like peptide-1 (GLP-1), produced similar reduction in resistin levels to sitagliptin in postinfarcted rats. Furthermore, the attenuated effects of sitagliptin on NGF levels can be reversed by wortmannin (a phosphatidylinositol 3-kinase antagonist) and exogenous resistin infusion. Sitagliptin protects ventricular arrhythmias by attenuating sympathetic innervation in the non-diabetic infarcted rats. Sitagliptin attenuated resistin expression via the GIP-dependent pathway, which inhibited sympathetic innervation through a signalling pathway involving phosphatidylinositol 3-kinase (PI3K) and Akt protein. PMID:26811539

  8. Sitagliptin decreases ventricular arrhythmias by attenuated glucose-dependent insulinotropic polypeptide (GIP)-dependent resistin signalling in infarcted rats

    PubMed Central

    Lee, Tsung-Ming; Chen, Wei-Ting; Chang, Nen-Chung

    2016-01-01

    Myocardial infarction (MI) was associated with insulin resistance, in which resistin acts as a critical mediator. We aimed to determine whether sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, can attenuate arrhythmias by regulating resistin-dependent nerve growth factor (NGF) expression in postinfarcted rats. Normoglycaemic male Wistar rats after ligating coronary artery were randomized to either vehicle or sitagliptin for 4 weeks starting 24 h after operation. Post-infarction was associated with increased myocardial noradrenaline [norepinephrine (NE)] levels and sympathetic hyperinnervation. Compared with vehicle, sympathetic innervation was blunted after administering sitagliptin, as assessed by immunofluorescent analysis of tyrosine hydroxylase, growth-associated factor 43 and neurofilament and western blotting and real-time quantitative RT-PCR of NGF. Arrhythmic scores in the sitagliptin-treated infarcted rats were significantly lower than those in vehicle. Furthermore, sitagliptin was associated with reduced resistin expression and increased Akt activity. Ex vivo studies showed that glucose-dependent insulinotropic polypeptide (GIP) infusion, but not glucagon-like peptide-1 (GLP-1), produced similar reduction in resistin levels to sitagliptin in postinfarcted rats. Furthermore, the attenuated effects of sitagliptin on NGF levels can be reversed by wortmannin (a phosphatidylinositol 3-kinase antagonist) and exogenous resistin infusion. Sitagliptin protects ventricular arrhythmias by attenuating sympathetic innervation in the non-diabetic infarcted rats. Sitagliptin attenuated resistin expression via the GIP-dependent pathway, which inhibited sympathetic innervation through a signalling pathway involving phosphatidylinositol 3-kinase (PI3K) and Akt protein. PMID:26811539

  9. Tea Dietary Fiber Improves Serum and Hepatic Lipid Profiles in Mice Fed a High Cholesterol Diet.

    PubMed

    Guo, Wenxin; Shu, Yang; Yang, Xiaoping

    2016-06-01

    Tea dietary fiber (TDF) was prepared from tea residues and modified to get cellulose-modified TDF (CTDF) by cellulase or micronized TDF (MTDF) by ultrafine grinding. The in vitro lipid-binding capacities of the three fibers and their effects on serum and hepatic lipid profiles in mice fed a high cholesterol diet were evaluated. The results showed that the three fibers had excellent lipid-binding capacities, and the cholesterol- and sodium cholate-binding capacities of CTDF and MTDF were significantly higher than those of TDF. Animal studies showed that, compared to model control, the three fibers significantly decreased mice average daily gain, gain: feed, and liver index, reduced total cholesterol (TC), triglyceride, and low density lipoprotein-cholesterol of serum and liver, increased serum and hepatic high density lipoprotein-cholesterol to TC ratio, and promoted the excretion of fecal lipids, and they also significantly increased the activities of superoxide dismutase and glutathione peroxidase of serum and liver, and decreased lipid peroxidation; moreover, the effects of CTDF and MTDF were better than that of TDF. It was concluded that the three fibers could improve serum and hepatic lipid profiles in mice fed a high cholesterol diet and the mechanism of action might be due to the promotion of fecal excretion of lipids through their lipid-binding ability and the inhibition of lipid peroxidation. These findings suggest that tea dietary fiber has the potential to be used as a functional ingredient to control cardiovascular disease. PMID:27040277

  10. Determination of myoglobin in human serum by high-performance liquid chromatography with chemiluminescence detection.

    PubMed

    Maltsev, V G; Zimina, T M; Khvatov, A B; Belenkii, B G

    1987-04-24

    A highly sensitive method for the determination of myoglobin in serum is described, based on high-performance size-exclusion chromatography with chemiluminescence detection. Serum proteins are separated according to their molecular masses on columns packed with TSK-SW gel and those containing haem are detected selectively by post-column chemiluminescence reaction with luminol using a conventional fluorimetric detector. The method is rapid (30 min) and sufficiently sensitive for the diagnosis of myocardial infarction. The minimum detectable myoglobin concentration is 10 ng/ml. PMID:3597641

  11. An evaluation of serum high density lipoproteins-phospholipids.

    PubMed

    Ide, H; Tsuji, M; Shimada, M; Kondo, T; Fujiya, S; Asanuma, Y; Agishi, Y

    1988-07-01

    Phospholipids in high density lipoproteins (HDL) is being used as a negative risk indicator of atherosclerosis. Phospholipids in HDL may not demonstrate the actual level of HDL-phospholipids when determined by the precipitation or ultracentrifugal methods, because HDL fractions contain very high density lipoproteins (VHDL) and albumin. In the present study, the true level of phospholipids in HDL was estimated using high performance liquid chromatography (HPLC), and it was compared with the level of phospholipids in HDL determined by the precipitation method. Sera from 18 healthy subjects were used as materials. In the HPLC method, the HDL fraction was extracted making sure that it contained no free albumin, which is albumin not bound to phospholipids. The HDL fraction was separated into subfractions. It was found that phospholipids in the VHDL fraction make a 20.2 +/- 7.3% (mean +/- S.D.) part of the total HDL-phospholipids. A large part of the VHDL fraction was constituted of albumin-bound phospholipids. A significant correlation was observed between HDL-phospholipids determined by the precipitation method, which contain albumin, and the actual HDL fraction phospholipids determined by HPLC, which do not contain VHDL (r = 0.903, p less than 0.01). These results suggest that HDL-phospholipids values determined by the precipitation method give useful clinical data. PMID:3176021

  12. Gastric Cancer with a Very High Serum CA 19-9 Level.

    PubMed

    Kato, Kazuya; Taniguchi, Masahiko; Kawakami, Takako; Nagase, Atsushi; Matsuda, Minoru; Onodea, Kazuhiko; Yamaguchi, Hidenori; Higuchi, Mineko; Furukawa, Hiroyuki

    2011-01-01

    Carbohydrate antigen 19-9 (CA 19-9) is a sensitive marker for pancreatic and hepatobiliary malignancies. The highest frequency of elevated serum CA 19-9 levels is found among patients with pancreatic cancer. CA 19-9 has recently been demonstrated to be a marker of digestive tract malignancies. We report the case of a patient with a gastric cancer and a very high serum CA 19-9 level. During laparotomy, a large mass was found in the antrum. A distal gastrectomy with D2 dissection of the lymph nodes was performed. Histological examination, including immunohistochemistry, revealed an adenocarcinoma of the stomach producing CA 19-9. To the best of our knowledge, no patient with an extremely high serum CA 19-9 level resulting from a gastric adenocarcinoma has been reported previously. PMID:21577374

  13. CHARACTERIZATION OF DRUG INTERACTIONS WITH SERUM PROTEINS BY USING HIGH-PERFORMANCE AFFINITY CHROMATOGRAPHY

    PubMed Central

    Hage, David S.; Anguizola, Jeanethe; Barnaby, Omar; Jackson, Abby; Yoo, Michelle J.; Papastavros, Efthimia; Pfaunmiller, Erika; Sobansky, Matt; Tong, Zenghan

    2011-01-01

    The binding of drugs with serum proteins can affect the activity, distribution, rate of excretion, and toxicity of pharmaceutical agents in the body. One tool that can be used to quickly analyze and characterize these interactions is high-performance affinity chromatography (HPAC). This review shows how HPAC can be used to study drug-protein binding and describes the various applications of this approach when examining drug interactions with serum proteins. Methods for determining binding constants, characterizing binding sites, examining drug-drug interactions, and studying drug-protein dissociation rates will be discussed. Applications that illustrate the use of HPAC with serum binding agents such as human serum albumin, α1-acid glycoprotein, and lipoproteins will be presented. Recent developments will also be examined, such as new methods for immobilizing serum proteins in HPAC columns, the utilization of HPAC as a tool in personalized medicine, and HPAC methods for the high-throughput screening and characterization of drug-protein binding. PMID:21395530

  14. Microfluidic system for high-throughput immunoglobulin-E analysis from clinical serum samples.

    PubMed

    Zheng, Lulu; Fu, Yongfeng; Jiang, Xiran; Man, Suqin; Ran, Wei; Feng, Meng; Liu, Sixiu; Cheng, Xunjia; Sui, Guodong

    2015-10-01

    Rapid and high-throughput analytical techniques for IgE that requires a small serum amount are very important, especially for pediatric patients. In these patients, blood is collected from veins, which is painful compared to fingertip blood collection. Herein, a novel microfluidic system capable of high-throughput parallel analyses of allergen-specific IgE from small amounts of patient serum was successfully developed. A six-plex immunoassay was constructed within a microfluidic chip, and the entire system was validated using samples from clinical patients. Major antigens from house dust mite (Dermatophagoides farinae and Blomia tropicalis), cat (Felis domesticus), fungus (Cladosporium herbarum), ragweed (Humulus japonicas), and tree pollen (Platanus acerifolia) were used as analysis targets. Sample consumption decreased to <0.05 µL compared with the 480µL serum consumption by fluoroenzyme immunoassay (UniCAP system Pharmacia Diagnostics AB, Uppsala, Sweden), the 50 µL serum consumption by enzyme-linked immune sorbent assay (ELISA), or the 1.5 µL serum consumption by conventional protein chip analysis. Analysis duration, reagent cost, and total cost for each measurement were also considerably decreased. The assay showed good accuracy and sensitivity toward the clinical samples. A significant correlation of allergen-specific IgE levels was found among the microfluidic assay, UniCAP system, and ELISA. PMID:26078132

  15. Ameliorative effects of boron on serum profile in buffalo (Bubalus bubalis) fed high fluoride ration.

    PubMed

    Bharti, Vijay K; Gupta, Meenakshi; Lall, D

    2008-02-01

    An experiment was undertaken to evaluate the protective role of boron on the serum profile of buffalo calves fed a high fluoride ration. Twelve male Murrah buffalo (Bubalus bubalis) calves of 6-8 months age, divided into three groups of four calves in each, were fed basal diets and supplemented with sodium fluoride (NaF, 60 ppm) alone or in combination with borax (Na2B4O7.10H2O, 140 ppm) for 90 days. Boron (B) was added in the ration as borax to make @140 ppm boron (elemental B) on DM basis in treatment II. Dietary F caused a significant (p<0.05) depressing effect on serum Ca and Zn on day 90 which was improved with B supplementation. However, serum Fe and Cu did not show any significant change on F or F+B supplementation. The serum ALP and phosphorus level were increased significantly (p<0.05) on F feeding but declined significantly (p<0.05) when B was fed. The findings suggested beneficial effect of boron on serum minerals and ALP in buffalo calves fed high fluoride ration. PMID:18422253

  16. Serum amyloid A changes high density lipoprotein's cellular affinity. A clue to serum amyloid A's principal function.

    PubMed

    Kisilevsky, R; Subrahmanyan, L

    1992-06-01

    The affinity of high density lipoproteins (HDL), or HDL carrying serum amyloid A (HDL/SAA), for hepatocytes or peritoneal macrophages was examined, as part of an investigation exploring the principal function of SAA and how this may be related to amyloidogenesis. The binding results in conjunction with SAA's existence primarily on HDL during inflammation, and HDL's known "reverse cholesterol transport" function suggest a clear role for SAA in the afferent arm of the reverse cholesterol transport pathway during the process of inflammation. The presence of SAA reduced HDL's affinity for normal hepatocytes by a factor of 2. In contrast, HDL/SAA had a 3- to 4-fold higher affinity for macrophages than HDL alone. Furthermore, the number of binding sites for HDL/SAA increased on macrophages during inflammation, while decreasing on hepatocytes. The net effect was a significant shift in HDL cholesterol carrying capacity towards the macrophage. Competition experiments demonstrated that HDL/SAA is only half as effective as HDL in inhibiting radiolabeled HDL binding to macrophages. This is in keeping with the reduced apolipoprotein A-1 content in HDL/SAA. Strikingly, although HDL contains twice as much apolipoprotein A-1 as HDL/SAA, it is only one-tenth as effective as HDL/SAA in inhibiting radiolabeled HDL/SAA binding to macrophages. The latter results suggest that there is a specific SAA binding site on macrophages. PMID:1602745

  17. Differential neutrophil responses to bacterial stimuli: Streptococcal strains are potent inducers of heparin-binding protein and resistin-release

    PubMed Central

    Snäll, Johanna; Linnér, Anna; Uhlmann, Julia; Siemens, Nikolai; Ibold, Heike; Janos, Marton; Linder, Adam; Kreikemeyer, Bernd; Herwald, Heiko; Johansson, Linda; Norrby-Teglund, Anna

    2016-01-01

    Neutrophils are critical for the control of bacterial infections, but they may also contribute to disease pathology. Here we explore neutrophil responses, in particular the release of sepsis-associated factors heparin-binding protein (HBP) and resistin in relation to specific bacterial stimuli and sepsis of varying aetiology. Analyses of HBP and resistin in plasma of septic patients revealed elevated levels as compared to non-infected critically ill patients. HBP and resistin correlated significantly in septic patients, with the strongest association seen in group A streptococcal (GAS) cases. In vitro stimulation of human neutrophils revealed that fixed streptococcal strains induced significantly higher release of HBP and resistin, as compared to Staphylococcus aureus or Escherichia coli. Similarly, neutrophils stimulated with the streptococcal M1-protein showed a significant increase in co-localization of HBP and resistin positive granules as well as exocytosis of these factors, as compared to LPS. Using a GAS strain deficient in M1-protein expression had negligible effect on neutrophil activation, while a strain deficient in the stand-alone regulator MsmR was significantly less stimulatory as compared to its wild type strain. Taken together, the findings suggest that the streptococcal activation of neutrophils is multifactorial and involves, but is not limited to, proteins encoded by the FCT-locus. PMID:26887258

  18. Heterogenetiy of glucocorticoid binders: a high affinity triamcinolone acetonide binder in bovine serum.

    PubMed

    Do, Y; Feldman, D

    1980-11-01

    While investigating glucocorticoid-binding proteins in bovine tissues, a new binder was found in fresh bovine serum which exhibited high affinity for certain synthetic glucocorticoids. This serum binder was characterized using [3H]triamcinolone acetonide (TA) as the ligand. On sucrose gradients, the [3H]TA peak sedimented at 8S, which was easily distinguishable from the [3H]cortisol-transcortin peak at 4S. Unlike the tissue receptor, which showed ionically dependent transformation from 8S in equilibrium or formed from 4S, the serum binder sedimented at 8S in both hypo- and hypertonic gradients. Binding properties were evaluated employing sephadex G-50 chromatography to separate bound from free steroid. Scatchard analysis of specific [3H]TA binding data revealed a straight line. The apparent equilibrium dissociation constant (Kd) was 7.8 +/- 0.7 X 10(-8) M, and the binding capacity was 772 +/- 70 fmol/mg serum protein. Hormonal specificity was determined by a competitive binding assay and revealed the following sequence: TA (100%) > betamethasone (47%) > triamcinolone (33%) > dexamethasone (2%) = cortisol = progesterone; aldosterone, estradiol, and testosterone exhibited negligible competitive activity. The serum binder was very stable, withstanding heating to 37 C for 60 min and long term storage in the frozen state. However, binding was significantly destroyed by trypsin. The binder was absent from fresh samples of chicken, mouse, rat, rabbit, dog, monkey, and human sera and frozen horse and porcine sera, but was clearly present in commercially available frozen calf, fetal calf, and lamb sera. At this time, we are unable to define the function of this binder, although its existence in both ovine and bovine sera suggests a possible role in ruminants. However, since bovine serum is routinely employed in tissue culture studies, the presence of this glucocorticoid binder might significantly influence many experiments. PMID:6775927

  19. HIGH SERUM PCBs ARE ASSOCIATED WITH ELEVATION OF SERUM LIPIDS AND CARDIOVASCULAR DISEASE IN A NATIVE AMERICAN POPULATION

    PubMed Central

    Goncharov, Alexey; Haase, Richard F.; Santiago-Rivera, Azara; Morse, Gayle; McCaffrey, Robert J.; Rej, Robert; Carpenter, David O.

    2008-01-01

    We have investigated the relationships among the concentration of total serum polychlorinated biphenyls (PCBs), various PCB congener groupings, and three pesticides to total serum lipids in humans with and without self-reported cardiovascular disease. Blood samples were obtained from 335 adult Akwesasne Mohawks, and were analyzed for 101 PCB congeners, mirex, DDE, and hexachlorobenzene (HCB), as well as serum triglycerides and cholesterol. Structural equation modeling, following the definition of latent variables by means of confirmatory factor analysis, was used to analyze the relationships between serum lipids with PCBs and heart disease. There were significant associations among PCBs, lipids, age, and body mass index (BMI), a fact which justified the application of the structural equation model. Gender of the participant was unrelated to any of the remaining study variables. The results of this study are consistent with a model in which age is considered as both an exogenous explanatory variable and a biological driving mechanism for the acquisition of PCBs. Moreover, the results of this study are consistent with the conclusion that PCBs, acting through P450 enzymes, are directly responsible for increased synthesis of cholesterol and triglycerides, substances known to be major risk factors for cardiovascular disease. PMID:18054906

  20. High-throughput assay for measuring monoclonal antibody self-association and aggregation in serum.

    PubMed

    Li, Xiaoning; Geng, Steven B; Chiu, Mark L; Saro, Dorina; Tessier, Peter M

    2015-03-18

    Subcutaneous delivery is one of the preferred administration routes for therapeutic monoclonal antibodies (mAbs). High antibody dosing requirements and small injection volumes necessitate formulation and delivery of highly concentrated mAb solutions. Such elevated antibody concentrations can lead to undesirable solution behaviors such as mAb self-association and aggregation, which are relatively straightforward to detect using various biophysical methods because of the high purity and concentration of antibody formulations. However, the biophysical properties of mAbs in serum can also impact antibody activity, but these properties are less well understood because of the difficulty characterizing mAbs in such a complex environment. Here we report a high-throughput assay for directly evaluating mAb self-association and aggregation in serum. Our approach involves immobilizing polyclonal antibodies specific for human mAbs on gold nanoparticles, and then using these conjugates to capture human antibodies at a range of subsaturating to saturating mAb concentrations in serum. Antibody aggregation is detected at subsaturating mAb concentrations via blue-shifted plasmon wavelengths due to the reduced efficiency of capturing mAb aggregates relative to monomers, which reduces affinity cross-capture of mAbs by multiple conjugates. In contrast, antibody self-association is detected at saturating mAb concentrations via red-shifted plasmon wavelengths due to attractive interparticle interactions between immobilized mAbs. The high-throughput nature of this assay along with its compatibility with unusually dilute mAb solutions (0.1-10 μg per mL) should make it useful for identifying antibody candidates with high serum stability during early antibody discovery. PMID:25714504

  1. Involvement of resistin-like molecule β in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice

    PubMed Central

    Okubo, Hirofumi; Kushiyama, Akifumi; Sakoda, Hideyuki; Nakatsu, Yusuke; Iizuka, Masaki; Taki, Naoyuki; Fujishiro, Midori; Fukushima, Toshiaki; Kamata, Hideaki; Nagamachi, Akiko; Inaba, Toshiya; Nishimura, Fusanori; Katagiri, Hideki; Asahara, Takashi; Yoshida, Yasuto; Chonan, Osamu; Encinas, Jeffery; Asano, Tomoichiro

    2016-01-01

    Resistin-like molecule β (RELMβ) reportedly has multiple functions including local immune responses in the gut. In this study, we investigated the possible contribution of RELMβ to non-alcoholic steatohepatitis (NASH) development. First, RELMβ knock-out (KO) mice were shown to be resistant to methionine-choline deficient (MCD) diet-induced NASH development. Since it was newly revealed that Kupffer cells in the liver express RELMβ and that RELMβ expression levels in the colon and the numbers of RELMβ-positive Kupffer cells were both increased in this model, we carried out further experiments using radiation chimeras between wild-type and RELMβ-KO mice to distinguish between the contributions of RELMβ in these two organs. These experiments revealed the requirement of RELMβ in both organs for full manifestation of NASH, while deletion of each one alone attenuated the development of NASH with reduced serum lipopolysaccharide (LPS) levels. The higher proportion of lactic acid bacteria in the gut microbiota of RELMβ-KO than in that of wild-type mice may be one of the mechanisms underlying the lower serum LPS level the former. These data suggest the contribution of increases in RELMβ in the gut and Kupffer cells to NASH development, raising the possibility of RELMβ being a novel therapeutic target for NASH. PMID:26818807

  2. Involvement of resistin-like molecule β in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice.

    PubMed

    Okubo, Hirofumi; Kushiyama, Akifumi; Sakoda, Hideyuki; Nakatsu, Yusuke; Iizuka, Masaki; Taki, Naoyuki; Fujishiro, Midori; Fukushima, Toshiaki; Kamata, Hideaki; Nagamachi, Akiko; Inaba, Toshiya; Nishimura, Fusanori; Katagiri, Hideki; Asahara, Takashi; Yoshida, Yasuto; Chonan, Osamu; Encinas, Jeffery; Asano, Tomoichiro

    2016-01-01

    Resistin-like molecule β (RELMβ) reportedly has multiple functions including local immune responses in the gut. In this study, we investigated the possible contribution of RELMβ to non-alcoholic steatohepatitis (NASH) development. First, RELMβ knock-out (KO) mice were shown to be resistant to methionine-choline deficient (MCD) diet-induced NASH development. Since it was newly revealed that Kupffer cells in the liver express RELMβ and that RELMβ expression levels in the colon and the numbers of RELMβ-positive Kupffer cells were both increased in this model, we carried out further experiments using radiation chimeras between wild-type and RELMβ-KO mice to distinguish between the contributions of RELMβ in these two organs. These experiments revealed the requirement of RELMβ in both organs for full manifestation of NASH, while deletion of each one alone attenuated the development of NASH with reduced serum lipopolysaccharide (LPS) levels. The higher proportion of lactic acid bacteria in the gut microbiota of RELMβ-KO than in that of wild-type mice may be one of the mechanisms underlying the lower serum LPS level the former. These data suggest the contribution of increases in RELMβ in the gut and Kupffer cells to NASH development, raising the possibility of RELMβ being a novel therapeutic target for NASH. PMID:26818807

  3. Proteomics tools reveal startlingly high amounts of oxytocin in plasma and serum.

    PubMed

    Brandtzaeg, Ole Kristian; Johnsen, Elin; Roberg-Larsen, Hanne; Seip, Knut Fredrik; MacLean, Evan L; Gesquiere, Laurence R; Leknes, Siri; Lundanes, Elsa; Wilson, Steven Ray

    2016-01-01

    The neuropeptide oxytocin (OT) is associated with a plethora of social behaviors, and is a key topic at the intersection of psychology and biology. However, tools for measuring OT are still not fully developed. We describe a robust nano liquid chromatography-mass spectrometry (nanoLC-MS) platform for measuring the total amount of OT in human plasma/serum. OT binds strongly to plasma proteins, but a reduction/alkylation (R/A) procedure breaks this bond, enabling ample detection of total OT. The method (R/A + robust nanoLC-MS) was used to determine total OT plasma/serum levels to startlingly high concentrations (high pg/mL-ng/mL). Similar results were obtained when combining R/A and ELISA. Compared to measuring free OT, measuring total OT can have advantages in e.g. biomarker studies. PMID:27528413

  4. Proteomics tools reveal startlingly high amounts of oxytocin in plasma and serum

    PubMed Central

    Brandtzaeg, Ole Kristian; Johnsen, Elin; Roberg-Larsen, Hanne; Seip, Knut Fredrik; MacLean, Evan L.; Gesquiere, Laurence R.; Leknes, Siri; Lundanes, Elsa; Wilson, Steven Ray

    2016-01-01

    The neuropeptide oxytocin (OT) is associated with a plethora of social behaviors, and is a key topic at the intersection of psychology and biology. However, tools for measuring OT are still not fully developed. We describe a robust nano liquid chromatography-mass spectrometry (nanoLC-MS) platform for measuring the total amount of OT in human plasma/serum. OT binds strongly to plasma proteins, but a reduction/alkylation (R/A) procedure breaks this bond, enabling ample detection of total OT. The method (R/A + robust nanoLC-MS) was used to determine total OT plasma/serum levels to startlingly high concentrations (high pg/mL-ng/mL). Similar results were obtained when combining R/A and ELISA. Compared to measuring free OT, measuring total OT can have advantages in e.g. biomarker studies. PMID:27528413

  5. High VEGF serum values are associated with locoregional spread of gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

    PubMed

    Cigrovski Berković, Maja; Čačev, Tamara; Catela Ivković, Tina; Marout, Jasminka; Ulamec, Monika; Zjačić-Rotkvić, Vanja; Kapitanović, Sanja

    2016-04-15

    Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are highly vascularized neoplasms, capable of synthethisizing VEGF-A, a key mediator of angiogenesis. In pancreatic neuroendocrine tumors (pNETs) VEGF expression is higher in benign and low-grade tumors and associated with good prognosis (neuroendocrine paradox) while the VEGF role in gastrointestinal NETs (GI-NETs) is still unclear. In this study, we examined the VEGF-1154A/G polymorphism in 145 GEP-NET patients and 150 controls. Next, we measured VEGF serum levels and VEGF tumor protein expression, comparing it with Ki67 and tumor grade. Patients' VEGF serum levels were compared with VEGF -1145A/G genotypes and metastatic status as well as with chromogranin A (CgA) and 5-hydroxyindolacetic acid (5-HIAA) in case of GI-NET patients. In this study GEP-NET patients had elevated VEGF serum values when compared to healthy controls (p = 0.0013). VEGF-1145G allele correlated with higher VEGF serum levels (p = 0.002). Patients with metastatic tumors had higher VEGF serum values when compared to patients without metastases (p = 0.033), and highest levels were observed in case of lymph node metastases (p = 0.008). VEGF-1145G allele was more frequent in non-functional GI-NET patients than in healthy controls (p = 0.041). CgA was superior to VEGF in tumor detection, while VEGF was superior to 5-HIAA. A correlation was observed between VEGF immunohistochemical staining and Ki-67 (p = 0.028). Tumours with weaker VEGF protein expression were more aggressive than tumours with stronger VEGF expression, confirming a "neuroendocrine paradox" in GI-NETs. Our results suggest the role of VEGF in GI-NETs locoregional spread. PMID:26805636

  6. High Serum Irisin Level as an Independent Predictor of Diabetes Mellitus

    PubMed Central

    Huh, Ji Hye; Ahn, Song Vogue; Choi, Jung Hye; Koh, Sang Baek; Chung, Choon Hee

    2016-01-01

    Abstract Irisin, a novel exercise-induced myokine, has been suggested to regulate energy homeostasis and insulin sensitivity. However, it remains unclear whether circulating irisin plays a role in the development of DM in human. We investigated the possible association between circulating irisin levels and incident DM in a 2.6-year longitudinal study of a population-based cohort comprised of rural Korean subjects. We conducted a longitudinal study within the Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population (KoGES-ARIRANG) study from November 2005 to January 2008. Cases (n=85) were patients with incident DM during the follow-up period and controls (n = 85) were matched to incident DM cases based on sex and age at baseline. The relative risk of serum irisin/adiponectin level for incident DM was analyzed using conditional logistic regression analysis. Baseline irisin_ENREF_1 levels were significantly higher in subjects who developed DM than in subjects who did not. The serum irisin level was positively associated with glycated hemoglobin (HbA1c) and postprandial glucose. Irisin was negatively associated with adiponectin (R = –0.189, P = 0.014). After adjustment for potential confounders, including body mass index, the odds ratios [95% confidence intervals] for incident DM increased in a graded manner as the serum irisin level increased (Quartile 1 vs Quartile 2 vs Quartile 3 vs Quartile 4 = 1 vs 0.80 [0.28–2.35] vs 3.33 [1.11–10.00] vs 4.10 [1.35–12.44], respectively), whereas the odds ratios for incident DM decreased in a graded manner as the serum adiponectin level increased. High serum irisin was independently associated with the development of DM, indicating that irisin may be a useful predictor of DM in Korean adults. PMID:27281072

  7. Leptin Production by Encapsulated Adipocytes Increases Brown Fat, Decreases Resistin, and Improves Glucose Intolerance in Obese Mice.

    PubMed

    DiSilvestro, David J; Melgar-Bermudez, Emiliano; Yasmeen, Rumana; Fadda, Paolo; Lee, L James; Kalyanasundaram, Anuradha; Gilor, Chen L; Ziouzenkova, Ouliana

    2016-01-01

    The neuroendocrine effects of leptin on metabolism hold promise to be translated into a complementary therapy to traditional insulin therapy for diabetes and obesity. However, injections of leptin can provoke inflammation. We tested the effects of leptin, produced in the physiological adipocyte location, on metabolism in mouse models of genetic and dietary obesity. We generated 3T3-L1 adipocytes constitutively secreting leptin and encapsulated them in a poly-L-lysine membrane, which protects the cells from immune rejection. Ob/ob mice (OB) were injected with capsules containing no cells (empty, OB[Emp]), adipocytes (OB[3T3]), or adipocytes overexpressing leptin (OB[Lep]) into both visceral fat depots. Leptin was found in the plasma of OB[Lep], but not OB[Emp] and OB[3T3] mice at the end of treatment (72 days). The OB[Lep] and OB[3T3] mice have transiently suppressed appetite and weight loss compared to OB[Emp]. Only OB[Lep] mice have greater brown fat mass, metabolic rate, and reduced resistin plasma levels compared to OB[Emp]. Glucose tolerance was markedly better in OB[Lep] vs. OB[Emp] and OB[3T3] mice as well as in wild type mice with high-fat diet-induced obesity and insulin resistance treated with encapsulated leptin-producing adipocytes. Our proof-of-principle study provides evidence of long-term improvement of glucose tolerance with encapsulated adipocytes producing leptin. PMID:27055280

  8. Leptin Production by Encapsulated Adipocytes Increases Brown Fat, Decreases Resistin, and Improves Glucose Intolerance in Obese Mice

    PubMed Central

    DiSilvestro, David J.; Melgar-Bermudez, Emiliano; Yasmeen, Rumana; Fadda, Paolo; Lee, L. James; Kalyanasundaram, Anuradha; Gilor, Chen L.; Ziouzenkova, Ouliana

    2016-01-01

    The neuroendocrine effects of leptin on metabolism hold promise to be translated into a complementary therapy to traditional insulin therapy for diabetes and obesity. However, injections of leptin can provoke inflammation. We tested the effects of leptin, produced in the physiological adipocyte location, on metabolism in mouse models of genetic and dietary obesity. We generated 3T3-L1 adipocytes constitutively secreting leptin and encapsulated them in a poly-L-lysine membrane, which protects the cells from immune rejection. Ob/ob mice (OB) were injected with capsules containing no cells (empty, OB[Emp]), adipocytes (OB[3T3]), or adipocytes overexpressing leptin (OB[Lep]) into both visceral fat depots. Leptin was found in the plasma of OB[Lep], but not OB[Emp] and OB[3T3] mice at the end of treatment (72 days). The OB[Lep] and OB[3T3] mice have transiently suppressed appetite and weight loss compared to OB[Emp]. Only OB[Lep] mice have greater brown fat mass, metabolic rate, and reduced resistin plasma levels compared to OB[Emp]. Glucose tolerance was markedly better in OB[Lep] vs. OB[Emp] and OB[3T3] mice as well as in wild type mice with high-fat diet-induced obesity and insulin resistance treated with encapsulated leptin-producing adipocytes. Our proof-of-principle study provides evidence of long-term improvement of glucose tolerance with encapsulated adipocytes producing leptin. PMID:27055280

  9. A biosensor of high-density lipoprotein of human serum on a liquid crystal and polymer composite film

    NASA Astrophysics Data System (ADS)

    Lin, Yi-Hsin; Chang, Kai-Han; Chu, Wei-Lin; Tsou, Yu-Shih; Wu, Li-Ching; Li, Chien-Feng

    2013-10-01

    A biosensor for the concentration of high-density lipoprotein (HDL) in human serum on a liquid crystal and polymer composite film (LCPCF) is demonstrated. The sensing mechanism is based on a polar-polar interaction between orientation of LC directors and HDL in human serum. The concentration of polar HDL in human serum affects the orientations of LC directors at the interface between LCPCF and the human serum. In addition, the surface free energy of LCPCF changes with the applied voltage due to the electrically tunable orientations of LC directors anchored among the polymer grains of LCPCF. As a result, the droplet motion of human serum on LCPCF under applied voltages can sense the concentration of HDL in human serum.

  10. Serum biomarker profile associated with high bone turnover and BMD in postmenopausal women.

    PubMed

    Bhattacharyya, Sudeepa; Siegel, Eric R; Achenbach, Sara J; Khosla, Sundeep; Suva, Larry J

    2008-07-01

    Early diagnosis of the onset of osteoporosis is key to the delivery of effective therapy. Biochemical markers of bone turnover provide a means of evaluating skeletal dynamics that complements static measurements of BMD by DXA. Conventional clinical measurements of bone turnover, primarily the estimation of collagen and its breakdown products in the blood or urine, lack both sensitivity and specificity as a reliable diagnostic tool. As a result, improved tests are needed to augment the use of BMD measurements as the principle diagnostic modality. In this study, the serum proteome of 58 postmenopausal women with high or low/normal bone turnover (training set) was analyzed by surface enhanced laser-desorption/ionization time-of-flight mass spectrometry, and a diagnostic fingerprint was identified using a variety of statistical and machine learning tools. The diagnostic fingerprint was validated in a separate distinct test set, consisting of serum samples from an additional 59 postmenopausal women obtained from the same Mayo cohort, with a gap of 2 yr. Specific protein peaks that discriminate between postmenopausal patients with high or low/normal bone turnover were identified and validated. Multiple supervised learning approaches were able to classify the level of bone turnover in the training set with 80% sensitivity and 100% specificity. In addition, the individual protein peaks were also significantly correlated with BMD measurements in these patients. Four of the major discriminatory peaks in the diagnostic profile were identified as fragments of interalpha-trypsin-inhibitor heavy chain H4 precursor (ITIH4), a plasma kallikrein-sensitive glycoprotein that is a component of the host response system. These data suggest that these serum protein fragments are the serum-borne reflection of the increased osteoclast activity, leading to the increased bone turnover that is associated with decreasing BMD and presumably an increased risk of fracture. In conjunction with the

  11. High concentrations of haptocorrin interfere with routine measurement of cobalamins in human serum and milk. A problem and its solution.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Human milk and occasional serum samples contain high concentrations of unsaturated haptocorrin (apoHC), which may influence measurement of cobalamins (Cbl). Methods: Cbl in serum samples spiked with increasing amounts of apoHC were measured employing the Centaur, Cobas and Architect anal...

  12. Serum testosterone levels and excessive erythrocytosis during the process of adaptation to high altitudes

    PubMed Central

    Gonzales, Gustavo F

    2013-01-01

    Populations living at high altitudes (HAs), particularly in the Peruvian Andes, are characterized by a mixture of subjects with erythrocytosis (16 g dl−121 g dl−1). Elevated haemoglobin values (EE) are associated with chronic mountain sickness, a condition reflecting the lack of adaptation to HA. According to current data, native men from regions of HA are not adequately adapted to live at such altitudes if they have elevated serum testosterone levels. This seems to be due to an increased conversion of dehydroepiandrosterone sulphate (DHEAS) to testosterone. Men with erythrocytosis at HAs show higher serum androstenedione levels and a lower testosterone/androstenedione ratio than men with EE, suggesting reduced 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activity. Lower 17beta-HSD activity via Δ4-steroid production in men with erythrocytosis at HA may protect against elevated serum testosterone levels, thus preventing EE. The higher conversion of DHEAS to testosterone in subjects with EE indicates increased 17beta-HSD activity via the Δ5-pathway. Currently, there are various situations in which people live (human biodiversity) with low or high haemoglobin levels at HA. Antiquity could be an important adaptation component for life at HA, and testosterone seems to participate in this process. PMID:23524530

  13. Immobilization of Bovine Serum Albumin Upon Multiwall Carbon Nanotube for High Speed Humidity Sensing Application.

    PubMed

    Bhattacharya, Sankhya; Sasmal, Milan

    2016-01-01

    We present a high-speed humidity sensor based on immobilization of bovine serum albumin upon multiwall carbon nanotube (IBC). A simple and versatile drop casting technique was employed to make the humidity sensor using novel material IBC at room temperature. IBC was synthesized using easy solution process technique. The working principle of the IBC humidity sensor depends upon the variation of output current or conductance with the exposure of different humidity level. Humidity sensing properties of our device is explained on the basis of charge transfer from water molecules to IBC and bovine serum albumin to multiwall carbon nanotube (MWCNT). Our sensor exhibits faster response time around 1.2 s and recovery time 1.5 s respectively. PMID:26841403

  14. Quantitative determination of fluoxetine in human serum by high performance thin layer chromatography.

    PubMed

    Mennickent, Sigrid; Fierro, Ricardo; Vega, Mario; De Diego, Marta; Godoy, C Gloria

    2010-07-01

    A high performance thin layer chromatographic method was developed and validated for the quantification of fluoxetine in human serum. Fluoxetine was extracted by liquid-liquid extraction method with diethyl ether as extraction solvent. Imipramine was used as internal standard. The chromatographic separation was achieved on precoated silica gel F 254 high performance thin layer chromatographic plates using a mixture of toluene/acetic acid glacial (4:5 v/v) as mobile phase. 4-Dimethylamino-azobenzene-4-sulphonyl chloride was used as derivatization reagent. Densitometric detection was done at 272 nm. The method was linear between 12.5 and 87.5 ng/spot, corresponding to 0.05 and 0.35 ng/microL of fluoxetine in human serum after extraction process and applying 25 microL to the chromatographic plates. The method correlation coefficient was 0.999. The intra-assay and inter-assay precisions, expressed as the RSD, were in the range of 0.70-2.01% (n=3) and 0.81-3.90% (n=9), respectively. The LOD was 0.23 ng, and the LOQ was 0.70 ng. The method proved be accurate, with a recovery between 94.75 and 98.95%, with a RSD not higher than 3.61% and was selective for the active principle tested. This method was successfully applied to quantify fluoxetine in patient serum samples. In conclusion, the method is useful for quantitative determination of fluoxetine in human serum. PMID:20533339

  15. Serum Vaspin Levels Are Associated with the Development of Clinically Manifest Arthritis in Autoantibody-Positive Individuals

    PubMed Central

    Maijer, Karen I.; Neumann, Elena; Müller-Ladner, Ulf; Drop, Daniël A. C. A. D.; Ramwadhdoebe, Tamara H.; Choi, Ivy Y. K.; Gerlag, Daniëlle M.; de Hair, Maria J. H.; Tak, Paul P.

    2015-01-01

    Objectives We have previously shown that overweight may increase the risk of developing rheumatoid arthritis (RA) in autoantibody positive individuals. Adipose tissue could contribute to the development of RA by production of various bioactive peptides. Therefore, we examined levels of adipokines in serum and synovial tissue of subjects at risk of RA. Methods Fifty-one individuals positive for immunoglobulin M rheumatoid factor (IgM-RF) and/or anti-citrullinated protein antibodies (ACPA), without arthritis, were included in this prospective study. Levels of adiponectin, vaspin, resistin, leptin, chemerin and omentin were determined in baseline fasting serum samples (n = 27). Synovial tissue was obtained by arthroscopy at baseline and we examined the expression of adiponectin, resistin and visfatin by immunohistochemistry. Results The development of clinically manifest arthritis after follow-up was associated with baseline serum vaspin levels (HR1.5 (95% CI 1.1 to 2.2); p = 0.020), also after adjustment for overweight (HR1.7 (95% CI 1.1 to 2.5); p = 0.016). This association was not seen for other adipokines. Various serum adipokine levels correlated with BMI (adiponectin r = -0.538, leptin r = 0.664; chemerin r = 0.529) and systemic markers of inflammation such as CRP levels at baseline (adiponectin r = -0.449, omentin r = -0.557, leptin r = 0.635, chemerin r = 0.619, resistin r = 0.520) and ESR (leptin r = 0.512, chemerin r = 0.708), p-value<0.05. Synovial expression of adiponectin, resistin and visfatin was not associated with development of clinically manifest arthritis. Conclusions In this exploratory study, serum adipokines were associated with an increased inflammatory state in autoantibody-positive individuals at risk of developing RA. Furthermore, serum vaspin levels may assist in predicting the development of arthritis in these individuals. PMID:26670468

  16. A highly sensitive colorimetric determination of serum zinc using water-soluble pyridylazo dye.

    PubMed

    Makino, T; Saito, M; Horiguchi, D; Kina, K

    1982-03-26

    A colorimetric method for precise and accurate determination of zinc in serum is presented. Only 0.3 ml of sample is necessary, because of the use of a new, highly sensitive reagent, 2-(5-bromo-2-pyridylazo)-5-(N-n-propyl-N-3-sulfopropylamino)-phenol (epsilon 554nm = 1.3 X 10(5) 1 . mol-1 . cm-1), which is water-soluble and has long-term stability. Interference of iron and copper in serum can be removed by co-precipitation of the iron fluoride complex with trichloroacetic acid precipitated proteins and the copper dithiocarboxy sarcosine complex, respectively. Within-run and day-to-day precision (CV) are in the range of 0.3-3.5% and 1.9-3.1%, respectively, depending on the serum zinc content. A good correlation (r = 0.98, p less than 0.05) was obtained between this method and atomic absorption spectrometry. In contrast to previous colorimetric methods, the present method does not involve heating, extraction with organic solvents, or a cyanide masking system. PMID:7067132

  17. TSLP Expression and High Serum TSLP Level Indicate a Poor Prognosis in Gastric Cancer Patients

    PubMed Central

    Watanabe, Joji; Saito, Hiroaki; Miyatani, Kozo; Ikeguchi, Masahide; Umekita, Yoshihisa

    2015-01-01

    Background Thymic stromal lymphopoietin (TSLP) plays an important role in promoting tumor survival, by manipulating the immune response and angiogenesis. However, the clinical significance of TSLP in gastric cancer is unclear. Methods Immunohistochemistry was used to investigate TSLP expression in non-cancerous gastric mucosa and gastric cancer tissue from patients with gastric cancer. Serum TSLP levels were measured using an enzyme-linked immunosorbent assay. Results Tumors with TSLP expression were significantly larger than those without TSLP expression. TSLP expression was observed more frequently in advanced (T2/T3/T4) than in early (T1) gastric cancer and in stage 3/4 than in stage 1/2. Lymph node metastasis, liver metastasis, positive peritoneal lavage cytology, lymphatic invasion, and vascular invasion occurred significantly more often in TSLP-expressing than in non-expressing tumors. The prognosis of patients with TSLP-positive tumors was significantly worse than that of patients with TSLP-negative tumors. Patients with high serum TSLP concentrations also had a significantly worse prognosis than those with low concentrations. Multivariate analysis identified serum TSLP level as an independent prognostic indicator. Conclusion TSLP is closely related to the progression of gastric cancer and may predict survival in these patients. PMID:26538800

  18. Serum Paraoxonase 1 Activity Is Associated with Fatty Acid Composition of High Density Lipoprotein

    PubMed Central

    Boshtam, Maryam; Pourfarzam, Morteza; Ani, Mohsen; Naderi, Gholam Ali; Basati, Gholam; Mansourian, Marjan; Dinani, Narges Jafari; Asgary, Seddigheh; Abdi, Soheila

    2013-01-01

    Introduction. Cardioprotective effect of high density lipoprotein (HDL) is, in part, dependent on its related enzyme, paraoxonase 1 (PON1). Fatty acid composition of HDL could affect its size and structure. On the other hand, PON1 activity is directly related to the structure of HDL. This study was designed to investigate the association between serum PON1 activity and fatty acid composition of HDL in healthy men. Methods. One hundred and forty healthy men participated in this research. HDL was separated by sequential ultracentrifugation, and its fatty acid composition was analyzed by gas chromatography. PON1 activity was measured spectrophotometrically using paraxon as substrate. Results. Serum PON1 activity was directly correlated with the amount of stearic acid and dihomo-gamma-linolenic acid (DGLA). PON1/HDL-C was directly correlated with the amount of miristic acid, stearic acid, and DGLA and was inversely correlated with total amount of ω6 fatty acids of HDL. Conclusion. The fatty acid composition of HDL could affect the activity of its associated enzyme, PON1. As dietary fats are the major determinants of serum lipids and lipoprotein composition, consuming some special dietary fatty acids may improve the activity of PON1 and thereby have beneficial effects on health. PMID:24167374

  19. Analysis of Lidocaine Interactions with Serum Proteins Using High-Performance Affinity Chromatography

    PubMed Central

    Soman, Sony; Yoo, Michelle J.; Jang, Yoon Jeong; Hage, David S.

    2010-01-01

    High-performance affinity chromatography was used to study binding by the drug lidocaine to human serum albumin (HSA) and α1–acid glycoprotein (AGP). AGP had strong binding to lidocaine, with an association equilibrium constant (Ka) of 1.1-1.7 × 105 M-1 at 37 °C and pH 7.4. Lidocaine had weak-to-moderate binding to HSA, with a Ka in the range of 103 to 104 M-1. Competitive experiments with site selective probes showed that lidocaine was interacting with Sudlow site II of HSA and the propranolol site of AGP. These results agree with previous observations in the literature and provide a better quantitative understanding of how lidocaine binds to these serum proteins and is transported in the circulation. This study also demonstrates how HPAC can be used to examine the binding of a drug with multiple serum proteins and provide detailed information on the interaction sites and equilibrium constants that are involved in such processes. PMID:20138813

  20. Resistin-Like Molecule-β in Scleroderma-Associated Pulmonary Hypertension

    PubMed Central

    Angelini, Daniel J.; Su, Qingning; Yamaji-Kegan, Kazuyo; Fan, Chunling; Teng, Xingwu; Hassoun, Paul M.; Yang, Stephen C.; Champion, Hunter C.; Tuder, Rubin M.; Johns, Roger A.

    2009-01-01

    Scleroderma is a systemic, mixed connective tissue disease that can impact the lungs through pulmonary fibrosis, vascular remodeling, and the development of pulmonary hypertension and right heart failure. Currently, little is known about the molecular mechanisms that drive this condition, but we have recently identified a novel gene product that is up-regulated in a murine model of hypoxia-induced pulmonary hypertension. This molecule, known as hypoxia-induced mitogenic factor (HIMF), is a member of the newly described resistin gene family. We have demonstrated that HIMF has mitogenic, angiogenic, vasoconstrictive, inflammatory, and chemokine-like properties, all of which are associated with vascular remodeling in the lung. Here, we demonstrate that the human homolog of HIMF, resistin-like molecule (RELM)-β, is expressed in the lung tissue of patients with scleroderma-associated pulmonary hypertension and is up-regulated compared with normal control subjects. Immunofluorescence colocalization revealed that RELM-β is expressed in the endothelium and vascular smooth muscle of remodeled vessels, as well as in plexiform lesions, macrophages, T cells, and myofibroblast-like cells. We also show that addition of recombinant RELM-β induces proliferation and activation of ERK1/2 in primary cultured human pulmonary endothelial and smooth muscle cells. These results suggest that RELM-β may be involved in the development of scleroderma-associated pulmonary hypertension. PMID:19251945

  1. Effects of serum amyloid A on the structure and antioxidant ability of high-density lipoprotein.

    PubMed

    Sato, Megumi; Ohkawa, Ryunosuke; Yoshimoto, Akira; Yano, Kouji; Ichimura, Naoya; Nishimori, Madoka; Okubo, Shigeo; Yatomi, Yutaka; Tozuka, Minoru

    2016-08-01

    Serum amyloid A (SAA) levels increase during acute and chronic inflammation and are mainly associated with high-density lipoprotein (HDL). In the present study, we investigated the effect of SAA on the composition, surface charge, particle size and antioxidant ability of HDL using recombinant human SAA (rhSAA) and HDL samples from patients with inflammation. We confirmed that rhSAA bound to HDL3 and released apolipoprotein A-I (apoA-I) from HDL without an apparent change in particle size. Forty-one patients were stratified into three groups based on serum SAA concentrations: Low (SAA ≤ 8 μg/ml), Middle (8 < SAA ≤ 100 μg/ml) and High (SAA > 100 μg/ml). The ratios of apoA-I to total protein mass, relative cholesterol content and negative charge of HDL samples obtained from patients with high SAA levels were lower than that for samples from patients with low SAA levels. Various particle sizes of HDL were observed in three groups regardless of serum SAA levels. Antioxidant ability of rhSAA, evaluated as the effect on the formation of conjugated diene in low-density lipoprotein (LDL) induced by oxidation using copper sulfate, was higher than that of apoA-I. Consistent with this result, reconstituted SAA-containing HDL (SAA-HDL) indicated higher antioxidant ability compared with normal HDL. Furthermore, HDL samples obtained from High SAA group patients also showed the highest antioxidant ability among the three groups. Consequently, SAA affects the composition and surface charge of HDL by displacement of apoA-I and enhances its antioxidant ability. PMID:27422844

  2. Effects of serum amyloid A on the structure and antioxidant ability of high-density lipoprotein

    PubMed Central

    Sato, Megumi; Ohkawa, Ryunosuke; Yoshimoto, Akira; Yano, Kouji; Ichimura, Naoya; Nishimori, Madoka; Okubo, Shigeo; Yatomi, Yutaka; Tozuka, Minoru

    2016-01-01

    Serum amyloid A (SAA) levels increase during acute and chronic inflammation and are mainly associated with high-density lipoprotein (HDL). In the present study, we investigated the effect of SAA on the composition, surface charge, particle size and antioxidant ability of HDL using recombinant human SAA (rhSAA) and HDL samples from patients with inflammation. We confirmed that rhSAA bound to HDL3 and released apolipoprotein A-I (apoA-I) from HDL without an apparent change in particle size. Forty-one patients were stratified into three groups based on serum SAA concentrations: Low (SAA ≤ 8 μg/ml), Middle (8 < SAA ≤ 100 μg/ml) and High (SAA > 100 μg/ml). The ratios of apoA-I to total protein mass, relative cholesterol content and negative charge of HDL samples obtained from patients with high SAA levels were lower than that for samples from patients with low SAA levels. Various particle sizes of HDL were observed in three groups regardless of serum SAA levels. Antioxidant ability of rhSAA, evaluated as the effect on the formation of conjugated diene in low-density lipoprotein (LDL) induced by oxidation using copper sulfate, was higher than that of apoA-I. Consistent with this result, reconstituted SAA-containing HDL (SAA-HDL) indicated higher antioxidant ability compared with normal HDL. Furthermore, HDL samples obtained from High SAA group patients also showed the highest antioxidant ability among the three groups. Consequently, SAA affects the composition and surface charge of HDL by displacement of apoA-I and enhances its antioxidant ability. PMID:27422844

  3. Primary colon cancer with a high serum PIVKA-II level

    PubMed Central

    Kato, Kazuya; Iwasaki, Yoshiaki; Taniguchi, Masahiko; Onodera, Kazuhiko; Matsuda, Minoru; Kawakami, Takako; Higuchi, Mineko; Kato, Kimitaka; Kato, Yurina; Furukawa, Hiroyuki

    2014-01-01

    Introduction Protein induced by vitamin K absence/antagonist-II (PIVKA-II) is an abnormal protein, and several reports have demonstrated the efficacy of PIVKA-II in the diagnosis of hepatocellular carcinoma (HCC). We report an extremely rare case of adenocarcinoma of the colon with a high serum PIVKA-II level. Presentation of Case A 95-year-old woman presented with right lower quadrant pain and appetite loss. An abdominal computed tomography scan and ultrasonography showed an ascending colon tumor and multiple metastatic tumors in the liver. The serum level of PIVKA-II was extremely high, 11,900 ng/mL. Colonoscopic examination revealed a tumor accompanied by an ulcer in the ascending colon, which was highly suspicious for malignancy. Multiple biopsies showed well-differentiated adenocarcinoma of the colon, which was evaluated as colon cancer, stage IV. PIVKA-II-productive colon cancer was confirmed. Chemotherapy with TS-1 was administered. The patient died 3 months after initial admission. Discussion The expression of PIVKA-II was detected in non-cancer areas, with non-specific expression observed in plasma cells in our case. There might be some possibility that hepatoid differentiation exists in other regions of the colon tumor or in the liver tumor, parenchymal cells or lung metastases, which were composed of PIVKA-II-positive and AFP-negative cells. Conclusion To the best of our knowledge, high serum levels of PIVKA-II resulting from colon adenocarcinoma have not been reported previously. We report this rare case together with a review of the literature. PMID:25528035

  4. Allelic variation in porcine resistin (RETN) gene is associated with fatness traits in a Wild Boar x Meishan reference family

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cloning and comparative sequencing of the porcine resistin (RETN) gene and 5’ flanking region, located at 64 cM on SSC2, revealed 9 SNPs and 2 indels. A European Wild Boar x Meishan family encompassing 335 F2 animals measured for 46 traits including growth, fat deposition and muscle accretion was sc...

  5. Approach to the evaluation of a patient with an increased serum osmolal gap and high-anion-gap metabolic acidosis.

    PubMed

    Kraut, Jeffrey A; Xing, Shelly Xiaolei

    2011-09-01

    An increase in serum osmolality and serum osmolal gap with or without high-anion-gap metabolic acidosis is an important clue to exposure to one of the toxic alcohols, which include methanol, ethylene glycol, diethylene glycol, propylene glycol, or isopropanol. However, the increase in serum osmolal gap and metabolic acidosis can occur either together or alone depending on several factors, including baseline serum osmolal gap, molecular weight of the alcohol, and stage of metabolism of the alcohol. In addition, other disorders, including diabetic or alcoholic ketoacidosis, acute kidney injury, chronic kidney disease, and lactic acidosis, can cause high-anion-gap metabolic acidosis associated with an increased serum osmolal gap and therefore should be explored in the differential diagnosis. It is essential for clinicians to understand the value and limitations of osmolal gap to assist in reaching the correct diagnosis and initiating appropriate treatment. In this teaching case, we present a systematic approach to diagnosing high serum osmolality and increased serum osmolal gap with or without high-anion-gap metabolic acidosis. PMID:21794966

  6. Gene Transfection in High Serum Levels: Case Studies with New Cholesterol Based Cationic Gemini Lipids

    PubMed Central

    Misra, Santosh K.; Biswas, Joydeep; Kondaiah, Paturu; Bhattacharya, Santanu

    2013-01-01

    Background Six new cationic gemini lipids based on cholesterol possessing different positional combinations of hydroxyethyl (-CH2CH2OH) and oligo-oxyethylene -(CH2CH2O)n- moieties were synthesized. For comparison the corresponding monomeric lipid was also prepared. Each new cationic lipid was found to form stable, clear suspensions in aqueous media. Methodology/Principal Findings To understand the nature of the individual lipid aggregates, we have studied the aggregation properties using transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential measurements and X-ray diffraction (XRD). We studied the lipid/DNA complex (lipoplex) formation and the release of the DNA from such lipoplexes using ethidium bromide. These gemini lipids in presence of a helper lipid, 1, 2-dioleoyl phophatidyl ethanol amine (DOPE) showed significant enhancements in the gene transfection compared to several commercially available transfection agents. Cholesterol based gemini having -CH2-CH2-OH groups at the head and one oxyethylene spacer was found to be the most effective lipid, which showed transfection activity even in presence of high serum levels (50%) greater than Effectene, one of the potent commercially available transfecting agents. Most of these geminis protected plasmid DNA remarkably against DNase I in serum, although the degree of stability was found to vary with their structural features. Conclusions/Significance -OH groups present on the cationic headgroups in combination with oxyethylene linkers on cholesterol based geminis, gave an optimized combination of new genera of gemini lipids possessing high transfection efficiency even in presence of very high percentage of serum. This property makes them preferential transfection reagents for possible in vivo studies. PMID:23861884

  7. Bilateral cataract and high serum ferritin: a new dominant genetic disorder?

    PubMed Central

    Bonneau, Dominique; Winter-Fuseau, Isabelle; Loiseau, Marie-Noëlle; Amati, Patrizia; Berthier, Michel; Oriot, Denis; Beaumont, Carole

    1995-01-01

    This paper reports the cosegregation in a three generation pedigree of dominantly inherited cataract with an abnormally high level of serum ferritin. In this family, circulating L ferritin was raised in all subjects affected by cataract independently of iron overload. We suggest that a disorder of ferritin metabolism could be a new genetic disorder leading to lens opacity. Cataract-hyperferritaemia syndrome could also be a new contiguous gene syndrome involving the L ferritin gene and the gene coding for the lens membrane protein (MP19), which both map to the same region of chromosome 19q. PMID:8558554

  8. Peritoneal Malignant Mesothelioma with Epithelioid Type, Demonstrating High Serum and Ascitic KL-6 Levels: Immunohistochemical Analyses

    PubMed Central

    Nahar, Saifun; Nakamoto, Manabu; Hokama, Akira; Kobashigawa, Chiharu; Kaida, Masatoshi; Kinjo, Tetsu; Hirata, Tetsuo; Kinjo, Nagisa; Saio, Masanao; Yoshimi, Naoki; Ohtsuki, Yuji; Fujita, Jiro

    2015-01-01

    We report a case of KL-6 producing peritoneal malignant mesothelioma. A 56-year-old woman was referred to our hospital on November 2005 with severe abdominal distention. Peritoneal malignant mesothelioma with epithelioid type was diagnosed by clinical symptoms, laboratory investigations, imaging studies, and immunohistochemical examination of known tumor markers. In addition, high serum and ascitic KL-6 levels were observed and the immunostaining of the tumor for KL-6 was evident. We thus consider KL-6 to be a potential novel marker for peritoneal malignant mesothelioma with epithelioid type. PMID:26500734

  9. Peritoneal Malignant Mesothelioma with Epithelioid Type, Demonstrating High Serum and Ascitic KL-6 Levels: Immunohistochemical Analyses.

    PubMed

    Nahar, Saifun; Nakamoto, Manabu; Hokama, Akira; Kobashigawa, Chiharu; Kaida, Masatoshi; Kinjo, Tetsu; Hirata, Tetsuo; Kinjo, Nagisa; Saio, Masanao; Yoshimi, Naoki; Ohtsuki, Yuji; Fujita, Jiro

    2015-09-01

    We report a case of KL-6 producing peritoneal malignant mesothelioma. A 56-year-old woman was referred to our hospital on November 2005 with severe abdominal distention. Peritoneal malignant mesothelioma with epithelioid type was diagnosed by clinical symptoms, laboratory investigations, imaging studies, and immunohistochemical examination of known tumor markers. In addition, high serum and ascitic KL-6 levels were observed and the immunostaining of the tumor for KL-6 was evident. We thus consider KL-6 to be a potential novel marker for peritoneal malignant mesothelioma with epithelioid type. PMID:26500734

  10. A case of hypocomplementaemic urticarial vasculitis with a high serum level of rheumatoid factor.

    PubMed

    Ashida, Atsuko; Murata, Hiroshi; Ohashi, Atsuko; Ogawa, Eisaku; Uhara, Hisashi; Okuyama, Ryuhei

    2013-08-01

    We report a case of hypocomplementaemic urticarial vasculitis with an elevated serum rheumatoid factor level. Hypocomplementaemic urticarial vasculitis is an immune complex-mediated disease characterised by urticarial eruptions. High levels of rheumatoid factor may be associated with hypocomplementaemia due to the consumption of complement, because the rheumatoid factor can form immune complexes with immunoglobulin. It is necessary to pay attention to the amounts of complement in cases of urticarial eruptions with elevated rheumatoid factor level. The eruptions were relieved with a combination of prednisolone and colchicine. PMID:23905981

  11. Running a Marathon Induces Changes in Adipokine Levels and in Markers of Cartilage Degradation – Novel Role for Resistin

    PubMed Central

    Vuolteenaho, Katriina; Leppänen, Tiina; Kekkonen, Riina; Korpela, Riitta; Moilanen, Eeva

    2014-01-01

    Running a marathon causes strenuous joint loading and increased energy expenditure. Adipokines regulate energy metabolism, but recent studies have indicated that they also exert a role in cartilage degradation in arthritis. Our aim was to investigate the effects of running a marathon on the levels of adipokines and indices of cartilage metabolism. Blood samples were obtained from 46 male marathoners before and after a marathon run. We measured levels of matrix metalloproteinase-3 (MMP-3), cartilage oligomeric protein (COMP) and chitinase 3-like protein 1 (YKL-40) as biomarkers of cartilage turnover and/or damage and plasma concentrations of adipokines adiponectin, leptin and resistin. Mean marathon time was 3∶30∶46±0∶02∶46 (h:min:sec). The exertion more than doubled MMP-3 levels and this change correlated negatively with the marathon time (r = –0.448, p = 0.002). YKL-40 levels increased by 56% and the effect on COMP release was variable. Running a marathon increased the levels of resistin and adiponectin, while leptin levels remained unchanged. The marathon-induced changes in resistin levels were positively associated with the changes in MMP-3 (r = 0.382, p = 0.009) and YKL-40 (r = 0.588, p<0.001) and the pre-marathon resistin levels correlated positively with the marathon induced change in YKL-40 (r = 0.386, p = 0.008). The present results show the impact of running a marathon, and possible load frequency, on cartilage metabolism: the faster the marathon was run, the greater was the increase in MMP-3 levels. Further, the results introduce pro-inflammatory adipocytokine resistin as a novel factor, which enhances during marathon race and associates with markers of cartilage degradation. PMID:25333960

  12. Body mass index, serum total cholesterol, and risk of gastric high-grade dysplasia

    PubMed Central

    Huang, Ya-Kai; Kang, Wei-Ming; Ma, Zhi-Qiang; Liu, Yu-Qin; Zhou, Li; Yu, Jian-Chun

    2016-01-01

    Abstract Obesity is related to an increased risk of gastric cardia cancer. However, the influences of excess body weight and serum total cholesterol on the risk of gastric high-grade dysplasia have not been fully characterized. A case–control study was conducted to explore the relationships between body mass index (BMI), serum total cholesterol level, and the risk of gastric high-grade dysplasia in Chinese adults. A total of 893 consecutive patients with gastric high-grade dysplasia (537 men and 356 women) and 902 controls (543 men and 359 women) were enrolled from January 2000 to October 2015. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated, and a multivariate analysis was conducted. After adjusting for age, alcohol consumption, smoking status, family history of gastric cancer or esophageal cancer, and serum total cholesterol level, a BMI ranging from 27.5 to 29.9 was significantly related to an increased risk of gastric high-grade dysplasia in both men (adjusted OR = 1.87, 95% CI = 1.24–2.81) and women (adjusted OR = 2.72, 95% CI = 1.44–5.16). The 2 highest BMI categories (27.5–29.9 and ≥30.0) were identified as risk factors for gastric cardia high-grade dysplasia in both men (BMI = 27.5–29.9: adjusted OR = 1.78, 95% CI = 1.02–3.10; BMI ≥ 30.0: adjusted OR = 2.54, 95% CI = 1.27–5.08) and women (BMI = 27.5–29.9: adjusted OR = 2.88, 95% CI = 1.27–6.55; BMI ≥ 30.0: adjusted OR = 2.77, 95% CI = 1.36–5.64), whereas only a BMI ranging from 27.5 to 29.9 was a risk factor for gastric noncardia high-grade dysplasia in both men (adjusted OR = 1.98, 95% CI = 1.25–3.14) and women (adjusted OR = 2.88, 95% CI = 1.43–5.81). In addition, higher serum total cholesterol was associated with an increased risk of gastric noncardia high-grade dysplasia (adjusted OR = 1.83, 95% CI = 1.25–2.69) in women. Increased BMI was associated with an increased risk

  13. Identification of a Proteinaceous Component in the Leaf of Moringa Oleifera lam. with Effects on High Serum Creatinine.

    PubMed

    Sahoo, S; Raghavendra, K M; Biswas, S

    2014-01-01

    Moringa oleifera Lam. has been an important plant in the history of mankind, both for its nutritional and medicinal uses. Apart from bactericidal effects, the parts of this plant have been effectively used in the treatment of circulatory, respiratory, endocrine, digestive as well as neural disorders. Till date, though, there has been no reported activity of the involvement of any proteinaceous extract from M. oleifera on high levels of serum creatinine. To address this issue, blood samples with high levels of serum creatinine (2 mg/dl and above) were treated with leaf extract from M. oleifera. The crude extract was partially purified initially and eventually purified to completion as well. All these proteinaceous fractions were used to treat samples with high levels of serum creatinine as mentioned above. While the treatment of serum sample having high creatinine with crude extract and partially purified protein fractions showed a decrease of approximately 20% in the levels of serum creatinine over a period of 24 h, the samples treated with purified protein fraction reduced the serum creatinine level by 50%. In light of the fact that increased level of serum creatinine levels have adverse downstream effects on the heart, lungs and other organs, this communication assumes significance because it suggests a way of reducing the level of serum creatinine as an emergency measure. Further, the identification and characterisation of this proteinaceous component and possible in vivo experiments would provide a major tool for the treatment of downstream complications associated with increased serum creatinine via a new sources, albeit a natural one. PMID:24799742

  14. Identification of a Proteinaceous Component in the Leaf of Moringa Oleifera lam. with Effects on High Serum Creatinine

    PubMed Central

    Sahoo, S.; Raghavendra, K. M.; Biswas, S.

    2014-01-01

    Moringa oleifera Lam. has been an important plant in the history of mankind, both for its nutritional and medicinal uses. Apart from bactericidal effects, the parts of this plant have been effectively used in the treatment of circulatory, respiratory, endocrine, digestive as well as neural disorders. Till date, though, there has been no reported activity of the involvement of any proteinaceous extract from M. oleifera on high levels of serum creatinine. To address this issue, blood samples with high levels of serum creatinine (2 mg/dl and above) were treated with leaf extract from M. oleifera. The crude extract was partially purified initially and eventually purified to completion as well. All these proteinaceous fractions were used to treat samples with high levels of serum creatinine as mentioned above. While the treatment of serum sample having high creatinine with crude extract and partially purified protein fractions showed a decrease of approximately 20% in the levels of serum creatinine over a period of 24 h, the samples treated with purified protein fraction reduced the serum creatinine level by 50%. In light of the fact that increased level of serum creatinine levels have adverse downstream effects on the heart, lungs and other organs, this communication assumes significance because it suggests a way of reducing the level of serum creatinine as an emergency measure. Further, the identification and characterisation of this proteinaceous component and possible in vivo experiments would provide a major tool for the treatment of downstream complications associated with increased serum creatinine via a new sources, albeit a natural one. PMID:24799742

  15. High-density lipoprotein inhibits ox-LDL-induced adipokine secretion by upregulating SR-BI expression and suppressing ER Stress pathway.

    PubMed

    Song, Guohua; Wu, Xia; Zhang, Pu; Yu, Yang; Yang, Mingfeng; Jiao, Peng; Wang, Ni; Song, Haiming; Wu, You; Zhang, Xiangjian; Liu, Huaxia; Qin, Shucun

    2016-01-01

    Endoplasmic reticulum stress (ERS) in adipocytes can modulate adipokines secretion. The aim of this study was to explore the protective effect of high-density lipoprotein (HDL) on oxidized low-density lipoprotein (ox-LDL)-induced ERS-C/EBP homologous protein (CHOP) pathway-mediated adipokine secretion. Our results showed that serum adipokines, including visfatin, resistin and TNF-α, correlated inversely with serum HDL cholesterol level in patients with abdominal obesity. In vitro, like ERS inhibitor 4-phenylbutyric acid (PBA), HDL inhibited ox-LDL- or tunicamycin (TM, an ERS inducer)-induced increase in visfatin and resistin secretion. Moreover, HDL inhibited ox-LDL-induced free cholesterol (FC) accumulation in whole cell lysate and in the endoplasmic reticulum. Additionally, like PBA, HDL inhibited ox-LDL- or TM-induced activation of ERS response as assessed by the decreased phosphorylation of protein kinase-like ER kinase and eukaryotic translation initiation factor 2α and reduced nuclear translocation of activating transcription factor 6 as well as the downregulation of Bip and CHOP. Furthermore, HDL increased scavenger receptor class B type I (SR-BI) expression and SR-BI siRNA treatment abolished the inhibitory effects of HDL on ox-LDL-induced FC accumulation and CHOP upregulation. These data indicate that HDL may suppress ox-LDL-induced FC accumulation in adipocytes through upregulation of SR-BI, subsequently preventing ox-LDL-induced ER stress-CHOP pathway-mediated adipocyte inflammation. PMID:27468698

  16. High-density lipoprotein inhibits ox-LDL-induced adipokine secretion by upregulating SR-BI expression and suppressing ER Stress pathway

    PubMed Central

    Song, Guohua; Wu, Xia; Zhang, Pu; Yu, Yang; Yang, Mingfeng; Jiao, Peng; Wang, Ni; Song, Haiming; Wu, You; Zhang, Xiangjian; Liu, Huaxia; Qin, Shucun

    2016-01-01

    Endoplasmic reticulum stress (ERS) in adipocytes can modulate adipokines secretion. The aim of this study was to explore the protective effect of high-density lipoprotein (HDL) on oxidized low-density lipoprotein (ox-LDL)-induced ERS-C/EBP homologous protein (CHOP) pathway-mediated adipokine secretion. Our results showed that serum adipokines, including visfatin, resistin and TNF-α, correlated inversely with serum HDL cholesterol level in patients with abdominal obesity. In vitro, like ERS inhibitor 4-phenylbutyric acid (PBA), HDL inhibited ox-LDL- or tunicamycin (TM, an ERS inducer)-induced increase in visfatin and resistin secretion. Moreover, HDL inhibited ox-LDL-induced free cholesterol (FC) accumulation in whole cell lysate and in the endoplasmic reticulum. Additionally, like PBA, HDL inhibited ox-LDL- or TM-induced activation of ERS response as assessed by the decreased phosphorylation of protein kinase-like ER kinase and eukaryotic translation initiation factor 2α and reduced nuclear translocation of activating transcription factor 6 as well as the downregulation of Bip and CHOP. Furthermore, HDL increased scavenger receptor class B type I (SR-BI) expression and SR-BI siRNA treatment abolished the inhibitory effects of HDL on ox-LDL-induced FC accumulation and CHOP upregulation. These data indicate that HDL may suppress ox-LDL-induced FC accumulation in adipocytes through upregulation of SR-BI, subsequently preventing ox-LDL-induced ER stress-CHOP pathway-mediated adipocyte inflammation. PMID:27468698

  17. Evaluation of Serum Homocysteine, High-Sensitivity CRP, and RBC Folate in Patients with Alopecia Areata

    PubMed Central

    Yousefi, Maryam; Namazi, Mohammad Reza; Rahimi, Hoda; Younespour, Shima; Ehsani, Amir Houshang; Shakoei, Safoura

    2014-01-01

    Introduction: Alopecia areata (AA) is a common type of hair loss with an autoimmune basis. As the role of homocysteine (Hcys), folate, and CRP has been considered in some autoimmune diseases. Objectives: To evaluate homocysteine, folate and CRP level in AA. Methods: This study was performed on 29 patients who had AA for at least 6 months affecting more than 20% of scalp, and 32 healthy controls. Levels of serum Hcys, blood high-sensitivity CRP, and RBC folate were measured in all subjects. Results: The mean level of RBC folate was significantly lower in the patient group than that in controls (P < 0.001). Also, the level of RBC folate was significantly lower in patients with extensive forms of disease (alopecia totalis/alopecia universalis) in comparison with more localized form (patchy hair loss) (P < 0.05). Patients with higher “Severity of Alopecia Total” (SALT) score had lower RBC folate, as well. Serum Hcys and blood high-sensitivity CRP levels did not show a significant difference in two groups. Conclusion: Patients with alopecia areata have lower level of RBC folate which is in negative correlation with both severity and extension of AA. PMID:25484412

  18. High resolution protein electrophoresis of 100 paired canine cerebrospinal fluid and serum.

    PubMed

    Behr, Sébastien; Trumel, Cathy; Cauzinille, Laurent; Palenché, Florence; Braun, Jean-Pierre

    2006-01-01

    This study was performed to investigate the diagnostic relevance of cerebrospinal fluid (CSF) high resolution electrophoresis. The laboratory technique was applied to 100 paired samples of canine CSF and serum, with paired samples tested during the same analytical run, as recommended in human medicine. Ninety four of the dogs had a neurological disease and 6 healthy dogs served as a control group. A strong linear correlation between CSF total protein concentration and the albumin quota (AQ) was found in the control group and in the inflammatory (infectious or noninfectious), neoplastic, and miscellaneous groups: AQ = 0.015 CSF total protein--0.102, r = 0.990. This correlation suggests that an increased CSF total protein concentration can be an indicator of blood brain barrier dysfunction. The highest median AQ value was found in the aseptic suppurative meningitis group, but no statistical differences were found between this and the other groups. The AQ, calculated with this technique, did not provide any additional information. Moreover, although unexpected, the electrophoretic profiles were not characteristic of any particular disease. In conclusion, this study did not confirm high resolution electrophoresis of paired CSF and serum samples to be a valuable ancillary diagnostic tool for canine neurological diseases. PMID:16734104

  19. High Serum IgG4 Concentrations in Patients with Hashimoto's Thyroiditis.

    PubMed

    Popławska-Kita, Anna; Kościuszko-Zdrodowska, Maria; Siewko, Katarzyna; Telejko, Beata; Hryniewicka, Justyna; Milewski, Robert; Abdelrazek, Saeid Soleman; Szelachowska, Małgorzata; Górska, Maria

    2015-01-01

    Purpose. Since recent reports suggest that Hashimoto thyroiditis (HT) may be associated with IgG4-related disease, we aimed to find out whether the measurement of serum IgG4 allows for the identification of distinct types of HT, with different clinical, sonographic, and serologic characteristics. Methods. The group studied consisted of 53 patients with HT and 28 healthy individuals who underwent thyroid ultrasonography and body composition analysis. Serum concentrations of IgG4, TSH, anti-peroxidase antibodies (TPOAb), anti-TSH receptor antibodies, TNF-α, TGF-β1, Fas Ligand, TRAIL, and chemokines (CXCL9, CXCL11, and CXCL10) were measured by ELISA or radioimmunoassay. Results. The group with IgG4 level >135 IU/ml accounted for 32.5% of the patients. The signs of fibrosis were present in 27.0% of the high-IgG4 patients and in 9.1% of the normal-IgG4 group. The patients with elevated IgG4 required higher doses of L-thyroxine and had significantly lower level of TPOAb (P=0.02) than the non-IgG4-HT individuals and higher TNF-α level in comparison with the controls (P=0.01). Conclusions. Our results suggest that the measurement of serum IgG4 allows for an identification of patients with more rapid progression of HT, requiring higher doses of L-thyroxine. Low TPOAb level and the absence of coexisting autoimmune diseases may suggest distinct pathomechanism of this type of thyroiditis. PMID:25784936

  20. Resistin gene variation is associated with systemic inflammation but not plasma adipokine levels, metabolic syndrome or coronary atherosclerosis in nondiabetic Caucasians

    PubMed Central

    Qasim, Atif N.; Metkus, Thomas S.; Tadesse, Mahlet; Lehrke, Michael; Restine, Stephanie; Wolfe, Megan L.; Hannenhalli, Sridhar; Cappola, Thomas; Rader, Daniel J.; Reilly, Muredach P.

    2011-01-01

    Summary Objective Resistin causes insulin resistance and diabetes in mice whereas in humans it is linked to inflammation and atherosclerosis. Few human genetic studies of resistin in inflammation and atherosclerosis have been performed. We hypothesized that the −420C>G putative gain-of-function resistin variant would be associated with inflammatory markers and atherosclerosis but not with metabolic syndrome or adipokines in humans. Design and methods We examined the association of three resistin polymorphisms, −852A>G, −420C>G and +157C>T, and related haplotypes with plasma resistin, cytokines, C-reactive protein (CRP), adipokines, plasma lipoproteins, metabolic syndrome and coronary artery calcification (CAC) in nondiabetic Caucasians (n = 851). Results Resistin levels were higher, dose-dependently, with the −420G allele (CC 5·9 ± 2·7 ng/ml, GC 6·5 ± 4·0 ng/ml and GG 7·2 ± 4·8 ng/ml, trend P = 0·04) after age and gender adjustment [fold higher for GC + GG vs. CC; 1·07 (1·00–1·15), P < 0·05)]. The −852A>G single nucleotide polymorphism (SNP) was associated with higher soluble tumour necrosis factor-receptor 2 (sol-TNFR2) levels in fully adjusted models [1·06 (95% CI 1·01–1·11), P = 0·01)]. The estimated resistin haplotype (GGT) was associated with sol-TNFR2 (P = 0·04) and the AGT haplotype was related to CRP (P = 0·04) in the fully adjusted models. Resistin SNPs and haplotypes were not associated with body mass index (BMI), fasting glucose, insulin resistance, metabolic syndrome, adipokines or CAC scores. Conclusions Despite modest associations with plasma resistin and inflammatory biomarkers, resistin 5′ variants were not associated with metabolic parameters or coronary calcification. This suggests that resistin is an inflammatory cytokine in humans but has little influence on adiposity, metabolic syndrome or atherosclerosis. PMID:18710472

  1. Lung tumor-associated dendritic cell-derived resistin promoted cancer progression by increasing Wolf-Hirschhorn syndrome candidate 1/Twist pathway.

    PubMed

    Kuo, Chih-Hsin; Chen, Kuei-Fang; Chou, Shah-Hwa; Huang, Ya-Fang; Wu, Cheng-Ying; Cheng, Da-En; Chen, Yu-Wen; Yang, Chih-Jen; Hung, Jen-Yu; Huang, Ming-Shyan

    2013-11-01

    The interaction between tumors and their microenvironments leads to a vicious cycle, which strengthens both immune suppression and cancer progression. The present study demonstrates for the first time that tumor-associated dendritic cells (TADCs) are a source of resistin, which is responsible for increasing lung cancer epithelial-to-mesenchymal transition. In addition, large amounts of resistin in the condition medium (CM) of TADCs increase cell migration and invasion, as well as the osteolytic bone metastatic properties of lung cancer cells. Neutralization of resistin from TADC-CM prevents the advanced malignancy-inducing features of TADC-CM. Significantly elevated levels of resistin have been observed in mice transplanted with lung cancer cells, tumor-infiltrating CD11c(+) DCs in human lung cancer samples and lung cancer patients' sera. Induction of lung cancer progression by TADC-derived resistin is associated with increased expression of Wolf-Hirschhorn syndrome candidate 1 (WHSC1), a histone methyltransferase. Resistin-induced WHSC1 increases the dimethylation of histone 3 at lysine 36 and decreases the trimethylation of histone 3 at lysine 27 on the promoter of Twist, resulting in an enhancement of the expression of Twist. Knockdown of WHSC1 by small interfering RNA transfection significantly decreases resistin-mediated cancer progression by decreasing the upregulation of Twist, suggesting that WHSC1 plays a critical role in the regulation of Twist by epigenetic modification. Furthermore, mice that received antiresistin antibodies showed a decreased incidence of cancer development and metastasis. These findings suggest that TADC-derived resistin may be a novel candidate in promoting the development of lung cancer. PMID:23955539

  2. The determination of inorganic sulphate in serum and synovial fluid by high performance ion chromatography.

    PubMed

    Kock, R; Schneider, H; Delvoux, B; Greiling, H

    1997-09-01

    A method for the determination of inorganic sulphate based on high performance ion chromatography is presented. The separation was performed on an anion-exchange column with a 1.8 mmol/l sodium carbonate/ 1.7 mmol/l sodium hydrogen carbonate-buffer, pH 10.35. Conductivity of the eluate was monitored after suppression of the background conductivity caused by the eluent-buffer. Serum and synovial fluid samples were prepared by ultrafiltration through membranes with a molecular mass cutoff of M(r) 10,000. The viscosity of the synovial fluids was reduced by treatment with hyaluronate lyase before ultrafiltration. The method showed a linear response for sulphate concentrations between 0.5 and 1000 mumol/l. The limit of detection was 1 mumol/l for aqueous standards. For serum the coefficient of variation within-run was 2.3%-2.4%, the coefficient of variation between days 2.9%-3.1%. For synovial fluids the coefficient of variation within-run was 3.1%-3.4%, the coefficient of variation between days 4.6%-5.7%. Standard recovery experiments performed by spiking pools of human sera containing low sulphate concentrations with sulphate concentrations between 5 mumol/l and 40 mumol/l showed recoveries between 98.9% and 100.6%. The corresponding experiments with pools of synovial fluids showed recoveries of 98.3% to 100.9%. As determined from 127 serum samples the reference range for sulphate was 262 mumol/l-420 mumol/l, with a mean value of 314 mumol/l. No dependence on age or sex was observed. The sulphate concentration in 36 synovial fluids from knees affected by inflammatory processes showed a mean value of 424 mumol/l and a standard deviation of 70 mumol/l. In 41 synovial fluids from knees affected by chronic degeneration joint disease, the sulphate concentrations were statistically significantly lower, with a mean of 374 mumol/l and a standard deviation of 58 mumol/l. The concentrations of sulphate in the synovial fluids were statistically significantly higher than those in

  3. Tuna extract reduces serum uric acid in gout-free subjects with insignificantly high serum uric acid: A randomized controlled trial

    PubMed Central

    Kubomura, Daiki; Yamada, Masanori; Masui, Ayano

    2016-01-01

    Long-term reduction of serum urate levels is vital in the treatment of gout. However, it is difficult to convince gout-free individuals of the necessity of treatment as few appropriate over-the-counter remedies and dietary supplements are available. Therefore, the present study aimed to investigate the antihyperuricemic efficacy and safety of a tuna extract containing the imidazole compounds to evaluate its potential as a functional food ingredient. A randomized, 4-week, double-blind, placebo-controlled study was conducted. A total of 48 male gout-free subjects with insignificantly high serum uric acid were randomly assigned to low- and high-dose tuna extract groups or a placebo group. The efficacy of the extract was assessed by measuring serum uric acid levels. Furthermore, a safety assessment was performed by physical parameters, hematology, blood biochemistry and urinalysis. The results indicated that the uric acid level was decreased at week 4 during the intervention in the tuna extract groups (low and high dose, −0.23 and −0.34 mg/dl, respectively) compared to the placebo group (−0.07 mg/dl). At week 4 after the intervention, a significant reduction in uric acid levels (−0.41 mg/dl; P<0.05) was observed in the high-dose tuna extract group compared with the placebo group (+0.11 mg/dl). No dose-related adverse events were observed during and following the intervention. Therefore, the present results suggest that oral administration of tuna extract containing the imidazole compounds has hypouricemic activity with no undesirable side effects. PMID:27446553

  4. Resistin, visfatin and insulin sensitivity in selected phases of annual training cycle of triathletes.

    PubMed

    Sliwicka, Ewa; Pilaczyńska-Szcześniak, L; Nowak, A; Zieliński, J

    2012-03-01

    The purpose of the study was to examine the effects of sport training on carbohydrate metabolic indices and adipokines concentrations in young male triathletes (n=10). Athletes performed the incremental running test in two periods of the training cycle: in the transitory and preparatory phases. In both analyzed terms, physical exercise was reflected by a significant increase in lactate (p≤0.01), insulin (p≤0.01), visfatin concentrations (p≤0.01, p<0.05, respectively) and only during transitory phase in glucose (p≤0.01) and resistin concentrations (p<0.05). Significant inter-period differences were noted in the pre-exercise insulin (p≤0.01) and also in pre- and post-exercise visfatin concentrations (p<0.05). Additionally, the differences (Δ) between post- and pre-exercise values of glucose (p<0.05) and visfatin (p≤0.01) significantly decreased in the preparatory phase comparing to the transitory phase. The inverse correlations between pre-exercise concentrations of visfatin and peak oxygen uptake (p<0.05) in the transitory phase and between post- and pre-exercise differences (Δ) of visfatin and lactate concentrations (p<0.05) in the preparatory phase were noted. During preparatory phase, pre-exercise visfatin concentrations inversely correlated with pre-exercise resistin, insulin and glucose levels (p<0.05). In conclusion, systematic training in elite triathletes modulates basal adipokine concentrations only to a small extent, however, influences on these molecules response on the acute exercise. PMID:22425808

  5. Serum Response Factor Protects Retinal Ganglion Cells Against High-Glucose Damage.

    PubMed

    Cao, Yan; Wang, Liang; Zhao, Junhong; Zhang, Hongbing; Tian, Ying; Liang, Houcheng; Ma, Qiang

    2016-06-01

    Serum response factor (SRF), which encodes the MADS-box family of related proteins, is a common transcription factor related to the expression of genes associated with cell survival. However, SRF's role in retinal ganglion cells (RGCs) after high-glucose injury remains unclear. In this study, we investigate the protective role of SRF after high-glucose injury and its underlying mechanism. The in vitro RGC model subjected to high glucose was established by employing a 50 mmol/L glucose culture environment. As detected by real-time quantitative PCR and Western blot, SRF was significantly upregulated in RGCs treated with high glucose. Overexpression of SRF significantly promoted survival among RGCs exposed to high glucose and inhibited RGC apoptosis. Knockdown of SRF exerted an inverse effect. Moreover, SRF upregulation enhanced expression of an antioxidant protein, nuclear factor erythroid 2-related factor (Nrf2), via control of the Fos-related antigen 1 (Fra-1). SRF upregulation also affected RGC survival after high-glucose treatment. Our findings showed that overexpression of SRF promoted survival of RGCs after high-glucose injury by regulating Fra-1 and Nrf2. PMID:26803311

  6. [Effects of high- and low-intensity training on cardiorespiratory system and serum lipids].

    PubMed

    Yanagibori, R; Aoki, K; Suzuki, Y; Gunji, A

    1991-08-01

    The differences between the effects of high- and low-intensity exercise training on cardiorespiratory system and serum lipid levels were examined under conditions in which the total work load was same. Twenty-two healthy, untrained female students, aged 18 to 24 years, participated in the 8-week training experiment. Two training groups exercised on bicycle ergometers 4-5d/wk for 8 wk with high-intensity (H: 70% VO2 max 13 min/session; N = 8) or in low-intensity (L: 36% VO2 max 33 min/session; N = 8). The control group (C: N = 6) continued its sedentary life style. Data of 6 students (H: N = 2, L: N = 2, C: N = 2) were excluded from the analysis, because they did not carry out their duties. The results of this study were as follows; 1) Aerobic capacity increased in both training groups. 2) After training, both heart rates and oxygen uptake during submaximal work loads significantly decreased in group H, but only heart rates significantly decreased in group L. 3) Heart rates with a same oxygen-uptake load during submaximal work seemed to increase in group H, but significantly decreased in group L. 4) The mechanical efficiency during the submaximal work load significantly increased in group H, but not in group L. 5) DBP and MBP during the submaximal work load in group L significantly decreased compared with those before the training. SBP with a same oxygen-uptake load during submaximal work increased in group H, but decreased in group L. 6) Rate pressure products both at rest and during submaximal exercise decreased significantly in group L. 7) Serum lipid levels remained in all groups. These results suggested that when the amount of exercise is the same, low-intensity exercise training with 35% VO2 max was more effective to increase endurance capacity and was safer than high-intensity exercise training. PMID:1956126

  7. High versus low vancomycin serum trough regimen for Gram-positive infections: a meta-analysis.

    PubMed

    Meng, Long; Fang, Yun; Chen, Yongfei; Zhu, Huaijun; Long, Rui

    2015-08-01

    This study aimed to evaluate the impact of high vancomycin serum trough concentrations (≧15 mg/l) on clinical outcomes and nephrotoxicity among adult subjects. We searched MEDLINE, Cochrane Library, and CNKI systematically. A total of 17 studies were included. Meta-analysis found that high trough group showed no significant difference comparing to low trough group in treatment failure [relative risk (RR) 0·91, 95% confidence interval (CI) 0·67-1·24; P = 0·57] and all-cause mortality (RR 1·14, 95% CI 0·81-1·59; P = 0·46). However, the high trough concentrations were associated with lower treatment failure in bacteremia subgroup (RR 0·72, 95% CI 0·59-0·88; P = 0·001). High trough concentrations were associated with an increased risk of vancomycin-induced nephrotoxicity (RR 2·06, 95% CI 1·52-2·79; P<0·00001). Our meta-analysis indicates that high trough concentrations were not significantly superior to low trough concentrations in lowering treatment failure and mortality. Moreover, high trough concentrations significantly increased the risk of nephrotoxicity. PMID:24641266

  8. Quantitative proteomic analysis for high-throughput screening of differential glycoproteins in hepatocellular carcinoma serum

    PubMed Central

    Gao, Hua-Jun; Chen, Ya-Jing; Zuo, Duo; Xiao, Ming-Ming; Li, Ying; Guo, Hua; Zhang, Ning; Chen, Rui-Bing

    2015-01-01

    Objective Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths. Novel serum biomarkers are required to increase the sensitivity and specificity of serum screening for early HCC diagnosis. This study employed a quantitative proteomic strategy to analyze the differential expression of serum glycoproteins between HCC and normal control serum samples. Methods Lectin affinity chromatography (LAC) was used to enrich glycoproteins from the serum samples. Quantitative mass spectrometric analysis combined with stable isotope dimethyl labeling and 2D liquid chromatography (LC) separations were performed to examine the differential levels of the detected proteins between HCC and control serum samples. Western blot was used to analyze the differential expression levels of the three serum proteins. Results A total of 2,280 protein groups were identified in the serum samples from HCC patients by using the 2D LC-MS/MS method. Up to 36 proteins were up-regulated in the HCC serum, whereas 19 proteins were down-regulated. Three differential glycoproteins, namely, fibrinogen gamma chain (FGG), FOS-like antigen 2 (FOSL2), and α-1,6-mannosylglycoprotein 6-β-N-acetylglucosaminyltransferase B (MGAT5B) were validated by Western blot. All these three proteins were up-regulated in the HCC serum samples. Conclusion A quantitative glycoproteomic method was established and proven useful to determine potential novel biomarkers for HCC. PMID:26487969

  9. Effects of moderate-dose versus high-dose trimethoprim on serum creatinine and creatinine clearance and adverse reactions.

    PubMed Central

    Naderer, O; Nafziger, A N; Bertino, J S

    1997-01-01

    The effects of a 10-day course of moderate-dose (10 mg/kg/day) or high-dose (20 mg/kg/day) trimethoprim therapy on serum creatinine, measured creatinine clearance, urinary creatinine excretion, and serum folate were studied in 20 healthy volunteers. Serum creatinine concentrations increased significantly during trimethoprim therapy, began to decrease near day 10, and returned to baseline during the washout phase at both dosage levels. At the same time, measured creatinine clearance and urine creatinine changed in the opposite direction. No clinical or statistical differences were noted between changes in the moderate- versus the high-dose phases. Serum folate concentration decreases during high-dose trimethoprim therapy were statistically significant. Adverse drug reactions in the two groups were statistically different during the first study period, with the high-dose group having a 75% incidence rate and the moderate-dose group having an 11% incidence rate (P < 0.02). Serum creatinine, measured creatinine clearance, and urinary creatinine excretion demonstrated statistically, but not clinically, significant changes during trimethoprim therapy. In addition, high-dose trimethoprim caused significantly more adverse drug reactions than moderate-dose trimethoprim in normal volunteers. PMID:9371351

  10. High frequency of low serum levels of vitamin 12 among patients attending Jordan University Hospital.

    PubMed

    Barghouti, F F; Younes, N A; Halaseh, L J; Said, T T; Ghraiz, S M

    2009-01-01

    This study aimed to estimate the status of serum vitamin B12 level in patients attending Jordan University Hospital in Amman, and to examine the relationship with demographic data, chronic illness, dietary habits, haematological parameters and symptoms related to vitamin B12 levels. A total of 838 patients completed a questionnaire and gave blood samples; 44.6% were vitamin B12 deficient (< 180 pg/mL) and 34.2% had hypovitaminosis (180-300 pg/mL). Vitamin B12 deficiency was associated with memory impairment, low meat intake and strict vegetarian (vegan) diets. The high frequency of low vitamin B12 warrants the development of a strategy to correct this problem in Jordan. PMID:20187536

  11. [Serial determinations of serum oxytocinase and ultrasonic biparietal cephalometry in normal and high-risk pregnancies].

    PubMed

    Mansani, F E; Serventi, G; Verrelli, D; Condemi, V; Ferrari, F

    1975-01-01

    The value of sonor biparietal cephalometry and serum oxytocinase that we have obtained with weekly simultaneous determinations in 14 females with normal pregnancy and in 5 with pathological pregnancy, from 24th to 39th week, show a statical positive relation. Serum oxitocinase determination against hormonal tests of the phetoplancental function (urinary oestriol, pregnandiol, serum HCS, ecc.) give advantages: it is the easyer, faster and less espandove determination. Therefore we think that it is helpful to determin togheter serial values of sonar biparietal cephalometry and serum oxytocinase to anticipate the endouterine fetal growth retardation. PMID:1212272

  12. Predictors of High Serum Casein Antibody Levels among Malnourished Infants and Young Children with Congenital Heart Disease

    PubMed Central

    El-Alameey, Inas R.; Ahmed, Hanaa H.; Monir, Zeinab M.; Rabah, Thanaa M.; Gawad, Ayman M. Abdel

    2015-01-01

    BACKGROUND: Factors predictive of growth retardation and malnutrition in patients with congenital heart disease remain unclear. OBJECTIVES: This study aimed to measure antibody response to bovine casein through assessing serum casein antibody levels in malnourished patients three year or younger with CHD, and to determine its relationship to gastrointestinal symptoms, anthropometric measures, and laboratory data. SUBJECTS AND METHODS: This cross sectional case control study was conducted in sixty patients with CHD aged 4 to 72 months. They were subdivided into thirty patients with cyanotic and thirty patients with acyanotic CHD compared with thirty apparently healthy children. RESULTS: On comparison with controls, patients showed highly significant lower anthropometric measures, calcium, iron, hemoglobin levels, and higher serum levels of casein antibody, total iron binding capacity, and alkaline phoshatase activity (P<0.000). Serum levels of casein antibody showed significantly positive correlations with serum total iron binding capacity and alkaline phosphatase activities and negatively correlated with the age at onset of symptoms, anthropometric measures, serum calcium, and iron levels. CONCLUSION: Serum casein antibody levels play a significant role in the pathogenesis of malnutrition. Encouragement of breast feeding and avoidance of early cow’s milk consumption could prevent the development of antibody response to bovine casein.

  13. Association of a high normalized protein catabolic rate and low serum albumin level with carpal tunnel syndrome in hemodialysis patients

    PubMed Central

    Huang, Wen-Hung; Hsu, Ching-Wei; Weng, Cheng-Hao; Yen, Tzung-Hai; Lin, Jui-Hsiang; Lee, Meng

    2016-01-01

    Abstract Carpal tunnel syndrome (CTS) is the most common mononeuropathy in patients with end-stage renal disease (ESRD). The association between chronic inflammation and CTS in hemodialysis (HD) patients has rarely been investigated. HD patients with a high normalized protein catabolic rate (nPCR) and low serum albumin level likely have adequate nutrition and inflammation. In this study, we assume that a low serum albumin level and high nPCR is associated with CTS in HD patients. We recruited 866 maintenance hemodialysis (MHD) patients and divided them into 4 groups according to their nPCR and serum albumin levels: (1) nPCR <1.2 g/kg/d and serum albumin level <4 g/dL; (2) nPCR ≥1.2 g/kg/d and serum albumin level <4 g/dL; (3) nPCR <1.2 g/kg/d and serum albumin level ≥4 g/dL; and (4) nPCR ≥1.2 g/kg/d and serum albumin level ≥4 g/dL. After adjustment for related variables, HD duration and nPCR ≥1.2 g/kg/d and serum albumin level <4 g/dL were positively correlated with CTS. By calculating the area under the receiver-operating characteristic curve, we calculated that the nPCR and HD duration cut-off points for obtaining the most favorable Youden index were 1.29 g/kg/d and 7.5 years, respectively. Advance multivariate logistic regression analysis revealed that in MHD patients, nPCR ≥1.29 g/kg/d and serum albumin <4 g/dL, and also HD duration >7.5 years were associated with CTS. A high nPCR and low serum albumin level, which likely reflect adequate nutrition and inflammation, were associated with CTS in MHD patients. PMID:27368039

  14. Association of a high normalized protein catabolic rate and low serum albumin level with carpal tunnel syndrome in hemodialysis patients.

    PubMed

    Huang, Wen-Hung; Hsu, Ching-Wei; Weng, Cheng-Hao; Yen, Tzung-Hai; Lin, Jui-Hsiang; Lee, Meng

    2016-06-01

    Carpal tunnel syndrome (CTS) is the most common mononeuropathy in patients with end-stage renal disease (ESRD). The association between chronic inflammation and CTS in hemodialysis (HD) patients has rarely been investigated. HD patients with a high normalized protein catabolic rate (nPCR) and low serum albumin level likely have adequate nutrition and inflammation. In this study, we assume that a low serum albumin level and high nPCR is associated with CTS in HD patients. We recruited 866 maintenance hemodialysis (MHD) patients and divided them into 4 groups according to their nPCR and serum albumin levels: (1) nPCR <1.2 g/kg/d and serum albumin level <4 g/dL; (2) nPCR ≥1.2 g/kg/d and serum albumin level <4 g/dL; (3) nPCR <1.2 g/kg/d and serum albumin level ≥4 g/dL; and (4) nPCR ≥1.2 g/kg/d and serum albumin level ≥4 g/dL. After adjustment for related variables, HD duration and nPCR ≥1.2 g/kg/d and serum albumin level <4 g/dL were positively correlated with CTS. By calculating the area under the receiver-operating characteristic curve, we calculated that the nPCR and HD duration cut-off points for obtaining the most favorable Youden index were 1.29 g/kg/d and 7.5 years, respectively. Advance multivariate logistic regression analysis revealed that in MHD patients, nPCR ≥1.29 g/kg/d and serum albumin <4 g/dL, and also HD duration >7.5 years were associated with CTS. A high nPCR and low serum albumin level, which likely reflect adequate nutrition and inflammation, were associated with CTS in MHD patients. PMID:27368039

  15. In Vitro Assessment of Serum-Saline Ratios for Fluid Simulator Testing of Highly Modular Spinal Implants With Articulating Surfaces

    PubMed Central

    Khandha, Ashutosh; Malcolmson, George; Timm, JP

    2008-01-01

    and lower bounds of predictive implant debris generation modeling, where saline represents a worst-case scenario and as little as 20% serum masks all weight loss completely in highly modular articulating implants. Clinical Relevance Clinical Relevance = 5 (Oxford Centre for Evidence-based Medicine Levels of Evidence). Study findings are limited to a greater understanding of the science associated with predictive wear testing of articulating spinal implants. PMID:25802619

  16. Development of Gel-Filter Method for High Enrichment of Low-Molecular Weight Proteins from Serum

    PubMed Central

    Chen, Lingsheng; Zhai, Linhui; Li, Yanchang; Li, Ning; Zhang, Chengpu; Ping, Lingyan; Chang, Lei; Wu, Junzhu; Li, Xiangping; Shi, Deshun; Xu, Ping

    2015-01-01

    The human serum proteome has been extensively screened for biomarkers. However, the large dynamic range of protein concentrations in serum and the presence of highly abundant and large molecular weight proteins, make identification and detection changes in the amount of low-molecular weight proteins (LMW, molecular weight ≤ 30kDa) difficult. Here, we developed a gel-filter method including four layers of different concentration of tricine SDS-PAGE-based gels to block high-molecular weight proteins and enrich LMW proteins. By utilizing this method, we identified 1,576 proteins (n = 2) from 10 μL serum. Among them, 559 (n = 2) proteins belonged to LMW proteins. Furthermore, this gel-filter method could identify 67.4% and 39.8% more LMW proteins than that in representative methods of glycine SDS-PAGE and optimized-DS, respectively. By utilizing SILAC-AQUA approach with labeled recombinant protein as internal standard, the recovery rate for GST spiked in serum during the treatment of gel-filter, optimized-DS, and ProteoMiner was 33.1 ± 0.01%, 18.7 ± 0.01% and 9.6 ± 0.03%, respectively. These results demonstrate that the gel-filter method offers a rapid, highly reproducible and efficient approach for screening biomarkers from serum through proteomic analyses. PMID:25723528

  17. Endurance exercise alters cellular immune status and resistin concentrations in men suffering from non-insulin-dependent type 2 diabetes.

    PubMed

    Wenning, P; Kreutz, T; Schmidt, A; Opitz, D; Graf, C; Voss, S; Bloch, W; Brixius, K

    2013-08-01

    It has been demonstrated that alterations of adipocytokines can alter immune status in type 2 diabetes. The present study investigated changes of adipocytokine plasma concentrations and cellular immune status in overweight men, suffering from non-insulin dependent type 2 diabetes (n=14, age 61.0±8.7 years, BMI 31.1±3.5 kg/cm2). Subjects underwent a 3 months endurance exercise intervention (twice per week for up to 45 min) cycling at a heart rate corresponding to a 2 mmol/l lactate threshold. Before and after the intervention testing for adipocytokines (leptin, adiponectin, resistin) and cellular immune status (including T memory-cells and regulative T-cells) was performed by RIA and FACS accordingly.The exercise intervention improved anthropometric and metabolic parameters of all subjects. We observed a significant decline for resistin and for the CD19+ B-cells. The CD4+CD25+CD127low Treg-cells decreased, however not statistically significant. All other parameters remained unchanged.In conclusion, even though only training twice a week, the exercise affected parts of the cellular immune system as well as resistin levels in men suffering from non-insulin dependent type 2 diabetes. PMID:24026829

  18. Resistin-induced stromal cell-derived factor-1 expression through Toll-like receptor 4 and activation of p38 MAPK/ NFκB signaling pathway in gastric cancer cells

    PubMed Central

    2014-01-01

    Background Stromal cell-derived factor-1 (SDF-1) (CXC chemokine ligand-12)/CXC chemokine receptor 4 (CXCR4) is involved in the carcinogenesis of human gastric cancer, where it stimulates angiogenesis and favors metastasis of tumor cells to distant organs. In addition, resistin is suggested to be an important link between obesity and the development of gastric cancer. Resistin has identified as an important player in inflammatory responses, and emerged as a mediator in inflammation-associated cancer. A limited number of studies have investigated the association of resistin and SDF-1 with gastric cancer. Herein, we investigated the molecular mechanisms by which resistin influences the expression of SDF-1 in gastric carcinoma cells. Results Human gastric cancer cell lines were exposed to doses of resistin; SDF-1 expression and secretion levels were then determined. Real-time polymerase chain reaction and western blotting analyses were performed to clarify molecular changes. Inhibition of Toll-like receptor 4 (TLR4) by a competitive antagonist inhibited resistin-induced SDF-1 expression. Pharmacological inhibitors and small interfering RNA (siRNA) demonstrated that activation of the p38 mitogen-activated protein kinase (MAPK) pathway is critical for resistin-induced SDF-1 expression mediated by TLR4. The promoter activity and transcription factor enzyme-linked immunosorbent assay revealed that resistin induced expression of SDF-1 mediated by NF-κB in gastric cancer cells. Inhibition of p38 MARK activation blocked the SDF-1-induced expression and the SDF-1 promoter activity in the cancer gastric cells. Chromatin immunoprecipitation assay revealed that inhibition of p38 MARK activation also blocked the resistin-increased NF-κB-DNA-binding activity. Conclusions Resistin-induced SDF-1 upregulation by activation of TLR4, p38 MARK and NF-κB may explain a new role of resistin in the link of obesity and gastric cancer. PMID:24929539

  19. High serum testosterone levels during postpartum period are associated with postpartum depression.

    PubMed

    Aswathi, A; Rajendiren, Soundravally; Nimesh, Archana; Philip, R Ravi; Kattimani, Shivanand; Jayalakshmi, D; Ananthanarayanan, P H; Dhiman, Pooja

    2015-10-01

    In view of the reported cases of mood disorders that occur in mothers following childbirth and believing that sex steroid hormones contribute to mood and behavioral changes, this study has been aimed to explore the role of sex steroid hormones as an etiological factor for postpartum depression (PPD). This study was conducted at JIPMER, Puducherry, India between January 2010 and 2011. 103 women were recruited in the study after childbirth, out of which 62 women who were believed to be suffering from PPD were categorized as cases and the remaining 41 with no mood changes as controls, using Edinburgh Postpartum Depression Scale (EPDS) (cases had EPDS score ≥10 at 24-28h, controls had score <10 at 24-48h postpartum). The hormones estimated in these two groups included estradiol, progesterone and testosterone, and their levels were compared between these two groups. A significantly high testosterone levels were observed in cases with PPD at 24-28h when compared to controls. Estradiol and progesterone levels did not show significant difference between cases and controls. ROC analysis done at 24-28h showed that testosterone levels beyond 42.71ng/mL predict the development of PPD with 79% sensitivity, 63% specificity, 68% positive predictive value, 74% negative predictive value with AUC being 0.708. This study shows that there is an association between persistent high serum testosterone level in women following childbirth and PPD. PMID:26372084

  20. Effect of digoxin on serum and urinary cation changes on acute induction to high altitude

    SciTech Connect

    Ohri, V.C.; Chatterji, J.C.; Sachdev, Y.R.; Das, B.K.; Akhtar, M.; Tiwari, S.C.; Bhattacharji, P.; Behl, A.; Dutta, S.K.

    1984-04-01

    Forty subjects each were rapidly inducted by road to altitudes of 3200 and 3771 meters (m). Half of subjects at each altitude were maintained on digoxin and the other half received placebos. The digoxin group showed higher serum potassium at both altitudes. Serum sodium remained unaltered. When compared to control groups, urinary volume changes were less marked in the digoxin group. Similarly, the alterations in calcium and magnesium in serum and urine at 3771 m were less pronounced. However, none of these changes in the digoxin groups were statistically significant when compared with control groups. 21 references.

  1. High-performance liquid chromatography-tandem mass spectrometry validation of medroxyprogesterone acetate in products of pork origin and serum.

    PubMed

    Giannetti, Luigi; Barchi, Daniela; Fiorucci, Fulvia; Gennuso, Elisa; Sanna, Patrizia; Pallagrosi, Marco; Neri, Bruno

    2005-08-01

    Different extraction and purification methods are described here to determine medroxyprogesterone acetate (MPA) in pork meat and serum. Spiked samples are investigated over the concentration range of MPA 0.5-20 ng/g. Pork meat tissues are subjected to extraction using organic solvent, and pork serum is simply diluted with acetate buffer. Clean-up is performed using solid-phase extraction on a C18 cartridge, and MPA is eluted with ethanol. Aliquots are injected into a high-performance liquid chromatography-mass spectrometry system. MPA content is determined on the basis of m/z 387-327 and 387-123 transitions. PMID:16176642

  2. Crevicular Fluid and Serum Concentrations of Progranulin and High Sensitivity CRP in Chronic Periodontitis and Type 2 Diabetes

    PubMed Central

    Priyanka, N.; Kumari, Minal; Kalra, Nitish; Arjun, P.; Naik, Savitha B.; Pradeep, A. R.

    2013-01-01

    Introduction. This study was designed to correlate the serum and gingival crevicular fluid (GCF) levels of progranulin (PGRN) and high sensitivity C-reactive protein (hs CRP) in chronic periodontitis and type 2 diabetes mellitus (DM). Design. PGRN and hs CRP levels were estimated in 3 groups: healthy, chronic periodontitis, and type 2 DM with chronic periodontitis. Results. The mean PGRN and hs CRP concentrations in serum and GCF were the highest for group 3 followed by group 2 and the least in group 1. Conclusion. PGRN and hs CRP may be biomarkers of the inflammatory response in type 2 DM and chronic periodontitis. PMID:24191130

  3. High Serum Thyrotropin Levels Are Associated with Current But Not with Incident Hypertension

    PubMed Central

    Tiller, Daniel; Meisinger, Christa; Agger, Carsten; Nauck, Matthias; Rettig, Rainer; Hofman, Albert; Jørgensen, Torben; Linneberg, Allan; Witteman, Jacqueline C.M.; Franco, Oscar H.; Greiser, Karin H.; Werdan, Karl; Döring, Angela; Kluttig, Alexander; Stricker, Bruno H.C.; Völzke, Henry

    2013-01-01

    Background Recent data from a population-based study in children and adolescents suggest that serum thyrotropin (TSH) levels are associated with arterial blood pressure and hypertension. These results are in agreement with some but not all population-based studies in adults. Discrepancies in results might be explained by drug intake, different iodine supplies, and sizes of populations investigated. In addition, it is not clear whether an association between TSH and hypertension exists longitudinally or only cross-sectionally. Thus, our aim was to investigate cross-sectional and longitudinal associations between thyroid function and arterial blood pressure in a large consortium of cohort studies in adults. Methods Data from five population-based studies were pooled resulting in 17,023 individuals being available for cross-sectional and 10,048 individuals for longitudinal analyses. Associations of baseline TSH with baseline blood pressure or hypertension were analyzed by multivariable median or logistic regression models. Multivariable median or Poisson regression models were used to investigate associations of baseline TSH with five-year change in arterial blood pressure or incident hypertension. Results There was a cross-sectional positive association of TSH with arterial blood pressure (p<0.001) and hypertension (odds ratio [OR]=1.76 [confidence interval (CI) 1.24–2.50], p=0.002). Likewise, hypothyroidism was associated with systolic (β=1.1 [CI 0.1–2.1], p=0.040) and diastolic blood pressure (β=1.4 [CI 0.7–2.0], p<0.001). TSH, however, was not consistently associated with a five-year change in blood pressure or incident hypertension. Conclusions High serum TSH levels were associated with current hypertension and blood pressure but not with a five-year change in blood pressure and incident hypertension. This argues for only a short-term effect of thyroid hormone levels on arterial blood pressure or a spurious association that needs further evaluation in

  4. Studies of drug interactions with glycated human serum albumin by high-performance affinity chromatography

    PubMed Central

    Matsuda, Ryan; Kye, So-Hwang; Anguizola, Jeanethe; Hage, David S.

    2015-01-01

    Diabetes is a health condition associated with elevated levels of glucose in the bloodstream and affects 366 million people worldwide. Type II diabetes is often treated with sulfonylurea drugs, which are known to bind tightly in blood to the transport protein human serum albumin (HSA). One consequence of the elevated levels of glucose in diabetes is the non-enzymatic glycation of proteins such as HSA. Several areas of HSA are now known to be affected by glycation-related modifications, which may in turn affect the binding of sulfonylurea drugs and other solutes to this protein. This review discusses some recent studies that have examined these changes in drug-protein binding by employing high-performance affinity chromatography (HPAC). A description of the theoretical and experimental techniques that were used in these studies is given. The information on drug interactions with glycated HSA, as obtained through this method, is also summarized. In addition, the potential advantages of this approach in the areas of biointeraction analysis and personalized medicine are considered. PMID:26526139

  5. Studies of drug interactions with glycated human serum albumin by high-performance affinity chromatography.

    PubMed

    Matsuda, Ryan; Kye, So-Hwang; Anguizola, Jeanethe; Hage, David S

    2014-08-01

    Diabetes is a health condition associated with elevated levels of glucose in the bloodstream and affects 366 million people worldwide. Type II diabetes is often treated with sulfonylurea drugs, which are known to bind tightly in blood to the transport protein human serum albumin (HSA). One consequence of the elevated levels of glucose in diabetes is the non-enzymatic glycation of proteins such as HSA. Several areas of HSA are now known to be affected by glycation-related modifications, which may in turn affect the binding of sulfonylurea drugs and other solutes to this protein. This review discusses some recent studies that have examined these changes in drug-protein binding by employing high-performance affinity chromatography (HPAC). A description of the theoretical and experimental techniques that were used in these studies is given. The information on drug interactions with glycated HSA, as obtained through this method, is also summarized. In addition, the potential advantages of this approach in the areas of biointeraction analysis and personalized medicine are considered. PMID:26526139

  6. Carbohydrate composition of serum low and high density lipoproteins of nonhuman primate species.

    PubMed

    Pargaonkar, P S; Radhakrishnamurthy, B; Srinivasan, S R; Berenson, G S

    1977-01-01

    1. Carbohydrate composition of serum low and high density lipoproteins obtained from 5 nonhuman primate species (chimpanzee, patas, baboon, rhesus, and spider) and humans was studied. 2. Individual lipoproteins were isolated from pooled sera of each species by ultracentrifugal flotation between the densities 1.019-1.063 for LDL-2; 1.063-1.12 for HDL-2; and 1.12-1.21 for HDL-3. After delipidation, sialic acid, fucose, glucosamine, mannose, galactose, and glucose were determined on apo LDL-2, apo HDL-2, and apo HDL-3. 3. Glucosamine, galactose, and mannose constituted a major component of the sugars in apo LDL-2, with similar relative proportions in all species. Sialic acid, fucose, and glucose formed a minor component, the proportions of which varied greatly among the species. 4. Unlike apo LDL-2, sialic acid, fucose, and glucosamine constituted the bulk of the sugars in apo HDL-2 and apo HDL-3. Mannose, galactose, and glucose were minor components, with galactose predominating. 5. Qualitative differences were observed in electrophoretic mobilities of apo HDL-2 and apo HDL-3 on polyacrylamide gel. One faster moving band was unique to chimpanzee. 6. Intraspecies differences in the content of sialic acid and fucose of apolipoproteins may be related to lipoprotein metabolism and species susceptibility (or resistance) to either spontaneous or diet-induced atherosclerosis. PMID:233783

  7. High rates of serum Se deficiency among HIV and HCV infected and uninfected drug users in Buenos Aires, Argentina

    PubMed Central

    Sheehan, Heidi B; Benetucci, Jorge; Muzzio, Estela; Redini, Liliana; Naveira, Jorge; Segura, Marcela; Weissenbacher, Mercedes; Tang, Alice M

    2012-01-01

    Objective To describe the prevalence and correlates of low serum Se and determine whether HIV, hepatitis C virus (HCV) and/or types of drugs used are associated with serum Se in a cohort of infected and uninfected drug users. Design Independent correlates of low serum Se levels based on data collected from food recalls, physical exams, and clinical status questionnaires were identified using multivariate analysis. Setting Buenos Aires, Argentina Subjects A total of 205 (25 females and 180 males) former and current drug users Results Drug users had an average serum Se level of 69.8±32.8 μg/dl, and 82% were considered deficient (< 85μg/l). Multivariate analyses found that HIV and/or HCV infection had lower mean Se compared to healthy, uninfected drug users (HIV/HCV co-infection: −25.3 μg/l (SE =7.6, p=0.001); HIV alone: −28.9 μg/l (SE=6.9, p<0.001); HCV alone −19.4 μg/l (SE = 7.1, p=0.006). Current and previous drug use was associated with higher serum Se. Cigarette smoking and heavy alcohol consumption were not found to be associated with Se status. Conclusions Low serum Se levels are highly prevalent among drug users in Buenos Aires, Argentina. Se supplementation and/or dietary interventions may be warranted in drug users who are at high risk of HIV and/or HCV infection. PMID:21740621

  8. A reversed-phase high performance liquid chromatography method for quantification of methotrexate in cancer patients serum.

    PubMed

    Li, Yuan-dong; Li, Yan; Liang, Ning-sheng; Yang, Fan; Kuang, Zhi-peng

    2015-10-01

    A simple, rapid and sensitive reversed-phase high performance liquid chromatography (HPLC) method has been developed for the determination of methotrexate in human serum. After deproteinization of the serum with 40% silver nitrate solution, methotrexate and internal standard (IS) were separated on a reversed-phase column with a mobile phase consisting of 10mM sodium phosphate buffer (pH6.40)-methanol (78:22%, v/v) and ultraviolet detection at 310nm. The linearity is evaluated by a calibration curve in the concentration range of 0.05-10.0μg/mL and presented a correlation coefficient of 0.9995. The absolute recoveries were 97.52±3.9% and 96.87±3.7% for methotrexate and ferulic acid (internal standard), respectively. The intra- and inter-day precision were less 6.19 and 5.89%, respectively (n=6). The limit of quantitation was 0.02μg/mL and the limit of detection was 0.006μg/mL. The complete analysis was achieved less than 10min with no interference from endogenous components or 22 examined drugs. This method was validated by using serum samples from high-dose methotrexate treated patients with osteosarcoma, breast cancer, acute leukemia and lymphoma. The method was demonstrated to be a simple, rapid and reliable approach in quantification of methotrexate in serum samples from patients with high-dose methotrexate therapy. PMID:26319303

  9. Relationship between High Serum Cystatin C Levels and the Risk of Gestational Diabetes Mellitus

    PubMed Central

    Li, Huaping; Huang, Yajuan; Liu, Fang; Tao, Minfang; Jia, Weiping

    2016-01-01

    Aims Serum cystatin C (CysC) has recently been shown to be associated with the incidence of type 2 diabetes mellitus (T2DM) and progression to the pre-diabetic state. The aim of this study was to explore the relationship between serum CysC and the risk of gestational diabetes mellitus (GDM) in Chinese pregnant women. Methods This cross-sectional study consisted of 400 pregnant women including111 with GDM and 289 with normal glucose tolerance at 24–28 weeks of gestation. The subjects were further divided into four groups according to the CysC quartiles, and their clinical characteristics were compared. The serum CysC concentration was measured using immunoturbidimetry and the degree of insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR). Results Serum CysC levels were significantly higher in pregnant women with GDM than in the healthy pregnant women[1.0(0.8–1.8) vs 0.7(0.6–1.0), P<0.01). The Spearman’s correlation analysis showed that serum CysC was positively associated with HOMA-IR(r = 0.118, P<0.05) and the occurrence of GDM(r = 0.348, P<0.01). The pregnant women were divided into quartiles according to their serum CysC concentrations. Compared to the first quartile, pregnant women in Q2 (OR, 2.441; P = 0.025), Q3 (OR, 3.383; P = 0.001) and Q4 (OR, 5.516; P<0.001) had higher risk of GDM after adjusted for age, BMI, HbA1c and HOMA-IR. Further, with a rise in the serum CysC, there was an increasing trend in the HOMA-IR levels (P<0.05). A binary logistic regression analysis after adjusting for other confounding variables revealed a significant and independent association between serum CysC and GDM [OR = 14.269; 95% confidence interval, 4.977–40.908, P<0.01].The receiver operating characteristic curve analysis revealed that the optimal cutoff point for serum CysC to indicate GDM was 0.95mg/L. Conclusions Serum CysC is significantly and independently associated with insulin resistance and GDM. It may be a

  10. REG4 Is Highly Expressed in Mucinous Ovarian Cancer: A Potential Novel Serum Biomarker

    PubMed Central

    Lehtinen, Laura; Vesterkvist, Pia; Roering, Pia; Korpela, Taina; Hattara, Liisa; Kaipio, Katja; Mpindi, John-Patrick; Hynninen, Johanna; Auranen, Annika; Davidson, Ben; Haglund, Caj; Iljin, Kristiina; Grenman, Seija; Siitari, Harri; Carpen, Olli

    2016-01-01

    Preoperative diagnostics of ovarian neoplasms rely on ultrasound imaging and the serum biomarkers CA125 and HE4. However, these markers may be elevated in non-neoplastic conditions and may fail to identify most non-serous epithelial cancer subtypes. The objective of this study was to identify histotype-specific serum biomarkers for mucinous ovarian cancer. The candidate genes with mucinous histotype specific expression profile were identified from publicly available gene-expression databases and further in silico data mining was performed utilizing the MediSapiens database. Candidate biomarker validation was done using qRT-PCR, western blotting and immunohistochemical staining of tumor tissue microarrays. The expression level of the candidate gene in serum was compared to the serum CA125 and HE4 levels in a patient cohort of prospectively collected advanced ovarian cancer. Database searches identified REG4 as a potential biomarker with specificity for the mucinous ovarian cancer subtype. The specific expression within epithelial ovarian tumors was further confirmed by mRNA analysis. Immunohistochemical staining of ovarian tumor tissue arrays showed distinctive cytoplasmic expression pattern only in mucinous carcinomas and suggested differential expression between benign and malignant mucinous neoplasms. Finally, an ELISA based serum biomarker assay demonstrated increased expression only in patients with mucinous ovarian cancer. This study identifies REG4 as a potential serum biomarker for histotype-specific detection of mucinous ovarian cancer and suggests serum REG4 measurement as a non-invasive diagnostic tool for postoperative follow-up of patients with mucinous ovarian cancer. PMID:26981633

  11. REG4 Is Highly Expressed in Mucinous Ovarian Cancer: A Potential Novel Serum Biomarker.

    PubMed

    Lehtinen, Laura; Vesterkvist, Pia; Roering, Pia; Korpela, Taina; Hattara, Liisa; Kaipio, Katja; Mpindi, John-Patrick; Hynninen, Johanna; Auranen, Annika; Davidson, Ben; Haglund, Caj; Iljin, Kristiina; Grenman, Seija; Siitari, Harri; Carpen, Olli

    2016-01-01

    Preoperative diagnostics of ovarian neoplasms rely on ultrasound imaging and the serum biomarkers CA125 and HE4. However, these markers may be elevated in non-neoplastic conditions and may fail to identify most non-serous epithelial cancer subtypes. The objective of this study was to identify histotype-specific serum biomarkers for mucinous ovarian cancer. The candidate genes with mucinous histotype specific expression profile were identified from publicly available gene-expression databases and further in silico data mining was performed utilizing the MediSapiens database. Candidate biomarker validation was done using qRT-PCR, western blotting and immunohistochemical staining of tumor tissue microarrays. The expression level of the candidate gene in serum was compared to the serum CA125 and HE4 levels in a patient cohort of prospectively collected advanced ovarian cancer. Database searches identified REG4 as a potential biomarker with specificity for the mucinous ovarian cancer subtype. The specific expression within epithelial ovarian tumors was further confirmed by mRNA analysis. Immunohistochemical staining of ovarian tumor tissue arrays showed distinctive cytoplasmic expression pattern only in mucinous carcinomas and suggested differential expression between benign and malignant mucinous neoplasms. Finally, an ELISA based serum biomarker assay demonstrated increased expression only in patients with mucinous ovarian cancer. This study identifies REG4 as a potential serum biomarker for histotype-specific detection of mucinous ovarian cancer and suggests serum REG4 measurement as a non-invasive diagnostic tool for postoperative follow-up of patients with mucinous ovarian cancer. PMID:26981633

  12. High serum selenium levels are associated with increased risk for diabetes mellitus independent of central obesity and insulin resistance

    PubMed Central

    Lu, Chia-Wen; Chang, Hao-Hsiang; Yang, Kuen-Cheh; Kuo, Chia-Sheng; Lee, Long-Teng; Huang, Kuo-Chin

    2016-01-01

    Objective Selenium is an essential micronutrient for human health. Although many observational and interventional studies have examined the associations between selenium and diabetes mellitus, the findings were inconclusive. This study aimed to investigate the relationship between serum selenium levels and prevalence of diabetes, and correlated the relationship to insulin resistance and central obesity. Research design and methods This was a hospital-based case–control study of 847 adults aged more than 40 years (diabetes: non-diabetes =1:2) in Northern Taiwan. Serum selenium was measured by an inductively coupled plasma-mass spectrometer. The association between serum selenium and diabetes was examined using multivariate logistic regression analyses. Results After adjusting for age, gender, current smoking, current drinking, and physical activity, the ORs (95% CI, p value) of having diabetes in the second (Q2), third (Q3), and fourth (Q4) selenium quartile groups were 1.24 (95% CI 0.78 to 1.98, p>0.05), 1.90 (95% CI 1.22 to 2.97, p<0.05), and 5.11 (95% CI 3.27 to 8.00, p<0.001), respectively, compared with the first (Q1) quartile group. Further adjustments for waist circumference and homeostatic model assessment-insulin resistance (HOMA-IR) largely removed the association of serum selenium levels with diabetes but not in the highest quartile (compared with Q1, Q3: 1.57, 95% CI 0.91 to 2.70, Q4: 3.79, 95% CI 2.17 to 6.32). Conclusions We found that serum selenium levels were positively associated with prevalence of diabetes. This is the first human study to link insulin resistance and central obesity to the association between selenium and diabetes. Furthermore, the association between selenium and diabetes was independent of insulin resistance and central obesity at high serum selenium levels. The mechanism behind warrants further confirmation. PMID:27547419

  13. Fatty liver and hepatic function for residents with markedly high serum PCDD/Fs levels in Taiwan.

    PubMed

    Lee, Ching-Chang; Yao, Yei-Jen; Chen, Hsiu-Ling; Guo, Yue-Liang; Su, Huey-Jen

    2006-03-01

    This study was designed to examine the associations between serum polychtorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) levels and adverse hepatic-related health outcomes. Residents living in the vicinity of a closed pentachlorophenol (PCP) manufacturing factory (exposure area) and other areas nearby (control area) were identified from prior investigation of serum PCDD/Fs measurements. A total of 85 subjects were recruited for the study, 52 from exposure area and 33 from control, respectively. Average level of serum PCDD/Fs was 80.1 6 50.9 pg WHO-TEQ/g lipid for those residing in exposure area, and 25.5 6 18.2 in control area. Statistically higher odds ratio (ORs) for fatty liver and gamma-glutamyltransferase (GGT) activity was found in subjects with higher serum PCDD/Fs levels and high body mass index (BMI) as compared to those with lower PCDD/Fs levels and less BMI. Data suggest that dioxin exposure and high lipid content affect the prevalence of fatty liver in exposed subjects. Future study should be directed to prevent continuous exposure to environmental PCDD/Fs from the defunct PCP factory, and to characterize prospectively, with a larger study sample size, the potential long-term consequences on hepatic function associated with contaminant exposure. PMID:16455615

  14. Serum levels of brain-derived neurotrophic factor in alcohol-dependent patients receiving high-dose baclofen.

    PubMed

    Geisel, Olga; Hellweg, Rainer; Müller, Christian A

    2016-06-30

    The neurotrophin brain-derived neurotrophic factor (BDNF) has been suggested to be involved in the development and maintenance of addictive and other psychiatric disorders. Also, interactions of γ-aminobutyric acid (GABA)-ergic compounds and BDNF have been reported. The objective of this study was to investigate serum levels of BDNF over time in alcohol-dependent patients receiving individually titrated high-dose treatment (30-270mg/d) with the GABA-B receptor agonist baclofen or placebo for up to 20 weeks. Serum levels of BDNF were measured in patients of the baclofen/placebo group at baseline (t0), 2 weeks after reaching individual high-dose of baclofen/placebo treatment (t1) and after termination of study medication (t2) in comparison to carefully matched healthy controls. No significant differences in serum levels of BDNF between the baclofen and the placebo group or healthy controls were found at t0, t1, or at t2. Based on these findings, it seems unlikely that baclofen exerts a direct effect on serum levels of BDNF in alcohol-dependent patients. Future studies are needed to further explore the mechanism of action of baclofen and its possible relationship to BDNF in alcohol use disorders. PMID:27107672

  15. Measurement of serum total glycerides and free glycerol by high-performance liquid chromatography.

    PubMed

    Li, Hongxia; Dong, Jun; Chen, Wenxiang; Wang, Shu; Guo, Hanbang; Man, Yong; Mo, Peisheng; Li, Jianzhai

    2006-09-01

    Serum levels of total glycerides and free glycerol are important indices of lipid metabolism and cardiovascular disease risk. Convenient enzymatic methods of measurement have been available, but they are susceptible to interference. Situations exist in both research and clinical laboratories in which more specific and precise methods are needed. We developed HPLC methods for the measurement of serum total glycerides and free glycerol. For total glycerides, serum was mixed with an internal standard (1,2,4-butanetriol) and treated with alcoholic sodium hydroxide to hydrolyze glycerides to glycerol. After deproteinization with tungstic acid, the glycerol was benzoylated with an optimized Schotten-Baumann reaction and analyzed by HPLC. For free glycerol, serum was equilibrated with the internal standard and deproteinized with tungstic acid to remove the glycerides. The glycerol was benzoylated and analyzed as for total glycerol. Various factors were investigated, and no significant sources of interference were detected. The total coefficients of variation ranged from 0.7% to 2.0% for total glycerides and from 1.7% to 3.2% for free glycerol. The analytical recoveries ranged from 98.5% to 101.6%. In conclusion, simple and reliable HPLC methods for serum total glycerides and free glycerol have been developed. The methods may also be used for the analyses of glycerol or glycerides in other biological samples. PMID:16788212

  16. Optimization of human serum albumin monoliths for chiral separations and high-performance affinity chromatography.

    PubMed

    Pfaunmiller, Erika L; Hartmann, Mahli; Dupper, Courtney M; Soman, Sony; Hage, David S

    2012-12-21

    Various organic-based monoliths were prepared and optimized for immobilization of the protein human serum albumin (HSA) as a binding agent for chiral separations and high-performance affinity chromatography. These monoliths contained co-polymers based on glycidyl methacrylate (GMA) and ethylene glycol dimethacrylate (EDMA) or GMA and trimethylolpropane trimethacrylate (TRIM). A mixture of cyclohexanol and 1-dodecanol was used as the porogen, with the ratio of these solvents being varied along with the polymerization temperature to generate a library of monoliths. These monoliths were used with both the Schiff base and epoxy immobilization methods and measured for their final content of HSA. Monoliths showing the highest protein content were further evaluated in chromatographic studies using R/S-warfarin and d/l-tryptophan as model chiral solutes. A 2.6-2.7-fold increase in HSA content was obtained in the final monoliths when compared to similar HSA monoliths prepared according to the literature. The increased protein content made it possible for the new monoliths to provide higher retention and/or two-fold faster separations for the tested solutes when using 4.6mm i.d.× 50 mm columns. These monoliths were also used to create 4.6mm i.d.× 10 mm HSA microcolumns that could separate the same chiral solutes in only 1.5-6.0 min. The approaches used in this study could be extended to the separation of other chiral solutes and to the optimization of organic monoliths for use with additional proteins as binding agents. PMID:23010249

  17. Optimization of human serum albumin monoliths for chiral separations and high-performance affinity chromatography

    PubMed Central

    Pfaunmiller, Erika L.; Hartmann, Mahli; Dupper, Courtney M.; Soman, Sony; Hage, David S.

    2012-01-01

    Various organic-based monoliths were prepared and optimized for immobilization of the protein human serum albumin (HSA) as a binding agent for chiral separations and high-performance affinity chromatography. These monoliths contained co-polymers based on glycidyl methacrylate (GMA) and ethylene glycol dimethacrylate (EDMA) or GMA and trimethylolpropane trimethacrylate (TRIM). A mixture of cyclohexanol and 1-dodecanol was used as the porogen, with the ratio of these solvents being varied along with the polymerization temperature to generate a library of monoliths. These monoliths were used with both the Schiff base and epoxy immobilization methods and measured for their final content of HSA. Monoliths showing the highest protein content were further evaluated in chromatographic studies using R/S-warfarin and d/l-tryptophan as model chiral solutes. A 2.6–2.7-fold increase in HSA content was obtained in the final monoliths when compared to similar HSA monoliths prepared according to the literature. The increased protein content made it possible for the new monoliths to provide higher retention and/or two-fold faster separations for the tested solutes when using 4.6 mm i.d. × 50 mm columns. These monoliths were also used to create 4.6 mm i.d. × 10 mm HSA microcolumns that could separate the same chiral solutes in only 1.5–6.0 min. The approaches used in this study could be extended to the separation of other chiral solutes and to the optimization of organic monoliths for use with additional proteins as binding agents. PMID:23010249

  18. Highly sensitive detection of bovine serum albumin based on the aggregation of triangular silver nanoplates

    NASA Astrophysics Data System (ADS)

    Zhang, Ling Ling; Ma, Fang Fang; Kuang, Yang Fang; Cheng, Shu; Long, Yun Fei; Xiao, Qiu Guo

    2016-02-01

    A simple, fast and highly sensitive spectrophotometric method for the determination of bovine serum albumin (BSA) has been developed based on the interactions between triangular silver nanoplates (TAgNPs) and BSA in the presence of Britton-Robison buffer solution (BR). Particularly, the wavelength of absorption maximum (λmax) of TAgNPs is red shifted in the presence of BSA together with Britton-Robinson buffer solution (BR, pH = 2.56), and the color of the solution changed from blue to light blue. This may be due to the interactions between BSA molecules on the surface of TAgNPs through electrostatic forces, hydrogen bonds, hydrophobic effects and van der Waals forces at pH 2.56, which leads to the aggregation of TAgNPs. The determination of BSA was achieved by measuring the change of λmax corresponding to localized surface plasmon resonance (LSPR) from UV-visible spectrophotometry. It was found that the shift value in the wavelength of absorption maximum (Δλ, the difference in absorption maxima of the TAgNPs/BSA/BR mixture and the TAgNPs/BR mixture) was proportionate to the concentration of BSA in the range of 1.0 ng mL- 1 to 100.0 ng mL- 1 with the correlation coefficient of r = 0.9969. The detection limit (3 σ/k) for BSA was found to be as low as 0.5 ng mL- 1.

  19. Serum YKL-40 is a marker of prognosis and disease status in high-grade gliomas.

    PubMed

    Iwamoto, Fabio M; Hottinger, Andreas F; Karimi, Sasan; Riedel, Elyn; Dantis, Jocelynn; Jahdi, Maryam; Panageas, Katherine S; Lassman, Andrew B; Abrey, Lauren E; Fleisher, Martin; DeAngelis, Lisa M; Holland, Eric C; Hormigo, Adília

    2011-11-01

    The objective of this study was to evaluate whether longitudinal levels of serum YKL-40 correlate with disease status or survival in adults with gliomas. Patients with histologically confirmed gliomas were eligible for this longitudinal study. Serum samples were collected prospectively and concurrently with MRI scans at multiple time points during the course of the disease. YKL-40 levels determined by ELISA were correlated with radiographic disease status and survival. We performed a multivariate survival analysis including well-known prognostic factors such as age, performance status, and extent of surgical resection. Three hundred and forty-three patients with gliomas (41 low-grade, 105 anaplastic, and 197 glioblastoma) were accrued. Two-year survival from registration was 29% for glioblastomas, 62% for anaplastic gliomas, and 83% for low-grade gliomas. A total of 1740 serum samples were collected, and 95.6% of samples had matching MRI scans. Serum YKL-40 level was significantly lower in patients with no radiographic disease compared with patients with radiographic disease in both the anaplastic glioma (P= .0008) and the glioblastoma (P= .0006) cohorts. Serum levels of YKL-40 in patients with low-grade gliomas were not associated with radiographic disease status. Increases in YKL-40 were independently associated with worse survival in anaplastic gliomas (hazard ratio [HR] = 1.4, P= .01) and glioblastomas (HR = 1.4, P< .0001). Longitudinal increases in serum YKL-40 are associated with increased risk of death in patients with glioblastomas and anaplastic gliomas. YKL-40 is also a putative indicator of disease status in these patients. PMID:21831900

  20. Serum YKL-40 is a marker of prognosis and disease status in high-grade gliomas†

    PubMed Central

    Iwamoto, Fabio M.; Hottinger, Andreas F.; Karimi, Sasan; Riedel, Elyn; Dantis, Jocelynn; Jahdi, Maryam; Panageas, Katherine S.; Lassman, Andrew B.; Abrey, Lauren E.; Fleisher, Martin; DeAngelis, Lisa M.; Holland, Eric C.; Hormigo, Adília

    2011-01-01

    The objective of this study was to evaluate whether longitudinal levels of serum YKL-40 correlate with disease status or survival in adults with gliomas. Patients with histologically confirmed gliomas were eligible for this longitudinal study. Serum samples were collected prospectively and concurrently with MRI scans at multiple time points during the course of the disease. YKL-40 levels determined by ELISA were correlated with radiographic disease status and survival. We performed a multivariate survival analysis including well-known prognostic factors such as age, performance status, and extent of surgical resection. Three hundred and forty-three patients with gliomas (41 low-grade, 105 anaplastic, and 197 glioblastoma) were accrued. Two-year survival from registration was 29% for glioblastomas, 62% for anaplastic gliomas, and 83% for low-grade gliomas. A total of 1740 serum samples were collected, and 95.6% of samples had matching MRI scans. Serum YKL-40 level was significantly lower in patients with no radiographic disease compared with patients with radiographic disease in both the anaplastic glioma (P= .0008) and the glioblastoma (P= .0006) cohorts. Serum levels of YKL-40 in patients with low-grade gliomas were not associated with radiographic disease status. Increases in YKL-40 were independently associated with worse survival in anaplastic gliomas (hazard ratio [HR] = 1.4, P= .01) and glioblastomas (HR = 1.4, P< .0001). Longitudinal increases in serum YKL-40 are associated with increased risk of death in patients with glioblastomas and anaplastic gliomas. YKL-40 is also a putative indicator of disease status in these patients. PMID:21831900

  1. Oral high-dose medroxyprogesterone acetate (MPA) treatment: cortisol/MPA serum profiles in relation to breast cancer regression.

    PubMed

    Mahlke, M; Grill, H J; Knapstein, P; Wiegand, U; Pollow, K

    1985-01-01

    Medroxyprogesterone acetate (MPA), a potent synthetic progestin, has been widely used in the hormonal treatment of advanced breast cancer, but presently with varying dose schedules. The availability of a sensitive RIA-method for determination of serum MPA has stimulated the research on MPA serum levels in patients after repeated MPA administration. The aim of this study was to assay blood level profiles of MPA as well as of cortisol during repeated high-dose orally administered MPA. 34 patients with metastatic breast cancer were enrolled in this study. 12 patients died already within the first 4 weeks of MPA treatment due to multiple metastases. The dosage regimen based on the daily oral administration of 1,000 mg MPA suspension. During MPA treatment, a decrease of cortisol serum levels was observed in nearly all patients. Within the observation time of 8 months out of 22 evaluable cases 18.2% responded to the therapy (complete and partial response). No change was observed in 36.4% and progression in 45.5% of the patients. Within the remission (complete and partial) group, a good correlation between constant MPA serum levels above 150 ng/ml and remission was observed. But in the groups with no change and progression no such correlation could be observed. PMID:4000617

  2. Highly sensitive detection of HER2 extracellular domain (ECD) in the serum of breast cancer patients by piezoelectric microcantilevers (PEMS)

    PubMed Central

    Loo, LiNa; Capobianco, Joseph A.; Wu, Wei; Gao, Xiaotong; Shih, Wan Y.; Shih, Wei-Heng; Pourrezaei, Kambiz; Robinson, Matthew K.; Adams, Gregory P.

    2011-01-01

    Rapid and sensitive detection of serum tumor biomarkers are needed to monitor cancer patients for disease progression. Highly sensitive piezoelectric microcantilever sensors (PEMS) offer an attractive tool for biomarker detection, however their utility in the complex environment encountered in serum has yet to be determined. As a proof of concept, we have functionalized PEMS with antibodies that specifically bind to HER2, a biomarker (antigen) that is commonly overexpressed in the blood of breast cancer patients. The function and sensitivity of these anti-HER2 PEMS biosensors was initially assessed using recombinant HER2 spiked into human serum. Their ability to detect native HER2 present in the serum of breast cancer patients was then determined. We have found that the anti-HER2 PEMS were able to accurately detect both recombinant and naturally occurring HER2 at clinically relevant levels (>2 ng/ml). This indicates that PEMS-based biosensors provide a potentially effective tool for biomarker detection. PMID:21449604

  3. Determination and Pharmacokinetic Study of Pirfenidone in Rat Serum by High-Performance Thin-Layer Chromatography.

    PubMed

    Thorat, Sonali G; Chikhale, Rupesh V

    2016-08-01

    A rapid, sensitive and selective high-performance thin-layer chromatography (HPTLC) method was developed and validated for the determination and pharmacokinetics of pirfenidone in rat serum. One-step protein precipitation by methanol is reported, and serum samples were separated by HPTLC using a simple mobile phase of toluene-methanol in the ratio of 8:2. The retardation factor of pirfenidone in the serum sample was 0.45 with the detection performed at 315 nm. The calibration curve was linear over the range of 100-1,200 ng/spot with a lower limit of quantitation of 40 ng/spot. The mean recovery of pirfenidone in serum was in the range of 70.6-75.8%, and intra-day and inter-day precision were both <14.1%. This method was successfully applied to the pharmacokinetic study of pirfenidone in rats on oral administration of the drug at a dose of 15.0 mg/kg. PMID:27406123

  4. Highly Specific Detection of Myostatin Prodomain by an Immunoradiometric Sandwich Assay in Serum of Healthy Individuals and Patients

    PubMed Central

    Widera, Christian; Gottlieb, Jens; Vogel, Arndt; Schmidt, Sebastian; Brandes, Gudrun; Heuft, Hans-Gert; Lichtinghagen, Ralf; Kempf, Tibor; Wollert, Kai C.; Bauersachs, Johann; Heineke, Joerg

    2013-01-01

    Background Myostatin is a muscle derived factor that functions as a negative regulator of skeletal muscle growth. Induction of myostatin expression was observed in rodent models of muscle wasting and in cachectic patients with cancer or pulmonary disease. Therefore, there is an increasing interest to use serum myostatin as a biomarker. Methods We established an immunoradiometric sandwich assay (IRMA), which uses a commercially available chicken polyclonal, affinity purified antibody directed against human myostatin prodomain. We determined the serum concentrations of myostatin prodomain in 249 healthy individuals as well as 169 patients with heart failure, 53 patients with cancer and 44 patients with chronic pulmonary disease. Results The IRMA had a detection limit of 0.7ng/ml, an intraassay imprecision of ≤14.1% and an interassay imprecision of ≤ 18.9%. The specificity of our assay was demonstrated by size exclusion chromatography, detection of myostatin by Western-blotting and a SMAD-dependent transcriptional-reporter assay in the signal-rich serum fractions, as well as lack of interference by unspecific substances like albumin, hemoglobin or lipids. Myostatin prodomain was stable at room temperature and resistant to freeze-thaw cycles. Apparently healthy individuals over the age of 55 had a median myostatin prodomain serum concentration of 3.9ng/ml (25th-75th percentiles, 2-7ng/ml) and we could not detect increased levels in patients with stable chronic heart failure or cancer related weight loss. In contrast, we found strongly elevated concentrations of myostatin prodomain (median 26.9ng/ml, 25th-75th percentiles, 7-100ng/ml) in the serum of underweight patients with chronic pulmonary disease. Conclusions We established a highly specific IRMA for the quantification of myostatin prodomain concentration in human serum. Our assay could be useful to study myostatin as a biomarker for example in patients with chronic pulmonary disease, as we detected highly

  5. Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: A recent clinical trial revealed that folic acid supplementation is associated with an increased incidence of prostate cancer (1). The present study evaluates serum and prostate tissue folate levels in men with prostate cancer, compared to histologically normal prostate glands from can...

  6. Variants of resistin gene and the risk of idiopathic dilated cardiomyopathy in Pakistan

    PubMed Central

    Hussain, Sabir; Haroon, Javeria; Ejaz, Shagufta; Javed, Qamar

    2016-01-01

    Background In cardiovascular disease phenotypes, a genetic factor is an important determinant of both familial and non-familial dilated cardiomyopathies. Resistin is a novel adipocyte derived peptide, associated with inflammation and suggested to be involved in contractile abnormalities of cardiomyocytes. Methods In this study, we examined the association of the RETN SNPs in − 420 and + 299 in patients with idiopathic dilated cardiomyopathy (IDCM). Patients with IDCM (n = 250) and healthy controls (n = 250) were enrolled in this study. RETN genotyping was performed by using PCR-RFLP method. Results RETN − 420C > G and + 299G > A polymorphisms were significantly more prevalent in patient group vs. controls (P < 0.0001 and P = 0.0007, respectively). GG genotype at − 420 and AA genotype at + 299 were higher in the patient group compared with healthy controls (OR = 11.4, P < 0.0001, and OR = 2.3, P = 0.030, respectively). We found that the − 420G allele increased the risk of developing IDCM in patients (P < 0.0001). Moreover, there was a significant difference between G and A alleles at RETN + 299 from IDCM cases and controls (P = 0.0032). The RETN − 420G and + 299A haplotypes were more prevalent in the patient vs. control group (P < 0.0001). Conclusion The results suggest that the RETN − 420C > G and + 299G > A polymorphisms may have a role in the pathogenesis of IDCM. PMID:27114921

  7. High Serum Irisin Level as an Independent Predictor of Diabetes Mellitus: A Longitudinal Population-Based Study.

    PubMed

    Huh, Ji Hye; Ahn, Song Vogue; Choi, Jung Hye; Koh, Sang Baek; Chung, Choon Hee

    2016-06-01

    Irisin, a novel exercise-induced myokine, has been suggested to regulate energy homeostasis and insulin sensitivity. However, it remains unclear whether circulating irisin plays a role in the development of DM in human. We investigated the possible association between circulating irisin levels and incident DM in a 2.6-year longitudinal study of a population-based cohort comprised of rural Korean subjects.We conducted a longitudinal study within the Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population (KoGES-ARIRANG) study from November 2005 to January 2008. Cases (n=85) were patients with incident DM during the follow-up period and controls (n = 85) were matched to incident DM cases based on sex and age at baseline. The relative risk of serum irisin/adiponectin level for incident DM was analyzed using conditional logistic regression analysis.Baseline irisin_ENREF_1 levels were significantly higher in subjects who developed DM than in subjects who did not. The serum irisin level was positively associated with glycated hemoglobin (HbA1c) and postprandial glucose. Irisin was negatively associated with adiponectin (R = -0.189, P = 0.014). After adjustment for potential confounders, including body mass index, the odds ratios [95% confidence intervals] for incident DM increased in a graded manner as the serum irisin level increased (Quartile 1 vs Quartile 2 vs Quartile 3 vs Quartile 4 = 1 vs 0.80 [0.28-2.35] vs 3.33 [1.11-10.00] vs 4.10 [1.35-12.44], respectively), whereas the odds ratios for incident DM decreased in a graded manner as the serum adiponectin level increased.High serum irisin was independently associated with the development of DM, indicating that irisin may be a useful predictor of DM in Korean adults. PMID:27281072

  8. Serum amyloid A1 levels and amyloid deposition following a high-fat diet challenge in transgenic mice overexpressing hepatic serum amyloid A1.

    PubMed

    Jang, Woo Young; Jeong, Jain; Kim, Seonggon; Kang, Min-Cheol; Sung, Yong Hun; Choi, Minjee; Park, Si Jun; Kim, Myoung Ok; Kim, Sung Hyun; Ryoo, Zae Young

    2016-06-01

    Serum amyloid A (SAA) is an acute-phase response protein in the liver, and SAA1 is the major precursor protein involved in amyloid A amyloidosis. This amyloidosis has been reported as a complication in chronic inflammatory conditions such as arthritis, lupus, and Crohn's disease. Obesity is also associated with chronic, low-grade inflammation and sustained, elevated levels of SAA1. However, the contribution of elevated circulating SAA1 to metabolic disturbances and their complications is unclear. Furthermore, in several recent studies of transgenic (TG) mice overexpressing SAA1 that were fed a high-fat diet (HFD) for a relatively short period, no relationship was found between SAA1 up-regulation and metabolic disturbances. Therefore, we generated TG mice overexpressing SAA1 in the liver, challenged these mice with an HFD, and investigated the influence of elevated SAA1 levels. Sustained, elevated levels of SAA1 were correlated with metabolic parameters and local cytokine expression in the liver following 16 weeks on the HFD. Moreover, prolonged consumption (52 weeks) of the HFD was associated with impaired glucose tolerance and elevated SAA1 levels and resulted in systemic SAA1-derived amyloid deposition in the kidney, liver, and spleen of TG mice. Thus, we concluded that elevated SAA1 levels under long-term HFD exposure result in extensive SAA1-derived amyloid deposits, which may contribute to the complications associated with HFD-induced obesity and metabolic disorders. PMID:27218680

  9. Relationship between high-mobility group box 1 overexpression in ovarian cancer tissue and serum: a meta-analysis

    PubMed Central

    Wang, Haipeng; Li, Zengjun; Sun, Yanlai; Xu, Zhongfa; Han, Jianjun; Song, Bao; Song, Wentao; Qin, Chen; Yin, Lei

    2015-01-01

    Objective To implement a meta-analysis to investigate the relationship between high-mobility group box 1 (HMGB1) overexpression in the tissue and serum of ovarian cancer patients, and to evaluate its prognostic significance. Methods Searches were made of China National Knowledge Infrastructure, EMBASE, WanFang, PubMed, MEDLINE, and Web of Science databases up to August 2015, with no language or style restrictions. Reference lists of related studies were also carefully reviewed to identify additional articles. Results The literature search identified a total of 12 relevant studies on HMGB1 expression for inclusion in the meta-analysis: seven in ovarian tumor tissue, four in ovarian tumor patient serum, and one in both tissue and serum. HMGB1 protein levels in ovarian cancer tissues were notably higher than those in normal ovarian tissues with no evidence of heterogeneity between studies (RD=0.64, 95% confidence interval (CI): 0.57–0.70, Z=18.70, P<0.00001, I2=15%), and also higher than those in benign tumor tissues with no evidence of heterogeneity between studies (RD=0.52, 95% CI: 0.43–0.61, Z=11.14, P<0.00001, I2=0). Serum HMGB1 levels were similarly significantly higher in ovarian cancer patients than those with benign tumors or normal ovaries. Pooled mean differences of HMGB1 in ovarian cancer patients compared with patients with benign tumors or normal ovaries were 99.32 with 95% CI: 67.82–130.81, Z=6.18, P<0.00001, and 95.34 with 95% CI: 62.11–128.57, Z=5.62, P<0.0001. The pooled relative risk of ovarian cancer with high vs low HMGB1 expression levels was 1.40 with 95% CI: 1.09–1.79, Z=2.66, P=0.008, heterogeneity I2=50%. Conclusion This meta-analysis suggested that HMGB1 levels in both tissue and serum of ovarian cancer patients were significantly higher than those of benign tumor and normal ovarian samples. High serum or tissue HMGB1 expression may therefore be an effective molecular marker for ovarian benign or malignant tumor diagnosis and

  10. Serum adipokine concentrations in dogs with diabetes mellitus: a pilot study

    PubMed Central

    Kim, Ah Young; Kim, Hye-Sun; Yang, Mhan-Pyo

    2015-01-01

    This study was conducted to determine whether serum adipokine concentrations differed between healthy dogs and dogs with diabetes mellitus (DM). To accomplish this, 19 dogs with newly diagnosed DM were compared to 20 otherwise healthy dogs. The serum concentrations of visfatin, leptin, IL-1β, IL-6, IL-18, and TNF-α were significantly higher in diabetic dogs than in healthy dogs, whereas the serum adiponectin concentrations were lower in diabetic dogs. However, there were no significant differences in the IL-10 and resistin levels between groups. The serum leptin concentrations in diabetic dogs with and without concurrent disorders differed significantly. Treatment with insulin induced a significant decrease in IL-6 in diabetic dogs without concurrent disorders. These results show that the clinical diabetic state of dogs could modulate the circulating visfatin and adiponectin concentrations directly, while upregulation of leptin was probably a result of concurrent disorders rather than an effect of persistent hyperglycemia as a result of DM. PMID:25643799

  11. Krill oil supplementation lowers serum triglycerides without increasing low-density lipoprotein cholesterol in adults with borderline high or high triglyceride levels.

    PubMed

    Berge, Kjetil; Musa-Veloso, Kathy; Harwood, Melody; Hoem, Nils; Burri, Lena

    2014-02-01

    The aim of the study was to explore the effects of 12 weeks daily krill oil supplementation on fasting serum triglyceride (TG) and lipoprotein particle levels in subjects whose habitual fish intake is low and who have borderline high or high fasting serum TG levels (150-499 mg/dL). We hypothesized that Krill oil lowers serum TG levels in subjects with borderline high or high fasting TG levels. To test our hypothesis 300 male and female subjects were included in a double-blind, randomized, multi-center, placebo-controlled study with five treatment groups: placebo (olive oil) or 0.5, 1, 2, or 4 g/day of krill oil. Serum lipids were measured after an overnight fast at baseline, 6 and 12 weeks. Due to a high intra-individual variability in TG levels, data from all subjects in the four krill oil groups were pooled to increase statistical power, and a general time- and dose-independent one-way analysis of variance was performed to assess efficacy. Relative to subjects in the placebo group, those administered krill oil had a statistically significant calculated reduction in serum TG levels of 10.2%. Moreover, LDL-C levels were not increased in the krill oil groups relative to the placebo group. The outcome of the pooled analysis suggests that krill oil is effective in reducing a cardiovascular risk factor. However, owing to the individual fluctuations of TG concentrations measured, a study with more individual measurements per treatment group is needed to increase the confidence of these findings. PMID:24461313

  12. Analysis of serum immune markers in seropositive and seronegative rheumatoid arthritis and in high-risk seropositive arthralgia patients

    PubMed Central

    Chalan, Paulina; Bijzet, Johan; van den Berg, Anke; Kluiver, Joost; Kroesen, Bart-Jan; Boots, Annemieke M. H.; Brouwer, Elisabeth

    2016-01-01

    Presence of autoantibodies precedes development of seropositive rheumatoid arthritis (SP RA) and seropositive arthralgia patients (SAP) are at risk of developing RA. The aims of the study are to identify additional serum immune markers discriminating between SP and seronegative (SN) RA, and markers identifying high-risk SAP. Sera from SAP (n = 27), SP RA (n = 22), SN RA (n = 11) and healthy controls (n = 20) were analyzed using the Human Cytokine 25-Plex Panel. Selected markers were validated in independent cohorts of SP RA (n = 35) and SN RA (n = 12) patients. Eleven of 27 SAP developed RA within 8 months (median follow-up time, range 1–32 months), and their baseline serum markers were compared to 16 non-progressing SAP. SAP and SP RA patients showed a marked overlap in their systemic immune profiles, while SN RA showed a distinct immune profile. Three of 4 markers discriminating between SP and SN RA (IL-1β, IL-15 and Eotaxin, but not CCL5) were similarly modulated in independent cohorts. SAP progressing to RA showed trends for increases in IL-5, MIP-1β, IL-1RA and IL-12 compared to non-progressing SAP. ROC analysis showed that serum IL-5 most accurately discriminated between the two SAP groups (AUC > 0.8), suggesting that baseline IL-5 levels may aid the identification of high-risk SAP. PMID:27189045

  13. Analysis of serum immune markers in seropositive and seronegative rheumatoid arthritis and in high-risk seropositive arthralgia patients.

    PubMed

    Chalan, Paulina; Bijzet, Johan; van den Berg, Anke; Kluiver, Joost; Kroesen, Bart-Jan; Boots, Annemieke M H; Brouwer, Elisabeth

    2016-01-01

    Presence of autoantibodies precedes development of seropositive rheumatoid arthritis (SP RA) and seropositive arthralgia patients (SAP) are at risk of developing RA. The aims of the study are to identify additional serum immune markers discriminating between SP and seronegative (SN) RA, and markers identifying high-risk SAP. Sera from SAP (n = 27), SP RA (n = 22), SN RA (n = 11) and healthy controls (n = 20) were analyzed using the Human Cytokine 25-Plex Panel. Selected markers were validated in independent cohorts of SP RA (n = 35) and SN RA (n = 12) patients. Eleven of 27 SAP developed RA within 8 months (median follow-up time, range 1-32 months), and their baseline serum markers were compared to 16 non-progressing SAP. SAP and SP RA patients showed a marked overlap in their systemic immune profiles, while SN RA showed a distinct immune profile. Three of 4 markers discriminating between SP and SN RA (IL-1β, IL-15 and Eotaxin, but not CCL5) were similarly modulated in independent cohorts. SAP progressing to RA showed trends for increases in IL-5, MIP-1β, IL-1RA and IL-12 compared to non-progressing SAP. ROC analysis showed that serum IL-5 most accurately discriminated between the two SAP groups (AUC > 0.8), suggesting that baseline IL-5 levels may aid the identification of high-risk SAP. PMID:27189045

  14. Serum protein electrophoresis by using high-resolution agarose gel in clinically healthy and Aspergillus species-infected falcons.

    PubMed

    Kummrow, Maya; Silvanose, Christudas; Di Somma, Antonio; Bailey, Thomas A; Vorbrüggen, Susanne

    2012-12-01

    Serum protein electrophoresis has gained importance in avian medicine during the past decade. Interpretation of electrophoretic patterns should be based on species-specific reference intervals and the electrophoresis gel system. In this study, serum protein electrophoresis by using high-resolution agarose gels was performed on blood samples collected from 105 falcons, including peregrine falcons (Falco peregrinus), gyrfalcons (Falco rusticolus), saker falcons (Falco cherrug), red-naped shaheens (Falco pelegrinoides babylonicus), and hybrid falcons, that were submitted to the Dubai Falcon Hospital (Dubai, United Arab Emirates) between 2003 and 2006. Reference values were established in clinically healthy birds and compared with values from falcons infected with Aspergillus species (n = 32). Falcons with confirmed aspergillosis showed significantly lower prealbumin values, which is a novel finding. Prealbumin has been documented in many avian species, but further investigation is required to illuminate the diagnostic significance of this negative acute-phase protein. PMID:23409432

  15. Quantitative analysis of human serum corticosterone by high-performance liquid chromatography coupled to electrospray ionization mass spectrometry.

    PubMed

    Ghulam, A; Kouach, M; Racadot, A; Boersma, A; Vantyghem, M C; Briand, G

    1999-04-30

    An original method based upon high-performance liquid chromatography coupled to electrospray ionization mass spectrometry has been developed for corticosterone (B) quantification in human serum. After extraction by diethyl ether using triamcinolone (T) as an internal standard, solutes are separated on a C18 microbore column (250 X 1.0 mm, I.D.), using acetonitrile-water-formic acid (40:59.9:0.1, v/v/v) as the mobile phase (flow-rate 40 microl/min). Detection is performed on an API 1 single quadrupole mass spectrometer equipped with a ESI interface and operated in positive ionization mode. Corticosterone quantifications were realized by computing peak area ratios (B/T) of the serum extracts analyzed in SIM mode (m/z 347 and m/z 395 for B and T. respectively), and comparing them with the calibration curve (r=0.998). PMID:10360442

  16. [Thymoma with extensive coagulative necrosis and high serum level of CYFRA 21-1; report of a case].

    PubMed

    Himuro, Naoya; Minakata, Takao; Oshima, Yutaka; Tomita, Yuri; Kataoka, Daisuke; Kadokura, Mitsutaka

    2014-12-01

    A 73-year-old woman complained of right chest discomfort. Chest X-ray during the follow-up for rheumatoid arthritis showed a mediastinal tumor. Chest computed tomography (CT) and magnetic resonance imaging (MRI) showed a 65-mm tumor in the right anterior mediastinum. A blood test showed high serum levels of CYFRA 21-1(29.8 ng/ml), white blood cells( WBC 10,800/µl), and C-reactive protein(CRP 16.1 mg/dl). Subsequently, inflammatory reactions improved, and the thymic tumor was resected. Histopathologically, the tumor was a type B2 thymoma with extensive coagulative necrosis. After resection, the serum CYFRA 21-1 level returned to the normal range. PMID:25434553

  17. High serum levels of soluble CD40-L in patients with undifferentiated nasopharyngeal carcinoma: pathogenic and clinical relevance

    PubMed Central

    Caggiari, Laura; Guidoboni, Massimo; Vaccher, Emanuela; Barzan, Luigi; Franchin, Giovanni; Gloghini, Annunziata; Martorelli, Debora; Zancai, Paola; Bortolin, Maria Teresa; Mazzucato, Mario; Serraino, Diego; Carbone, Antonino; De Paoli, Paolo; Dolcetti, Riccardo

    2007-01-01

    Background Engagement of CD40 promotes survival of undifferentiated nasopharyngeal carcinoma (UNPC) cells and similar effects are induced by the EBV oncoprotein LMP-1 that is expressed in a fraction of cases. Considering that CD40 may be activated also by the soluble isoform of CD40L (sCD40L), we investigated the serum levels of sCD40L in a series of 61 UNPC patients from Italy, a non-endemic area for this disease. Results At diagnosis, serum samples of UNPC patients contained significantly higher levels of sCD40L than age-matched healthy controls (p < 0.001). High levels of sCD40L (i.e., >18 ng/ml) were more frequently found in patients <40 years of age (p = 0.03) and with distant metastases at presentation (p = 0.03). Serum levels of sCD40L were inversely associated with the expression of the EBV oncoprotein LMP-1 (p = 0.03), which mimics a constitutively activated CD40. The amount of sCD40L decreased in a fraction of patients treated with local radiotherapy alone. Moreover, CD40L+ lymphoid cells admixed to neoplastic UNPC cells were detected in cases with high serum levels of sCD40L, suggesting that sCD40L is probably produced within the tumor mass. Conclusion sCD40L may contribute to CD40 activation in UNPC cells, particularly of LMP-1-negative cases, further supporting the crucial role of CD40 signalling in the pathogenesis of UNPC. sCD40L levels may be useful to identify UNPC patients with occult distant metastases at presentation. PMID:17331231

  18. Lack of evidence for intermolecular epistatic interactions between adiponectin and resistin gene polymorphisms in Malaysian male subjects

    PubMed Central

    Lau, Cia-Hin; Muniandy, Sekaran

    2012-01-01

    Epistasis (gene-gene interaction) is a ubiquitous component of the genetic architecture of complex traits such as susceptibility to common human diseases. Given the strong negative correlation between circulating adiponectin and resistin levels, the potential intermolecular epistatic interactions between ADIPOQ (SNP+45T > G, SNP+276G > T, SNP+639T > C and SNP+1212A > G) and RETN (SNP-420C > G and SNP+299G > A) gene polymorphisms in the genetic risk underlying type 2 diabetes (T2DM) and metabolic syndrome (MS) were assessed. The potential mutual influence of the ADIPOQ and RETN genes on their adipokine levels was also examined. The rare homozygous genotype (risk alleles) of SNP-420C > G at the RETN locus tended to be co-inherited together with the common homozygous genotypes (protective alleles) of SNP+639T > C and SNP+1212A > G at the ADIPOQ locus. Despite the close structural relationship between the ADIPOQ and RETN genes, there was no evidence of an intermolecular epistatic interaction between these genes. There was also no reciprocal effect of the ADIPOQ and RETN genes on their adipokine levels, i.e., ADIPOQ did not affect resistin levels nor did RETN affect adiponectin levels. The possible influence of the ADIPOQ gene on RETN expression warrants further investigation. PMID:22481872

  19. High serum carotenoids are associated with lower risk for developing elevated serum alanine aminotransferase among Japanese subjects: the Mikkabi cohort study.

    PubMed

    Sugiura, Minoru; Nakamura, Mieko; Ogawa, Kazunori; Ikoma, Yoshinori; Yano, Masamichi

    2016-04-01

    Many recent studies have shown that antioxidant vitamins and/or carotenoids may reduce liver disease, but this association has not been well established with thorough longitudinal cohort studies. The objective of this study was to longitudinally investigate whether serum carotenoids at baseline are associated with the risk of developing elevated serum alanine aminotransferase (ALT) among Japanese subjects. We conducted a follow-up study of 1073 males and females aged between 30 and 79 years at baseline from the Mikkabi prospective cohort study. Those who participated in the baseline study and completed follow-up surveys were examined longitudinally. Exclusions included excessive alcohol consumption (≥60 g alcohol/d), hepatitis B and C and having a history of medication use for liver disease. A cohort of 213 males and 574 females free of elevated serum ALT (>30 IU/ml) at baseline was studied. Over a mean follow-up period of 7·4 (sd 3·1) years, thirty-one males and forty-nine females developed new elevated serum ALT. After adjustments for confounders, the hazard ratios for elevated serum ALT in the highest tertiles of basal serum β-carotene, β-cryptoxanthin and total provitamin A carotenoids against the lowest tertiles were 0·43 (95 % CI 0·22, 0·81), 0·51 (CI 0·27, 0·94) and 0·52 (CI 0·28, 0·97), respectively. For α-carotene and lycopene, borderline reduced risks were also observed; however, these were not significant. Our results further support the hypothesis that antioxidant carotenoids, especially provitamin A carotenoids, might help prevent earlier pathogenesis of non-alcoholic liver disease in Japanese subjects. PMID:26916997

  20. Differentiated quantification of human bile acids in serum by high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Burkard, Ines; von Eckardstein, Arnold; Rentsch, Katharina M

    2005-11-01

    Determination of quantitative changes in the pattern of serum bile acids is important for the monitoring of diseases affecting bile acid metabolism. A sensitive and specific high-performance liquid chromatography (HPLC)-MS/MS method was developed for the differentiated quantification of unconjugated as well as glycine- and taurine-conjugated cholic, chenodeoxycholic (CDCA), deoxycholic (DCA), ursodeoxycholic (UDCA) and lithocholic acid (LCA) in serum samples. After solid-phase extraction and reversed-phase HPLC separation, detection of the conjugated bile acids was performed using electrospray ionization (ESI)-MS/MS and selected reaction monitoring mode, whereas unconjugated bile acids were determined by ESI-MS and selected ion monitoring mode. The within-day and between-day coefficients of variation were below 7% for all bile acids and the recovery rates of the extraction procedure were between 84.9 and 105%. The developed method was applied to a group of 21 healthy volunteers and preliminary reference intervals in serum were established. In patients with drug-induced cholestasis, an elevation of primary bile acids has been shown. PMID:16182619

  1. Method development and validation for ultra-high-pressure LC/MS/MS determination of hop prenylflavonoids in human serum.

    PubMed

    Yuan, Yang; Qiu, Xi; Nikolic, Dejan; Dahl, Jeffrey H; van Breemen, Richard B

    2012-01-01

    Hops (Humulus lupulus L.) are used in the brewing of beer, and hop extracts containing prenylated compounds, such as xanthohumol (XN) and 8-prenylnaringenin (8-PN), are under investigation as dietary supplements for cancer chemoprevention and the management of hot flashes in menopausal women. To facilitate clinical studies of hop safety and efficacy, a selective, sensitive, and fast ultra-high-pressure LC (UHPLC) tandem MS method was developed and validated for the simultaneous determination of the hop prenylflavonoids XN, isoxanthohumol (IX), 6-prenylnaringenin (6-PN), and 8-PN in human serum. The analytical method requires 300 microL of human serum, which is processed using liquid-liquid extraction. UHPLC separation was carried out in 2.5 min with gradient elution using an RP C18 column containing 1.6 pm particle size packing material. Prenylflavonoids were measured using negative ion electrospray MS with collision-induced dissociation and selected reaction monitoring. The method was validated and showed good accuracy and precision with an LOQ of 0.50 ng/mL for XN (1.4 nM) and 1.0 ng/mL for 6-PN, 8-PN (2.94 nM), and IX (2.82 nM) in serum. PMID:23451393

  2. Quantification of phylloquinone and menaquinones in feces, serum, and food by high-performance liquid chromatography-mass spectrometry.

    PubMed

    Karl, J Philip; Fu, Xueyan; Dolnikowski, Gregory G; Saltzman, Edward; Booth, Sarah L

    2014-07-15

    Vitamin K, comprising phylloquinone (PK) and menaquinones (MKn), is a family of vitamers found in multiple biological and environmental matrices. Advancing emerging evidence for novel and distinct physiologic roles of these vitamers in human health and disease necessitates sensitive and selective methods for quantifying PK and MKn in these matrices. We developed a novel method employing high-performance liquid chromatography-mass spectrometry with atmospheric pressure chemical ionization (LC-APCI-MS) for simultaneous quantification of 11 vitamin K vitamers that can be applied in feces, serum and food. Minimal detectable concentrations of vitamin K vitamers ranged from 1 pmol/g to 30 pmol/g. Limits of quantification ranged from 5 pmol/g to 90 pmol/g. Inter-assay and intra-assay variations were <17% and <8%, respectively, in food, and <12% and <8%, respectively, in feces. Recovery exceeded 80% for all vitamers in both food and feces. The method successfully quantified PK and MKn concentrations in rat chow, feces and serum. In summary, this LC-APCI-MS method provides a sensitive and selective tool for quantifying vitamin K vitamers in feces, serum and food. This method can be applied in human and animal studies examining the role of vitamin K vitamers derived from the diet and gut bacteria synthesis in health and disease. PMID:24956079

  3. Cross-sectional study of serum parathyroid hormone level in high-risk pregnancies as compared to nonpregnant control

    PubMed Central

    Sharma, J. B.; Sharma, Subhadra; Usha, B. R.; Yadav, Manisha; Kumar, Sunesh; Mukhopadhyay, A. K.

    2016-01-01

    Objectives: To note the value of serum parathyroid hormone (PTH) levels in normal and high-risk pregnancies (HRP) in patients attending antenatal visits at All India Institute of Medical Sciences (AIIMS). Materials and Methods: This is a cross-sectional study where a total of 282 patients attending Gynecology Outpatient Department at AIIMS, New Delhi were recruited. Among the 282 subjects, 251 were pregnant, and 31 were controls. The serum was tested for serum PTH levels using Beckman coulter access 2 immunoassay. Results: The median value of PTH level in pregnant women was 31.6 pg/ml with range being 0.8–505.5 pg/ml in contrast to 45.9 pg/ml with range being 19–102.7 pg/ml in nonpregnant female. This difference was statistically significant (P = 0.0012). There was no significant difference in median level of PTH in different age group. Although the median PTH levels were lower in second trimester (25.25 pg/ml) than in first trimester (35.5 pg/ml) and in third trimester (32.4 pg/ml), the difference was not statistically significant. There was no significant difference in PTH level in HRP (median value – 31.6 pg/ml) as compared to low-risk pregnancies (31.5 pg/ml). Conclusion: Serum PTH levels are significantly lower during pregnancy as compared to nonpregnant state. However, age, parity, and HRP did not alter PTH level during pregnancy. PMID:26904475

  4. High Maternal Serum Estradiol Levels Induce Dyslipidemia in Human Newborns via a Hepatic HMGCR Estrogen Response Element

    PubMed Central

    Meng, Ye; Lv, Ping-Ping; Ding, Guo-Lian; Yu, Tian-Tian; Liu, Ye; Shen, Yan; Hu, Xiao-Ling; Lin, Xian-Hua; Tian, Shen; Lv, Min; Song, Yang; Guo, Meng-Xi; Ke, Zhang-Hong; Xu, Hong; Sheng, Jian-Zhong; Shi, Feng-Tao; Huang, He-Feng

    2015-01-01

    While the intrauterine environment is essential for the health of offspring, the impact of high maternal serum estradiol (E2) on lipid metabolism in offspring and the mechanisms are unknown. We found that ovarian stimulation (OS) could result in high E2 levels in women throughout pregnancy. Strikingly, their newborns showed elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels that were positively related with E2 in newborns. In vitro, E2 dose-dependently stimulated TC and LDL-C secretion, and increased expression of the cholesterol synthesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) in HepG2 cells and mouse fetal hepatocytes. In vivo, high maternal E2 was detected and fetal livers also showed significantly higher HMGCR expression in an OS mouse model. Notably, an estrogen response element (ERE) was identified in the HMGCR promoter, indicating that high maternal serum E2 could up-regulate HMGCR expression in fetal hepatocytes via an ERE that in turn induces elevated levels of TC and LDL-C in offspring. Conclusion: OS can induce a high maternal E2 environment, which up-regulates HMGCR expression in fetal hepatocytes via an ERE in the promoter, and induces elevated levels of TC and LDL-C in newborns that may be related to increased risk of metabolic disease in adulthood. PMID:25961186

  5. Prostate cancer biomarker discovery using high performance mass spectral serum profiling.

    PubMed

    Oh, Jung Hun; Lotan, Yair; Gurnani, Prem; Rosenblatt, Kevin P; Gao, Jean

    2009-10-01

    Prostate-specific antigen (PSA) is the most widely used serum biomarker for early detection of prostate cancer (PCA). Nevertheless, PSA level can be falsely elevated due to prostatic enlargement, inflammation or infection, which limits the PSA test specificity. The objective of this study is to use a machine learning approach for the analysis of mass spectrometry data to discover more reliable biomarkers that distinguish PCA from benign specimens. Serum samples from 179 prostate cancer patients and 74 benign patients were analyzed. These samples were processed using ProXPRESSION Biomarker Enrichment Kits (PerkinElmer). Mass spectra were acquired using a prOTOF 2000 matrix-assisted laser desorption/ionization orthogonal time-of-flight (MALDI-O-TOF) mass spectrometer. In this study, we search for potential biomarkers using our feature selection method, the Extended Markov Blanket (EMB). From the new marker selection algorithm, a panel of 26 peaks achieved an accuracy of 80.7%, a sensitivity of 83.5%, a specificity of 74.4%, a positive predictive value (PPV) of 87.9%, and a negative predictive value (NPV) of 68.2%. On the other hand, when PSA alone was used (with a cutoff of 4.0ng/ml), a sensitivity of 66.7%, a specificity of 53.6%, a PPV of 73.5%, and a NPV of 45.4% were obtained. PMID:19423179

  6. A multiplexed targeted assay for high-throughput quantitative analysis of serum methylamines by ultra performance liquid chromatography coupled to high resolution mass spectrometry.

    PubMed

    Kadar, Hanane; Dubus, Justine; Dutot, Jérémie; Hedjazi, Lyamine; Srinivasa, Suman; Fitch, Kathleen V; Grinspoon, Steven K; Nicholson, Jeremy K; Dumas, Marc-Emmanuel; Gauguier, Dominique

    2016-05-01

    Methylamines are biologically-active metabolites present in serum and urine samples, which play complex roles in metabolic diseases. Methylamines can be detected by proton nuclear magnetic resonance (NMR), but specific methods remain to be developed for their routine assay in human serum in clinical settings. Here we developed and validated a novel reliable "methylamine panel" method for simultaneous quantitative analysis of trimethylamine (TMA), its major detoxification metabolite trimethylamine-N-oxide (TMAO), and precursors choline, betaine and l-carnitine in human serum using Ultra Performance Liquid Chromatography (UPLC) coupled to High Resolution Mass Spectrometry (HRMS). Metabolite separation was carried out on a HILIC stationary phase. For all metabolites, the assay was linear in the range of 0.25-12.5 μmol/L and enabled to reach limit of detection of about 0.10 μmol/L. Relative standard deviations were below 16% for the three levels of concentrations. We demonstrated the strong reliability and robustness of the method, which was applied to serum samples from healthy individuals to establish the range of concentrations of the metabolites and their correlation relationships and detect gender differences. Our data provide original information for implementing in a clinical environment a MS-based diagnostic method with potential for targeted metabolic screening of patients at risk of cardiometabolic diseases. PMID:27036856

  7. High serum phosphate concentration as the result of smoking might underlie the lower risk of Parkinson's disease.

    PubMed

    Håglin, L

    2015-09-01

    Epidemiological studies have found a negative association between cigarette smoking and Parkinson's disease (PD): PD patients are approximately 50% less likely to have smoked cigarettes than age- and sex-matched controls. In both women and men, the PD protection effect of smoking may be explained by higher levels of phosphate in serum (S-P) and triglycerides (S-TG) in smokers compared to non-smokers. That is, the protecting effect from smoking could be mediated by either a high S-P or high S-TG levels. I suggest that higher S-P as the result of smoking may be associated with intracellular depletion of Pi in skeletal muscle and that this depletion of Pi is associated with increased availability of phosphate for the brain. This increased phosphate availability would protect against PD, as oxidative phosphorylation in the mitochondria is a central and persistent phenomenon in the pathogenesis cascade of PD. Phosphate is necessary for energy production in the form of creatine phosphate (CP) and adenosine-tri-phosphate (ATP) in the brain and skeletal muscle. As such, hypophosphatemia increases risk of cell death. In some clinical instances, this energy depletion may pre-dispose to dopamine neuron death. Mitochondrial dysfunction is associated with the generation of oxidative stress and mediates the induction of apoptosis. Studies with NMR spectroscopy reveal that an energy deficit in brain cells is a strong mark for PD although this differed for men and women. Compared to women, men had lower serum phosphate and ATP levels in the brain (about 15% lower). In addition to sex differences, age, stress, and malnutrition may cause low serum phosphate levels, a situation that could contribute to the lack of energy available to the brain and the risk of PD. As hypophosphatemia is present in overnutrition and has an inverse relation with a high BMI, both obesity and malnutrition are considered to be presumptive risk factor for PD. PMID:26206759

  8. Identification and mapping of linear antibody epitopes in human serum albumin using high-density Peptide arrays.

    PubMed

    Hansen, Lajla Bruntse; Buus, Soren; Schafer-Nielsen, Claus

    2013-01-01

    We have recently developed a high-density photolithographic, peptide array technology with a theoretical upper limit of 2 million different peptides per array of 2 cm(2). Here, we have used this to perform complete and exhaustive analyses of linear B cell epitopes of a medium sized protein target using human serum albumin (HSA) as an example. All possible overlapping 15-mers from HSA were synthesized and probed with a commercially available polyclonal rabbit anti-HSA antibody preparation. To allow for identification of even the weakest epitopes and at the same time perform a detailed characterization of key residues involved in antibody binding, the array also included complete single substitution scans (i.e. including each of the 20 common amino acids) at each position of each 15-mer peptide. As specificity controls, all possible 15-mer peptides from bovine serum albumin (BSA) and from rabbit serum albumin (RSA) were included as well. The resulting layout contained more than 200.000 peptide fields and could be synthesized in a single array on a microscope slide. More than 20 linear epitope candidates were identified and characterized at high resolution i.e. identifying which amino acids in which positions were needed, or not needed, for antibody interaction. As expected, moderate cross-reaction with some peptides in BSA was identified whereas no cross-reaction was observed with peptides from RSA. We conclude that high-density peptide microarrays are a very powerful methodology to identify and characterize linear antibody epitopes, and should advance detailed description of individual specificities at the single antibody level as well as serologic analysis at the proteome-wide level. PMID:23894373

  9. Subacute cognitive deterioration with high serum anti-thyroid peroxidase antibodies: two cases and a plea for pragmatism.

    PubMed

    Segers, Kurt; Braconnier, Philippe; Corazza, Francis; Divano, Luisa; Mabrouk, Asmaa; Robberecht, Jean; Surquin, Murielle

    2013-09-01

    Autoimmune encephalopathy is a rare but potentially reversible cause of cognitive deterioration and neuropsychiatric disturbances. We describe two older female patients with subacute cognitive decline and marked neuropsychiatric disturbances in the presence of high serum anti-thyroid peroxidase antibodies and with normal dosage of free thyroxine 4. One patient recovered almost completely after oral corticotherapy. Differential diagnosis and the role of biomarkers, in particular, are discussed. We support a pragmatic approach involving a short empirical therapeutic trial with intravenous or oral corticoids; this should be considered in all patients with subacute encephalopathy and with laboratory arguments for an underlying autoimmune aetiology. PMID:25913766

  10. Sailing between Scylla and Charybdis: the high serum K-low dialysate K quandary.

    PubMed

    Labriola, Laura; Jadoul, Michel

    2014-01-01

    In HD patients, the optimal choice of dialysate K concentration is of paramount importance. Recent large observational studies have documented an association between low dialysate K concentration (< 2 or even <3 mEq/L) and a higher risk of sudden death. In this review, we first briefly discuss the available data concerning the link between hypokalemia and negative outcomes in non-CKD populations, especially after an acute myocardial infarction or in congestive heart failure. We next review the pathophysiology of the arrhythmogenic effect related to K fluxes during HD and discuss the dialytic strategies aiming at making potassium fall more gradual and thus at reducing the electrical disturbances triggered by the HD session. We conclude with practical recommendations regarding the optimal choice of K bath and the importance of more frequent monitoring of serum K in some clinical scenarios. PMID:24824161

  11. High fasting serum insulin level due to autoantibody interference in insulin immunoassay discloses autoimmune insulin syndrome: a case report.

    PubMed

    Lamy, Pierre-Jean; Sault, Corinne; Renard, Eric

    2016-08-01

    Insulin-antibodies are a cause of misleading results in insulin immunoassays. They may also mediate deleterious blood glucose variations. A patient presented with overtiredness, recurrent episodes of sweating, dizziness and fainting fits. A fasting serum insulin assay performed on a Modular platform (Modular analytic E170, Roche Diagnostic, Meylan, France) showed a highly elevated value of 194.7 mIU/L, whereas on the same sample glucose and C-peptide levels were normal. Other immunometric insulin assays were performed, as well as antibodies anti-insulin radiobinding assay (RBA) and gel filtration chromatography (GFC). While complementary insulin assays yielded closer to normal fasting levels, the free insulin concentration assessed after PEG precipitation was 14.0 mIU/L and the RBA was positive. GFC revealed that most of the insulin was complexed with a 150 kDa molecule, corresponding to an immunoglobulin G (IgG). A high fasting serum insulin level in a patient with neuroglucopenic symptoms was related to a high insulin-antibody level, suggesting an insulin autoimmune syndrome. PMID:27492703

  12. Greater Cognitive Decline with Aging among Elders with High Serum Concentrations of Organochlorine Pesticides

    PubMed Central

    Kim, Se-A; Lee, Yu-Mi; Lee, Ho-Won; Jacobs, David R; Lee, Duk-Hee

    2015-01-01

    Although cognitive decline is very common in elders, age-related cognitive decline substantially differs among elders and the determinants of the differences in age-related cognitive decline are unclear. We investigated our hypothesis that the association between age and cognition was stronger in those with higher serum concentrations of organochlorine (OC) pesticides, common persistent and strongly lipophilic neurotoxic chemicals. Participants were 644 elders aged 60-85, participating in the National Health and Nutrition Examination Survey 1999-2002. Six OC pesticides (p,p'-dichlorodiphenyltrichloroethane (DDT), p,p'-dichlorodipenyldichloroethylene (DDE), β-hexachlorocyclohexane, trans-nonachlor, oxychlordane, and heptachlor epoxide) were evaluated. “Lower cognitive function” was defined as having a low Digit-Symbol Substitution Test (DSST) score (<25th percentile of DSST score, cutpoint 28 symbols substituted). Higher levels of β-hexachlorocyclohexane, trans-nonachlor, oxychlordane, and heptachlor epoxide modified the associations between age and lower cognitive function (Pinteraction<0.01, 0.03, <0.01, and 0.02, respectively). Elders in the 3rd tertile of these chemicals demonstrated a greater risk of lower cognitive function with aging, compared to those in the combined 1st and 2nd tertiles. Among those with highest OC pesticides (3rd tertile), the odds ratio for the risk of lower cognitive function was about 6 to 11 for the highest quintile of age (80-85 years) vs. the first quintile of age (60-63 years), while the association between age and lower cognitive function became flatter in those with lower OC pesticides (combined 1st and 2nd tertiles). Both DDT and DDE showed no interaction, with lower DSST scores for higher age irrespective of serum concentrations of DDT or DDE. Even though DSST score measures only one aspect of cognition, several OC pesticides modified aging-related prevalence of low cognitive score, a finding which should be evaluated in

  13. Highly sensitive and selective measurement of underivatized methylmalonic acid in serum and plasma by liquid chromatography-tandem mass spectrometry.

    PubMed

    Yuan, Chao; Gabler, Jessica; El-Khoury, Joe M; Spatholt, Regina; Wang, Sihe

    2012-07-01

    Methylmalonic acid (MMA) is a functional biomarker of vitamin B12 deficiency. Measurement of plasma MMA is challenging due to its small molecular weight and hydrophilic nature. Several liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods have been developed for measuring plasma MMA. However, these methods involve lengthy sample preparation, long chromatographic run time, inadequate sensitivity, or interference from succinic acid (SA). Here we report a novel LC-MS/MS method for quantitation of underivatized MMA in serum or heparinized plasma with high sensitivity and selectivity. Sample preparation involved only strong anion exchange solid phase extraction. The extract was purified by online turbulent flow and analyzed on an Organic Acids column. MS/MS analysis was performed in negative electrospray mode, and the analytical time was 6 min. The use of ion ratio confirmation in combination with chromatographic resolution from SA greatly enhanced the selectivity. No interference was observed. This method was linear from 26.2 to 26,010.0 nM with an accuracy of 98-111 %. Total coefficient of variation was less than 4.6 % for three concentration levels tested. Comparison with a reference laboratory LC-MS/MS method using leftover patient serum specimens (n = 48) showed a mean bias of -2.3 nM (-0.61 %) with a Deming regression slope of 1.016, intercept of -6.6 nM, standard error of estimate of 25.3 nM, and a correlation coefficient of 0.9945. In conclusion, this LC-MS/MS method offers highly sensitive and selective quantitation of MMA in serum and plasma with simple sample preparation. PMID:22618327

  14. Serum-circulating miRNAs predict neuroblastoma progression in mouse model of high-risk metastatic disease

    PubMed Central

    Ramraj, Satish Kumar; Aravindan, Sheeja; Somasundaram, Dinesh Babu; Herman, Terence S.; Natarajan, Mohan; Aravindan, Natarajan

    2016-01-01

    Background Circulating miRNAs have momentous clinical relevance as prognostic biomarkers and in the progression of solid tumors. Recognizing novel candidates of neuroblastoma-specific circulating miRNAs would allow us to identify potential prognostic biomarkers that could predict the switch from favorable to high-risk metastatic neuroblastoma (HR-NB). Results Utilizing mouse models of favorable and HR-NB and whole miRnome profiling, we identified high serum levels of 34 and low levels of 46 miRNAs in animals with HR-NB. Preferential sequence homology exclusion of mouse miRNAs identified 25 (11 increased; 14 decreased) human-specific prognostic marker candidates, of which, 21 were unique to HR-NB. miRNA QPCR validated miRnome profile. Target analysis defined the candidate miRNAs' signal transduction flow-through and demonstrated their converged roles in tumor progression. miRNA silencing studies verified the function of select miRNAs on the translation of at least 14 target proteins. Expressions of critical targets that correlate tumor progression in tissue of multifarious organs identify the orchestration of HR-NB. Significant (>10 fold) increase in serum levels of miR-381, miR-548h, and miR-580 identify them as potential prognostic markers for neuroblastoma progression. Conclusion For the first time, we identified serum-circulating miRNAs that predict the switch from favorable to HR-NB and, further imply that these miRNAs could play a functional role in tumor progression. PMID:26921195

  15. Pregnancy-associated serum N-glycome changes studied by high-throughput MALDI-TOF-MS.

    PubMed

    Jansen, Bas C; Bondt, Albert; Reiding, Karli R; Lonardi, Emanuela; de Jong, Coen J; Falck, David; Kammeijer, Guinevere S M; Dolhain, Radboud J E M; Rombouts, Yoann; Wuhrer, Manfred

    2016-01-01

    Pregnancy requires partial suppression of the immune system to ensure maternal-foetal tolerance. Protein glycosylation, and especially terminal sialic acid linkages, are of prime importance in regulating the pro- and anti-inflammatory immune responses. However, little is known about pregnancy-associated changes of the serum N-glycome and sialic acid linkages. Using a combination of recently developed methods, i.e. derivatisation that allows the distinction between α2,3- and α2,6-linked sialic acids by high-throughput MALDI-TOF-MS and software-assisted data processing, we analysed the serum N-glycome of a cohort of 29 healthy women at 6 time points during and after pregnancy. A total of 77 N-glycans were followed over time, confirming in part previous findings while also revealing novel associations (e.g. an increase of FA2BG1S1(6), FA2G1S1(6) and A2BG2S2(6) with delivery). From the individual glycans we calculated 42 derived traits. With these, an increase during pregnancy and decrease after delivery was observed for both α2,3- and α2,6-linked sialylation. Additionally, a difference in the recovery speed after delivery was observed for α2,3- and α2,6-linked sialylation of triantennary glycans. In conclusion, our new high-throughput workflow allowed the identification of novel plasma glycosylation changes with pregnancy. PMID:27075729

  16. Pregnancy-associated serum N-glycome changes studied by high-throughput MALDI-TOF-MS

    PubMed Central

    Jansen, Bas C.; Bondt, Albert; Reiding, Karli R.; Lonardi, Emanuela; de Jong, Coen J.; Falck, David; Kammeijer, Guinevere S. M.; Dolhain, Radboud J. E. M.; Rombouts, Yoann; Wuhrer, Manfred

    2016-01-01

    Pregnancy requires partial suppression of the immune system to ensure maternal-foetal tolerance. Protein glycosylation, and especially terminal sialic acid linkages, are of prime importance in regulating the pro- and anti-inflammatory immune responses. However, little is known about pregnancy-associated changes of the serum N-glycome and sialic acid linkages. Using a combination of recently developed methods, i.e. derivatisation that allows the distinction between α2,3- and α2,6-linked sialic acids by high-throughput MALDI-TOF-MS and software-assisted data processing, we analysed the serum N-glycome of a cohort of 29 healthy women at 6 time points during and after pregnancy. A total of 77 N-glycans were followed over time, confirming in part previous findings while also revealing novel associations (e.g. an increase of FA2BG1S1(6), FA2G1S1(6) and A2BG2S2(6) with delivery). From the individual glycans we calculated 42 derived traits. With these, an increase during pregnancy and decrease after delivery was observed for both α2,3- and α2,6-linked sialylation. Additionally, a difference in the recovery speed after delivery was observed for α2,3- and α2,6-linked sialylation of triantennary glycans. In conclusion, our new high-throughput workflow allowed the identification of novel plasma glycosylation changes with pregnancy. PMID:27075729

  17. Supplementation of broccoli or Bifidobacterium longum-fermented broccoli suppresses serum lipid peroxidation and osteoclast differentiation on alveolar bone surface in rats fed a high-cholesterol diet.

    PubMed

    Tomofuji, Takaaki; Ekuni, Daisuke; Azuma, Tetsuji; Irie, Koichiro; Endo, Yasumasa; Yamamoto, Tatsuo; Ishikado, Atsushi; Sato, Takehiko; Harada, Kayo; Suido, Hirohisa; Morita, Manabu

    2012-04-01

    High-cholesterol diet enhances osteoclastic activity on alveolar bone by increasing serum lipid peroxidation. We hypothesized that supplementation with dietary antioxidants, such as found in broccoli and its fermented products, might suppress increases in serum lipid peroxidation, contributing to the inhibition of osteoclastic activity after high-cholesterol diet intake. The purpose of the present study was to investigate the effects of broccoli and fermented broccoli consumption on serum lipid peroxidation and osteoclast differentiation in alveolar bone of rats fed a high-cholesterol diet. In this 12-week study, rats were divided into 4 groups (n = 6/group): a control group (fed regular diet) and 3 experimental groups (fed a high-cholesterol [1% wt/wt] diet, or a high-cholesterol diet supplemented with either broccoli powder [5% wt/wt] or Bifidobacterium longum-fermented broccoli powder [5% wt/wt]). Serum hexanoyl-lysine (HEL) levels were measured as a parameter of lipid peroxidation. The number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in alveolar bone was enumerated to evaluate osteoclast differentiation. When compared with regular diet, the high-cholesterol diet increased serum HEL levels and resulted in a higher number of TRAP-positive osteoclasts at 12 weeks. The high-cholesterol diet supplemented with broccoli or B. longum-fermented broccoli showed lower levels of serum HEL and fewer TRAP-positive osteoclasts than the high-cholesterol diet at 12 weeks. In conclusion, consumption of broccoli, or its fermented product, inhibited the effects of a high-cholesterol diet on osteoclast differentiation in rat alveolar bone by suppressing serum lipid peroxidation. PMID:22575044

  18. WDR1 and CLNK gene polymorphisms correlate with serum glucose and high-density lipoprotein levels in Tibetan gout patients.

    PubMed

    Lan, Bing; Chen, Peng; Jiri, Mutu; He, Na; Feng, Tian; Liu, Kai; Jin, Tianbo; Kang, Longli

    2016-03-01

    Current evidence suggests heredity and metabolic syndrome contributes to gout progression. Specifically, the WDR1 and CLNK genes may play a role in gout progression in European ancestry populations. However, no studies have focused on Chinese populations, especially Tibetan individuals. This study aims to determine whether variations in these two genes correlate with gout-related indices in Chinese-Tibetan gout patients. Eleven single-nucleotide polymorphisms in the WDR1 and CLNK genes were detected in 319 Chinese-Tibetan gout patients and 318 controls. We used one-way analysis of variance to evaluate the polymorphisms' effects on gout based on mean serum levels of metabolism indicators, such as albumin, glucose (GLU), triglycerides, cholesterol, high-density lipoproteins (HDL-C), creatinine, and uric acid, from fasting venous blood samples. All p values were Bonferroni corrected. Polymorphisms of the WDR1 and CLNK genes affected multiple risk factors for gout development. Significant differences in serum GLU levels were detected between different genotypic groups with WDRI polymorphisms rs4604059 (p = 0.005) and rs12498927 (p = 0.005). In addition, significant differences in serum HDL-C levels were detected between different genotypic groups with the CLNK polymorphism rs2041215 (p = 0.001). Polymorphisms of CLNK also affected levels of albumin, triglycerides, and creatinine. This study is the first to investigate and identify positive correlations between WDR1 and CLNK gene polymorphisms in Chinese-Tibetan populations. Our findings provide significant evidence for the effect of genetic polymorphisms on gout-related factors in Chinese-Tibetan populations. PMID:26438387

  19. A Serum Vitamin D Level <25nmol/L Pose High Tuberculosis Risk: A Meta-Analysis

    PubMed Central

    Yang, Wen; Gu, Xiaoling; Liang, Wenjun; Yao, Yanwen; Song, Yong

    2015-01-01

    Background Low serum Vitamin D is considered to be associated with tuberculosis while the “dangerous” level was not clear. The aim of this study was to identify the association between tuberculosis and serum Vitamin D levels via synthesis of available evidence. Methods A search of EMBASE, Medline, ISI Web of knowledge, and Pubmed was conducted. The number of subjects of tuberculosis and no-tuberculosis groups in four Vitamin D range. Meta-analyses were performed and presented by odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Results A total of 15 studies involving 1440 cases and 2558 controls were included. A significantly increased risk of tuberculosis was found in two ranges: ≤ 12.5 nmol/L: pooled OR = 4.556, 95% CI = 2.200-9.435; 13-25 nmol/L: pooled OR = 3.797, 95% CI = 1.935-7.405. No statistically significant risk of tuberculosis was found in the range of 26–50 nmol/L (pooled OR = 1.561, 95% CI =0.997-2.442). In range 51–75 nmol/L, no positive association was found (pooled OR =1.160, 95% CI = 0.708-1.900). Conclusions This study found that a serum Vitamin D level ≤ 25 nmol/L was significantly associated with an increased risk of tuberculosis while the range of 51–75 nmol/L was not. The range 26-50nmol/L posed potential high tuberculosis risk. Future large-scale, well-designed studies are needed to verify these results. PMID:25938683

  20. Elevated Serum MicroRNA Levels Associate with Absence of High-Grade Prostate Cancer in a Retrospective Cohort

    PubMed Central

    Mihelich, Brittany L.; Maranville, Joseph C.; Nolley, Rosalie; Peehl, Donna M.; Nonn, Larisa

    2015-01-01

    To reduce treatment of indolent prostate cancer (PCa), biomarkers are needed to improve identification of patients with a low-risk of having aggressive disease. Over-treatment of these patients occurs because of uncertainty in the aggressiveness of the entire tumor based on the biopsies, which do not accurately sample multifocal tumors. Circulating microRNAs (miRNAs) are stable serum markers and differential miRNA levels occur in men with PCa. The goal of this study was to identify circulating miRNAs that were associated with aggressive or indolent PCa. We measured circulating miRNAs in 150 patients prior to surgery and compared the miRNA levels to the pathology of the entire radical prostatectomy specimen. For this study we used an exceptionally well-characterized cohort of patients who had benign prostatic hyperplasia (BPH), low-grade or high-grade PCa. Low-grade was defined as patients with 100% Gleason grade 3 tumor as determined by step-wise sectioning. High-grade PCa patients had 30-90% Gleason grade 4+5 in the tumor. BPH patients had at least two biopsies negative for PCa. Twenty one miRNAs were selected for analysis. The miRNAs were quantified by RT-qPCR and analyzed by logistic regression. High levels of 14 miRNAs were exclusively present in the serum from patients with low-grade PCa or BPH, compared to men with high-grade PCa who had consistently low levels. The expression levels of the 14 miRNAs were combined into a “miR Score” which had a negative predictive value (NPV) of 0.939 to predict absence of high-grade PCa among PCa and BPH patients. Biochemical recurrence (BCR) was known for the PCa patients and a combined “miR Risk Score” accurately classified a subset of patients with low risk of BCR (NPV 0.941). In summary, measurement of serum miRNAs may have pre-surgical utility in combination with clinical risk calculators to identify patients with low risk of harboring aggressive PCa. PMID:25874774

  1. Performance characteristics of bioassay, radioenzymatic assay, homogeneous enzyme immunoassay, and high-performance liquid chromatographic determination of serum gentamicin

    SciTech Connect

    Delaney, C.J.; Opheim, K.E.; Smith, A.L.; Plorde, J.J.

    1982-01-01

    We compared the accuracy, precision, and between-method error of the microbiological assay, the radioenzymatic assay, the homogeneous enzyme immunoassay, and the high-performance liquid chromatographic assay for the quantitation of gentamicin in serum. Precision and accuracy were evaluated by reference samples prepared to contain 0.0 to 32.7 micrograms of gentamicin per ml. Correlations between the methods utilized patient sera with gentamicin concentrations ranging from 0.6 to 13.3 micrograms/ml. All methods were reliable within acceptable limits for routine clinical use; intermethod correlation coefficients exceeded 0.96. Relative to the microbiological assay, the alternative methods offer the advantage of rapid analysis. The elapsed times for acquiring data on a set of 10 specimens under routine operating conditions were 0.5 h by the enzyme immunoassay, 4 h by the radioenzymatic assay, 5 h by the high-performance liquid chromatographic assay, and 10 h by the microbiological assay.

  2. Performance characteristics of bioassay, radioenzymatic assay, homogeneous enzyme immunoassay, and high-performance liquid chromatographic determination of serum gentamicin.

    PubMed Central

    Delaney, C J; Opheim, K E; Smith, A L; Plorde, J J

    1982-01-01

    We compared the accuracy, precision, and between-method error of the microbiological assay, the radioenzymatic assay, the homogeneous enzyme immunoassay, and the high-performance liquid chromatographic assay for the quantitation of gentamicin in serum. Precision and accuracy were evaluated by reference samples prepared to contain 0.0 to 32.7 micrograms of gentamicin per ml. Correlations between the methods utilized patient sera with gentamicin concentrations ranging from 0.6 to 13.3 micrograms/ml. All methods were reliable within acceptable limits for routine clinical use; intermethod correlation coefficients exceeded 0.96. Relative to the microbiological assay, the alternative methods offer the advantage of rapid analysis. The elapsed times for acquiring data on a set of 10 specimens under routine operating conditions were 0.5 h by the enzyme immunoassay, 4 h by the radioenzymatic assay, 5 h by the high-performance liquid chromatographic assay, and 10 h by the microbiological assay. PMID:7044297

  3. The importance of low serum levels of high-density lipoprotein cholesterol (HDL-C) as a cardiovascular risk factor.

    PubMed

    Espinosa-Larrañaga, Francisco; Vejar-Jalaf, Margarita; Medina-Santillán, Roberto

    2005-10-01

    In order to discuss and establish a joint position on the treatment of low serum levels of high-density lipoprotein cholesterol (HDL-C), a group of experts involved in the care of people with dyslipidaemia and at risk of cardiovascular disease met in Miami, Florida, U.S., on 5th and 6th March 2005. The experts came from the Latin American countries Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico and Venezuela and had at least five years of experience in the care of patients with dyslipidaemia and low HDL-C. The main objective of the meeting was to discuss and propose a treatment for low serum HDL-C levels as a cardiovascular risk factor in patients and to create a group of useful recommendations in this regard, applicable to the daily clinical practice of physicians dealing with patients with dyslipidaemia and cardiovascular disease. This document describes the methodology developed to obtain these recommendations and presents the results of this academic meeting. PMID:16342610

  4. Liver- and bone-derived isoenzymes of alkaline phosphatase in serum as determined by high-performance affinity chromatography.

    PubMed

    Anderson, D J; Branum, E L; O'Brien, J F

    1990-02-01

    To separate liver and bone alkaline phosphatase (ALP) isoenzymes in human serum, we used high-performance affinity chromatography (HPAC) on a column of wheat-germ lectin conjugated to 7-microns-diameter silica particles and an eluent containing N-acetyl-D-glucosamine (NAG). On-line spectrophotometric detection of ALP involved pumping diethanolamine-buffered p-nitrophenyl phosphate solution post-column. Bone and liver isoenzymes could be separated into two peaks with only 10% overlap when an exponential gradient was used. A linear-step gradient separated 80.9% of liver ALP and 91.6% of bone ALP in two distinct peaks. True bone and liver ALP peak areas for the linear-step gradient were determined by using correction factors, because each peak contained a co-eluted portion of the other ALP isoenzyme. The detection limit improved 10-fold over those of other techniques for ALP isoenzymes, owing to the relatively large sample that could be applied to the column. Correlation with a urea-inactivation procedure was reasonable for patients' serum samples (r = 0.98 and 0.79 for liver ALP and bone ALP, respectively). PMID:2302767

  5. High performance liquid chromatographic measurement of iothalamate in human serum and urine for evaluation of glomerular filtration rate.

    PubMed

    Bi, Daoqin; Leary, Kevin J; Weitz, Julie A; Cherstniakova, Svetlana A; Reil, Michael A; Roy, Michael J; Cantilena, Louis R

    2007-09-01

    A simple and sensitive HPLC-UV assay was developed for the measurement of iothalamate (IOT) in human serum and urine. Chromatographic separation was achieved using an embedded-carbamate-group bonded RP18 column and mobile phase consisting of 50 mM monobasic sodium phosphate and methanol (90:10, v/v) without the addition of ion-pair reagents. The assay demonstrated a high analytical reliability within the IOT concentration range of 1-150 microg/ml in serum and 25-1500 microg/ml in urine. The relative standard deviations (RSDs) for intra- and inter-day analysis were less than 5.1% in all cases. This method has been used for the evaluation of glomerular filtration rate (GFR) in subjects participating in a phase I clinical trial of a novel antimalarial medicine. The average baseline GFR was 100.41+/-19.99 ml/min/1.73 m(2) in 119 healthy volunteers. The assay may also allow the simultaneous measurements of p-aminohippuric acid (PAH), N-acetyl PAH (aPAH), and IOT with some modification. PAH, IOT, aPAH, and beta-hydroxyethyl-theophylline internal standard peaks appeared approximately at 2.5, 3.7, 5.9, and 11.8 min, respectively, in an isocratic run. PMID:17599846

  6. High dose flaxseed oil supplementation may affect fasting blood serum glucose management in human type 2 diabetics.

    PubMed

    Barre, Douglas E; Mizier-Barre, Kazimiera A; Griscti, Odette; Hafez, Kevin

    2008-01-01

    Type 2 diabetes is characterized partially by elevated fasting blood serum glucose and insulin concentrations and the percentage of hemoglobin as HbA1c. It was hypothesized that each of blood glucose and its co-factors insulin and HbA1c and would show a more favorable profile as the result of flaxseed oil supplementation. Patients were recruited at random from a population pool responding to a recruitment advertisement in the local newspaper and 2 area physicians. Completing the trial were 10 flaxseed oil males, 8 flaxseed oil females, 8 safflower (placebo) oil males and 6 safflower oil females. Patients visited on two pre-treatment occasions each three months apart (visits 1 and 2). At visit 2 subjects were randomly assigned in double blind fashion and in equal gender numbers to take flaxseed oil or safflower oil for three further months until visit 3. Oil consumption in both groups was approximately 10 g/d. ALA intake in the intervention group was approximately 5.5 g/d. Power was 0.80 to see a difference of 1 mmol of glucose /L using 12 subjects per group with a p < 0.05. Flaxseed oil had no impact on fasting blood serum glucose, insulin or HbA1c levels. It is concluded that high doses of flaxseed oil have no effect on glycemic control in type 2 diabetics. PMID:18391475

  7. Is the serum amyloid A protein in acute phase plasma high density lipoprotein the precursor of AA amyloid fibrils?

    PubMed Central

    Baltz, M L; Rowe, I F; Caspi, D; Turnell, W G; Pepys, M B

    1986-01-01

    Serum amyloid A protein (SAA), an apolipoprotein of high density lipoprotein (HDL), is generally considered to be the precursor of AA protein, which forms the fibrils in reactive systemic amyloidosis in man and animals. This view is based on amino acid sequence identity between AA and the amino-terminal portion of SAA. However, in extensive and well-controlled studies of experimentally induced murine AA amyloidosis, we were unable to demonstrate a direct precursor-product relationship between SAA, in SAA-rich HDL preparations from acute phase or amyloidotic mouse or human serum, and AA protein in the amyloid deposits. This raises the possibility that SAA in its usual form, as an apolipoprotein of HDL synthesized during the acute phase response, may not be the major precursor of AA fibrils. The amyloidogenic forms of circulating SAA molecules may not be isolated during the preparation of HDL. Alternatively, particularly in the light of recent evidence that SAA mRNA is expressed in many different tissues throughout the body of appropriately stimulated animals, amyloidogenic SAA may be derived from sources other than the liver cells in which SAA-rich HDL is synthesized. PMID:3105937

  8. MULTISCREEN SERUM ANALYSIS OF HIGHLY SENSITIZED RENAL DIALYSIS PATIENTS FOR ANTIBODIES TOWARD PUBLIC AND PRIVATE CLASS I HLA DETERMINANTS

    PubMed Central

    Duquesnoy, Rene J.; White, Linda T.; Fierst, Janet W.; Vanek, Marian; Banner, Barbara F.; Iwaki, Yuichi; Starzl, Thomas E.

    2010-01-01

    A multi screen serum analysis program has been developed that permits a determination of antibody specificity for the vast majority of highly sensitized patients awaiting transplantation. This program is based on a 2 × 2 table analysis of correlations between serum reactivity with an HLA-typed cell panel and incorporates two modifications. One implements the concept of public HLA determinants based on the serologic crossreactivity among class I HLA antigens. The other modification derives from the premise that most highly sensitized patients maintain the same PRA and antibody profiles over many months and even years. Monthly screening results for patients with persistent PRA values can therefore be combined for analysis. For 132 of 150 highly sensitized patients with >50% PRA, this multiscreen serum analysis program yielded information about antibody specificity toward public and private class I HLA determinants. The vast majority of patients (108 of 112) with PRA values between 50 and 89% showed antibody specificity generally toward one, two, or three public markers and/or the more common private HLA-A, B antigens. For 24 of 38 patients with >90% PRA, it was possible to define one or few HLA-specific antibodies. The primary objective of the multiscreen program was to develop an algorithm about computer-predicted acceptable and unacceptable donor HLA-A, B antigens for patients with preformed antibodies. A retrospective analysis of kidney transplants into 89 highly sensitized patients has demonstrated that allografts with unacceptable HLA-A, B mismatches had significantly lower actuarial survival rates than those with acceptable mismatches (P = 0.01). This was shown for both groups of 32 primary transplants (44% vs. 67% after 1 year) and 60 retransplants (50% vs. 68%). Also, serum creatinine levels were significantly higher in patients with unacceptable class I mismatches (3.0 vs. 8.4 mg% [P = 0.007] after 2 weeks; 3.9 vs. 9.1 mg% [P = 0.014] after 4 weeks

  9. High-Throughput Serum 25-Hydroxy Vitamin D Testing with Automated Sample Preparation.

    PubMed

    Stone, Judy

    2016-01-01

    Serum from bar-coded tubes, and then internal standard, are pipetted to 96-well plates with an 8-channel automated liquid handler (ALH). The first precipitation reagent (methanol:ZnSO4) is added and mixed with the 8-channel ALH. A second protein precipitating agent, 1 % formic acid in acetonitrile, is added and mixed with a 96-channel ALH. After a 4-min delay for larger precipitates to settle to the bottom of the plate, the upper 36 % of the precipitate/supernatant mix is transferred with the 96-channel ALH to a Sigma Hybrid SPE(®) plate and vacuumed through for removal of phospholipids and precipitated proteins. The filtrate is collected in a second 96-well plate (collection plate) which is foil-sealed, placed in the autosampler (ALS), and injected into a multiplexed LC-MS/MS system running AB Sciex Cliquid(®) and MPX(®) software. Two Shimadzu LC stacks, with multiplex timing controlled by MPX(®) software, inject alternately to one AB Sciex API-5000 MS/MS using positive atmospheric pressure chemical ionization (APCI) and a 1.87 min water/acetonitrile LC gradient with a 2.1 × 20 mm, 2.7 μm, C18 fused core particle column (Sigma Ascentis Express). LC-MS/MS through put is ~44 samples/h/LC-MS/MS system with dual-LC channel multiplexing. Plate maps are transferred electronically from the ALH and reformatted into LC-MS/MS sample table format using the Data Innovations LLC (DI) Instrument Manager middleware application. Before collection plates are loaded into the ALS, the plate bar code is manually scanned to download the sample table from the DI middleware to the LC-MS/MS. After acquisition-LC-MS/MS data is analyzed with AB Sciex Multiquant(®) software using customized queries, and then results are transferred electronically via a DI interface to the LIS. 2500 samples/day can be extracted by two analysts using four ALHs in 4-6 h. LC-MS/MS analysis of those samples on three dual-channel LC multiplexed LC-MS/MS systems requires 19-21 h and data analysis can be

  10. Pre-Treatment Serum C-Reactive Protein Level Is An Independent Risk Factor for Development of Nephrotoxicity in Patients Receiving High-Dose Vancomycin.

    PubMed

    He, Juan; Mao, En-Qiang; Jing, Feng; Jiang, Hui-Ting; Yang, Wan-Hua; Chen, Er-Zhen

    2016-01-01

    High-dose vancomycin treatment increases the likelihood of vancomycin-related nephrotoxicity. C-reactive protein (CRP) is a sensitive marker of systemic inflammation. In this study, we evaluated the pre-treatment serum CRP level as a risk factor of the development of nephrotoxicity in patients receiving high total daily doses (>2.5 g) of vancomycin. Data extracted from medical records for 174 patients who received total daily doses of >2.5 g of intravenous vancomycin for a minimum of 48 h and had their serum CRP level and erythrocyte sedimentation rate tested within 24 h before vancomycin treatment were subject to final analyses. Univariate analyses showed that patients who developed nephrotoxicity during vancomycin treatment had significantly higher median vancomycin serum concentration, duration of vancomycin treatment, and the serum CRP level within 24 h before vancomycin treatment than the non-nephrotoxicity group. Multivariate logistic regression analysis showed that after adjustment for potential confounders, median vancomycin serum concentration, duration of treatment, serum CRP level within 24 h before vancomycin treatment, and nephrotoxic medication were found significantly associated with the development of nephrotoxicity. This was confirmed by multivariate hazard ratio analysis after adjustment for potential confounders. In conclusion, this study provides the first evidence supporting the fact that the serum CRP level within 24 h before vancomycin treatment is an independent risk factor for the development of nephrotoxicity in patients receiving total daily doses of >2.5 g of vancomycin. Therefore, the serum CRP level within 24 h before vancomycin treatment could be a potential biomarker or prognostic factor for the development of vancomycin nephrotoxicity. PMID:26919511

  11. Fatty acid composition in serum correlates with that in the liver and non-alcoholic fatty liver disease activity scores in mice fed a high-fat diet.

    PubMed

    Wang, Xing-He; Li, Chun-Yan; Muhammad, Ishfaq; Zhang, Xiu-Ying

    2016-06-01

    In this study, we investigated the correlation between the serum fatty acid composition and hepatic steatosis, inflammation, hepatocellular ballooning scores, and liver fatty acids composition in mice fed a high-fat diet. Livers were collected for non-alcoholic fatty liver disease score analysis. Fatty acid compositions were analysed by gas chromatography. Correlations were determined by Pearson correlation coefficient. Exposed to a high-fat diet, mice developed fatty liver disease with varying severity without fibrosis. The serum fatty acid variation became more severe with prolonged exposure to a high-fat diet. This variation also correlated significantly with the variation in livers, with the types of fatty acids corresponding to liver steatosis, inflammation, and hepatocellular ballooning scores. Results of this study lead to the following hypothesis: the extent of serum fatty acid variation may be a preliminary biomarker of fatty liver disease caused by high-fat intake. PMID:27179602

  12. Effects of regular exercise on obesity and type 2 diabete mellitus in Korean children: improvements glycemic control and serum adipokines level

    PubMed Central

    Lee, Sung Soo; Kang, Sunghwun

    2015-01-01

    [Purpose] The aim of the study was to clarify the effects of regular exercise on lipid profiles and serum adipokines in Korean children. [Subjects and Methods] Subjects were divided into controls (n=10), children who were obese (n=10), and children with type 2 diabetes mellitus (n=10). Maximal oxygen uptake (VO2max), body composition, lipid profiles, glucagon, insulin and adipokines (leptin, resistin, visfatin and retinol binding protein 4) were measured before to and after a 12-week exercise program. [Results] Body weight, body mass index, and percentage body fat were significantly higher in the obese and diabetes groups compared with the control group. Total cholesterol, triglycerides, low-density lipoprotein cholesterol and glycemic control levels were significantly decreased after the exercise program in the obese and diabetes groups, while high-density lipoprotein cholesterol levels were significantly increased. Adipokines were higher in the obese and diabetes groups compared with the control group prior to the exercise program, and were significantly lower following completion. [Conclusion] These results suggest that regular exercise has positive effects on obesity and type 2 diabetes mellitus in Korean children by improving glycemic control and reducing body weight, thereby lowering cardiovascular risk factors and adipokine levels. PMID:26180345

  13. Comparative analysis of conjugated bile acids in human serum using high-performance liquid chromatography and capillary electrophoresis.

    PubMed

    Lee, B L; New, A L; Ong, C N

    1997-12-19

    This paper describes the analysis of conjugated bile acids in human serum using reversed-phase high-performance liquid chromatography (HPLC) and micellar electrokinetic capillary electrophoresis (CE). Samples of healthy subjects and patients with different hepatic diseases were pretreated with a simple preparation procedure using a solid-phase extraction technique. The optimal analytical conditions of both chromatographic methods were investigated for the convenience and reliability for routine analysis. Both HPLC and CE methods were found to be reliable and compatible. The recoveries of nine bile acid conjugates using both methods were generally >85% and reproducibility >90%. The day-to-day variation of retention time was <5% for HPLC, while the variation of migration time for CE was <3%. Although the detection limit of the HPLC method (1 nmol/ml) was five times more sensitive than that of the CE method, the CE method was considered to be more time and cost effective. PMID:9518169

  14. Alpha slow-moving high-density-lipoprotein subfraction in serum of a patient with radiation enteritis and peritoneal carcinosis

    SciTech Connect

    Peynet, J.; Legrand, A.; Messing, B.; Thuillier, F.; Rousselet, F.

    1989-04-01

    An alpha slow-moving high-density-lipoprotein (HDL) subfraction was seen in a patient presenting with radiation enteritis and peritoneal carcinosis, who was given long-term cyclic parenteral nutrition. This subfraction, observed in addition to normal HDL, was precipitated with low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL) by sodium phosphotungstate-magnesium chloride. The patient's serum lipoproteins were analyzed after fractionation by density gradient ultracentrifugation. The alpha slow-moving HDL floated in the ultracentrifugation subfractions with densities ranging from 1.028 to 1.084 kg/L, and their main apolipoproteins included apolipoprotein E in addition to apolipoprotein A-I. These HDL were larger than HDL2. The pathogenesis of this unusual HDL subfraction is hypothesized.

  15. High-performance liquid chromatographic determination of loracarbef, a potential metabolite, cefaclor and cephalexin in human plasma, serum and urine.

    PubMed

    Kovach, P M; Lantz, R J; Brier, G

    1991-06-14

    A high-performance liquid chromatographic (HPLC) method is reported for the determination of a new carbacephem antibiotic, loracarbef, a hydroxylated analogue, and two cephalosporins, cefaclor and cephalexin, in plasma, serum, and urine. The antibiotics are extracted from plasma by means of C18 solid-phase cartridges. Urine samples are diluted with water and directly injected on the HPLC system. The HPLC system utilizes a Supelcosil LC-18-DB (250 mm x 4.6 mm I.D.) reversed-phase column and ultraviolet detection at 265 nm. The limit of quantitation is 0.5 micrograms/ml for each compound. Excellent correlation of plasma concentrations is shown between results determined by HPLC and those obtained by microbiological agar-well diffusion assays. Stability studies of loracarbef in human plasma show the antibiotic to be stable for at least 24 h at room temperature and for at least twelve months at -20 degrees C. PMID:1918240

  16. Serum cytokine, chemokine and hormone levels in Saudi adults with pre-diabetes: a one-year prospective study.

    PubMed

    Al-Daghri, Nasser M; Al-Ajlan, Abdulrahman Sm; Alfawaz, Hanan; Yakout, Sobhy M; Aljohani, Naji; Kumar, Sudhesh; Alokail, Majed S

    2015-01-01

    Approximately 5-10% of subjects with pre-diabetes eventually progress to diabetes every year. While inflammation is thought to be involved in the development of obesity-related type 2 diabetes mellitus (T2DM), the relation between inflammation and pre-diabetes remains largely unexplored. In this study we examined a comprehensive panel of 10 serum biomarkers involved in overweight and obese subjects with pre-diabetes. A total of 98 subjects (23 males, 75 females) were advised to reduce total intake of fat, increase fiber intake and physical activity. Serum cytokines, MCP and other hormones were assessed by multiplex cytokine profiling. Results show that CRP, IL-6, leptin, IL-10, MCP, resistin, serpin, and TNF-α were significantly lower after 12-months than baseline. Serum concentrations of other adipocytokines, including adipsin and leptin were modestly lower in the 12-month follow-up than baseline, but failed to reach statistical significance. Changes in HbA1c was found to be positively correlated with adipsin, CRP, IL-6, IL-10, resistin, serpin, and TNF-α. The results suggest that promotion of lifestyle changes for one year among overweight and obese subjects modestly changes several circulating inflammatory biomarkers which maybe favorable in reducing risk for T2DM progression. PMID:26617895

  17. Norepinephrine stimulates progesterone production in highly estrogenic bovine granulosa cells cultured under serum-free, chemically defined conditions

    PubMed Central

    2012-01-01

    Background Since noradrenergic innervation was described in the ovarian follicle, the actions of the intraovarian catecholaminergic system have been the focus of a variety of studies. We aimed to determine the gonadotropin-independent effects of the catecholamine norepinephrine (NE) in the steroid hormone profile of a serum-free granulosa cell (GC) culture system in the context of follicular development and dominance. Methods Primary bovine GCs were cultivated in a serum-free, chemically defined culture system supplemented with 0.1% polyvinyl alcohol. The culture features were assessed by hormone measurements and ultrastructural characteristics of GCs. Results GCs produced increasing amounts of estradiol and pregnenolone for 144h and maintained ultrastructural features of healthy steroidogenic cells. Progesterone production was also detected, although it significantly increased only after 96h of culture. There was a highly significant positive correlation between estradiol and pregnenolone production in high E2-producing cultures. The effects of NE were further evaluated in a dose–response study. The highest tested concentration of NE (10 (−7) M) resulted in a significant increase in progesterone production, but not in estradiol or pregnenolone production. The specificity of NE effects on progesterone productio n was further investigated by incubating GCs with propranolol (10 (−8) M), a non-selective beta-adrenergic antagonist. Conclusions The present culture system represents a robust model to study the impact of intrafollicular factors, such as catecholamines, in ovarian steroidogenesis and follicular development. The results of noradrenergic effects in the steroidogenesis of GC have implications on physiological follicular fate and on certain pathological ovarian conditions such as cyst formation and anovulation. PMID:23171052

  18. Purified human pancreatic duct cell culture conditions defined by serum-free high-content growth factor screening.

    PubMed

    Hoesli, Corinne A; Johnson, James D; Piret, James M

    2012-01-01

    The proliferation of pancreatic duct-like CK19+ cells has implications for multiple disease states including pancreatic cancer and diabetes mellitus. The in vitro study of this important cell type has been hampered by their limited expansion compared to fibroblast-like vimentin+ cells that overgrow primary cultures. We aimed to develop a screening platform for duct cell mitogens after depletion of the vimentin+ population. The CD90 cell surface marker was used to remove the vimentin+ cells from islet-depleted human pancreas cell cultures by magnetic-activated cell sorting. Cell sorting decreased CD90+ cell contamination of the cultures from 34±20% to 1.3±0.6%, yielding purified CK19+ cultures with epithelial morphology. A full-factorial experimental design was then applied to test the mitogenic effects of bFGF, EGF, HGF, KGF and VEGF. After 6 days in test conditions, the cells were labelled with BrdU, stained and analyzed by high-throughput imaging. This screening assay confirmed the expected mitogenic effects of bFGF, EGF, HGF and KGF on CK19+ cells and additionally revealed interactions between these factors and VEGF. A serum-free medium containing bFGF, EGF, HGF and KGF led to CK19+ cell expansion comparable to the addition of 10% serum. The methods developed in this work should advance pancreatic cancer and diabetes research by providing effective cell culture and high-throughput screening platforms to study purified primary pancreatic CK19+ cells. PMID:22442738

  19. High throughput LC-MS/MS method for the simultaneous analysis of multiple vitamin D analytes in serum.

    PubMed

    Jenkinson, Carl; Taylor, Angela E; Hassan-Smith, Zaki K; Adams, John S; Stewart, Paul M; Hewison, Martin; Keevil, Brian G

    2016-03-01

    Recent studies suggest that vitamin D-deficiency is linked to increased risk of common human health problems. To define vitamin D 'status' most routine analytical methods quantify one particular vitamin D metabolite, 25-hydroxyvitamin D3 (25OHD3). However, vitamin D is characterized by complex metabolic pathways, and simultaneous measurement of multiple vitamin D metabolites may provide a more accurate interpretation of vitamin D status. To address this we developed a high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to analyse multiple vitamin D analytes, with particular emphasis on the separation of epimer metabolites. A supportive liquid-liquid extraction (SLE) and LC-MS/MS method was developed to quantify 10 vitamin D metabolites as well as separation of an interfering 7α-hydroxy-4-cholesten-3-one (7αC4) isobar (precursor of bile acid), and validated by analysis of human serum samples. In a cohort of 116 healthy subjects, circulating concentrations of 25-hydroxyvitamin D3 (25OHD3), 3-epi-25-hydroxyvitamin D3 (3-epi-25OHD3), 24,25-dihydroxyvitamin D3 (24R,25(OH)2D3), 1,25-dihydroxyvitamin D3 (1α,25(OH)2D3), and 25-hydroxyvitamin D2 (25OHD2) were quantifiable using 220μL of serum, with 25OHD3 and 24R,25(OH)2D3 showing significant seasonal variations. This high-throughput LC-MS/MS method provides a novel strategy for assessing the impact of vitamin D on human health and disease. PMID:26874878

  20. High Uric Acid (UA) Negatively Affects Serum Tartrate-Resistant Acid Phosphatase 5b (TRACP 5b) Immunoassay

    PubMed Central

    Wu, Zhi-Qi; Zhang, Yan; Xie, Erfu; Song, Wei-Juan; Yang, Rui-Xia; Yan, Cheng-Jing; Zhang, Bing-Feng; Xu, Hua-Guo

    2016-01-01

    Background Bone metastases often occur in the majority of patients with advanced cancer, such as prostate cancer, lung cancer and breast cancer. Serum tartrate-resistant acid phosphatase 5b (TRACP 5b), a novel bone resorption marker, has been used gradually in the clinics as a specific and sensitive marker of bone resorption for the early diagnosis of cancer patients with bone metastasis. Here, we reported that high concentrations of uric acid (UA) lead to decrease of TRACP 5b levels and determined whether TRACP 5b level was associated with UA in interference experiment. Methods A total of 77 patients with high concentrations of UA and 77 healthy subjects were tested to evaluate the differences in their TRACP 5b levels. Serial dilutions of UA were respectively spiked with a known concentration of TRACP 5b standard sample, then Serum TRACP 5b was detected by using bone TRAP® Assay. A correction equation was set to eliminate UA-derived TRACP 5b false-decrease. The effect of this correction was evaluated in high-UA individuals. Results The average TRACP level of the high-UA individuals (1.47± 0.62 U/L) was significantly lower than that of the healthy subjects (2.62 ± 0.63 U/L) (t-test, p<0.0001). The UA correction equation derived: ΔTRACP 5b = -1.9751lgΔUA + 3.7365 with an R2 = 0.98899. Application of the UA correction equation resulted in a statistically non-significant difference in TRACP 5b values between the healthy subjects and high-UA individuals (p = 0.24). Conclusions High UA concentrations can falsely decrease TRACP 5b levels due to a method-related systematic error. To avoid misdiagnoses or inappropriate therapeutic decisions, increased attention should be paid to UA interference, when TRACP 5b is used for early diagnosis of cancer patients with bone metastasis, evaluation of the aggressiveness of osteosarcoma or prediction of survival in prostate cancer and breast cancer with bone metastases. PMID:26800211

  1. Association between serum levels of high sensitive C-reactive protein and inflammation activity in chronic gastritis patients.

    PubMed

    Rahmani, Asghar; Moradkhani, Atefeh; Hafezi Ahmadi, Mohammad Reza; Jafari Heirdarlo, Ali; Abangah, Ghobad; Asadollahi, Khairollah; Sayehmiri, Kourosh

    2016-05-01

    Background Gastritis is an important premalignant lesion and recent studies suggested a production of inflammatory cytokine-like C-reactive protein during gastritis. This study aimed to determine any relationship between high sensitive C-reactive protein (hs-CRP) and inflammation activity among patients with gastritis. Methods Demographic and clinical variables of participants were collected by a validated questionnaire. Using histology of the gastric mucosa, Helicobacter pylori status was investigated and serum concentrations of hs-CRP were measured among dyspeptic patients. Correlation between hs-CRP serum levels and inflammation activities was evaluated by logistic regression analysis. The relation between active inflammation and other variables was evaluated by logic link function model. Results Totally 239 patients (56.6% female) were analysed. The prevalence of mild, moderate and severe inflammation activities was 66.5%, 23.8% and 9.6% respectively. Mean ± SD of hs-CRP among men and women were 2.85 ± 2.84 mg/dl and 2.80 ± 4.80 mg/dl (p = 0.047) respectively. Mean ± SD of hs-CRP among patients with H. pylori infection, gland atrophy, metaplasia and dysplasia were 2.83 ± 3.80 mg/dl, 3.52 ± 5.1 mg/dl, 2.22 ± 2.3 mg/dl and 5.3 ± 5.04 mg/dl respectively. Relationship between hs-CRP and inflammation activities (p < 0.01) was significant. A significant relationship between dysplasia and hs-CRP (p < 0.04) was revealed. A significant relationship between age and hs-CRP was detected (p < 0.05). Conclusion Although serum hs-CRP is not a specific biomarker for gastritis, elevated hs-CRP levels may be considered as a predictive marker of changes in gastric mucosa and a promising therapeutic target for patients with gastritis. PMID:26758551

  2. High Levels of Serum DPP-4 Activity Are Associated with Low Bone Mineral Density in Obese Postmenopausal Women

    PubMed Central

    2016-01-01

    Background Dipeptidyl peptidase 4/CD26 (DPP-4) is a widely expressed cell surface serine protease. DPP-4 inhibitors, one of common anti-diabetic agents play a protective role in bone metabolism in recent studies. A soluble form of DPP-4 is found in serum, and exhibits DPP-4 enzymatic activity. However, the physiological role of serum or soluble DPP-4 and its relationship with DPP-4 enzymatic function remain poorly understood. The aims of current study were to determine the association between serum DPP-4 activity and bone mineral density (BMD) in postmenopausal women. Methods We recruited data and serum samples from 124 consecutive healthy postmenopausal women aged >50 years. We divided study subjects into obese (body mass index [BMI] ≥25 kg/m2) and non-obese (BMI <25 kg/m2) postmenopausal women and examined the correlation between serum DPP-4 activity and clinical variables in each groups. Results A total of 124 postmenopausal women was enrolled, with a mean age of 59.9±7.1 years. The mean BMI of the study patients was 24.4±2.8 kg/m2. Regarding bone turnover markers, serum DPP-4 activity was positively correlated with serum calcium concentrations, intact parathyroid hormone, and serum C-telopeptide levels in all of the study subjects. However, there was no association between serum DPP-4 activity and BMD in the spine or femoral neck in all of the study subjects. Serum DPP-4 activity was negatively correlated (R=−0.288, P=0.038) with BMD of the spine in obese postmenopausal women. Conclusion This study demonstrated for the first time that serum soluble DPP-4 activity was negatively correlated with BMD in obese postmenopausal women. PMID:26676330

  3. Analysis of glipizide binding to normal and glycated human serum albumin by high-performance affinity chromatography.

    PubMed

    Matsuda, Ryan; Li, Zhao; Zheng, Xiwei; Hage, David S

    2015-07-01

    In diabetes, the elevated levels of glucose in the bloodstream can result in the nonenzymatic glycation of proteins such as human serum albumin (HSA). This type of modification has been shown to affect the interactions of some drugs with HSA, including several sulfonylurea drugs that are used to treat type II diabetes. This study used high-performance affinity chromatography (HPAC) to examine the interactions of glipizide (i.e., a second-generation sulfonylurea drug) with normal HSA or HSA that contained various levels of in vitro glycation. Frontal analysis indicated that glipizide was interacting with both normal and glycated HSA through two general groups of sites: a set of relatively strong interactions and a set of weaker interactions with average association equilibrium constants at pH 7.4 and 37 °C in the range of 2.4-6.0 × 10(5) and 1.7-3.7 × 10(4) M(-1), respectively. Zonal elution competition studies revealed that glipizide was interacting at both Sudlow sites I and II, which were estimated to have affinities of 3.2-3.9 × 10(5) and 1.1-1.4 × 10(4) M(-1). Allosteric effects were also noted to occur for this drug between the tamoxifen site and the binding of R-warfarin at Sudlow site I. Up to an 18% decrease in the affinity for glipizide was observed at Sudlow site I ongoing from normal HSA to glycated HSA, while up to a 27% increase was noted at Sudlow site II. This information should be useful in indicating how HPAC can be used to investigate other drugs that have complex interactions with proteins. These results should also be valuable in providing a better understanding of how glycation may affect drug-protein interactions and the serum transport of drugs such as glipizide during diabetes. PMID:25912461

  4. Analysis of naltrexone and its metabolite 6-beta-naltrexol in serum with high-performance liquid chromatography

    PubMed Central

    2012-01-01

    Background Naltrexone has been proven to be an effective treatment option for the treatment of alcohol dependency. In this article we introduce a reliable and simple method developed for the simultaneous determination of naltrexone and 6-β-naltrexol in human serum by using high-performance liquid chromatography (HPLC). Findings Liquid-liquid extraction with butyl acetate from basic solutions (pH 9) was chosen for extraction with nalorphine as an internal standard (IS). Analytes were back-extracted from organic solvent into perchloric acid. The acid extract was chromatographed by HPLC with a reverse-phase ODS-column and electrochemical detector. The mobile phase was a NaH2PO4-solution with acetonitrile as an organic modifier and octanesulphonic acid and tetraethylammonium hydrogen sulphate as ion-pair reagents. The recovery of the extraction method was 48% for naltrexone and 75% for 6-β-naltrexol. The limit of quantification was 5.0 ng/ml for naltrexone and 1.0 ng/ml for 6-β-naltrexol. The analysed concentrations of naltrexone differed from the theoretic concentrations by 0.7 to 2.3% and those of 6-β-naltrexol by 2.6%. The relative standard deviation of within-day assay was from 0.9 to 5.7% for naltrexone and from 0.8 to 4.2% for 6-β-naltrexol; for the between-day assay it was 5.7% and 4.2%, respectively. Conclusions Our results indicate that the developed method is suitable for determination of naltrexone and 6-β-naltrexol in human serum. PMID:22894733

  5. Identification and quantification of bleomycin in serum and tumor tissue by liquid chromatography coupled to high resolution mass spectrometry.

    PubMed

    Kosjek, Tina; Krajnc, Anja; Gornik, Tjasa; Zigon, Dusan; Groselj, Ales; Sersa, Gregor; Cemazar, Maja

    2016-11-01

    Bleomycin is a cytotoxic antibiotic available as a compost of structurally strongly related glycopeptides, which is in vivo found chelated with several metals. Its pharmacotherapy has merely been based on experimental dose - response data, whereas its biodistribution and pharmacokinetics remain fundamentally unknown. This is reasoned by an absence of a specific and sensitive mass spectrometry-based analytical method for its determination in biological tissues. We herein reveal the results of our study on the mass spectrometric behavior of two main bleomycin fractions A2 and B2, including their metal complexes, particularly the predominant copper chelates. In the electrospray ion source bleomycin forms double charged species, where for the metal-free fraction A2 and its copper complex m/z 707.76 and m/z 707.21 are seen, respectively. Hence, the second isotopic ion of the chelate (m/z 707.71) nearly coincides with the first isotopic ion of the metal-free fraction. This phenomenon can only be followed by high-resolution mass spectrometry, and is considered the plausible reason, why the attempts to determine bleomycin with mass spectrometry have been so scarce. The presented paper further describes a sensitive and selective liquid chromatography - mass spectrometry analytical method for determination of bleomycin in serum and tumor tissues. This newly developed method was employed for bleomycin pharmacokinetic studies in serum and tumors of laboratory animals. Additionally, the method was employed for determination of bleomycin pharmacokinetic parameters in elderly patients in order to determine the effective therapeutic window of electrochemotherapy with bleomycin. PMID:27591601

  6. The V227A polymorphism at the PPARA locus is associated with serum lipid concentrations and modulates the association between dietary polyunsaturated fatty acid intake and serum high density lipoprotein concentrations in Chinese women.

    PubMed

    Chan, Edmund; Tan, Chuen Seng; Deurenberg-Yap, Mabel; Chia, Kee Seng; Chew, Suok Kai; Tai, E Shyong

    2006-08-01

    Peroxisome proliferators activated receptor alpha (PPARalpha) regulates the transcription of several proteins involved in human lipoprotein metabolism. We screened the PPARA locus for polymorphisms in 20 unrelated subjects from each of three ethnic groups (Chinese, Malays and Asian Indians). Only the V227A polymorphism was observed. We genotyped 4248 subjects (2899 Chinese, 761 Malay and 588 Asian Indians) and found allele frequencies for the A227 allele of 0.04 in Chinese, 0.006 in Malays and 0.003 in Asian Indians. We examined the associations between this polymorphism and serum lipid concentrations in Chinese. In women, but not in men, the presence of the A227 allele was associated with lower serum concentrations of total cholesterol [5.38mmol/l (95%CI: 5.22-5.54) versus 5.21mmol/l (95%CI: 4.99-5.43), p=0.047] and triglycerides [1.19mmol/l (95%CI: 1.10-1.28) versus 1.09mmol/l (95%CI: 0.98-1.21), p=0.048]. We also found that the V227A polymorphism modulates the association between dietary polyunsaturated fatty acid intake and serum high density lipoprotein concentration (p-value for interaction=0.049). Our findings implicate PPARalpha in the lipid lowering associated with diets high in PUFA and suggests that genetic variation at the PPARA locus may determine the lipid response to changes in PUFA intake. PMID:16288935

  7. A fluorescence-based high throughput assay for the determination of small molecule–human serum albumin protein binding

    PubMed Central

    McCallum, Megan M.; Pawlak, Alan J.; Shadrick, William R.; Simeonov, Anton; Jadhav, Ajit; Yasgar, Adam; Maloney, David J.; Arnold, Leggy A.

    2014-01-01

    Herein, we describe the development of a fluorescence-based high throughput assay to determine the small molecule binding towards human serum albumin (HSA). This innovative competition assay is based on the use of a novel fluorescent small molecule Red Mega 500 with unique spectroscopic and binding properties. The commercially available probe displays a large fluorescence intensity difference between the protein-bound and protein-unbound state. The competition of small molecules for HSA binding in the presence of probe resulted in low fluorescence intensities. The assay was evaluated with the LOPAC small molecule library of 1280 compounds identifying known high protein binders. The small molecule competition of HSA–Red Mega 500 binding was saturable at higher compound concentrations and exhibited IC50 values between 3–24 μM. The compound affinity towards HSA was confirmed by isothermal titration calorimetry indicating that the new protein binding assay is a valid high throughput assay to determine plasma protein binding. PMID:24390461

  8. High-throughput sequencing enhanced phage display enables the identification of patient-specific epitope motifs in serum

    PubMed Central

    Christiansen, Anders; Kringelum, Jens V.; Hansen, Christian S.; Bøgh, Katrine L.; Sullivan, Eric; Patel, Jigar; Rigby, Neil M.; Eiwegger, Thomas; Szépfalusi, Zsolt; Masi, Federico de; Nielsen, Morten; Lund, Ole; Dufva, Martin

    2015-01-01

    Phage display is a prominent screening technique with a multitude of applications including therapeutic antibody development and mapping of antigen epitopes. In this study, phages were selected based on their interaction with patient serum and exhaustively characterised by high-throughput sequencing. A bioinformatics approach was developed in order to identify peptide motifs of interest based on clustering and contrasting to control samples. Comparison of patient and control samples confirmed a major issue in phage display, namely the selection of unspecific peptides. The potential of the bioinformatic approach was demonstrated by identifying epitopes of a prominent peanut allergen, Ara h 1, in sera from patients with severe peanut allergy. The identified epitopes were confirmed by high-density peptide micro-arrays. The present study demonstrates that high-throughput sequencing can empower phage display by (i) enabling the analysis of complex biological samples, (ii) circumventing the traditional laborious picking and functional testing of individual phage clones and (iii) reducing the number of selection rounds. PMID:26246327

  9. High-Throughput Analysis of Serum Antigens Using Sandwich ELISAs on Microarrays

    SciTech Connect

    Servoss, Shannon; Gonzalez, Rachel M.; Varnum, Susan M.; Zangar, Richard C.

    2009-05-11

    Enzyme-linked immunosorbent assay (ELISA) microarrays promise to be a powerful tool for the detection and validation of disease biomarkers. ELISA microarrays are capable of simultaneous detection of many proteins using a small sample volume. Although there are many potential pitfalls to the use of ELISA microarrays, these can be avoided by careful planning of experiments. In this chapter we describe a high-throughput protocol for processing ELISA microarrays that will result in reliable and reproducible data.

  10. Highly absorptive curcumin reduces serum atherosclerotic low-density lipoprotein levels in patients with mild COPD

    PubMed Central

    Funamoto, Masafumi; Sunagawa, Yoichi; Katanasaka, Yasufumi; Miyazaki, Yusuke; Imaizumi, Atsushi; Kakeya, Hideaki; Yamakage, Hajime; Satoh-Asahara, Noriko; Komiyama, Maki; Wada, Hiromichi; Hasegawa, Koji; Morimoto, Tatsuya

    2016-01-01

    Purpose COPD is mainly caused by tobacco smoking and is associated with a high frequency of coronary artery disease. There is growing recognition that the inflammation in COPD is not only confined to the lungs but also involves the systemic circulation and can impact nonpulmonary organs, including blood vessels. α1-antitrypsin–low-density lipoprotein (AT-LDL) complex is an oxidatively modified LDL that accelerates atherosclerosis. Curcumin, one of the best-investigated natural products, is a powerful antioxidant. However, the effects of curcumin on AT-LDL remain unknown. We hypothesized that Theracurmin®, a highly absorptive curcumin with improved bioavailability using a drug delivery system, ameliorates the inflammatory status in subjects with mild COPD. Patients and methods This is a randomized, double-blind, parallel-group study. Subjects with stages I–II COPD according to the Japanese Respiratory Society criteria were randomly assigned to receive 90 mg Theracurmin® or placebo twice a day for 24 weeks, and changes in inflammatory parameters were evaluated. Results There were no differences between the Theracurmin® and placebo groups in terms of age, male/female ratio, or body mass index in 39 evaluable subjects. The percent changes in blood pressure and hemoglobin A1c and LDL-cholesterol, triglyceride, or high-density lipoprotein-cholesterol levels after treatment were similar for the two groups. However, the percent change in the AT-LDL level was significantly (P=0.020) lower in the Theracurmin® group compared with the placebo group. Conclusion Theracurmin® reduced levels of atherosclerotic AT-LDL, which may lead to the prevention of future cardiovascular events in mild COPD subjects. PMID:27616885