Prasmickaite, Lina; Berge, Gisle; Bettum, Ingrid J
patients with poor prognosis that might benefit from IFN-α. The choice of osteopontin was based on the knowledge about the dual role of this protein in cancer and immune response, an apparent association between OPN and IFN signaling and a prognostic value of OPN in multiple other tumor types. Serum...... relapse-free survival, the effect on overall survival is not significant. However, a small subset of patients benefits from the treatment, signifying the need for biomarkers able to identify a responding subgroup. Here we evaluated whether serum osteopontin (OPN) could function as a biomarker identifying...... samples from 275 high-risk melanoma patients enrolled in the Nordic Adjuvant IFN Melanoma trial were analyzed for circulating OPN concentrations and OPN promoter polymorphisms in position -443. The potential relation between serum OPN levels, the genotypes and survival in non-treated patients and patients...
Background: Crystalline silica is a commonly used mineral in various industries and construction activities, and it is so important introducing potential biomarkers to identify early indicators of biological effects in its high‑risk occupational exposures. Aim: The present study was aimed to assess the blood and urinary neopterin ...
Bilibio, João P; Souza, Carlos A B; Rodini, Gustavo P; Andreoli, Carolina G; Genro, Vanesa K; de Conto, Emily; Cunha-Filho, João S L
To evaluate serum prolactin and CA-125 levels as biomarkers for the diagnosis of peritoneal endometriosis. A prospective study was performed. Blood samples were drawn from a peripheral vein during the secretory phase of the menstrual cycle (day 19-21 prior to the surgery) to analyze through relative operating characteristic curve the serum prolactin and CA-125 levels for diagnosis of peritoneal endometriosis. The study was performed with 97 participants, 63 women with peritoneal endometriosis and 34 healthy women. The sensitivity and specificity of peritoneal endometriosis diagnosis were equivalent for prolactin (21 and 99%) and for CA-125 (27 and 97%; p = 0.58). These two markers were used in a parallel test utilizing the usual cutoff (prolactin 20.0 ng/ml and CA-125 35 U/I). The sensitivity and specificity were 44 and 99%. However, by utilizing the best cutoff (prolactin 14.8 ng/ml and for CA-125 19.8 U/I), sensitivity, specificity and negative predictive value were 77, 88 and 97%, respectively. Serum CA-125 and prolactin levels assessed together, and considering the cutoff for CA-125 (19.9 U/I) and prolactin (14.8 ng/ml), allow the diagnosis of peritoneal endometriosis with acceptable sensitivity and specificity (77 and 88%) and a high negative predictive value (97%). © 2014 S. Karger AG, Basel.
Full Text Available There are controversial results about the role of serum leptin and adiponectin levels as biomarkers of the severity of proteinuria in lupus nephritis.The aim of this study was to evaluate the relationship between serum leptin and adiponectin levels with severity of proteinuria secondary to lupus nephritis (LN.In a cross-sectional study, 103 women with systemic lupus erythematosus (SLE were evaluated for kidney involvement. We compared 30 SLE patients with LN, all of them with proteinuria, versus 73 SLE patients without renal involvement (no LN. A comprehensive set of clinical and laboratory variables was assessed, including serum levels of leptin and adiponectin by ELISA. Multivariate analyses were used to adjust for potential confounders associated with proteinuria in LN.We found higher adiponectin levels in the LN group compared with the no LN group (20.4 ± 10.3 vs 15.6 ± 7.8 μg/mL; p = 0.02, whereas no differences were observed in leptin levels (33.3 ± 31.4 vs 22.5 ± 25.5 ng/mL; p = 0.07. Severity of proteinuria correlated with an increase in adiponectin levels (r = 0.31; p = 0.001, but no correlation was observed with leptin. Adiponectin levels were not related to anti-dsDNA or anti-nucleosome antibodies. In the logistic regression, adiponectin levels were associated with a high risk of proteinuria in SLE (OR = 1.06; 95% CI 1.01-1.12; p = 0.02. Instead, leptin was not associated with LN.These findings indicate that adiponectin levels are useful markers associated with proteinuria in LN. Further longitudinal studies are required to identify if these levels are predictive of renal relapse.
Jason W Bauer
Full Text Available Systemic lupus erythematosus (SLE is a serious systemic autoimmune disorder that affects multiple organ systems and is characterized by unpredictable flares of disease. Recent evidence indicates a role for type I interferon (IFN in SLE pathogenesis; however, the downstream effects of IFN pathway activation are not well understood. Here we test the hypothesis that type I IFN-regulated proteins are present in the serum of SLE patients and correlate with disease activity.We performed a comprehensive survey of the serologic proteome in human SLE and identified dysregulated levels of 30 cytokines, chemokines, growth factors, and soluble receptors. Particularly striking was the highly coordinated up-regulation of 12 inflammatory and/or homeostatic chemokines, molecules that direct the movement of leukocytes in the body. Most of the identified chemokines were inducible by type I IFN, and their levels correlated strongly with clinical and laboratory measures of disease activity.These data suggest that severely disrupted chemokine gradients may contribute to the systemic autoimmunity observed in human SLE. Furthermore, the levels of serum chemokines may serve as convenient biomarkers for disease activity in lupus.
Karaca, Oguz; Guler, Gamze B; Guler, Ekrem; Gunes, H Murat; Alizade, Elnur; Agus, Hicaz Z; Gol, Gokhan; Kahveci, Gokhan; Esen, Ozlem; Esen, A Metin; Turkmen, Muhsin
The authors investigated the prognostic relevance of serum carbohydrate antigen 125 (CA125) levels in nonischemic dilated cardiomyopathy (NICMP) and assessed whether increased levels relate to the degree of functional mitral regurgitation (FMR). Seventy-seven patients with NICMP were enrolled and followed-up for 10 ± 2 months in this prospective study. Receiver-operating characteristic analysis established a cutoff CA125 value of 25 U/mL for predicting mortality. Patients were divided into two groups according to their CA125 levels (CA125 <25 U/mL [n=58] and CA125 ≥ 25 U/mL [n=19]). Patients with high CA125 values had statistically worse functional status, higher B-type natriuretic peptide (BNP) levels, higher left ventricular volumes, lower ejection fraction, higher E/Em ratio, higher pulmonary artery systolic pressure, and more severe FMR. On the multivariate analysis, serum CA125 (P=.002) and severe FMR (P=.04) were identified as the independent predictors of mortality. Serum CA125 levels also correlated with BNP levels and FMR severity (P<.001). Serum CA125 is a powerful prognostic biomarker that is associated with the severity of heart failure, serum BNP levels and several echocardiographic parameters including left ventricular volumes, systolic and diastolic functions, pulmonary artery pressure, and the degree of FMR. Serum CA125 was also shown as an independent predictor of mortality during 10 ± 2 months of follow-up. © 2011 Wiley Periodicals, Inc.
Tu, Huakang; Sun, Liping; Dong, Xiao; Gong, Yuehua; Xu, Qian; Jing, Jingjing; Yuan, Yuan
OBJECTIVE. Clinical implications of serum anti-Helicobacter pylori immunoglobulin G (IgG) titer were unclear. This study investigated the associations of serum anti-H. pylori IgG titer with grade of histological gastritis, mucosal bacterial density and levels of serum biomarkers, including pepsinogen (PG) I, PGII, PGI/II ratio and gastrin-17. MATERIAL AND METHODS. Study participants were from a screening program in northern China. Serum anti-H. pylori IgG measurements were available for 5922 patients with superficial gastritis. Serum anti-H. pylori IgG titer and serum biomarkers were measured using ELISA, and gastric biopsies were evaluated using standardized criteria. RESULTS. In patients with mild, moderate or severe superficial gastritis, the mean serum anti-H. pylori IgG titers were 17.3, 33.4 and 54.4 EIU (p for trend pylori density score increased from 0 to 3, the mean serum anti-H. pylori IgG titers also increased from 24.7 to 44.8 EIU (p for trend pylori IgG titer was associated positively with serum PGI, PGII and gastrin-17 concentrations and negatively with PGI/II ratio, and the association was the strongest for PGII. The mean PGII concentration of the patients in the highest quartile of IgG titer was twice the mean concentration of the patients in the lowest quartile (17.2 vs. 8.6 EIU, p pylori IgG titer was associated positively with grade of histological gastritis, mucosal bacterial density and concentrations of serum PGI, PGII and gastrin-17, and negatively with PGI/II ratio.
Full Text Available Background: Recommendations have been made, following the multicenter Surviving Sepsis Campaign study, to standardize the definition of severe sepsis with reference to several parameters such as haemodynamic stability, acid-base balance, bilirubin, creatinine, International Normalized Ratio (INR, urine output and pulmonary functional value of the ratio between arterial oxigen partial pressure and inspiratory oxigen concentration. Procalcitonin (PCT is considered to be a gold standard biomarker for the inflammatory response, and recent studies have shown that it may help to discover whether a seriously ill person is developing sepsis. C-reactive protein (CRP is also used as a marker of inflammation in the body, as its blood levels increase if there is any inflammation in the body. The aim of this study was to evaluate serum procalcitonin and C-reactive protein levels as diagnostic and prognostic biomarkers of severe sepsis.
Saleh, A; George, J; Faour, M; Klika, A K; Higuera, C A
The diagnosis of periprosthetic joint infection (PJI) is difficult and requires a battery of tests and clinical findings. The purpose of this review is to summarize all current evidence for common and new serum biomarkers utilized in the diagnosis of PJI. We searched two literature databases, using terms that encompass all hip and knee arthroplasty procedures, as well as PJI and statistical terms reflecting diagnostic parameters. The findings are summarized as a narrative review. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were the two most commonly published serum biomarkers. Most evidence did not identify other serum biomarkers that are clearly superior to ESR and CRP. Other serum biomarkers have not demonstrated superior sensitivity and have failed to replace CRP and ESR as first-line screening tests. D-dimer appears to be a promising biomarker, but more research is necessary. Factors that influence serum biomarkers include temporal trends, stage of revision, and implant-related factors (metallosis). Our review helped to identify factors that can influence serum biomarkers' level changes; the recognition of such factors can help improve their diagnostic utility. As such, we cannot rely on ESR and CRP alone for the diagnosis of PJI prior to second-stage reimplantation, or in metal-on-metal or corrosion cases. The future of serum biomarkers will likely shift towards using genomics and proteomics to identify proteins transcribed via messenger RNA in response to infection and sepsis. Cite this article: Bone Joint Res 2018;7:85-93. © 2018 Saleh et al.
Full Text Available As there is effective intervention for delaying or preventing metabolic diseases, which are often present for years before becoming clinically apparent, novel biomarkers that would mark metabolic complications before the onset of metabolic disease should be identified. We investigated the role of fasting serum amino acids and their associations with inflammatory markers, adipokines, and metabolic syndrome (MetS components in subjects prior to the onset of insulin resistance (IR. Anthropometric measurements, food records, adipokines, biochemical markers, and serum levels of amino acids were determined in 96 asymptomatic subjects aged 25–49 years divided into three groups according to the number of MetS components present. Cysteine and tyrosine were significantly higher already in group with one component of MetS present compared to subjects without MetS components. Serum amino acid levels correlated with markers of inflammation and adipokines. Alanine and glycine explained 10% of insulin resistance variability. The role of tyrosine and cysteine, that were higher already with 1 component of MetS present, should be further investigated as they might point to future insulin disturbances.
Zhou, Jiyuan; Deng, Yongqiong; Yan, Linlin; Zhao, Hong; Wang, Guiqiang
Few studies have investigated serum levels of platelet-derived growth factor (PDGF) in patients with chronic hepatitis B (CHB). The present study aimed to determine whether PDGF-BB could serve as a potential biomarker for the detection of liver fibrosis. From October 2013 to August 2015, 465 patients with CHB were enrolled prospectively in this study. All patients underwent liver biopsy and staging based on the Ishak system. The serum PDGF-BB level was measured quantitatively by ELISA. The serum PDGF-BB level was negatively correlated with fibrosis stage in all patients (p = 0.003, Spearman's rho=-0.16) and was significantly different between fibrosis stages. The areas under the receiver operating characteristics curves (AUROCs) for serum PDGF-BB level and PGT score (a combination of PDGF-BB, gamma-glutamyl transpeptidase, and platelet levels) were 0.667 and 0.831, respectively, for patients with significant fibrosis and normal alanine aminotransferase (ALT) levels. The AUROCs for aspartate aminotransferase-to-platelet ratio (APRI) and fibrosis index based on four factors (FIB-4) were 0.823 and 0.821, respectively. Importantly, a cut-off value of 1.05 and 1.43, respectively, resulted in a sensitivity of 0.95 and 0.52, a specificity of 0.29 and 0.95, a positive predictive value of 0.30 and 0.79, and a negative predictive value of 0.96 and 0.86. The rate of correct diagnosis was up to 88.4% when using cut-offs of 1.05 and 1.43 for the absence or presence of significant fibrosis, respectively. Serum PDGF-BB decreased remarkably as fibrosis progressed, and this could be used as a non-invasive biomarker for the assessment of fibrosis stage in patients with CHB. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Haupt, Thomas H; Kallemose, Thomas; Ladelund, Steen
The soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of mortality risk in various patient populations. However, little is known about the implications of lifestyle for suPAR levels in the general population. Lifestyle, demographic, and cardiovascular disease (CVD) risk factor...... data were collected from 5,538 participants in the Danish population-based Inter99 study. Their suPAR levels were measured using a sandwich enzyme-linked immunosorbent assay. In the final adjusted model, smoking and morbid obesity were strongly associated with higher suPAR levels (P
Kor-Anantakul, Ounjai; Suntharasaj, Thitima; Suwanrath, Chitkasaem; Hanprasertpong, Tharangrut; Pranpanus, Savitree; Pruksanusak, Ninlapa; Janwadee, Suthiraporn; Geater, Alan
To establish normative weight-adjusted models for the median levels of first trimester serum biomarkers for trisomy 21 screening in southern Thai women, and to compare these reference levels with Caucasian-specific and northern Thai models. A cross-sectional study was conducted in 1,150 normal singleton pregnancy women to determine serum pregnancy-associated plasma protein-A (PAPP-A) and free β-human chorionic gonadotropin (β-hCG) concentrations in women from southern Thailand. The predicted median values were compared with published equations for Caucasians and northern Thai women. The best-fitting regression equations for the expected median serum levels of PAPP-A (mIU/L) and free β- hCG (ng/mL) according to maternal weight (Wt in kg) and gestational age (GA in days) were: [Formula: see text] and [Formula: see text] Both equations were selected with a statistically significant contribution (pmodel, the median values of PAPP-A were higher and the median values of free β-hCG were lower in the southern Thai women. And compared with the northern Thai models, the median values of both biomarkers were lower in southern Thai women. The study has successfully developed maternal-weight- and gestational-age-adjusted median normative models to convert the PAPP-A and free β-hCG levels into their Multiple of Median equivalents in southern Thai women. These models confirmed ethnic differences.
Mosbah, Alaa; Nabiel, Yasmin; Khashaba, Eman
To compare levels of interleukin-6 (IL-6), intracellular adhesion molecule-1 (ICAM-1), and glycodelin A in serum and peritoneal fluid of patients with and without endometriosis, and to correlate levels with disease stage. An observational study was undertaken at Mansoura University Hospital, Egypt, between March 2014 and June 2015. Patients aged 21-48 years laparoscopically diagnosed with endometriosis and those without endometriosis who underwent laparoscopy for tubal ligation were included. Levels of IL-6, ICAM-1, and glycodelin A were measured in samples of serum and peritoneal fluid. Receiver operating characteristic curves were used to evaluate diagnostic accuracy. Forty-eight women with endometriosis and 20 without the disorder were included. IL-6 and glycodelin A levels in serum and peritoneal fluid were higher in the endometriosis group than in the control group (Pperitoneal fluid markers were 85.4% and 89.0%, 60.4% and 50.0%, and 89.6% and 90.0%, respectively. IL-6 and glycodelin A levels in serum and peritoneal fluid increased with disease stage (Pendometriosis and are positively correlated with the disease stage. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
Fawzy, A.; Gaafar, R.; Kasem, F.; Ali, Sh.S.; Elshafei, M.; Eldeib, M.
Angio genesis is an essential process in cancer growth maintenance, and Lung cancer; metastasis. Appointing-2 promotes tumor angio genesis by priming the vasculature and potentiating the effects of cytokines at the front of active neovascularization. Enhanced expression of Angiopoietin-2 has been reported in lung cancer tissue. Survivin is one of the inhibitors of apoptosis Survivin; protein that has been shown to play a key role in cancer progression, and in tumor angio genesis. Also plays a key role in tumor cell resistance to anticancer agents and ionizing radiation. Aim: To measure the serum levels of angiopoietin-2 and survivin as possible angiogenic factors in lung cancer patients with the assessment of their interrelationships and clinical significance. Patients and methods: Patients with lung cancer as NSCLC (n = 70) and healthy volunteers (n = 10) were enrolled. Serum angiopoietin-2 and survivin concentrations were measured using enzyme-linked immunosorbent assay (ELIZA). Results: Median serum angiopoietin-2 levels with lung cancer (2730 pg/mL) ranged from 1171 to 6541 pg/mL was higher than the median of the control group (1795 pg/mL) ranged from 1076 to 2730/mL, p < 0.001. Median serum survivin levels were also higher in patients with lung cancer (53.0 pg/mL) ranged from 39.3 to 96.3 pg/mL than the median of the control group (48.8 pg/mL) ranged from 38.0 to 74.6pg/mL, but did not reach statistical significance p = 0.206. In all patients with lung cancer, serum angiopoietin-2 was not significantly correlated with survivin (r = 0.073, p = 0.657). Neither serum angiopoietin-2 nor survivin showed significant relation with the serum angiopoietin-2 or survivin levels depending on the cell types, stage progression, and metastasis among the patients with NSCLC. Conclusions: Our study suggests that serum angiopoietin-2 is a useful marker for the diagnosis of NSCLC by ELIZA technique
Full Text Available The role of cystatin C (Cys-C in tumorigenesis and progression of bladder urothelial tumors (BUT is still indefinite. We retrospectively collected the clinical information from the records of 425 BUT patients. Pretreatment serum Cys-C levels were compared across the various groups. Then we subgroup the patients with GFR ≥ 90 mg/min/1.73 m2, to exclude the effects of lower renal function on cystatin C. No statistically significant differences in the levels of serum Cys-C were found among the tumor characteristics (all P>0.05. In conclusion, circulating Cys-C was not a reliable predictor for clinicopathological characteristics of BUT patients.
Chadha, Kailash C.; Miller, Austin; Nair, Bindukumar B.; Schwartz, Stanley A.; Trump, Donald L.; Underwood, Willie
Background Prostate-specific antigen (PSA) is currently used as a biomarker for diagnosis and management of prostate cancer (CaP). However, PSA typically lacks the sensitivity and specificity desired of a diagnostic marker. Objective The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign versus malignant prostate disease and/or localized CaP versus metastatic CaP. Methods Concurrent measurements of circulating interleukin-8 (IL-8), Tumor necrosis factor-α (TNF-α) and soluble tumor necrosis factor-α receptors 1 (sTNFR1) were obtained from four groups of men: (1) Controls (2) with elevated prostate-specific antigen with a negative prostate biopsy (elPSA_negBx) (3) with clinically localized CaP and (4) with castration resistant prostate cancer. Results TNF-α Area under the receiver operating characteristic curve (AUC = 0.93) and sTNFR1 (AUC = 0.97) were strong predictors of elPSA_negBx (vs. CaP). The best predictor of elPSA_negBx vs CaP was sTNFR1 and IL-8 combined (AUC = 0.997). The strongest single predictors of localized versus metastatic CaP were TNF-α (AUC = 0.992) and PSA (AUC = 0.963) levels. Conclusions The specificity and sensitivity of a PSA-based CaP diagnosis can be significantly enhanced by concurrent serum measurements of IL-8, TNF-α and sTNFR1. In view of the concerns about the ability of PSA to distinguish clinically relevant CaP from indolent disease, assessment of these biomarkers in the larger cohort is warranted. PMID:25593898
Guo, Suyang; Yang, Bo; Liu, Hongli; Li, Yuzhi; Li, Shengze; Ma, Ling; Liu, Jian; Guo, Wei
The aim of this study was to evaluate the serum expression levels of squamous cell carcinoma antigen (SCC-Ag), highly sensitive C-reactive protein (hs-CRP), and CA-125 as potential serum biomarkers for recurrence of cervical cancer. Eighty-six cervical cancer patients who received radical treatment were retrospectively included in this study from February 2011 to January 2014. Of the included 86 cases, 23 were recurred within the 36 months (recurrence group [RG]) and other 63 patients did not (non-RG [NRG]). The serum levels of SCC-Ag, hs-CRP, and CA-125 were examined and compared between the two groups. The prediction recurrence sensitivity, specificity area under the receiver operating characteristic curve were calculated by STATA11.0 software (http://www.stata.com). The correlation among SCC-Ag, hs-CRP, and CA-125 were analyzed by Pearson correlation test. The serum levels of SCC-Ag, hs-CRP, and CA-125 were 1.29 (0.21-33.20) mg/mL, 4.78 (0.22-175.20) mg/mL, and 11.56 (2.028-123.66) IU/mL for NRG and 5.64 (0.50-136.80) mg/mL, 22.41 (0.56-588.90) mg/mL, and 25.41 (3.658-3687.00) IU/mL for RG, respectively. The serum levels of SCC-Ag, hs-CRP, and CA-125 in NG group were significant higher than those of NRG group (P CA-125. Significant positive correlation between SCC-Ag and hs-CRP (rpearson = 0.20, P = 0.04), SCC-Ag and CA-125 (rpearson = 0.64, P CA-125 (rpearson= -0.13, P = 0.56) was found in the RG patients. Serum SCC-Ag, hs-CRP, and CA-125 were higher in recurrence cervical patients which could be potential biomarkers for predicting cervical cancer recurrence risk.
Full Text Available To establish normative weight-adjusted models for the median levels of first trimester serum biomarkers for trisomy 21 screening in southern Thai women, and to compare these reference levels with Caucasian-specific and northern Thai models.A cross-sectional study was conducted in 1,150 normal singleton pregnancy women to determine serum pregnancy-associated plasma protein-A (PAPP-A and free β-human chorionic gonadotropin (β-hCG concentrations in women from southern Thailand. The predicted median values were compared with published equations for Caucasians and northern Thai women.The best-fitting regression equations for the expected median serum levels of PAPP-A (mIU/L and free β- hCG (ng/mL according to maternal weight (Wt in kg and gestational age (GA in days were: [Formula: see text] and [Formula: see text] Both equations were selected with a statistically significant contribution (p< 0.05. Compared with the Caucasian model, the median values of PAPP-A were higher and the median values of free β-hCG were lower in the southern Thai women. And compared with the northern Thai models, the median values of both biomarkers were lower in southern Thai women.The study has successfully developed maternal-weight- and gestational-age-adjusted median normative models to convert the PAPP-A and free β-hCG levels into their Multiple of Median equivalents in southern Thai women. These models confirmed ethnic differences.
Ozer, Josef; Ratner, Marcia; Shaw, Martin; Bailey, Wendy; Schomaker, Shelli
The level of serum alanine aminotransferase (ALT) activity reflects damage to hepatocytes and is considered to be a highly sensitive and fairly specific preclinical and clinical biomarker of hepatotoxicity. However, an increase in serum ALT activity level has also been associated with other organ toxicities, thus, indicating that the enzyme has specificity beyond liver in the absence of correlative histomorphologic alteration in liver. Thus, unidentified non-hepatic sources of serum ALT activity may inadvertently influence the decision of whether to continue development of a novel pharmaceutical compound. To assess the risk of false positives due to extraneous sources of serum ALT activity, additional biomarkers are sought with improved specificity for liver function compared to serum ALT activity alone. Current published biomarker candidates are reviewed herein and compared with ALT performance in preclinical and on occasion, clinical studies. An examination of the current state of hepatotoxic biomarkers indicates that serum F protein, arginase I, and glutathione-S-transferase alpha (GSTalpha) levels, all measured by ELISA, may show utility, however, antibody availability and high cost per run may present limitations to widespread applicability in preclinical safety studies. In contrast, the enzymatic markers sorbitol dehydrogenase, glutamate dehydrogenase, paraxonase, malate dehydrogenase, and purine nucleoside phosphorylase are all readily measured by photometric methods and use reagents that work across preclinical species and humans and are commercially available. The published literature suggests that these markers, once examined collectively in a large qualification study, could provide additional information relative to serum ALT and aspartate aminotransferase (AST) values. Since these biomarkers are found in the serum/plasma of treated humans and rats, they have potential to be utilized as bridging markers to monitor acute drug-induced liver injury in
Ozer, Josef; Ratner, Marcia; Shaw, Martin; Bailey, Wendy; Schomaker, Shelli
The level of serum alanine aminotransferase (ALT) activity reflects damage to hepatocytes and is considered to be a highly sensitive and fairly specific preclinical and clinical biomarker of hepatotoxicity. However, an increase in serum ALT activity level has also been associated with other organ toxicities, thus, indicating that the enzyme has specificity beyond liver in the absence of correlative histomorphologic alteration in liver. Thus, unidentified non-hepatic sources of serum ALT activity may inadvertently influence the decision of whether to continue development of a novel pharmaceutical compound. To assess the risk of false positives due to extraneous sources of serum ALT activity, additional biomarkers are sought with improved specificity for liver function compared to serum ALT activity alone. Current published biomarker candidates are reviewed herein and compared with ALT performance in preclinical and on occasion, clinical studies. An examination of the current state of hepatotoxic biomarkers indicates that serum F protein, arginase I, and glutathione-S-transferase alpha (GSTα) levels, all measured by ELISA, may show utility, however, antibody availability and high cost per run may present limitations to widespread applicability in preclinical safety studies. In contrast, the enzymatic markers sorbitol dehydrogenase, glutamate dehydrogenase, paraxonase, malate dehydrogenase, and purine nucleoside phosphorylase are all readily measured by photometric methods and use reagents that work across preclinical species and humans and are commercially available. The published literature suggests that these markers, once examined collectively in a large qualification study, could provide additional information relative to serum ALT and aspartate aminotransferase (AST) values. Since these biomarkers are found in the serum/plasma of treated humans and rats, they have potential to be utilized as bridging markers to monitor acute drug-induced liver injury in early
45-56. Singh VK. (2009) Phenotypic expression of autoimmune autistic disorder (AAD): A major subset of autism. Ann Clin Psychiat. 21:148-160. 5...spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in communication (verbal and nonverbal), social interactions, and... autoimmunity ; in particular, the generation of antibodies reactive against brain and CNS proteins. The goal of this grant is to identify serum
Aggerholm-Pedersen, Ninna; Maretty-Kongstad, Katja; Keller, Johnny
OBJECTIVE: Certain biomarkers such as the C-reactive protein, serum albumin, and the neutrophils to lymphocyte ratio are of prognostic significance regarding survival in different types of cancers. Data from sarcoma patients are sparse and mainly derived from soft tissue sarcoma and/or metastatic...... cases. Adjusting for confounders such as comorbidity and age is an essential safeguard against erroneous conclusions regarding the possible prognostic value of these biomarkers. The aim of this study was to assess the prognostic value of a battery of pretreatment biomarkers in the serum of patients...... with localized bone sarcomas and to adjust for potential confounders. MATERIAL AND METHODS: All patients diagnosed with localized intermediate and high-grade bone sarcoma during 1994 to 2008 were extracted from the Aarhus Sarcoma Registry. The serum levels of albumin, C-reactive protein, hemoglobin, neutrophils...
would like to thank Dr. Schlager, Applied Biotechnology Branch Chief, and his Wright State University committee members, Dr. David Cool and Dr. Khalid...IH4P as a biomarker of kidney damage ( Canter et al., 2008). The data from this research provided only a tentative identification due to an overall...renal allograft injury‖ Kidney Int. 2002 61(2):686-696. Canter MP, Graham CA, Heit MH, Blackwell LS, Wilkey DW, Klein JB, and Merchant ML
Pierozan, Paula; Jernerén, Fredrik; Ransome, Yusuf; Karlsson, Oskar
The impact of euthanasia methods on endocrine and metabolic parameters in rodent tissues and biological fluids is highly relevant for the accuracy and reliability of the data collected. However, few studies concerning this issue are found in the literature. We compared the effects of three euthanasia methods currently used in animal experimentation (i.e. decapitation, CO 2 inhalation and pentobarbital injection) on the serum levels of corticosterone, insulin, glucose, triglycerides, cholesterol and a range of free fatty acids in rats. The corticosterone and insulin levels were not significantly affected by the euthanasia protocol used. However, euthanasia by an overdose of pentobarbital (120 mg/kg intraperitoneal injection) increased the serum levels of glucose, and decreased cholesterol, stearic and arachidonic acids levels compared with euthanasia by CO 2 inhalation and decapitation. CO 2 inhalation appears to increase the serum levels of triglycerides, while euthanasia by decapitation induced no individual discrepant biomarker level. We conclude that choice of the euthanasia methods is critical for the reliability of serum biomarkers and indicate the importance of selecting adequate euthanasia methods for metabolic analysis in rodents. Decapitation without anaesthesia may be the most adequate method of euthanasia when taking both animal welfare and data quality in consideration. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
Associations of serum insulin-like growth factor-I and insulin-like growth factor-binding protein 3 levels with biomarker-calibrated protein, dairy product and milk intake in the Women's Health Initiative.
Beasley, Jeannette M; Gunter, Marc J; LaCroix, Andrea Z; Prentice, Ross L; Neuhouser, Marian L; Tinker, Lesley F; Vitolins, Mara Z; Strickler, Howard D
It is well established that protein-energy malnutrition decreases serum insulin-like growth factor (IGF)-I levels, and supplementation of 30 g of whey protein daily has been shown to increase serum IGF-I levels by 8 % after 2 years in a clinical trial. Cohort studies provide the opportunity to assess associations between dietary protein intake and IGF axis protein levels under more typical eating conditions. In the present study, we assessed the associations of circulating IGF axis protein levels (ELISA, Diagnostic Systems Laboratories) with total biomarker-calibrated protein intake, as well as with dairy product and milk intake, among postmenopausal women enrolled in the Women's Health Initiative (n 747). Analyses were carried out using multivariate linear regression models that adjusted for age, BMI, race/ethnicity, education, biomarker-calibrated energy intake, alcohol intake, smoking, physical activity and hormone therapy use. There was a positive association between milk intake and free IGF-I levels. A three-serving increase in milk intake per d (approximately 30 g of protein) was associated with an estimated average 18·6 % higher increase in free IGF-I levels (95 % CI 0·9, 39·3 %). However, total IGF-I and insulin-like growth factor-binding protein 3 (IGFBP-3) levels were not associated with milk consumption and nor were there associations between biomarker-calibrated protein intake, biomarker-calibrated energy intake, and free IGF-I, total IGF-I or IGFBP-3 levels. The findings of the present study carried out in postmenopausal women are consistent with clinical trial data suggesting a specific relationship between milk consumption and serum IGF-I levels, although in the present study this association was only statistically significant for free, but not total, IGF-I or IGFBP-3 levels.
Haematological and serum enzymes biomarkers of heavy metals in Chrysichthys Nigrodigitatus and Cynoglossus senegalensis. ... Haematological and serum enzymes activities are predilective biomarkers for the detection and monitoring of aquatic ecosystems pollution. The inclusion of Allium sativum at 1.5g/kg is ...
An investigation was carried out in donkeys to discover serum biomarkers of oxidative stress during moderate and extremely hot conditions. Serum biomarkers included vitamin A, vitamin C, vitamin E, glutathione, catalase, superoxide dismutase, monoamine oxidase, glutathione reductase, xanthine oxidase, oxidase and ...
Dantas, Andréa Tavares; Gonçalves, Sayonara Maria Calado; de Almeida, Anderson Rodrigues; Gonçalves, Rafaela Silva Guimarães; Sampaio, Maria Clara Pinheiro Duarte; Vilar, Kamila de Melo; Pereira, Michelly Cristiny; Rêgo, Moacyr Jesus Barreto de Melo; Pitta, Ivan da Rocha; Marques, Claudia Diniz Lopes; Duarte, Angela Luzia Branco Pinto; Pitta, Maira Galdino da Rocha
Objective . To determine active TGF- β 1 (aTGF- β 1) levels in serum, skin, and peripheral blood mononuclear cell (PBMC) culture supernatants and to understand their associations with clinical parameters in systemic sclerosis (SSc) patients. Methods . We evaluated serum samples from 56 SSc patients and 24 healthy controls (HC). In 20 SSc patients, we quantified spontaneous or anti-CD3/CD28 stimulated production of aTGF- β 1 by PBMC. The aTGF- β 1 levels were measured by ELISA. Skin biopsies were obtained from 13 SSc patients and six HC, and TGFB1 expression was analyzed by RT-PCR. Results . TGF- β 1 serum levels were significantly higher in SSc patients than in HC ( p skin compared with HC skin. Conclusion . Raised active TGF- β 1 serum levels and their association with clinical manifestations in scleroderma patients suggest that this cytokine could be a marker of fibrotic and vascular involvement in SSc.
Suenaga, Mitsukuni; Mashima, Tetsuo; Kawata, Naomi; Wakatsuki, Takeru; Horiike, Yuki; Matsusaka, Satoshi; Dan, Shingo; Shinozaki, Eiji; Seimiya, Hiroyuki; Mizunuma, Nobuyuki; Yamaguchi, Kensei; Yamaguchi, Toshiharu
Regorafenib is an oral multi-kinase inhibitor used as salvage therapy for metastatic colorectal cancer (mCRC). We tested whether serum cytokine levels are associated with clinical outcome in the mCRC patients receiving regorafenib. Serum samples were collected before treatment start, day 21, and progressive disease, and eleven angiogenic and inflammatory cytokine serum levels were examined. Fifty-four patients of a total of 62 enrolled patients were eligible for the analyses. The chemokine ligand 5 (CCL5) levels ≤ cut-off value (59959 pg/ml) at baseline was associated with relative tumor shrinkage (P = 0.021), better progression-free survival (PFS) (P = 0.036) and overall survival (OS) (P = 0.019). Vascular endothelial growth factor A (VEGF-A) levels showing a decrease on day 21 were significantly associated with a better PFS (P = 0.021). CCL5 levels ≤ cut-off was associated with any grade hand-foot skin reaction (HFSR) (P = 0.025) and thrombocytopenia (P = 0.013). Low chemokine ligand 2 levels at baseline were associated with grade 2 ≤ HFSR. High angiopoietin-2 and basic fibroblast growth factor (bFGF) levels at baseline were associated with grade 3 ≤ total bilirubin increase and transaminases increase, respectively. Low bFGF levels at baseline were associated with grade 3 ≤ hypertension. No correlation with severe events was observed. Baseline serum CCL5 levels and decrease of the serum VEGF-A levels may serve as potential predictive markers for survival or treatment-specific toxicities in mCRC patients receiving regorafenib. PMID:27166185
Ye, Xiaoyun; Zhou, Xiaoliu; Furr, Johnathan; Ahn, Ki Chang; Hammock, Bruce D.; Gray, Earl L.; Calafat, Antonia M.
3, 4, 4’- Trichlorocarbanilide (triclocarban, TCC) is widely used as an antimicrobial agent in a variety of consumer and personal care products. TCC is considered a potential endocrine disruptor, but its potential toxic effects in humans are still largely unknown. Because of its widespread uses, the potential for human exposure to TCC is high. In order to identify adequate exposure biomarkers of TCC, we investigated the metabolic profile of TCC in adult female Sprague Dawley rats after administering TCC once (500 mg/kg body weight) by oral gavage. Urine was collected 0–24 hours before dosing, and 0–24 hours and 24–48 hours after dosing. Serum was collected at necropsy 48 h after dosing. We identified several metabolites of TCC in urine and serum by on-line solid phase extraction-high performance liquid chromatography- mass spectrometry. We unambiguously identified two major oxidative metabolites of TCC, 3’-hydroxy-TCC and 2’-hydroxy-TCC, by comparing their chromatographic behavior and mass spectral fragmentation patterns with those of authentic standards. By contrast, compared to these oxidative metabolites, we detected very low levels of TCC in the urine or serum. Taken together these data suggest that in rats, oxidation of TCC is a major metabolic pathway. We also measured TCC and its oxidative metabolites in 50 urine and 16 serum samples collected from adults in the United States. The results suggest differences in the metabolic profile of TCC in rats and in humans; oxidation appears to be a minor metabolic pathway in humans. Total (free plus conjugated) TCC could serve as a potential biomarker for human exposure to TCC. PMID:21635932
Jiang, Hua; Wen, Yang; Hu, Lingmin; Miao, Tingting; Zhang, Ming; Dong, Jing
Macrosomia is defined as an infant's birth weight of more than 4000 g. Although microRNAs (miRNAs) have been implicated in the pathogenesis of various diseases, the associations between serum miRNAs and macrosomia have been rarely reported. We used the Taqman Low Density Array followed by quantitative reverse transcriptase polymerase chain reaction assays to screen for miRNAs associated with macrosomia using serum samples collected 1 week before delivery. Profiling results showed that 1 miRNA was significantly upregulated and 10 miRNAs were significantly downregulated in serum samples of macrosomia (ΔΔCt > 3-fold). The expression levels of miR-21 were significantly decreased in macrosomia as compared to the controls in the third trimester. Receiver operating characteristic (ROC) curve analyses showed that the area under the ROC curve for miR-21 was 67.7% (sensitivity = 66.7% and specificity = 70.0%). miR-21 in maternal serum is differentially expressed between macrosomia and controls, and miR-21 could be used as a candidate biomarker to predict macrosomia. © The Author(s) 2014.
Guiraud, Simon; Edwards, Benjamin; Squire, Sarah E; Babbs, Arran; Shah, Nandini; Berg, Adam; Chen, Huijia; Davies, Kay E
Despite promising therapeutic avenues, there is currently no effective treatment for Duchenne muscular dystrophy (DMD), a lethal monogenic disorder caused by the loss of the large cytoskeletal protein, dystrophin. A highly promising approach to therapy, applicable to all DMD patients irrespective to their genetic defect, is to modulate utrophin, a functional paralogue of dystrophin, able to compensate for the primary defects of DMD restoring sarcolemmal stability. One of the major difficulties in assessing the effectiveness of therapeutic strategies is to define appropriate outcome measures. In the present study, we utilised an aptamer based proteomics approach to profile 1,310 proteins in plasma of wild-type, mdx and Fiona (mdx overexpressing utrophin) mice. Comparison of the C57 and mdx sera revealed 83 proteins with statistically significant >2 fold changes in dystrophic serum abundance. A large majority of previously described biomarkers (ANP32B, THBS4, CAMK2A/B/D, CYCS, CAPNI) were normalised towards wild-type levels in Fiona animals. This work also identified potential mdx markers specific to increased utrophin (DUS3, TPI1) and highlights novel mdx biomarkers (GITR, MYBPC1, HSP60, SIRT2, SMAD3, CNTN1). We define a panel of putative protein mdx biomarkers to evaluate utrophin based strategies which may help to accelerate their translation to the clinic.
Liu, Weiling; Wang, Zhizhong; Ma, Jie; Hou, Yangyang; Zhao, Jiuzhou; Dong, Bing; Tu, Shichun; Wang, Li; Guo, Yongjun
In this study, we determined whether serum tumor markers (STMs), including CA125, are associated with BRCA mutation status and if they can be used prognostically in sporadic ovarian cancer (SOC) and familial ovarian cancer (FOC). BRCA gene mutations were screened using next-generation sequencing (NGS) in 31 FOC and 66 SOC patients enrolled between 2013 and 2014. The serum levels of STM CEA, CA125, CA199, and HE4 were also measured in these patients to determine the prognostic potential of these markers and their association with BRCA mutations. Elevated levels of CA125, but not the other three STMs, were associated with FOC and BRCA mutations. Median progression-free survival (PFS) was significantly longer in patients with FOC, higher CA125 expression (>2000 U/mL), and BRCA mutation. Strikingly, the median PFS was not reached in either BRCA+/higher CA125 or FOC/higher CA125 patient groups and these patients had significantly longer PFS than those in other groups. As reported previously, we also detected more BRCA mutations in FOC than in SOC. No significant differences were observed in onset age, menopausal status, tumor stage, and distant metastasis between FOC and SOC patients or between BRCA+ and BRCA- patients. Elevated levels of serum CA125 are associated with FOC and BRCA mutations, which can be further exploited as a prognostic marker in OC.
Full Text Available Background and objective Lung cancer is the leading cause of cancer death worldwide and very few specific biomarkers could be used in clinical diagnosis at present. The aim of this study is to find novel potential serum biomarkers for lung cancer using Surface Enhanced Laser Desorption/Ionization (SELDI technique. Methods Serumsample of 227 cases including 146 lung cancer, 13 pneumonia, 28 tuberculous pleurisy and 40 normal individuals were analyzed by CM10 chips. The candidate biomarkers were identified by ESI/MS-MS and database searching, and further confirmed by immunoprecipitation. The same sets of serum sample from all groups were re-measured by ELISA assay. Results Three protein peaks with the molecular weight 13.78 kDa, 13.90 kDa and 14.07 kDa were found significantlydecreased in lung cancer serum compared to the other groups and were all automatically selected as specific biomarkers by Biomarker Wizard software. The candidate biomarkers obtained from 1-D SDS gel bands by matching the molecular weight with peaks on CM10 chips were identified by Mass spectrometry as the native transthyretin (nativeTTR, cysTTR and glutTTR, and the identity was further validated by immunoprecipitation using commercial TTR antibodies. Downregulated of TTR was found in both ELISA and SELDI analysis. Conclusion TTRs acted as the potentially useful biomarkers for lung cancer by SELDI technique.
Full Text Available Physical medicine therapies are often used in treating widespread musculoskeletal disorders, such as neck and low back pain. Herbal cataplasms containing rubefacient substances, such as Cayenne pepper, or galenic preparations like Munari cataplasm are commonly used as natural medications to treat painful areas. In this paper we show the effects of a 20-min application of Cayenne pepper and kaolin powder cataplasm (CPC on healthy subjects. Treatment effects were evaluated by cold/hot feeling on visual analogue scale, blood pressure, body temperature, skin light touch sensations, two-point discrimination, and pain threshold to a mechanical stimulus, before and immediately after, 15 min after and 30 min after different concentration of Cayenne pepper in CPC preparation on healthy subjects. Maximal voluntary trunk extension force and trunk extension submaximal force matching error were also measured. In addition, the resulting optimal CPC mixture was tested for its safety by measuring changes in circulating levels of inflammatory-related biomarkers after 20-min application. The results indicate that the 5% concentration of Cayenne pepper in the preparation of CPC is the best choice, since no additional effects can be obtained with the 10% concentration, and the effects are higher than those observed at the 2.5% concentration. Importantly, 5% CPC application did not induce a significant increase of inflammatory-related biomarkers, suggesting that 20-min application has no negative side effects at systemic levels. Further studies are needed to investigate the immediate and long-term effects of repeated CPC applications as well as to understand the intersecting underlying mechanisms activated by Capsaicin and other identified factors, in order to be more extensively used in the field of physical medicine therapies.
Rachakonda, Vikrant; Borhani, Amir A.; Dunn, Michael A.; Andrzejewski, Margaret; Martin, Kelly; Behari, Jaideep
Background and Aims Malnutrition is a leading cause of morbidity and mortality in cirrhosis. There is no consensus as to the optimal approach for identifying malnutrition in end-stage liver disease. The aim of this study was to measure biochemical, serologic, hormonal, radiographic, and anthropometric features in a cohort of hospitalized cirrhotic patients to characterize biomarkers for identification of malnutrition. Design In this prospective observational cohort study, 52 hospitalized cirrhotic patients were classified as malnourished (42.3%) or nourished (57.7%) based on mid-arm muscle circumference malnutrition. Results Subjects with and without malnutrition differed in several key features of metabolic phenotype including wet and dry BMI, skeletal muscle index, visceral fat index and HOMA-IR. Serum leptin levels were lower and INR was higher in malnourished subjects. Serum leptin was significantly correlated with HOMA-IR, wet and dry BMI, mid-arm muscle circumference, skeletal muscle index, and visceral fat index. Logistic regression analysis revealed that INR and log-transformed leptin were independently associated with malnutrition. Conclusions Low serum leptin and elevated INR are associated with malnutrition in hospitalized patients with end-stage liver disease. PMID:27583675
Ressom, Habtom W; Varghese, Rency S; Abdel-Hamid, Mohamed; Eissa, Sohair Abdel-Latif; Saha, Daniel; Goldman, Lenka; Petricoin, Emanuel F; Conrads, Thomas P; Veenstra, Timothy D; Loffredo, Christopher A; Goldman, Radoslav
Mass spectrometric profiles of peptides and proteins obtained by current technologies are characterized by complex spectra, high dimensionality and substantial noise. These characteristics generate challenges in the discovery of proteins and protein-profiles that distinguish disease states, e.g. cancer patients from healthy individuals. We present low-level methods for the processing of mass spectral data and a machine learning method that combines support vector machines, with particle swarm optimization for biomarker selection. The proposed method identified mass points that achieved high prediction accuracy in distinguishing liver cancer patients from healthy individuals in SELDI-QqTOF profiles of serum. MATLAB scripts to implement the methods described in this paper are available from the HWR's lab website http://lombardi.georgetown.edu/labpage
Full Text Available Objective: We have previously analyzed protein profi les using Surface Enhanced Laser Desorption and Ionization Time-Of-Flight Mass Spectroscopy (SELDI-TOF-MS [Kozak et al. 2003, Proc. Natl. Acad. Sci. U.S.A. 100:12343–8] and identified 3 differentially expressed serum proteins for the diagnosis of ovarian cancer (OC [Kozak et al. 2005, Proteomics, 5:4589–96], namely, apolipoprotein A-I (apoA-I, transthyretin (TTR and transferin (TF. The objective of the present study is to determine the efficacy of the three OC biomarkers for the detection of early stage (ES OC, in direct comparison to CA125.Methods: The levels of CA125, apoA-I, TTR and TF were measured in 392 serum samples [82 women with normal ovaries (N, 24 women with benign ovarian tumors (B, 85 women with ovarian tumors of low malignant potential (LMP, 126 women with early stage ovarian cancer (ESOC, and 75 women with late stage ovarian cancer (LSOC], obtained through the GOG and Cooperative Human Tissue Network. Following statistical analysis, multivariate regression models were built to evaluate the utility of the three OC markers in early detection.Results: Multiple logistic regression models (MLRM utilizing all biomarker values (CA125, TTR, TF and apoA-I from all histological subtypes (serous, mucinous, and endometrioid adenocarcinoma distinguished normal samples from LMP with 91% sensitivity (specifi city 92%, and normal samples from ESOC with a sensitivity of 89% (specifi city 92%. MLRM, utilizing values of all four markers from only the mucinous histological subtype showed that collectively, CA125, TTR, TF and apoA-I, were able to distinguish normal samples from mucinous LMP with 90% sensitivity, and further distinguished normal samples from early stage mucinous ovarian cancer with a sensitivity of 95%. In contrast, in serum samples from patients with mucinous tumors, CA125 alone was able to distinguish normal samples from LMP and early stage ovarian cancer with a sensitivity of
Ueda, Yutaka; Enomoto, Takayuki, E-mail: email@example.com; Kimura, Toshihiro; Miyatake, Takashi; Yoshino, Kiyoshi; Fujita, Masami; Kimura, Tadashi [Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, 565-0871 (Japan)
Ovarian, endometrial, and cervical cancers are three of the most common malignancies of the female reproductive organs. CA 125, historically the most reliable serum marker for ovarian cancer, is elevated in 50% of early-stage ovarian tumors. For endometrial cancers, there are no established serum markers. SCC, which is the best studied serum marker for squamous cell carcinomas, has been unreliable; SCC is elevated in cervical squamous cell carcinomas ranging from 28–85% of the time. Recent proteomics-based analyses show great promise for the discovery of new and more useful biomarkers. In this review, we will discuss the currently utilized serum tumor markers for gynecologic cancers and the novel biomarkers that are now under investigation.
Full Text Available Hepatocellular carcinoma (HCC, one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single-nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future.
José M Vilar
Full Text Available The aim of this study was to evaluate the use of serum type II collagen cleavage epitope and serum hyaluronic acid as biomarkers for treatment monitoring in osteoarthritic dogs. For this purpose, a treatment model based on mesenchymal stem cells derived from adipose tissue combined with plasma rich in growth factors was used. This clinical study included 10 dogs with hip osteoarthritis. Both analytes were measured in serum at baseline, just before applying the treatment, and 1, 3, and 6 months after treatment. These results were compared with those obtained from force plate analysis using the same animals during the same study period. Levels of type II collagen cleavage epitope decreased and those of hyaluronic acid increased with clinical improvement objectively verified via force plate analysis, suggesting these two biomarkers could be effective as indicators of clinical development of joint disease in dogs.
Mazzone, Peter J; Wang, Xiao-Feng; Han, Xiaozhen; Choi, Humberto; Seeley, Meredith; Scherer, Richard; Doseeva, Victoria
A panel of 3 serum proteins and 1 autoantibody has been developed to assist with the detection of lung cancer. We aimed to validate the accuracy of the biomarker panel in an independent test set and explore the impact of adding a fourth serum protein to the panel, as well as the impact of combining molecular and clinical variables. The training set of serum samples was purchased from commercially available biorepositories. The testing set was from a biorepository at the Cleveland Clinic. All lung cancer and control subjects were >50 years old and had smoked a minimum of 20 pack-years. A panel of biomarkers including CEA (carcinoembryonic antigen), CYFRA21-1 (cytokeratin-19 fragment 21-1), CA125 (carbohydrate antigen 125), HGF (hepatocyte growth factor), and NY-ESO-1 (New York esophageal cancer-1 antibody) was measured using immunoassay techniques. The multiple of the median method, multivariate logistic regression, and random forest modeling was used to analyze the results. The training set consisted of 604 patient samples (268 with lung cancer and 336 controls) and the testing set of 400 patient samples (155 with lung cancer and 245 controls). With a threshold established from the training set, the sensitivity and specificity of both the 4- and 5-biomarker panels on the testing set was 49% and 96%, respectively. Models built on the testing set using only clinical variables had an area under the receiver operating characteristic curve of 0.68, using the biomarker panel 0.81 and by combining clinical and biomarker variables 0.86. This study validates the accuracy of a panel of proteins and an autoantibody in a population relevant to lung cancer detection and suggests a benefit to combining clinical features with the biomarker results.
Ziad J. Sahab
Full Text Available Biomarkers are biomolecules that serve as indicators of biological and pathological processes, or physiological and pharmacological responses to a drug treatment. Because of the high abundance of albumin and heterogeneity of plasma lipoproteins and glycoproteins, biomarkers are difficult to identify in human serum. Due to the clinical significance the identification of disease biomarkers in serum holds great promise for personalized medicine, especially for disease diagnosis and prognosis. This review summarizes some common and emerging proteomics techniques utilized in the separation of serum samples and identification of disease signatures. The practical application of each protein separation or identification technique is analyzed using specific examples. Biomarkers of cancers of prostate, breast, ovary, and lung in human serum have been reviewed, as well as those of heart disease, arthritis, asthma, and cystic fibrosis. Despite the advancement of technology few biomarkers have been approved by the Food and Drug Administration for disease diagnosis and prognosis due to the complexity of structure and function of protein biomarkers and lack of high sensitivity, specificity, and reproducibility for those putative biomarkers. The combination of different types of technologies and statistical analysis may provide more effective methods to identify and validate new disease biomarkers in blood.Abbreviations: 2-DE, two-dimensional gel electrophoresis; 2DLC-MS, two-dimensional liquid chromatography mass spectrometry; CA 15.3, cancer antigen 15.3; CA 19–9, cancer antigen 19–9, a tumor-associated antigen; CA125, cancer antigen 125, a mucin-like protein; CEA, carcinoembryonic antigen; CF, Cystic Fibrosis; CRP, C-reactive protein; ELISA, enzyme-linked immunosorbent assay; ESI-MS/MS, electrospray ionization tandem mass spectrometry; FDA, Food and Drug Administration; IPG, immobilized pH gradient; MALDI-TOF-MS, matrix-assisted laser desorption
Nyström, Harriet; Dring, Ann M.; Svenningsson, Anders; Piehl, Fredrik; Nelson, David W.; Bellander, Bo-Michael
Traumatic brain injury (TBI) is a common cause of death and disability, worldwide. Early determination of injury severity is essential to improve care. Neurofilament light (NF-L) has been introduced as a marker of neuroaxonal injury in neuroinflammatory/-degenerative diseases. In this study we determined the predictive power of serum (s-) and cerebrospinal fluid (CSF-) NF-L levels towards outcome, and explored their potential correlation to diffuse axonal injury (DAI). A total of 182 patients suffering from TBI admitted to the neurointensive care unit at a level 1 trauma center were included. S-NF-L levels were acquired, together with S100B and neuron-specific enolase (NSE). CSF-NF-L was measured in a subcohort (n = 84) with ventriculostomies. Clinical and neuro-radiological parameters, including computerized tomography (CT) and magnetic resonance imaging, were included in the analyses. Outcome was assessed 6 to 12 months after injury using the Glasgow Outcome Score (1-5). In univariate proportional odds analyses mean s-NF-L, -S100B and -NSE levels presented a pseudo-R2 Nagelkerke of 0.062, 0.214 and 0.074 in correlation to outcome, respectively. In a multivariate analysis, in addition to a model including core parameters (pseudo-R2 0.33 towards outcome; Age, Glasgow Coma Scale, pupil response, Stockholm CT score, abbreviated injury severity score, S100B), S-NF-L yielded an extra 0.023 pseudo-R2 and a significantly better model (p = 0.006) No correlation between DAI or CT assessed-intracranial damage and NF-L was found. Our study thus demonstrates that S-NF-L correlates to TBI outcome, even if used in models with S100B, indicating an independent contribution to the prediction, perhaps by reflecting different pathophysiological processes, not possible to monitor using conventional neuroradiology. Although we did not find a predictive value of NF-L for DAI, this cannot be completely excluded. We suggest further studies, with volume quantification of axonal injury
Faiez Al Nimer
Full Text Available Traumatic brain injury (TBI is a common cause of death and disability, worldwide. Early determination of injury severity is essential to improve care. Neurofilament light (NF-L has been introduced as a marker of neuroaxonal injury in neuroinflammatory/-degenerative diseases. In this study we determined the predictive power of serum (s- and cerebrospinal fluid (CSF- NF-L levels towards outcome, and explored their potential correlation to diffuse axonal injury (DAI. A total of 182 patients suffering from TBI admitted to the neurointensive care unit at a level 1 trauma center were included. S-NF-L levels were acquired, together with S100B and neuron-specific enolase (NSE. CSF-NF-L was measured in a subcohort (n = 84 with ventriculostomies. Clinical and neuro-radiological parameters, including computerized tomography (CT and magnetic resonance imaging, were included in the analyses. Outcome was assessed 6 to 12 months after injury using the Glasgow Outcome Score (1-5. In univariate proportional odds analyses mean s-NF-L, -S100B and -NSE levels presented a pseudo-R2 Nagelkerke of 0.062, 0.214 and 0.074 in correlation to outcome, respectively. In a multivariate analysis, in addition to a model including core parameters (pseudo-R2 0.33 towards outcome; Age, Glasgow Coma Scale, pupil response, Stockholm CT score, abbreviated injury severity score, S100B, S-NF-L yielded an extra 0.023 pseudo-R2 and a significantly better model (p = 0.006 No correlation between DAI or CT assessed-intracranial damage and NF-L was found. Our study thus demonstrates that S-NF-L correlates to TBI outcome, even if used in models with S100B, indicating an independent contribution to the prediction, perhaps by reflecting different pathophysiological processes, not possible to monitor using conventional neuroradiology. Although we did not find a predictive value of NF-L for DAI, this cannot be completely excluded. We suggest further studies, with volume quantification of axonal
Nzoumbou-Boko, Romaric; Dethoua, Mariette; Gabriel, Fréderic; Buguet, Alain; Cespuglio, Raymond; Courtois, Pierrette; Daulouède, Sylvie; Bouteille, Bernard; Ngampo, Stéphane; Mpandzou, Ghislain; Semballa, Silla
Arginase serum levels were increased in human African trypanosomiasis patients and returned to control values after treatment. Arginase hydrolyzes l-arginine to l-ornithine, which is essential for parasite growth. Moreover, l-arginine depletion impairs immune functions. Arginase may be considered as a biomarker for treatment efficacy. PMID:23554207
Gottschalk, M G; Cooper, J D; Chan, M K; Bot, M; Penninx, B W J H; Bahn, S
Panic disorder with or without comorbid agoraphobia (PD/PDA) has been linked to an increased risk to develop subsequent depressive episodes, yet the underlying pathophysiology of these disorders remains poorly understood. We aimed to identify a biomarker panel predictive for the development of a depressive disorder (major depressive disorder and/or dysthymia) within a 2-year-follow-up period. Blood serum concentrations of 165 analytes were evaluated in 120 PD/PDA patients without depressive disorder baseline diagnosis (6-month-recency) in the Netherlands Study of Depression and Anxiety (NESDA). We assessed the predictive performance of serum biomarkers, clinical, and self-report variables using receiver operating characteristics curves (ROC) and the area under the ROC curve (AUC). False-discovery-rate corrected logistic regression model selection of serum analytes and covariates identified an optimal predictive panel comprised of tetranectin and creatine kinase MB along with patient gender and scores from the Inventory of Depressive Symptomatology (IDS) rating scale. Combined, an AUC of 0.87 was reached for identifying the PD/PDA patients who developed a depressive disorder within 2 years (n = 44). The addition of biomarkers represented a significant (p = 0.010) improvement over using gender and IDS alone as predictors (AUC = 0.78). For the first time, we report on a combination of biological serum markers, clinical variables and self-report inventories that can detect PD/PDA patients at increased risk of developing subsequent depressive disorders with good predictive performance in a naturalistic cohort design. After an independent validation our proposed biomarkers could prove useful in the detection of at-risk PD/PDA patients, allowing for early therapeutic interventions and improving clinical outcome. Copyright © 2015 Elsevier Ltd. All rights reserved.
Keikhaei, B.; Badavi, M.; Pedram, M.; Zandian, K.
To compare serum zinc level between Thalassemia Major (TM) patients and normal population at Shafa Hospital in South West of Iran. A total of 25 male and 36 female of TM patients were enrolled in this study. Out of 61 patients thirty were treated by deferroxamine (DFO) and 31 were on the combination of DFO and deferiprone (DEF) protocol therapy. Sixty normal subjects of the matching age and gender were recruited as controls. From each patient and control group 2 ml of blood was taken in fasting condition. Cell blood count and serum zinc were carried out for both thalassemia patients and normal subjects. The mean age of patients and control group was 15+- 5 years. Mean serum zinc level was 68.97+- 21.12 mu g/dl, 78.10-28.50 mu g/dl, and 80.16+- 26.54 mu g/dl in the TM with DFO, TM with DFO + DEF combination protocol and control group respectively. There was no significant correlation between patients and control group. However 50 percent of TM with DFO, 38.7 percent of TM with DFO + DEF and 32.8 percent of control group had hypozincemia. Nearly 40 to 50 percent of TM patients and one third of normal subjects are suffering from hypozincemia. This study shows that low level of serum zinc is a health problem in both thalassemia patients and normal population in South West of Iran. (author)
Full Text Available Previous studies suggest a role for eotaxin-3, TARC/CCL17 and IgG4 in newly-diagnosed patients with eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss with highly active disease. The role of these biomarkers in relapsing disease is unclear.Serum levels of TARC/CCL17, eotaxin-3, IgG4, and IgG4/IgG ratio were determined in serum samples from a longitudinal cohort of patients with EGPA (105 visits of 25 patients. Epidemiological, clinical and laboratory data were available for all visits.At the first visit, 80% of patients were using glucocorticoids and 68% additional immunosuppressive drugs. Disease flares were seen at 18 visits. The median BVAS and BVAS/WG scores at time of relapse were 4 and 2, respectively. None of the biomarkers tested were useful to discriminate between active disease and remission. Patients treated with prednisone had lower eotaxin-3 and eosinophil levels compared to patients not taking glucocorticoids irrespective of disease activity. Use of immunosuppressive agents was not associated with biomarker levels.Serum levels of TARC/CCL17, eotaxin-3, IgG4, and IgG4/IgG ratio do not clearly differentiate active and inactive disease in established EGPA. Defining biomarkers in EGPA remains a challenge especially during times of glucocorticoid use.
Ahmed A Alkhateeb
Full Text Available Approximately half of all HER2/neu-overexpressing breast cancer patients do not respond to trastuzumab-containing therapy. Therefore, there remains an urgent and unmet clinical need for the development of predictive biomarkers for trastuzumab response. Recently, several lines of evidence have demonstrated that the inflammatory tumor microenvironment is a major contributor to therapy resistance in breast cancer. In order to explore the predictive value of inflammation in breast cancer patients, we measured the inflammatory biomarkers serum ferritin and C-reactive protein (CRP in 66 patients immediately before undergoing trastuzumab-containing therapy and evaluated their progression-free and overall survival. The elevation in pre-treatment serum ferritin (>250 ng/ml or CRP (>7.25 mg/l was a significant predictor of reduced progression-free survival and shorter overall survival. When patients were stratified based on their serum ferritin and CRP levels, patients with elevation in both inflammatory biomarkers had a markedly poorer response to trastuzumab-containing therapy. Therefore, the elevation in inflammatory serum biomarkers may reflect a pathological state that decreases the clinical efficacy of this therapy. Anti-inflammatory drugs and life-style changes to decrease inflammation in cancer patients should be explored as possible strategies to sensitize patients to anti-cancer therapeutics.
Hao, Wende; Zhang, Xuhui; Xiu, Bingshui; Yang, Xiqin; Hu, Shuofeng; Liu, Zhiqiang; Duan, Cuimi; Jin, Shujuan; Ying, Xiaomin; Zhao, Yanfeng; Han, Xiaowei; Hao, Xiaopeng; Fan, Yawen; Johnson, Heather; Meng, Di; Persson, Jenny L; Zhang, Heqiu; Feng, XiaoYan; Huang, Yan
Breast cancer is the most common cancer in women worldwide, identification of new biomarkers for early diagnosis and detection will improve the clinical outcome of breast cancer patients. In the present study, we determined serum levels of vitronectin (VN) in 93 breast cancer patients, 30 benign breast lesions, 9 precancerous lesions, and 30 healthy individuals by enzyme-linked immunosorbent assays. Serum VN level was significantly higher in patients with stage 0-I primary breast cancer than in healthy individuals, patients with benign breast lesion or precancerous lesions, as well as those with breast cancer of higher stages. Serum VN level was significantly and negatively correlated with tumor size, lymph node status, and clinical stage (p cancer antigen 15-3 (CA 15-3) (0.69, 95 % CI [0.58-0.81]) when used to distinguish stage 0-I cancer and normal control. Importantly, the combined use of three biomarkers yielded an improvement in receiver operating characteristic curve with an AUC of 0.83, 95 % CI [0.74-0.92]. Taken together, our current study showed for the first time that serum VN is a promising biomarker for early diagnosis of breast cancer when combined with CEA and CA15-3.
Farwell, Wildon R; Taylor, Eric N
In vitro data suggest that lower extracellular pH activates the immune system. We conducted a population-based study of the relation between serum acid-base status and inflammation. We examined the serum anion gap and serum levels of bicarbonate and inflammatory biomarkers in 4525 healthy adults who participated in the National Health and Nutrition Examination Survey during 1999-2006. We excluded participants who had chronic disease, recent infection and an estimated glomerular filtration rate of less than 60 mL/min per 1.73 m2. The mean values of serum anion gap, bicarbonate level, leukocyte count and C-reactive protein level were all within normal limits. After adjustment for age, sex, ethnic background, body mass index, serum albumin level and other factors, we found that a higher anion gap and lower bicarbonate level were associated with a higher leukocyte count and higher C-reactive protein level. Compared with participants in the lowest quartile of anion gap, those in the highest quartile had a leukocyte count that was 1.0x10(9)/L higher and a C-reactive protein level that was 10.9 nmol/L higher (panion gap and lower bicarbonate level were also associated with a higher platelet count, a larger mean platelet volume and a higher ferritin level. A higher serum anion gap and lower bicarbonate level were associated with higher levels of inflammatory biomarkers in a healthy sample of the general population. Further studies are needed to elucidate the relation between acid-base status and inflammation.
Wang, Long; Hu, Ya-Qian; Zhao, Zhuo-Jie; Zhang, Hong-Yang; Gao, Bo; Lu, Wei-Guang; Xu, Xiao-Long; Lin, Xi-Sheng; Wang, Jin-Peng; Jie, Qiang; Luo, Zhuo-Jing; Yang, Liu
Postmenopausal osteoporosis is one of the most prominent worldwide public health problems and the morbidity is increasing with the aging population. It has been demonstrated that early diagnosis and intervention delay the disease progression and improve the outcome. Therefore, searching for biomarkers that are able to identify postmenopausal women at high risk for developing osteoporosis is an effective way to improve the quality of life of patients, and alleviate social and economic burdens. In the present study, a protein array was used to identify potential biomarkers. The bone mineral densities of 10 rats were dynamically measured in an ovariectomized model by micro‑computed tomography assessment, and the early stage of osteoporosis was defined. Through the protein array‑based screening, the expression levels of six serum protein biomarkers in ovariectomized rats were observed to alter at the initiation stage of the postmenopausal osteoporosis. Fractalkine, tissue inhibitor of metalloproteinases‑1 and monocyte chemotactic protein‑1 were finally demonstrated to be increased in the serum of eight enrolled postmenopausal osteoporosis patients using ELISA assay and were correlated with the severity of progressive bone loss. These biomarkers may be explored as potential early biomarkers to readily evaluate and diagnose postmenopausal osteoporosis in the clinic.
Gashenko, Elena A; Lebedeva, Valentina A; Brak, Ivan V; Tsykalenko, Elena A; Vinokurova, Galina V; Korolenko, Tatyana A
To evaluate procathepsin B, as well as endogenous inhibitors of cysteine proteases (cystatin B and cystatin C) in biological fluids as possible biomarkers of ovarian cancer. To observe levels of serum procathepsin B in different age groups. The sample (N=27) of women with gynaecological tumours included 18 patients with ovarian cancer (n=18) and 9 patients with benign ovarian tumours (n=9); 72 healthy women were in the control group. All patients were treated in Novosibirsk Regional Oncological Center, Russia. Serum samples of healthy women (n=40) aged 18-70 years were used as controls for common biomarker of ovarian cancer CA-125. In the Procathepsin B study, serum samples of healthy women (n=32) aged 18-40 years (n=14), 41-55 years (n=10) and 56-80 (n=8) years were used as controls. Common biomarker of ovarian cancer, CA-125, was assayed by using a commercial kit (Vector, Koltsovo, Novosibirsk Region, Russia). Procathepsin B was measured by means of a commercial kit for human procathepsin B (R&D, USA); cystatin C was measured by commercial ELISA kits for human (BioVendor, Czechia); cystatin B was measured by ELISA kits for human (USCN Life Science Inc., Wuhan, China). Statistical analysis was performed by one-way ANOVA (Statistica 10 Program). In the control group, serum procathepsin B concentration did not reveal age dependency. In the ovarian cancer group, both levels of serum procathepsin B and standard biomarker CA-125 increased significantly (both pcystatin B level increased up to 1.7-fold in the ovarian cancer group compared to the control group. The increase of serum CA-125 was about 3.5-fold higher (p=0.017) and procathepsin B was 1.8-fold higher (pcancer group compared to the benign tumour group. Cystatin B in ascites fluid increased equally in both ovarian cancer (pCystatin C concentration in ascites fluid increased only in patients with ovarian cancer (pcystatin C (1.8-fold, pcystatin B levels (1.4 fold, pcancer compared to the control serum. The
Teitelbaum, Susan L; Li, Qian; Lambertini, Luca; Belpoggi, Fiorella; Manservisi, Fabiana; Falcioni, Laura; Bua, Luciano; Silva, Manori J; Ye, Xiaoyun; Calafat, Antonia M; Chen, Jia
Exposure to environmental chemicals, including phthalates and phenols such as parabens and triclosan, is ubiquitous within the U.S. general population. This proof-of-concept rodent study examined the relationship between oral doses of three widely used personal care product ingredients [diethyl phthalate (DEP), methyl paraben (MPB), and triclosan] and urine and serum concentrations of their respective biomarkers. Using female Sprague-Dawley rats, we carried out two rounds of experiments with oral gavage doses selected in accordance with no observed adverse effect levels (NOAELs) derived from previous studies: 1,735 (DEP), 1,050 (MPB), 50 (triclosan) mg/kg/day. Administered doses ranged from 0.005 to 173 mg/kg/day, 10-100,000 times below the NOAEL for each chemical. Controls for the MPB and triclosan experiments were animals treated with olive oil (vehicle) only; controls for the DEP serum experiments were animals treated with the lowest doses of MPB and triclosan. Doses were administered for 5 days with five rats in each treatment group. Urine and blood serum, collected on the last day of exposure, were analyzed for biomarkers. Relationships between oral dose and biomarker concentrations were assessed using linear regression. Biomarkers were detected in all control urine samples at parts-per-billion levels, suggesting a low endemic environmental exposure to the three chemicals that could not be controlled even with all of the precautionary measures undertaken. Among the exposed animals, urinary concentrations of all three biomarkers were orders of magnitude higher than those in serum. A consistently positive linear relationship between oral dose and urinary concentration was observed (R2 > 0.80); this relationship was inconsistent in serum. Our study highlights the importance of carefully considering the oral dose used in animal experiments and provides useful information in selecting doses for future studies. Teitelbaum SL, Li Q, Lambertini L, Belpoggi F
Full Text Available Abstract Background Ovarian cancer is the most lethal gynecologic malignancy, with the majority of cases diagnosed at an advanced stage when treatments are less successful. Novel serum protein markers are needed to detect ovarian cancer in its earliest stage; when detected early, survival rates are over 90%. The identification of new serum biomarkers is hindered by the presence of a small number of highly abundant proteins that comprise approximately 95% of serum total protein. In this study, we used pooled serum depleted of the most highly abundant proteins to reduce the dynamic range of proteins, and thereby enhance the identification of serum biomarkers using the quantitative proteomic method iTRAQ®. Results Medium and low abundance proteins from 6 serum pools of 10 patients each from women with serous ovarian carcinoma, and 6 non-cancer control pools were labeled with isobaric tags using iTRAQ® to determine the relative abundance of serum proteins identified by MS. A total of 220 unique proteins were identified and fourteen proteins were elevated in ovarian cancer compared to control serum pools, including several novel candidate ovarian cancer biomarkers: extracellular matrix protein-1, leucine-rich alpha-2 glycoprotein-1, lipopolysaccharide binding protein-1, and proteoglycan-4. Western immunoblotting validated the relative increases in serum protein levels for several of the proteins identified. Conclusions This study provides the first analysis of immunodepleted serum in combination with iTRAQ® to measure relative protein expression in ovarian cancer patients for the pursuit of serum biomarkers. Several candidate biomarkers were identified which warrant further development.
Full Text Available The Janus serum bank, established in 1973, contains sera stored at –25 degrees collected from 330,000 originally healthy individuals. The number of cancer cases have increased from zero in 1973 to more than 50,000 in 2005, including invasive and non-invasive cancers. Information on cases have been obtained by coupling the Janus file against the Norwegian Cancer Registry. The sera have been used in over 70 different cancers research projects, usually in case-control studies and in collaboration with national and international research groups. The type of biomarker analysed include antibodies against Chlamydia, CMV, Epstein Barr virus, HPV and Helicobacter pylori. Leptin, long chain fatty acids, androgens and other hormones, vitamins as well as environmental toxins such as organochlorines are other types of cancer biomarkers investigated. Mutation analyses (BRCA-1 etc have been possible using PCR and the trace amounts of DNA remaining in the sera.Janus serum bank ble etablert i 1973 og inneholder sera lagret ved –25 grader, innsamlet fra 330.000 opprinnelig friske personer. Antall krefttilfeller har steget fra null i 1973 til over 50.000 i år 2005, inkludert både invasiv og ikke-invasiv kreft. Informasjon om kasus er tilgjengelig ved å koble Janus-filene mot Kreftregisterets databaser. Serumprøvene er blitt benyttet i over 70 forskjellige kreftforskningsprosjekter, som oftest i kasus-kontroll studier og i samarbeide med en rekke nasjonale og internasjonale forskningsgrupper. Mange ulike biomarkører på kreft er blitt analysert, bl.a. antistoffer mot Chlamydia, CMV, Epstein Barr virus, HPV og Helicobacter pylori. Leptin, lange fettsyrer, androgener og andre hormoner, vitaminer såvel som miljøgifter av typen organiske klorforbindelser er eksempler på andre kreftbiomarkører som er undersøkt. Det har også vært mulig å gjøre mutasjonsanalyser (BRCA-1 etc ved å bruke PCR til å amplifisere opp den spormengden DNA som finnes i serum.
Elena A. Gashenko
Full Text Available Objectives. To evaluate procathepsin B, as well as endogenous inhibitors of cysteine proteases (cystatin B and cystatin C in biological fluids as possible biomarkers of ovarian cancer. To observe levels of serum procathepsin B in different age groups. Study design. The sample (N=27 of women with gynaecological tumours included 18 patients with ovarian cancer (n=18 and 9 patients with benign ovarian tumours (n=9; 72 healthy women were in the control group. All patients were treated in Novosibirsk Regional Oncological Center, Russia. Serum samples of healthy women (n=40 aged 18–70 years were used as controls for common biomarker of ovarian cancer CA-125. In the Procathepsin B study, serum samples of healthy women (n=32 aged 18–40 years (n=14, 41–55 years (n=10 and 56–80 (n=8 years were used as controls. Methods. Common biomarker of ovarian cancer, CA-125, was assayed by using a commercial kit (Vector, Koltsovo, Novosibirsk Region, Russia. Procathepsin B was measured by means of a commercial kit for human procathepsin B (R&D, USA; cystatin C was measured by commercial ELISA kits for human (BioVendor, Czechia; cystatin B was measured by ELISA kits for human (USCN Life Science Inc., Wuhan, China. Statistical analysis was performed by one-way ANOVA (Statistica 10 Program. Results. In the control group, serum procathepsin B concentration did not reveal age dependency. In the ovarian cancer group, both levels of serum procathepsin B and standard biomarker CA-125 increased significantly (both p<0.001 compared with the control group. In the benign ovarian tumour group, serum procathepsin B (p<0.001 and CA-125 (p=0.004 increased about 2.5- and 8-fold compared to the control group. Serum cystatin B level increased up to 1.7-fold in the ovarian cancer group compared to the control group. The increase of serum CA-125 was about 3.5-fold higher (p=0.017 and procathepsin B was 1.8-fold higher (p<0.05 in the ovarian cancer group compared to the benign
Pham, Minh Nguyet; Kolb, Hubert; Mandrup-Poulsen, Thomas
We investigated the adipokines adiponectin, leptin and resistin as serum biomarkers of beta-cell function in patients with type 1 diabetes.......We investigated the adipokines adiponectin, leptin and resistin as serum biomarkers of beta-cell function in patients with type 1 diabetes....
Moser, Virginia C.; Stewart, Nicholas; Freeborn, Danielle L.; Crooks, James; MacMillan, Denise K.; Hedge, Joan M.; Wood, Charles E.; McMahen, Rebecca L.; Strynar, Mark J.; Herr, David W.
There is increasing emphasis on the use of biomarkers of adverse outcomes in safety assessment and translational research. We evaluated serum biomarkers and targeted metabolite profiles after exposure to pesticides (permethrin, deltamethrin, imidacloprid, carbaryl, triadimefon, fipronil) with different neurotoxic actions. Adult male Long–Evans rats were evaluated after single exposure to vehicle or one of two doses of each pesticide at the time of peak effect. The doses were selected to produce similar magnitude of behavioral effects across chemicals. Serum or plasma was analyzed using commercial cytokine/protein panels and targeted metabolomics. Additional studies of fipronil used lower doses (lacking behavioral effects), singly or for 14 days, and included additional markers of exposure and biological activity. Biomarker profiles varied in the number of altered analytes and patterns of change across pesticide classes, and discriminant analysis could separate treatment groups from control. Low doses of fipronil produced greater effects when given for 14 days compared to a single dose. Changes in thyroid hormones and relative amounts of fipronil and its sulfone metabolite also differed between the dosing regimens. Most cytokine changes reflected alterations in inflammatory responses, hormone levels, and products of phospholipid, fatty acid, and amino acid metabolism. These findings demonstrate distinct blood-based analyte profiles across pesticide classes, dose levels, and exposure duration. These results show promise for detailed analyses of these biomarkers and their linkages to biological pathways. - Highlights: • Pesticides typical of different classes produced distinct patterns of change in biomarker panels. • Based on the panels used, alterations suggest impacts on immune, metabolism, and homeostasis functions. • Some changes may reflect actions on neurotransmitter systems involved in immune modulation. • Fipronil effects on thyroid and kinetics
Moser, Virginia C., E-mail: Moser.firstname.lastname@example.org [Neurotoxicology Branch/Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Stewart, Nicholas; Freeborn, Danielle L. [Neurotoxicology Branch/Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Crooks, James; MacMillan, Denise K. [Analytical Chemistry Research Core/Research Cores Unit, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Hedge, Joan M.; Wood, Charles E. [Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); McMahen, Rebecca L. [ORISE fellow, Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Strynar, Mark J. [Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Herr, David W. [Neurotoxicology Branch/Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)
There is increasing emphasis on the use of biomarkers of adverse outcomes in safety assessment and translational research. We evaluated serum biomarkers and targeted metabolite profiles after exposure to pesticides (permethrin, deltamethrin, imidacloprid, carbaryl, triadimefon, fipronil) with different neurotoxic actions. Adult male Long–Evans rats were evaluated after single exposure to vehicle or one of two doses of each pesticide at the time of peak effect. The doses were selected to produce similar magnitude of behavioral effects across chemicals. Serum or plasma was analyzed using commercial cytokine/protein panels and targeted metabolomics. Additional studies of fipronil used lower doses (lacking behavioral effects), singly or for 14 days, and included additional markers of exposure and biological activity. Biomarker profiles varied in the number of altered analytes and patterns of change across pesticide classes, and discriminant analysis could separate treatment groups from control. Low doses of fipronil produced greater effects when given for 14 days compared to a single dose. Changes in thyroid hormones and relative amounts of fipronil and its sulfone metabolite also differed between the dosing regimens. Most cytokine changes reflected alterations in inflammatory responses, hormone levels, and products of phospholipid, fatty acid, and amino acid metabolism. These findings demonstrate distinct blood-based analyte profiles across pesticide classes, dose levels, and exposure duration. These results show promise for detailed analyses of these biomarkers and their linkages to biological pathways. - Highlights: • Pesticides typical of different classes produced distinct patterns of change in biomarker panels. • Based on the panels used, alterations suggest impacts on immune, metabolism, and homeostasis functions. • Some changes may reflect actions on neurotransmitter systems involved in immune modulation. • Fipronil effects on thyroid and kinetics
Full Text Available To evaluate the clinical value of serum α-L-fucosidase (AFU, 5’-nucleotidase (5’-NT and alpha fetoprotein (AFP as biomarkers for primary hepatocellular carcinoma (PHC diagnosis. Methods: Thirty six primary hepatocellular carcinoma (PHC patients and 36 healthy controls were recruited in this study from February 2014 to January 2016 in the Second People’s Hospital of Tianjin. The serum level of AFU, 5’-NT and AFP were examined and compared between the two groups. The diagnostic sensitivity, specificity area under the receiver operating characteristic (ROC curve were calculated by STATA11.0 software. Results: The serum level of AFU, 5’-NT, AFP were 30.87±10.43(U/L, 5.58±3.89(U/L, 233.60±226.60 (μg/L respectively for primary hepatocellular carcinoma group and 19.96±6.73 (U/L, 1.87±0.84 (U/L, 16.64±14.17 (μg/L for healthy control groups. The serum level of AFU, 5’-NT and AFP in primary hepatocellular carcinoma group were significant higher than those of healthy control group (P<0.001. The diagnostic sensitivity and specificity were 0.78 (95%CI:l0.61-0.90, 0.64 (95%CI:0.46-0.79 for serum AFU, 0.75(95%CI:0.58-0.88, 0.72(95%CI:0.55- 0.86 for serum 5’-NT and 0.72 (95%CI:0.55-0.86, 0.92 (95%CI:0.78-0.98 for serum AFP respectively. The AUC under the ROC curve were 0.80 (0.69-0.90, 0.80 (0.69-0.91 and 0.87 (0.780-0.96 for serum AFU, 5’-NT and AFP respectively. Positive correlation between AFU and 5’-NT (rpearson=0.63, P<0.05, AFU and AFP (rpearson=0.49, P<0.05, 5’-NT and AFP(rpearson=0.44, P<0.05 were found in the primary hepatocellular carcinoma patients. Conclusion: Serum AFU, 5’-NT and AFP were higher in PHC patients than those of healthy controls. The difference between PHC patients and healthy controls made serum AFU, 5’-NT and AFP potential biomarker for PHC diagnosis.
Full Text Available Purpose: to establish efficiency of a range of uric and serum biomarkers of bladder cancer for diagnostics and the prognosis of risk of development of disease recurrence. Material and methods: TPA and TPS, VEGF level research in blood serum, UBC in urine in 176 people, among which 135 patients with bladder cancer (RMP have been conducted. Group of comparison has included16 patients (patients with cystitis. The control group has been made of 25 almost healthy men. 75 patients had non-muscle invasive RMP (Ta-1N0M0. Results. It has been statistically determined that reliable growth of of TPA, TPS in blood serum and UBC in urine in patients with non-muscle invasive RMP in comparison with patients in groups of control and comparison has been established. The increase of UBC in urine of patients of this group with recurrence of tumoral growth within a year has been noted. In comparison with cytological research of urine sedimentation, molecular markers of RMP (the uric UBC and serum TPA, TPS possess diagnostic sensitivity, allow to confirm the presence of disease, to carry out diagnostics of stages of organ and extra invasion. RMP is possible to consider as an additional prognostic serum marker increase in the VEGF level in blood serum. Conclusion. Inclusion in diagnostic process in the clinical research of biomarkers showed that identification of NMIRMP increased from 18,1% in 2006 to 55,6% in 2011. The chosen volume of complex treatment allowed to reduce recurrence and lethality in the first two years from 32 to 15,5%.
Ciarla, Sara; Struglia, Manuela; Giorgini, Paolo; Striuli, Rinaldo; Necozione, Stefano; Properzi, Giuliana; Ferri, Claudio
To investigate the relationship among serum uric acid levels and metabolic syndrome. Anthropometric parameters, serum uric acid and metabolic parameters were evaluated in 139 subjects. Serum uric acid levels were significantly higher in subjects with than without metabolic syndrome (p metabolic syndrome components (p for trend uric acid significantly correlated with various anthropometric and serum metabolic parameters. Serum uric acid levels were higher in individuals with rather than without metabolic syndrome and raised gradually as the number of metabolic syndrome components increased. The relationship between serum uric acid levels and various metabolic parameters suggests that uric acid might be considered as a component of metabolic syndrome. Hyperuricemia is a common finding in patients with the metabolic syndrome. Recent studies indicated that hyperuricemia may be also a predictor of metabolic syndrome development.
Tsao, Yu-Chung; Gu, Po-Wen; Liu, Su-Hsun; Tzeng, I-Shiang; Chen, Jau-Yuan; Luo, Jiin-Chyuan John
The mechanism of nickel-induced pathogenesis remains elusive. To examine effects of nickel exposure on plasma oxidative and anti-oxidative biomarkers. Biomarker data were collected from 154 workers with various levels of nickel exposure and from 73 controls. Correlations between nickel exposure and oxidative and anti-oxidative biomarkers were determined using linear regression models. Workers with a exposure to high nickel levels had significantly lower levels of anti-oxidants (glutathione and catalase) than those with a lower exposure to nickel; however, only glutathione showed an independent association after multivariable adjustment. Exposure to high levels of nickel may reduce serum anti-oxidative capacity.
Lipid peroxidation levels and total oxidant/antioxidant status in serum and saliva from patients with chronic and aggressive periodontitis. Oxidative stress index: a new biomarker for periodontal disease?
Baltacıoğlu, Esra; Yuva, Pınar; Aydın, Güven; Alver, Ahmet; Kahraman, Cemil; Karabulut, Erdem; Akalın, Ferda Alev
In this study, levels of malondialdehyde (MDA), which is a significant product of lipid peroxidation (LPO), total oxidant status (TOS), total antioxidant capacity (TAOC), and the oxidative stress index (OSI), a novel value as a marker of periodontal disease activity, are investigated in serum and saliva from patients with chronic (CP) and generalized aggressive (GAgP) periodontitis. A total of 98 patients (33 with CP, 35 patients with GAgP, and 30 periodontally healthy controls) enrolled in the study. After clinical measurements and sample collection, the MDA level, TOS, and TAOC were measured by high-performance liquid chromatography and a novel automatic colorimetric method. The OSI was calculated as [(TOS/TAOC) × 100]. Although the salivary MDA levels and serum and salivary TOS and OSI values were significantly higher in the periodontitis groups than in the control group (P 0.05). Furthermore, oxidative stress parameters were higher in the GAgP group than in the CP group (except the serum and salivary MDA levels and serum TAOC). Significant positive and negative correlations were observed between periodontal parameters and the MDA levels and TOS, TAOC, and OSI values (except serum MDA) (P periodontitis and are closely associated with clinical periodontal status. Furthermore, the OSI may be a useful and practical parameter for evaluating periodontal disease activity.
The studies aimed to assess a set of biomarkers for their correlations with disease activity/severity of patients with ankylosing spondylitis (AS). A total of 24 AS patients were treated with etanercept and prospectively followed for 12 weeks. Serum levels of TNF-alpha, IFN-gamma, TGF-beta, IL6, IL1...
Arantes, Lidia Maria Rebolho Batista; De Carvalho, Ana Carolina; Melendez, Matias Eliseo; Lopes Carvalho, André
Head and neck squamous cell carcinoma (HNSCC) encompasses tumors arising from several locations (oral and nasal cavities, paranasal sinuses, salivary glands, pharynx, and larynx) and currently stands as the sixth most common cancer worldwide. The most important risk factors identified so far are tobacco and alcohol consumption, and, for a subgroup of HNSCCs, infection with high-risk types of human papillomavirus (HPV). Despite several improvements in the treatment of these tumors in the last decades, overall survival rates have only improved marginally, mainly due to the advanced clinical stage at diagnosis and the high rates of treatment failure associated with this late diagnosis. Areas covered: This review will focus on the feasibility of evaluating molecular-based biomarkers (mRNA, microRNA, lncRNA, DNA methylation and protein expression) in body fluids (serum, plasma, and saliva) as markers for diagnosis, prognosis, and surveillance. Expert commentary: The potential use of those markers in the clinical setting would allow for early diagnosis, prediction of treatment response, improvement in treatment selection and provide disease monitoring for early detection of tumor recurrence. It can ultimately be translated into better survival rates and improved quality of life for HNSCC patients.
Bonella, Francesco; Long, Xiaoping; He, Xuan; Ohshimo, Shinichiro; Griese, Matthias; Guzman, Josune; Costabel, Ulrich
Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by alveolar filling. YKL-40, a chitinase-like protein produced by macrophages and epithelial cells, is increased in patients with interstitial lung diseases. We aimed to evaluate the role of YKL-40 as a biomarker for PAP. A total of 34 patients with autoimmune PAP and 50 healthy controls were studied. YKL-40 was measured by ELISA in serum and bronchoalveolar lavage fluid (BALF). Chitinase coding gene polymorphisms (CHI3L1-329 and -131) were detected by PCR and pyrosequencing. Correlations between serum YKL-40 levels and disease outcome were analysed. Baseline serum and BALF levels of YKL-40 were higher in PAP patients than in controls (286 ± 27 ng/mL vs 42 ± 4 ng/mL, P 40 levels correlated with diffusing capacity of the lung for carbon monoxide (DL CO ) at baseline (P = 0.002) and over time (P 40 levels than those who remained stable or improved (P 40. YKL-40 is elevated in serum and BALF of PAP patients, and may be of clinical utility to predict outcome in PAP. © 2017 Asian Pacific Society of Respirology.
Nazarinia, Mohammadali; Shams, Mesbah; Kamali Sarvestani, Eskandar; Shenavande, Saeede; Khademalhosseini, Maryam; Khademalhosseini, Zeinab
Systemic Sclerosis (SSc) is a systemic connective tissue disease. In this study, we compared the serum Homocystein (Hcy) level between patients with SSc and normal control group. The current study was conducted to determine whether serum Hcy levels are elevated in SSc patients and whether there is any correlation between Hcy levels and RP, Gastro intestinal and lung involvement. Forty one patients who fulfilled the diagnostic criteria for SSc (39 females and 5 males) and Forty four community-based healthy individuals (sex and age matched) were enrolled in to the study. Serum Hcy, vitamin B12, and folate levels were determined. Thirty three patients (70.45%) had GI involvement, twenty two patients (50%) had lung involvement and twenty seven patients (61.36%) had Raynaud's phenomena. Mean serum Hcy level in control group was 22.78 ± 6.018 μmol/L and in case group was 19.43 ± 7.205 μmol/L, shows that the serum Hcy level in control group was significantly higher than patients (P = 0.020). Serum Hcy level is significantly lower in SSc patients than in control group. There is no statistically significant correlation between serum Hcy level and organ involvements.
Full Text Available Background. Macrosomia has become a worldwide problem with the rapid economic growth in the past few years. However, the detailed mechanism of how the macrosomia happened remains unknown. Growing evidence indicates that miRNAs are involved in maintaining metabolic homeostasis. We hypothesized that serum miRNAs are potential biomarkers for macrosomia. Methods. We performed miRNAs profiling using TLDA chips in the discovery phase in two pooled samples from 30 cases and 30 controls, respectively. Individual qRT-PCR was conducted for the discovery phase samples. To confirm the results, we detected the miRNAs which were differentially expressed in the microarray assays and individual qRT-PCR in external validation phase with another 30 cases and 30 controls. Results. In the discovery stage, miR-194 and miR-376a expression levels were significantly different between macrosomia group and controls (P=0.048 for miR-194 and P=0.018 for miR-376a, resp.. Further evaluation of the two miRNAs on a total of 120 serum samples showed that the miR-376a remains significantly lower in macrosomia (P=0.032. Receiver operating characteristic curve analyses showed that the area under curve for miR-376a was 67.8% (sensitivity = 96.7% and specificity = 40.0%. Conclusions. Serum miR-376a may serve as a potential noninvasive biomarker in detecting macrosomia.
Hu, Lingmin; Han, Jing; Zheng, Fangxiu; Ma, Hongxia; Chen, Jiaping; Jiang, Yue; Jiang, Hua
Macrosomia has become a worldwide problem with the rapid economic growth in the past few years. However, the detailed mechanism of how the macrosomia happened remains unknown. Growing evidence indicates that miRNAs are involved in maintaining metabolic homeostasis. We hypothesized that serum miRNAs are potential biomarkers for macrosomia. We performed miRNAs profiling using TLDA chips in the discovery phase in two pooled samples from 30 cases and 30 controls, respectively. Individual qRT-PCR was conducted for the discovery phase samples. To confirm the results, we detected the miRNAs which were differentially expressed in the microarray assays and individual qRT-PCR in external validation phase with another 30 cases and 30 controls. In the discovery stage, miR-194 and miR-376a expression levels were significantly different between macrosomia group and controls (P=0.048 for miR-194 and P=0.018 for miR-376a, resp.). Further evaluation of the two miRNAs on a total of 120 serum samples showed that the miR-376a remains significantly lower in macrosomia (P=0.032). Receiver operating characteristic curve analyses showed that the area under curve for miR-376a was 67.8% (sensitivity=96.7% and specificity=40.0%). Serum miR-376a may serve as a potential noninvasive biomarker in detecting macrosomia.
Full Text Available The aim of this study was to evaluate the diagnostic and differential diagnostic power of serum N-glycans for light chain multiple myeloma (LCMM. A total of 167 cases of subjects, including 42 LCMM, 42 IgG myeloma, 41 IgA myeloma, and 42 healthy controls were recruited in this study. DNA sequencer-assisted fluorophore-assisted capillary electrophoresis (DSA-FACE was applied to determine the quantitive abundance of serum N-glycans. The core fucosylated, bisecting and sialylated modifications were analyzed in serum of LCMM patients (n=20 and healthy controls (n=20 randomly selected from the same cohort by lectin blot. Moreover, serum sialic acid (SA level was measured by enzymatic method. We found two N-glycan structures (NG1A2F, Peak3; NA2FB, Peak7 showed the optimum diagnostic efficacy with area under the ROC curve (AUC 0.939 and 0.940 between LCMM and healthy control. The sensitivity and specificity of Peak3 were 88.1% and 92.9%, while Peak7 were 92.9% and 97.6%, respectively. The abundance of Peak3 could differentiate LCMM from IgG myeloma with AUC 0.899, sensitivity 100% and specificity 76.2%, and Peak7 could be used to differentiate LCMM from IgA myeloma with AUC 0.922, sensitivity 92.9% and specificity 82.9%. Serum SA level was significantly higher in patients with LCMM than that in healthy controls. Moreover, the decreased core fucosylation, bisecting and increased sialylation characters of serum glycoproteins were observed in patients with LCMM. We concluded that serum N-glycan could provide a simple, reliable and non-invasive biomarker for LCMM diagnosis and abnormal glycosylation might imply a new potential therapeutic target in LCMM.
Value of soluble TREM-1, procalcitonin, and C-reactive protein serum levels as biomarkers for detecting bacteremia among sepsis patients with new fever in intensive care units: a prospective cohort study
Full Text Available Abstract Background The purpose of this study was to explore the diagnostic value of soluble triggering receptor expressed on myeloid cells 1 (sTREM-1, procalcitonin (PCT, and C-reactive protein (CRP serum levels for differentiating sepsis from SIRS, identifying new fever caused by bacteremia, and assessing prognosis when new fever occurred. Methods We enrolled 144 intensive care unit (ICU patients: 60 with systemic inflammatory response syndrome (SIRS and 84 with sepsis complicated by new fever at more than 48 h after ICU admission. Serum sTREM-1, PCT, and CRP levels were measured on the day of admission and at the occurrence of new fever (>38.3°C during hospitalization. Based on the blood culture results, the patients were divided into a blood culture-positive bacteremia group (33 patients and blood culture-negative group (51 patients. Based on 28-day survival, all patients, both blood culture-positive and -negative, were further divided into survivor and nonsurvivor groups. Results On ICU day 1, the sepsis group had higher serum sTREM-1, PCT, and CRP levels compared with the SIRS group (P P Conclusions Serum sTREM-1, PCT, and CRP levels each have a role in the early diagnosis of sepsis. Serum sTREM-1, with the highest sensitivity and specificity of all indicators studied, is especially notable. sTREM-1, PCT, and CRP levels are of no use in determining new fever caused by bacteremia in ICU patients, but sTREM-1 levels reflect the prognosis of bacteremia. Trial registration ClinicalTrial.gov identifier NCT01410578
Breast cancer is the most common form of cancer among women. Compared with other serum polypeptides, autoantibodies have many appealing features as biomarkers including sensitivity, stability, and easy detection...
Sui, W; Yang, M; Li, F; Chen, H; Chen, J; Ou, M; Zhang, Y; Lin, H; Xue, W; Dai, Y
In the present study, we compared the expression levels of 3 microRNAs (miRNAs) between patients who had undergone kidney transplantation and healthy individuals in a search for a new diagnostic biomarker after kidney transplantation. We used real-time quantitative polymerase chain reaction to investigate the expression levels of miR-181a, miR-483-5p, and miR-557 in the serum of 15 kidney transplantation patients before transplantation on the first, third, and seventh days after transplantation. The study was performed in the Guilin 181st Hospital between 2010 and 2012. The results of this study may assist with early diagnosis and treatment and contribute to our understanding of the pathological parameters. Receiver operating characteristic (ROC) analysis was performed to determine the area under the curve of each equation to predict evolution to rejection. ROC curves were performed to explore miRNAs to predict rejection occurrence after transplantation showed pre-transplantation expression levels of miR-181a to be a potential factor with a significant area under the curve (AUC = 0.985, P .05). Serum miR-181a, miR-483-5p, and miR-557 could serve as circulating biomarkers for the early diagnosis of active situations of before and after kidney transplantation. Copyright © 2014 Elsevier Inc. All rights reserved.
Ramsey, Jordan M.; Cooper, Jason D.; Penninx, Brenda W. J. H.; Bahn, Sabine
Few serum biomarker tests are implemented in clinical practice and recent reports raise concerns about poor reproducibility of biomarker studies. Here, we investigated the potential role of sex and female hormonal status in this widespread irreproducibility. We examined 171 serum proteins and small molecules measured in 1,676 participants from the Netherlands Study of Depression and Anxiety. Concentrations of 96 molecules varied with sex and 66 molecules varied between oral contraceptive pill...
Yamashita, Taku; Shimada, Hideaki; Tanaka, Shingo; Araki, Koji; Tomifuji, Masayuki; Mizokami, Daisuke; Tanaka, Nobuaki; Kamide, Daisuke; Miyagawa, Yoshihiro; Suzuki, Hiroshi; Tanaka, Yuya; Shiotani, Akihiro
Improved therapies for individuals with head and neck squamous cell carcinoma (HNSCC) may be developed by identification of appropriate biomarkers. The aim of this study was to evaluate the usefulness of serum midkine measurement as a biomarker for HNSCC. Pretreatment serum midkine concentrations were measured in 103 patients with HNSCC and 116 control individuals by enzyme-linked immunosorbent assay. Midkine expression in tumor tissues from 33 patients with HNSCC who underwent definitive surgical resection without preoperative treatment was examined by immunohistochemistry. The cut-off serum midkine concentrations for predicting the presence of head and neck malignancy and chemosensitivity to induction chemotherapy, as determined using receiver operating characteristic curves, were 482 and 626 pg/mL, respectively. Spearman bivariate correlations showed positive correlations between serum midkine levels and immunohistochemistry staining score (r = 0.612, P < 0.001). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of serum midkine concentration for detection of HNSCC were 57.3, 85.3, 77.6, 69.2, and 72.1%, respectively. However, for predicting the response to induction chemotherapy, the values were 84.6, 60.9, 71.0, 77.8, and 73.5%, respectively. Serum midkine concentration was identified as an independent prognostic factor by multivariate analysis, using Cox's proportional hazards model (P = 0.027). Overexpression of serum midkine yielded a relative risk of death of 3.77, with 95% confidence limits ranging from 1.15 to 17.0. Serum midkine levels in patients with HNSCC were associated with malignancy, chemosensitivity, and prognosis. Serum midkine may be a useful, minimally invasive biomarker for early detection, therapeutic decision-making, and predicting prognosis
Calvano, Jacqueline; Edwards, Gwendolyn; Hixson, Clifford; Burr, Holly; Mangipudy, Raja; Tirmenstein, Mark
Pancreatic injury in rats is primarily detected through histopathological changes and conventional serum biomarkers such as amylase and lipase. However, amylase and lipase have a short half-life and are markers of acinar, not islet cell injury. We investigated whether circulating microRNA (miR) levels that are enriched in acinar cells (miR-217, miR-216a/b) or islet cells (miR-375) could serve as markers of pancreatic injury. Rats were treated with a single dose of either vehicle, streptozotocin (STZ), caerulein, or acetaminophen (APAP), and necropsied at 4, 24, and 48h. Pancreas, liver, heart, kidney and skeletal muscle were analyzed for histopathology. Blood was collected at necropsy and processed to serum for amylase/lipase enzymatic determinations and miR qPCR analysis. Caerulein induced degeneration/necrosis of acinar cells at 4h that persisted for 48h. Caerulein-induced injury was associated with increases in serum amylase/lipase (4h), miR-216a/b (4, 24h). In contrast, serum miR-217 was detected at all time points examined. STZ did not induce increases in either amylase or lipase but did induce increases in miR-375 levels at 4 and 24h. No increases in miR-375 were observed in caerulein-treated rats, and no increases were observed in miR-217 and miR-216a/b in STZ-treated rats. APAP induced centrilobular necrosis in the liver 24h after treatment, but did not induce pancreatic injury or increases in miR-217 or miR-375. Our results suggest that miR-217 and miR-375 represent promising biomarkers of pancreatic injury in rats. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Carbone, Javier; Calahorra, Leticia; Navarro, Joaquin; Sarmiento, Elizabeth
We evaluated the potential role of serum B-cell activating factor (BAFF) as a biomarker in HIV infection and analyzed the relationship between BAFF concentration and the immunophenotypic activation status of T-cells. We tested the hypothesis that higher serum BAFF concentrations are associated with risk for development of AIDS in HIV positive individuals. Forty-one HIV patients (CDC category A 17, category B 24) were evaluated retrospectively. Serum BAFF concentrations were assessed using a commercial enzyme-linked immunosorbent assay. Cox regression was used to estimate the probability for development of AIDS. Patients with higher BAFF concentrations (> 2100 pg/mL) were at greater risk of developing AIDS (relative hazard 5.69; p = 0.0033). BAFF levels were independently associated with risk of AIDS after adjustment by clinical risk factors. Serum BAFF was correlated with activated T-cell subsets and with neopterin levels. BAFF is a good candidate for further evaluation as a nonspecific surrogate marker in HIV infection.
Wang, Huihua; Gao, Bo; Wu, Zaigui; Wang, Hanzhi; Dong, Minyue
To clarify the alterations in serum adropin and preptin concentrations in preeclampsia, we determined serum adropin and preptin levels in 29 women with normal pregnancy and 32 women with preeclampsia. We found that maternal age, body mass index and fetal gender were not significantly different between two groups; however, blood pressure, gestational age and neonatal birth weight were significantly different. Serum adropin levels were significantly increased in women with preeclampsia compared with those with normal pregnancy but there were no significant differences in preptin levels. An increase in maternal serum adropin level was found in preeclampsia, and this may be a compensation for pregnancy complicated with preeclampsia. Copyright © 2017 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.
Huang, Peiwu; Ren, Xiaohu; Huang, Zhijun; Yang, Xifei; Hong, Wenxu; Zhang, Yanfang; Zhang, Hang; Liu, Wei; Huang, Haiyan; Huang, Xinfeng; Wu, Desheng; Yang, Linqing; Tang, Haiyan; Zhou, Li; Li, Xuan; Liu, Jianjun
Trichloroethylene (TCE) is an industrial solvent with widespread occupational exposure and also a major environmental contaminant. Occupational medicamentosa-like dermatitis induced by trichloroethylene (OMLDT) is an autoimmune disease and it has become one major hazard in China. In this study, sera from 3 healthy controls and 3 OMLDT patients at different disease stages were used for a screening study by 2D-DIGE and MALDI-TOF-MS/MS. Eight proteins including transthyretin (TTR), retinol binding protein 4 (RBP4), haptoglobin, clusterin, serum amyloid A protein (SAA), apolipoprotein A-I, apolipoprotein C-III and apolipoprotein C-II were found to be significantly altered among the healthy, acute-stage, healing-stage and healed-stage groups. Specifically, the altered expression of TTR, RBP4 and haptoglobin were further validated by Western blot analysis and ELISA. Our data not only suggested that TTR, RBP4 and haptoglobin could serve as potential serum biomarkers of OMLDT, but also indicated that measurement of TTR, RBP4 and haptoglobin or their combination could help aid in the diagnosis, monitoring the progression and therapy of the disease. Copyright © 2014. Published by Elsevier Ireland Ltd.
Full Text Available Abstract Background Although gastric caner (GC remains the second cause of cancer-related death, useful biomarkers for prognosis are still unavailable. We present here the attempt of mining novel biomarkers for GC prognosis by using serum proteomics. Methods Sera from 43 GC patients and 41 controls with gastritis as Group 1 and 11 GC patients as Group 2 was successively detected by Surface Enhanced Laser Desorption/ionization Time of Flight Mass Spectrometry (SELDI-TOF-MS with Q10 chip. Peaks were acquired by Ciphergen ProteinChip Software 3.2.0 and analyzed by Zhejiang University-ProteinChip Data Analysis System (ZJU-PDAS. CEA level were evaluated by chemiluminescence immunoassay. Results After median follow-up periods of 33 months, Group 1 with 4 GC patients lost was divided into 20 good-prognosis GC patients (overall survival more than 24 months and 19 poor-prognosis GC patients (no more than 24 months. The established prognosis pattern consisted of 5 novel prognosis biomarkers with 84.2% sensitivity and 85.0% specificity, which were significantly higher than those of carcinoembryonic antigen (CEA and TNM stage. We also tested prognosis pattern blindly in Group 2 with 66.7% sensitivity and 80.0% specificity. Moreover, we found that 4474-Da peak elevated significantly in GC and was associated with advanced stage (III+IV and short survival (p Conclusion We have identified a number of novel biomarkers for prognosis prediction of GC by using SELDI-TOF-MS combined with sophisticated bioinformatics. Particularly, elevated expression of 4474-Da peak showed very promising to be developed into a novel biomarker associated with biologically aggressive features of GC.
Full Text Available Background: Ectopic pregnancy (EP refers to the implantation of the zygote outside the uterine cavity. In clinical practice, the diagnosis of EP relies on a combination of ultrasound findings and serum human chorionic gonadotrophin (hCG measurements. However, the need for serial hCG measurements increases the risk of tubal rupture and death, underscoring the need to identify biomarkers for the early detection of EP. Methods: The serum concentrations of 21 microRNAs (miRNAs associated with pregnancy or with known placental expression, as well as serum hCG and progesterone levels were analyzed 36 patients with viable intrauterine pregnancy (VIP, 30 patients with spontaneous abortion (SA, and 34 patients with EP using specific assay kits and reverse transcription PCR. The diagnostic performance of the different serum markers for detecting EP was analyzed by ROC curve analysis. Results: Five miRNAs were differentially expressed between the three groups, of which miR-873 and miR-223 were significantly lower in EP than in VIP and SA patients and did not change significantly according to gestational age, and miR-323 was significantly higher in EP than in VIP and SA. As a single marker, miR-873 had the highest sensitivity for detecting EP at 61.76% (at a fixed specificity of 90%. In comparison, the combination of hCG, progesterone and miR-873 had the highest sensitivity for detecting EP at 79.41% (at a fixed specificity of 90%. Conclusion: Although further validation in large-scale prospective studies is necessary, our results suggest that miR-873 could be a valuable noninvasive and stable biomarker for the early detection of EP.
Ando, Izumi; Karasawa, Kaoru; Matsuda, Hiroshi; Tanaka, Akane
Serum nerve growth factor (NGF) levels are increased by the external stress in mice, humans and horses; however, similar variations have been unclear in dogs. Since dogs are usually subjected to conditions of work, exercise and activity as important partners of humans, we measured serum NGF levels post-exercise and compared them with serum cortisol levels, as a biomarker of physical stress. Serum cortisol levels were immediately elevated post-exercise and returned to basal levels within 1 hr. On the other hand, serum NGF levels were significantly increased 1 hr post-exercise and gradually returned to basal levels. Further research is necessary; nevertheless, we have demonstrated for the first time that serum NGF levels respond to exercise stress in dogs.
Lizio, Andrea; Maestri, Eleonora; Sansone, Valeria Ada; Mora, Gabriele; Miller, Robert G.; Appel, Stanley H.; Chiò, Adriano
Importance Various factors have been proposed as possible candidates associated with the prognosis of amyotrophic lateral sclerosis (ALS); however, there is still no consensus on which biomarkers are reliable prognostic factors. C-reactive protein (CRP) is a biomarker of the inflammatory response that shows significant prognostic value for several diseases. Objective To examine the prognostic significance of CRP in ALS. Design, Setting, and Participants Patients’ serum CRP levels were evaluated from January 1, 2009, to June 30, 2015, in a large cohort of patients with ALS observed by an Italian tertiary multidisciplinary center. Results were replicated in an independent cohort obtained from a population-based registry of patients with ALS. A post hoc analysis was performed of the phase 2 trial of NP001 to determine whether stratification by levels of CRP improves differentiation of responders and nonresponders to the drug. Main Outcomes and Measures Serum CRP levels from the first examination were recorded to assess their effect on disease progression and survival. Results A total of 394 patients with ALS (168 women and 226 men; mean [SD] age at diagnosis, 60.18 [13.60] years) were observed in a tertiary multidisciplinary center, and the analysis was replicated in an independent cohort of 116 patients with ALS (50 women and 66 men; mean [SD] age at diagnosis, 67.00 [10.74] years) identified through a regional population-based registry. Serum CRP levels in the 394 patients with ALS correlated with severity of functional impairment, as measured by total score on the ALS Functional Rating Scale–Revised, at first evaluation (r = –0.14818; P = .004), and with patient survival (hazard ratio, 1.129; 95% CI, 1.033-1.234; P = .007). Similar results were found in the independent cohort (hazard ratio, 1.044; 95% CI, 1.016-1.056; P ≤ .001). Moreover, a post hoc analysis of the phase 2 trial of NP001 using the same CRP threshold showed that patients with
Full Text Available Abstract Background Pulmonary tuberculosis (TB is a highly lethal infectious disease and early diagnosis of TB is critical for the control of disease progression. The objective of this study was to profile a panel of serum microRNAs (miRNAs as potential biomarkers for the early diagnosis of pulmonary TB infection. Methods Using TaqMan Low-Density Array (TLDA analysis followed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR validation, expression levels of miRNAs in serum samples from 30 patients with active tuberculosis and 60 patients with Bordetella pertussis (BP, varicella-zoster virus (VZV and enterovirus (EV were analyzed. Results The Low-Density Array data showed that 97 miRNAs were differentially expressed in pulmonary TB patient sera compared with healthy controls (90 up-regulated and 7 down-regulated. Following qRT-PCR confirmation and receiver operational curve (ROC analysis, three miRNAs (miR-361-5p, miR-889 and miR-576-3p were shown to distinguish TB infected patients from healthy controls and other microbial infections with moderate sensitivity and specificity (area under curve (AUC value range, 0.711-0.848. Multiple logistic regression analysis of a combination of these three miRNAs showed an enhanced ability to discriminate between these two groups with an AUC value of 0.863. Conclusions Our study suggests that altered levels of serum miRNAs have great potential to serve as non-invasive biomarkers for early detection of pulmonary TB infection.
Qi, Yuhua; Cui, Lunbiao; Ge, Yiyue; Shi, Zhiyang; Zhao, Kangchen; Guo, Xiling; Yang, Dandan; Yu, Hao; Cui, Lan; Shan, Yunfeng; Zhou, Minghao; Wang, Hua; Lu, Zuhong
Pulmonary tuberculosis (TB) is a highly lethal infectious disease and early diagnosis of TB is critical for the control of disease progression. The objective of this study was to profile a panel of serum microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary TB infection. Using TaqMan Low-Density Array (TLDA) analysis followed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) validation, expression levels of miRNAs in serum samples from 30 patients with active tuberculosis and 60 patients with Bordetella pertussis (BP), varicella-zoster virus (VZV) and enterovirus (EV) were analyzed. The Low-Density Array data showed that 97 miRNAs were differentially expressed in pulmonary TB patient sera compared with healthy controls (90 up-regulated and 7 down-regulated). Following qRT-PCR confirmation and receiver operational curve (ROC) analysis, three miRNAs (miR-361-5p, miR-889 and miR-576-3p) were shown to distinguish TB infected patients from healthy controls and other microbial infections with moderate sensitivity and specificity (area under curve (AUC) value range, 0.711-0.848). Multiple logistic regression analysis of a combination of these three miRNAs showed an enhanced ability to discriminate between these two groups with an AUC value of 0.863. Our study suggests that altered levels of serum miRNAs have great potential to serve as non-invasive biomarkers for early detection of pulmonary TB infection.
Ozdemir, B; Köksal, B T; Karakaş, N M; Ozbek, O Y
Acute urticaria is an immune-inflammatory disease, characterised by acute immune activation. There has been increasing evidence showing that vitamin D deficiency is associated with increased incidence and severity of immune-inflammatory disorders. The aim of this study was to evaluate serum vitamin D levels in acute urticaria. We enrolled 30 children with acute urticaria and 30 control subjects. Concentrations of 25-hydroxyvitamin D [25(OH)D], a biomarker of vitamin D status, were measured in serum of acute urticaria patients and compared with the control group. There were no significant differences in baseline variables (age, gender, weight) between the groups. Vitamin D deficiency (urticaria than in control patients. Serum 25(OH)D levels were significantly lower in the study group compared to those in the control group (13.1±4.3 vs 28.2±7.4ng/mL, purticaria and serum vitamin D levels (purticaria and an inverse relationship with disease duration. These findings may open up the possibility of the clinical use of vitamin D as a contributing factor in the pathogenesis of acute urticaria and a predictive marker for disease activity in acute urticaria. A potential role of vitamin D in pathogenesis and additive therapy in acute urticaria needs to be examined. Copyright © 2016 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.
Ahmad, T.M.; Mahmood, M.T.; Baluch, G.R.; Bhatti, M.T.
Serum zinc level amongst children with protein energy malnutrition (PEM) was evaluated in a control study conducted in the Department of Paediatrics, Allama Iqbal Medical College and Jinnah Hospital, Lahore. Twenty-five children with PEM and 25 healthy children as control from the community were screened. Mean serum zinc level was found to be 54.48 -+ 18.91 mg/dl in children with PEM while it was 72.72 -+ 8.21 mg/dl in control group (P < 0.001). No significant difference in zinc level was noted between both sexes in each group. Marasmic 16 children revealed mean serum zinc level of 57.55 -+ 18.16 mg/dl while in Kwashiorkor it was 44.57 -+ 13.66 mg/dl. Serum zinc was significantly low in Kwashiorkor than in marasmus (P < 0.001). It was also significantly low in children with acute or chronic diarrhea associated with malnutrition (44.66 -+ 16.0 mg/dl). Acute respiratory infections in these children were not associated with low serum zinc level (71.66 -+ 16.51 mg/dl). (author)
Xiao, Jun Feng; Varghese, Rency S.; Zhou, Bin; Nezami Ranjbar, Mohammad R.; Zhao, Yi; Tsai, Tsung-Heng; Di Poto, Cristina; Wang, Jinlian; Goerlitz, David; Luo, Yue; Cheema, Amrita K.; Sarhan, Naglaa; Soliman, Hanan; Tadesse, Mahlet G.; Ziada, Dina Hazem; Ressom, Habtom W.
Although hepatocellular carcinoma (HCC) has been subjected to continuous investigation and its symptoms are well known, early-stage diagnosis of this disease remains difficult and the survival rate after diagnosis is typically very low (3–5%). Early and accurate detection of metabolic changes in the sera of patients with liver cirrhosis can help improve the prognosis of HCC and lead to a better understanding of its mechanism at the molecular level, thus providing patients with in-time treatment of the disease. In this study, we compared metabolite levels in sera of 40 HCC patients and 49 cirrhosis patients from Egypt by using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer (UPLC-QTOF MS). Following data preprocessing, the most relevant ions in distinguishing HCC cases from cirrhotic controls are selected by statistical methods. Putative metabolite identifications for these ions are obtained through mass-based database search. The identities of some of the putative identifications are verified by comparing their MS/MS fragmentation patterns and retention times with those from authentic compounds. Finally, the serum samples are reanalyzed for quantitation of selected metabolites along with other metabolites previously selected as candidate biomarkers of HCC. This quantitation was performed using isotope dilution by selected reaction monitoring (SRM) on a triple quadrupole linear ion trap (QqQLIT) coupled to UPLC. Statistical analysis of the UPLC-QTOF data identified 274 monoisotopic ion masses with statistically significant differences in ion intensities between HCC cases and cirrhotic controls. Putative identifications were obtained for 158 ions by mass based search against databases. We verified the identities of selected putative identifications including glycholic acid (GCA), glycodeoxycholic acid (GDCA), 3beta, 6beta-dihydroxy-5beta-cholan-24-oic acid, oleoyl carnitine, and Phe-Phe. SRM-based quantitation
Wiredu Edwin K
Full Text Available Abstract Background Plasmodium falciparum can cause a diffuse encephalopathy known as cerebral malaria (CM, a major contributor to malaria associated mortality. Despite treatment, mortality due to CM can be as high as 30% while 10% of survivors of the disease may experience short- and long-term neurological complications. The pathogenesis of CM and other forms of severe malaria is multi-factorial and appear to involve cytokine and chemokine homeostasis, inflammation and vascular injury/repair. Identification of prognostic markers that can predict CM severity will enable development of better intervention. Methods Postmortem serum and cerebrospinal fluid (CSF samples were obtained within 2–4 hours of death in Ghanaian children dying of CM, severe malarial anemia (SMA, and non-malarial (NM causes. Serum and CSF levels of 36 different biomarkers (IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70, IL-13, IL-15, IL-17, Eotaxin, FGF basic protein, CRP, G-CSF, GM-CSF, IFN-γ, TNF-α, IP-10, MCP-1 (MCAF, MIP-1α, MIP-1β, RANTES, SDF-1α, CXCL11 (I-TAC, Fas-ligand [Fas-L], soluble Fas [sFas], sTNF-R1 (p55, sTNF-R2 (p75, MMP-9, TGF-β1, PDGF bb and VEGF were measured and the results compared between the 3 groups. Results After Bonferroni adjustment for other biomarkers, IP-10 was the only serum biomarker independently associated with CM mortality when compared to SMA and NM deaths. Eight CSF biomarkers (IL-1ra, IL-8, IP-10, PDGFbb, MIP-1β, Fas-L, sTNF-R1, and sTNF-R2 were significantly elevated in CM mortality group when compared to SMA and NM deaths. Additionally, CSF IP-10/PDGFbb median ratio was statistically significantly higher in the CM group compared to SMA and NM groups. Conclusion The parasite-induced local cerebral dysregulation in the production of IP-10, 1L-8, MIP-1β, PDGFbb, IL-1ra, Fas-L, sTNF-R1, and sTNF-R2 may be involved in CM neuropathology, and their immunoassay may have potential utility in predicting
Eric Peter Thelin
Full Text Available BackgroundThe proteins S100B, neuron-specific enolase (NSE, glial fibrillary acidic protein (GFAP, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1, and neurofilament light (NF-L have been serially sampled in serum of patients suffering from traumatic brain injury (TBI in order to assess injury severity and tissue fate. We review the current literature of serum level dynamics of these proteins following TBI and used the term “effective half-life” (t1/2 in order to describe the “fall” rate in serum.Materials and methodsThrough searches on EMBASE, Medline, and Scopus, we looked for articles where these proteins had been serially sampled in serum in human TBI. We excluded animal studies, studies with only one presented sample and studies without neuroradiological examinations.ResultsFollowing screening (10,389 papers, n = 122 papers were included. The proteins S100B (n = 66 and NSE (n = 27 were the two most frequent biomarkers that were serially sampled. For S100B in severe TBI, a majority of studies indicate a t1/2 of about 24 h, even if very early sampling in these patients reveals rapid decreases (1–2 h though possibly of non-cerebral origin. In contrast, the t1/2 for NSE is comparably longer, ranging from 48 to 72 h in severe TBI cases. The protein GFAP (n = 18 appears to have t1/2 of about 24–48 h in severe TBI. The protein UCH-L1 (n = 9 presents a t1/2 around 7 h in mild TBI and about 10 h in severe. Frequent sampling of these proteins revealed different trajectories with persisting high serum levels, or secondary peaks, in patients with unfavorable outcome or in patients developing secondary detrimental events. Finally, NF-L (n = 2 only increased in the few studies available, suggesting a serum availability of >10 days. To date, automated assays are available for S100B and NSE making them faster and more practical to use.ConclusionSerial sampling of brain-specific proteins in serum reveals
Full Text Available BACKGROUND: One major impediment to improving the management of breast cancer is the current lack of tumor marker with sufficient sensitivity and specificity. A growing body of evidence implicates the diagnostic potential of circulating miRNAs in cancer detection. MiR-155 plays an important role in the pathogenesis of breast cancer. However, the level of circulating miR-155 and its clinical relevance are not well established. The objective of the current study was to learn more about serum miR-155 in patients with breast cancer. METHODOLOGY/PRINCIPAL FINDINGS: Using quantitative reverse transcription polymerase chain reaction (RT-qPCR, we demonstrated that serum miR-155 had significant increased levels in breast cancer patients (n = 103 compared with healthy subjects (n = 55 (p<0.001, which had a mean fold change of 2.94. Receiver operating characteristic (ROC analysis revealed that miR-155 had considerable diagnostic accuracy, yielding an ROC-AUC (the areas under the ROC curve of 0.801 (sensitivity 65.0%, specificity 81.8%. In addition, sera from a subset of breast cancer patients (n = 29 were collected after surgery and after four cycles of chemotherapy to evaluate the effects of clinical treatment on serum levels of candidate miRNAs. Surprisingly, a decreased level of serum miR-155 was found; whereas the concentrations of carbohydrate antigen 15-3 (CA15-3, carcinoembryonic antigen (CEA and tissue polypeptide specific antigen (TPS did not show this trend. Our results revealed that 79% patients showed response or stable disease after therapy had declined levels of serum miR-155. CONCLUSIONS/SIGNIFICANCE: Our results suggest that serum miR-155 is a potential biomarker to discriminate breast cancer patients from healthy subjects. For the first time, we demonstrated a declined trend of miR-155 after surgery and chemotherapy, which raises the possibility to use it as an indicator for treatment response.
Full Text Available Introduction: Olanzapine is a commonly used antipsychotic. Prolactin elevation is a common adverse effect of anstipsychotics, and serum prolactin elevation is seen in about 30% patients treated with olanzapine. There are confounding results about dose dependency of olanzapine and prolactin elevation, and also the duration of treatment. Method: Fifty six patients, 36 male and 20 female, who were taking olanzapine for any condition for more than a month at a constant dose were enrolled in the study. Patients’ age, weight, body mass index (BMI, serum prolactin levels, and some biochemical values were recorded. Patients were taken from the review outpatient department (OPD after due consent. Results: Five each in male and female groups showed elevation of serum prolactin (estimated to be high if >20 ng/dl for males, and >25 ng/dl for females. In females, the elevation was found at lesser dose of olanzapine (13 mg/day, in males 18 mg/day and early in the treatment (2.4 months vs. 9.7 months in males. Males tended to show raised prolactin with higher doses of olanzapine (mean 18 mg/day. Females (26.31% also showed higher prevalence of prolactin elevation compared to males (13.51%. No other parameter was found to modify the prolactin levels. Conclusion: Olanzapine causes elevation of serum prolactin, though lesser degree than some other antipsychotics. Females are more prone to have raised serum prolactin with olanzapine compared to males. However, the elevation seems to be transient. Higher doses of olanzapine tend to cause elevation of serum prolactin. Serum prolactin estimation in patients taking olanzapine may be undertaken to maintain quality life, particularly in females.
Lau, Cheryl K; Guo, Maggie; Viczko, Jeannine A; Naugler, Christopher T
Prostate cancer is one of the most common cancers in men. Traditional screening and diagnostic methods include digital rectal examinations (DREs), biopsies and serum prostate-specific antigen (PSA) tests, with the latter being the more popular. PSA is a biomarker for prostate cancer; however, it is highly sensitive to external factors as well as other prostate diseases. As such, the reliability of of the serum PSA level as a sole screening and diagnostic tool for prostate cancer is controversial. Recently, it has been shown that fasting extremes can affect concentrations of serum chemistry analytes, thus raising the question of whether or not fasting has an effect on the highly sensitive PSA biomarker. Patients testing for serum PSA levels are often concomitantly submitting to other tests that require fasting, subjecting certain patients to a fasting PSA level while others not. The objective of this study was to investigate whether this discrepancy in fasting state translates into an effect on serum PSA levels. Serum PSA levels and fasting time records for 157 276 men who underwent testing at Calgary Laboratory Services (CLS; Calgary, Alberta, Canada) between 01 January 2010 and 31 March 2013 were accessed. Linear regression models of mean PSA levels and fasting times revealed a statistically important relationship at certain fasting times. Applying a dynamic mathematical model to explore the clinical effect of fasting suggests minimal impact on serum PSA result interpretation. Thus, patients can be tested for serum PSA levels regardless of their fasting state.
Full Text Available Multiple sclerosis (MS is an autoimmune inflammatory demyelinating disease of the central nervous system. At present, the molecular mechanisms causing the initiation, development and progression of MS are poorly understood, and no reliable proteinaceous disease markers are available. In this study, we used an immunoproteomics approach to identify autoreactive antibodies in the cerebrospinal fluid of MS patients to use as candidate markers with potential diagnostic value. We identified an autoreactive anti-transferrin antibody that may have a potential link with the development and progression of MS. We found this antibody at high levels also in the serum of MS patients and created an immunoenzymatic assay to detect it. Because of the complexity and heterogeneity of multiple sclerosis, it is difficult to find a single marker for all of the processes involved in the origin and progression of the disease, so the development of a panel of biomarkers is desirable, and anti-transferrin antibody could be one of these.
Full Text Available Background. In an attempt to correlate biomarkers with disease, serum-based biomarkers often are compared between individuals with osteoarthritis (OA and control subjects. However, variable results have been reported. Some studies have suggested an association between certain adipokines and insulin and OA. We know that there are racial differences in OA prevalence and incidence, and from general population-based studies, those of Asian race consistently demonstrate a unique adipokine/insulin serum concentration profile as compared to Caucasians. Whether similar racial differences exist within OA samples is unknown and may have implications for selecting appropriate controls in comparative studies. Methods. Serum levels of adipokines, leptin, and adiponectin, along with insulin, were determined by ELISA in patients scheduled for total hip or knee replacement surgery for OA. Fifteen Asian patients were matched 1 : 1 on age (±2 years, gender, body mass index (±1.5 kg/m2, and surgical joint with Caucasian patients. Differences in serum concentrations were tested using paired t-tests. Results. Serum leptin and insulin levels were significantly higher in Asians compared to Caucasians (p<0.05. While serum adiponectin levels were lower among Asians, the difference did not reach statistical significance (p=0.12. Conclusion. Findings from this work suggest that when studying serum biomarker concentrations in OA versus controls, race may be an important factor to consider. Our findings warrant confirmation in larger studies.
Bruchim, Yaron; Segev, Gilad; Kelmer, Efrat; Codner, Carolina; Marisat, Ahmad; Horowitz, Michal
Heatstroke is a serious illness in dogs characterized by core temperatures above 41°C with central nervous system dysfunction. Experimental heatstroke models have tried to correlate biomarker levels with the severity of the syndrome. Serum heat shock protein (eHSP70) levels were recently evaluated as a biomarker of heat tolerance and acclimation, their role as a marker of heatstroke is inconclusive. Here, we monitored eHSP70 levels in correlation with systemic biomarkers in 30 naturally occurring canine heatstroke cases. Thirty dogs diagnosed with environmental (33%) or exertional (66%) heatstroke admitted to hospital (0-14 h post-injury) were tested for biomarkers of organ damage and coagulation parameters. eHSP70 levels were measured upon admission and 4, 12, and 24 h later (T1, T2, and T3, respectively). No differences were found between exertional and environmental heatstroke cases. The eHSP profile demonstrated an inverted bell shape, with the lowest levels at the 12 h time point. A positive correlation between eHSP70, lactate, and aPPT was also noted at T2 in all the dogs in the study. Twenty-four h after presentation, eHSP70 levels returned to those measured upon admission, this change was only significant in the survivors. The obtained results suggest that eHSP72 level profile may be predictive of survival.
Pritam Kumar MANKAPURE
Full Text Available Detection of abnormally elevated levels of molecules in patients with oral cancer may be useful in early diagnosis. These markers can be included in current Histopathology grading and in TNM staging systems of Oral Squamous Cell Carcinoma (OSCC to make it more efficient. Several pro-angiogenic molecules have been assessed for the same reason. Endothelin-1 (ET-1 is a vasoactive peptide associated with the development and spread of many solid tumors, including Squamous Cell Carcinoma (SCC, but its utility in OSCC has not been confirmed.Objective This study aims to evaluate the role of the serum big ET-1 as a biomarker of OSCC, by correlating it with the clinical staging and the histopathological grading.Material and Methods Serum levels of big ET-1 measured by the sandwich Enzyme-Linked Immunosorbent Assay (ELISA in 40 OSCC cases were compared with the levels from the control group using independent t-test. Clinical stages and histopathological grades of OSCC cases were compared in relation to their mean levels of serum big ET-1, one using the Analysis of Variance (ANOVA test and the other the independent t-test, respectively. The significance of the mean difference between the groups was evaluated by Tukey’s multiple comparison test. All statistical analyses were performed on GraphPad statistical software version 5.0.Results By comparing the mean of the big ET-1 concentrations of cases and controls, the independent t-test revealed significant higher big ET-1 concentration of OSCC cases when compared to controls (p<0.0001. Tukey’s multiple comparison test also revealed statistically significant difference among all OSCC stages in relation to the mean levels of serum big ET-1. However, the mean of the big ET-1 concentrations of cases of grade I and of grade II did not differ statistically (p=0.729.Conclusion Serum big ET-1 levels may be useful as a diagnostic tool in OSCC and as an adjunct to OSCC staging. However, its use as a prognostic
Baran, Anna; Myśliwiec, Hanna; Kiluk, Paulina; Świderska, Magdalena; Flisiak, Iwona
Irisin has been proposed to regulate metabolic diseases such as obesity, diabetes or metabolic syndrome which are common comorbidities in psoriasis. The aim of this study was to evaluate the serum irisin level in psoriasis and elucidate possible associations with disease activity, inflammatory or metabolic parameters and topical treatment. Thirty-seven individuals with active plaque-type psoriasis and 15 healthy controls were enrolled. Blood samples were collected before and after two weeks of therapy. Serum irisin concentrations were examined by enzyme-linked immunosorbent assay (ELISA). The results were correlated with psoriasis area and severity index (PASI), body mass index (BMI), inflammatory and biochemical markers, lipid profile and effectiveness of topical treatment. Irisin serum levels were insignificantly increased in psoriatic patients in comparison to the controls (p = 0.38). No significant correlations between investigated adipokine and several indicators of metabolic disorders, nor BMI (p = 0.37) or PASI (p = 0.5) were found. Significant positive correlations with C-reactive protein (CRP) (0.009), lipocalin-2 (p = 0.02), age (p = 0.02) and disease duration (p = 0.008) were noted. After topical treatment, serum irisin level did not significantly change (p = 0.31), despite clinical improvement. Irisin might be a marker of inflammation in psoriatic patients, but may not be a reliable indicator of metabolic conditions, severity of psoriasis nor efficacy of antipsoriatic treatment.
Man, Johnny Hon-Wai; Chow, Ariel Ka-Man; Iyer, Deepak; Chen, Guanghua; Yau, Thomas Chung-Cheung; Lo, Oswens Siu-Hung; Foo, Dominic Chi-Chung; Poon, Jensen Tung-Chung; Leung, Wai-Keung; Pang, Roberta Wen-Chi; Law, Wai-Lun
Aberrant levels of circulating microRNAs are potential biomarkers for the early detection of colorectal cancer. The aim of this study was to study miR-139-3p and miR-622 in serum as a non-invasive biomarker for colorectal cancer diagnosis. We applied quantitative polymerase chain reaction to determine the levels of miR-139-3p and miR-622 in 42 pairs of tumor and adjacent non-tumor tissues, and in serum samples of 117 patients and 90 control subjects. Our results showed that miR-139-3p was silenced whereas miR-622 was overexpressed in colorectal cancer. Similarly, serum miR-139-3p level was significantly lower in colorectal cancer patients than in control subjects whereas miR-622 was more frequently detectable in patients. ROC analysis showed that AUC of miR-139-3p was 0.9935, with a sensitivity of 96.6% and specificity of 97.8%. Serum miR-139-3p level showed high sensitivity and specificity for both early and late stage CRCs and proximal and distal CRCs. Detectable serum miR-622 showed a sensitivity of 87.5% and specificity of 63.5% for discriminating CRC patients, but the sensitivity dropped for late stage patients (72.7%). We also included analyses of the blood CEA level for comparing the diagnostic performance of these blood-based biomarkers. The median level in CRC patients (3.6 ng/ml) was significantly higher than that in control (1.8 ng/ml). The AUC value of CEA in diagnosing CRC patients was 0.7515. CEA showed a positive correlation with tumor stage and age of patients and its level was higher in male. Collectively, serum miR-139-3p has strong potential as a promising non-invasive biomarker in colorectal cancer detection. PMID:28404964
Ye, Xiaoyun; Zhou, Xiaoliu; Furr, Johnathan; Ahn, Ki Chang; Hammock, Bruce D.; Gray, Earl L.; Calafat, Antonia M.
3, 4, 4’- Trichlorocarbanilide (triclocarban, TCC) is widely used as an antimicrobial agent in a variety of consumer and personal care products. TCC is considered a potential endocrine disruptor, but its potential toxic effects in humans are still largely unknown. Because of its widespread uses, the potential for human exposure to TCC is high. In order to identify adequate exposure biomarkers of TCC, we investigated the metabolic profile of TCC in adult female Sprague Dawley rats after admini...
Full Text Available This study aimed to evaluate the role of serum lipid profiles as novel biomarkers in predicting pathological characteristics of prostate cancer (PCa. We retrospectively analyzed 322 consecutive patients with clinically localized PCa receiving radical prostatectomy (RP and extended pelvic lymphadenectomy. Unconditional logistic regression was used to estimate the prostatectomy Gleason score (pGS, pathological stage and lymph node involvement (LNI in RP specimens. Preoperative prostate-specific antigen (PSA levels, biopsy GS (bGS, and preoperative tumor, node, metastasis staging were used as basic variables to predict postoperative pathological characteristics. Preoperative serum lipid profiles were introduced as potential predictors. A receiver operating characteristic (ROC curve was used to determine predictive efficacy. Significant differences in pathological characteristics were observed among patients with normal and abnormal total cholesterol (TC, triglyceride (TG, and low-density lipoprotein (LDL levels, with the exception of pGS in the TG group. Multivariable regression analysis revealed that the odds ratio for high levels of TC for LNI compared with normal TC levels was 6.386 (95% confidence interval [CI] 1.510-27.010, 3.270 (95% CI: 1.470-7.278 for high levels of TG for pT3-4 disease, and 2.670 (95% CI: 1.134-6.287 for high levels of LDL for pGS. The area under the ROC curve of the models with dyslipidemia was larger than that in models without dyslipidemia, in predicting pathological characteristics. Abnormal TC, TG, and LDL levels are significantly associated with postoperative pathological status in PCa patients. Together with preoperative PSA levels, bGS, and clinical stage, dyslipidemia is more accurate in predicting pathological characteristics.
Gao, Xiang; Zhang, Weidong; Wang, Yongbo; Pedram, Pardis; Cahill, Farrell; Zhai, Guangju; Randell, Edward; Gulliver, Wayne; Sun, Guang
Metabolic abnormalities are more associated with central obesity than peripheral obesity, but the underlying mechanisms are largely unknown. The present study was to identify serum metabolic biomarkers which distinguish metabolically unhealthy centrally obese (MUCO) from metabolically healthy peripherally obese (MHPO) individuals. A two-stage case-control study design was employed. In the discovery stage, 20 individuals (10 MHPO and 10 MUCO) were included and in the following validation stage, 79 individuals (20 normal weight (NW), 30 MHPO, 29 MUCO) were utilized. Study groups were matched for age, sex, physical activity and total dietary calorie intake with MHPO and MUCO additionally matched for BMI. Metabolic abnormality was defined as: 1) HOMA-IR > 4.27 (90(th) percentile), 2) high-density lipoprotein cholesterol 102 cm in men and > 88 cm in women. MUCO individuals had all of these abnormalities whereas MHPO and NW individuals had none of them. A targeted metabolomics approach was performed on fasting serum samples, which can simultaneously identify and quantify 186 metabolites. In the discovery stage, serum leucine, isoleucine, tyrosine, valine, phenylalanine, alpha-aminoadipic acid, methioninesulfoxide and propionylcarnitine were found to be significantly higher in MUCO, compared with MHPO group after multiple testing adjustment. Significant changes of five metabolites (leucine, isoleucine, valine, alpha-aminoadipic acid, propionylcarnitine) were confirmed in the validation stage. Significantly higher levels of serum leucine, isoleucine, valine, alpha-aminoadipic acid, propionylcarnitine are characteristic of metabolically unhealthy centrally obese patients. The finding provides novel insights into the pathogenesis of metabolic abnormalities in obesity.
Chaigneau, Christine; Cabioch, Thomas; Beaumont, Katy; Betsou, Fotini
One of the main issues in biobanking is the establishment of standard operating procedures for specimen collection, preparation and storage to control for pre-analytical variation. For biological fluids such as serum, there is currently a lack of sensitive biomarkers for the quality control of cryopreservation conditions. The process approach was used to establish an ISO 9001:2000 quality management system. Immunoenzymatic and functional assays were used to assess the stability of the following candidate quality control biomarkers: secretory phospholipase A2, matrix metalloprotease 7, transforming growth factor beta1 and anti-HBs immunoglobulin. Five product processes and their corresponding indicators were identified. In the preparation-aliquoting-storage process, no quality control indicator for serum was identified. Only matrix metalloprotease 7 showed moderate susceptibility to freeze-thaw cycles. Biomarkers that have an on-off response to temperature variation could serve as quality indicators for the core processes of biobanking, which are the preparation and storage of biological fluids. The identification of such biomarkers is needed.
Lee, Min Young; Kim, Eun Young; Kim, Se Hyun; Cho, Kyung-Cho; Ha, Kyooseob; Kim, Kwang Pyo; Ahn, Yong Min
Major depressive disorder (MDD) is a systemic and multifactorial disorder involving complex interactions between genetic predisposition and disturbances of various molecular pathways. Its underlying molecular pathophysiology remains unclear, and no valid and objective diagnostic tools for the condition are available. We performed large-scale proteomic profiling to identify novel peripheral biomarkers implicated in the pathophysiology of MDD in 25 drug-free female MDD patients and 25 healthy controls. First, quantitative serum proteome profiles were obtained and analyzed by liquid chromatography-tandem mass spectrometry using serum samples from 10 MDD patients and 10 healthy controls. Next, candidate biomarker sets, including differentially expressed proteins from the profiling experiment and those identified in the literature, were verified using multiple-reaction monitoring in 25 patients and 25 healthy controls. The final panel of potential biomarkers was selected using multiparametric statistical analysis. We identified a serum biomarker panel consisting of six proteins: apolipoprotein D, apolipoprotein B, vitamin D-binding protein, ceruloplasmin, hornerin, and profilin 1, which could be used to distinguish MDD patients from controls with 68% diagnostic accuracy. Our results suggest that modulation of the immune and inflammatory systems and lipid metabolism are involved in the pathophysiology of MDD. Our findings of functional proteomic changes in the peripheral blood of patients with MDD further clarify the molecular biological pathway underlying depression. Further studies using larger, independent cohorts are needed to verify the role of these candidate biomarkers for the diagnosis of MDD. Copyright © 2016 Elsevier Inc. All rights reserved.
Ozone (03) is an air pollutant that is associated with cardiovascular and respiratory diseases. Older adults are considered to be particularly susceptible to oxidant air pollutants such as 03. Serum biomarkers are being sought that would lead to better predictions of susceptibili...
Alshaarawy, Omayma; Elbaz, Hosam A
The aim of the current study is to examine the association of environmental tobacco smoke (ETS) exposure evident by serum cotinine level, and diabetes mellitus in never smokers. Previous studies suggest that active tobacco cigarette smoking is associated with diabetes mellitus risk. However it is not clear if the low-level "background" ETS exposure is associated with diabetes among never smokers. We present evidence from five independent replications based on the US nationally representative National Health and Nutrition Examination Surveys (NHANES) conducted 2003-12. Our exposure of interest is ETS exposure among never smokers, measured by serum cotinine levels (ng/mL), and our main outcome is diabetes mellitus assessed via self-reported physician-diagnosis, current use of insulin and/or oral hypoglycemic medications, plasma fasting glucose levels ≥126mg/dL or glycohemoglobin levels ≥6.5%. The conceptual model encompassed age, sex, ethnic self-identification, education, poverty-income ratio, alcohol drinking, total cholesterol and body mass index. In never smokers, higher serum cotinine levels were positively associated with diabetes mellitus (the meta-analytic summary estimate is 1.2, 95% CI=1.1, 1.2). This association was not evident among never smokers with cotinine levels below 3ng/mL. These replications help sustain evidence of ETS-diabetes mellitus association, which might be explained by shared psychosocial characteristics. Prospective studies with appropriate biomarkers are needed to further investigate this association. Copyright © 2015 Elsevier Inc. All rights reserved.
Galland, F.; Geslin, P.; Kerjean, J.; Six, P.; Tadei, A.; Jallet, P.
This work undertakes, in a second part, the clinical exploration of 947 serum digoxin levels of 281 hospitalized patients on a cardiology ward. Our results, which coincide with those of other researchers, have led us to draw certain practical conclusions: the posology is determined first of all according to kidney function, weight and age of the patient. When the treatment is insufficient or, on the other hand, poorly tolerated, a serum digoxin level is performed permitting thus: in the case of ineffective treatment: to be sure of the patient's cooperation, to increase the posology if the serum digoxin level is not in the toxic zone, to discover an eventual pharmacokinetic problem; to establish the responsability of digitalis (when there are signs of intolerance or of intoxication), in case of arrhythmia, in patients with pacemakers, when associated drugs are capable of causing similar adverse effects; to better manage a digitalis treatment in a high risk patient (unstable renal function, advanced myocardial disease, chronic obstructive disease) [fr
Tissera, Hasitha; Rathore, Abhay P S; Leong, Wei Yee; Pike, Brian L; Warkentien, Tyler E; Farouk, Farouk S; Syenina, Ayesa; Eong Ooi, Eng; Gubler, Duane J; Wilder-Smith, Annelies; St John, Ashley L
Most patients with dengue experience mild disease, dengue fever (DF), while few develop the life-threatening diseases dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). No laboratory tests predict DHF or DSS. We evaluated whether the serum chymase level can predict DHF or DSS in adult and pediatric patients and the influence of preexisting conditions (PECs) on chymase levels. Serum chymase levels were measured in patients presenting with undifferentiated fever to hospitals in Colombo District, Sri Lanka. The value of serum the chymase concentration and clinical signs and symptoms as predictors of DHF and/or DSS was evaluated by multivariate analysis. We assessed the influence of age, PECs, and day after fever onset on the robustness of the chymase level as a biomarker for DHF and/or DSS. An elevated chymase level in acute phase blood samples was highly indicative of later diagnosis of DHF or DSS for pediatric and adult patients with dengue. No recorded PECs prevented an increase in the chymase level during DHF. However, certain PECs (obesity and cardiac or lung-associated diseases) resulted in a concomitant increase in chymase levels among adult patients with DHF. These results show that patients with acute dengue who present with high levels of serum chymase consistently are at greater risk of DHF. The chymase level is a robust prognostic biomarker of severe dengue for adult and pediatric patients. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
Full Text Available Background/Aims: Aortic dissection (AD is also known as intramural hematoma. This study aimed to screen peripheral blood biomarkers of small molecule metabolites for AD using high-performance liquid chromatography-mass spectrometry (HPLC-MS. Methods: Sera from 25 healthy subjects, 25 patients with well-established AD, and 25 patients with well-established hypertension were investigated by HPLC-MS to detect metabolites, screen differentially expressed metabolites, and analyze metabolic pathways. Results: Twenty-six and four metabolites were significantly up- and down-regulated in the hypertensive patients compared with the healthy subjects; 165 metabolites were significantly up-regulated and 109 significantly down-regulated in the AD patients compared with the hypertensive patients. Of these metabolites, 35 were up-regulated and 105 down-regulated only in AD patients. The metabolites that were differentially expressed in AD are mainly involved in tryptophan, histidine, glycerophospholipid, ether lipid, and choline metabolic pathways. As AD alters the peripheral blood metabolome, analysis of peripheral blood metabolites can be used in auxiliary diagnosis of AD. Conclusion: Eight metabolites are potential biomarkers for AD, 3 of which were differentially expressed and can be used for auxiliary diagnosis of AD and evaluation of treatment effectiveness.
Ren, Yong; Tang, Qizhu; Liu, Wenwei; Tang, Yongqian; Zhu, Rui; Li, Bin
Aortic dissection (AD) is also known as intramural hematoma. This study aimed to screen peripheral blood biomarkers of small molecule metabolites for AD using high-performance liquid chromatography-mass spectrometry (HPLC-MS). Sera from 25 healthy subjects, 25 patients with well-established AD, and 25 patients with well-established hypertension were investigated by HPLC-MS to detect metabolites, screen differentially expressed metabolites, and analyze metabolic pathways. Twenty-six and four metabolites were significantly up- and down-regulated in the hypertensive patients compared with the healthy subjects; 165 metabolites were significantly up-regulated and 109 significantly down-regulated in the AD patients compared with the hypertensive patients. Of these metabolites, 35 were up-regulated and 105 down-regulated only in AD patients. The metabolites that were differentially expressed in AD are mainly involved in tryptophan, histidine, glycerophospholipid, ether lipid, and choline metabolic pathways. As AD alters the peripheral blood metabolome, analysis of peripheral blood metabolites can be used in auxiliary diagnosis of AD. Eight metabolites are potential biomarkers for AD, 3 of which were differentially expressed and can be used for auxiliary diagnosis of AD and evaluation of treatment effectiveness. © 2017 The Author(s). Published by S. Karger AG, Basel.
Markel, Gal; Imazio, Massimo; Koren-Morag, Nira; Galore-Haskel, Gilli; Schachter, Jacob; Besser, Michal; Cumetti, Davide; Maestroni, Silvia; Altman, Arie; Shoenfeld, Yehuda; Brucato, Antonio; Adler, Yehuda
The immune response plays a significant role in pericarditis, but the mechanisms of disease are poorly defined. Further, efficient monitoring and predictive clinical tools are unavailable. Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is an immune-inhibitory protein, while MHC class I chain related protein A (MICA) and B (MICB) have an immune-stimulating function. Serum CEACAM1, MICA and MICB concentrations were measured by ELISA in ~50 subjects of each group: acute pericarditis (AP), recurrent pericarditis (RP) and lupus (SLE) patients, metastatic melanoma patients as well as healthy donors. Serum CEACAM1 was dramatically elevated in AP and RP patients, but not in SLE patients, and displayed a highly accurate profile in ROC curve analyses. MICA and MICB were elevated in some pericarditis patients. All markers were enhanced in metastatic melanoma patients irrespective of neoplastic pericardial involvement. Etiology-guided analysis of RP patients showed that very low MICA levels were associated with idiopathic RP, while high MICA was associated with autoimmune and post-operative RP. Importantly, MICA was significantly associated with recurrences, independently of other potentially confounding parameters such as age, time of follow up or treatment modality. Here we report for the first time on CEACAM1 as a potentially novel biomarker for pericarditis, as well as on MICA as an innovative prognostic marker in these patients. Determination of the roles of these immune factors, as well as their diagnostic and prognostic values should be determined in future prospective studies.
Muto, Mayumi; Mori, Masahiro; Liu, Jia; Uzawa, Akiyuki; Uchida, Tomohiko; Masuda, Hiroki; Ohtani, Ryohei; Sugimoto, Kazuo; Kuwabara, Satoshi
Previously, we identified anti-Talin-1 antibodies in the serum of MS. In this case, we measured the serum soluble Talin-1 (sTalin-1) levels by enzyme-linked immunosorbent assay. The serum sTalin-1 levels were significantly higher in 40 patients with MS than in 43 normal controls and in the acute phase of disease than in the remission phase. Interestingly, serum sTalin-1 levels were associated with a sustained increase in disability after MS attack but not with serum anti-Talin-1 antibody levels. sTalin-1 may be a biomarker for the acute phase of MS and may be used for the short-term prognosis of MS. Copyright © 2017 Elsevier B.V. All rights reserved.
Dhiman, Pooja; Senthilkumar, G P; Rajendiran, Soundravally; Sivaraman, K; Soundararaghavan, S; Kulandhasamy, Maheshwari
We evaluated the diagnostic accuracy of activin B in discriminating tubal ectopic pregnancy (tEP) from intrauterine miscarriages (IUM), and normal viable intrauterine pregnancy (IUP). We included 28 women with tEP, 31 women with IUM, and 29 normal IUP, confirmed both by clinical examination and ultrasonography. Serum activin B concentration was measured at the time of admission using the ELISA kit. The median serum activin B concentration was found to be significantly decreased in both tEP (p=0.004) and IUM (p=0.022) compared to normal IUP. When compared between tEP and IUM, activin B concentrations did not differ significantly. ROC analysis of activin B and free β-hCG demonstrated AUC of 0.722 and 0.805, respectively to discriminate tEP from viable IUP. The model including both activin B and free β-hCG improved the discriminating potential with greater AUC (0.824), and specificity (93%) than individual one. To discriminate tEP from IUM, activin B, free β-hCG and combination of both performed poorly. We conclude that serum activin B concentration is lower in tubal ectopic pregnancy, and can discriminate it from normal pregnancy with moderate accuracy. It also shows improved diagnostic potential along with free β-hCG, but cannot distinguish tEP from IUM reliably. Copyright © 2016. Published by Elsevier Inc.
Duncker, David; Oswald, Hanno; Gardiwal, Ajmal; Lüsebrink, Ulrich; König, Thorben; Schreyer, Hendrik; Klein, Gunnar
Dronedarone is a new antiarrhythmic drug for patients with nonpermanent atrial fibrillation (AF). A relatively consistent finding in all trials studying dronedarone was a moderate but significant elevation of serum creatinine. Since dronedarone competes for the same organic cation transporter in the distal renal tubule with creatinine, serum creatinine and its derived estimated glomerular filtration rate might not reflect true renal function in patients on dronedarone. We therefore investigated alternative markers for renal function in these patients. We prospectively included 20 patients with nonpermanent AF in whom dronedarone 400 mg twice daily was started. Patients had normal renal function and serum creatinine; serum cystatin C and creatinine clearance were measured before treatment and 10 and 90 days after treatment started. Mean serum creatinine level for all 20 patients at baseline (day 0) was 84.55 ± 12.14 and 87.8 ± 17.59 µmol/L on day 10. This slight increase in all patients was not significant. Patients were now divided into the predefined groups of "increased creatinine" (increase in serum creatinine level > 1 standard deviation) and "not increased creatinine." Patients with increased creatinine levels (n = 5) showed a significant elevation of serum creatinine levels from day 0 to day 10 (82.4 ± 9.18 to 104.4 ± 12.74 µmol/L; P = .003), whereas change in serum creatinine levels in the not increased creatinine group (n = 15) was not significant. Serum cystatin C levels remained stable in both of these groups (increased creatinine group: 0.76 ± 0.08 to 0.78 ± 0.08 mg/L; P = .65; not increased creatinine group: 0.77 ± 0.108 to 0.77 ± 0.107 mg/L; P = .906). In conclusion, cystatin C represents an easily available and reliable biomarker for estimation of true renal function in patients on dronedarone treatment.
Awan, A.Y.; Channa, N.A.; Solangi, D.A.; Tabassum, N.
Objective: Females with different menopausal status are compared for serum lipids to explore the role of menopausal status in developing gallstones. Methodology: This study was conducted at Institute of Biochemistry, University of Sindh Jamshoro, Pakistan. A total number of 135 female gallstone patients admitted at Liaquat University Hospital, Wali Bhai Rajputana Hospital, Hyderabad and other hospitals of Hyderabad, Pakistan and 170 age and gender matched control subjects were selected for the study. The serum samples of patients of different menopausal status and control group were analyzed for the lipid contents. Gallstones recovered from the patients were also analyzed for the composition by FTIR. Results: Serum total cholesterol (TC) and serum high density lipoprotein cholesterol (HDL-C) were significantly varied among all age groups while serum triglycerides (TG), serum very low density lipoprotein cholesterol (VLDL-C) and serum total lipids (TL) were found to be significantly differed among four different types of gallstone formers. Consumers of non-branded oil and non-branded ghee were found with significant lipid alterations in comparison to control group. Major lipid alterations were found in female gallstone patients with pre and peri-menopause. Conclusion: Raised serum TC, serum TG and decreased serum HDL-C in addition to pre- and peri-menopausal status may be considered as biomarkers for female gallstone patients.
Chovanec, Josef; Serlingerova, Iveta; Greplova, Kristina
Background: We investigated the efficacy of circulating biomarkers together with histological grade and age to predict deep myometrial invasion (dMI) in endometrial cancer patients. Methods: HE4ren was developed adjusting HE4 serum levels towards decreased glomerular filtration rate as quantified...... based on single-institution data from 120 EC patients and validated against multicentric data from 379 EC patients. Results: In non-cancer individuals, serum HE4 levels increase log-linearly with reduced glomerular filtration of eGFR = 90 ml/min/1.73 m2. HE4ren, adjusting HE4 serum levels to decreased e...
Borba, Ericksen Mielle; Duarte, Juliana Avila; Bristot, Giovana; Scotton, Ellen; Camozzato, Ana Luiza; Chaves, M?rcia Lorena Fagundes
Background/Aims: Hippocampal atrophy is a recognized biomarker of Alzheimer disease (AD) pathology. Serum brain-derived neurotrophic factor (BDNF) reduction has been associated with neurodegeneration. We aimed to evaluate BDNF serum levels and hippocampal volume in clinical AD (dementia and mild cognitive impairment [MCI]). Methods: Participants were 10 patients with MCI and 13 with dementia due to AD as well as 10 healthy controls. BDNF serum levels were determined by ELISA and volumetric me...
Amir Hooshang Mohammadpour
Full Text Available Objective. There is a strong need for biomarkers to identify patients at risk for future cardiovascular events related with progressive atherosclerotic disease. Osteoprotegerin (OPG protects the skeleton from excessive bone resorption by binding to receptor activator of nuclear factor-κB ligand (RANKL and preventing it from binding to its receptor, receptor activator of nuclear factor-κB. However, conflicting results have been obtained about association of serum level of OPG or RANKL with coronary artery disease (CAD. Based on their role in inflammation and matrix degradation and the fact that atherosclerotic plaque formation is an inflammatory process, we hypothesized that RANKL : OPG ratio could be a better biomarker for CAD. Methods. In this cross-sectional study, the correlation between RANKL : OPG ratio serum concentration and coronary artery calcification (CAC in 50 patients with ischemic coronary disease has been investigated. We used ELISA method for measuring RANKL and OPG serum concentrations. Results. There was a significant correlation between RANKL : OPG serum concentration ratio and CAC in our study population (P=0.01. Conclusion. Our results suggested that RANKL : OPG ratio concentration has a potential of being used as a marker for coronary artery disease.
Røen, Bent Tore; Opstad, Aase Mari; Haavind, Anniken; Tønsager, Janne
Ricinine is an alkaloid present in the castor bean plant (Ricinus communis) that can be used as a biomarker for ricin poisoning. Serial ricinine levels are reported in the serum and urine of a patient suffering from intentional ricin intoxication. The patient was brought to the hospital 4 h after injection and oral intake of a castor bean extract, but died 38 h later, despite intensive medical care. Ricinine was isolated from the samples by solid-phase extraction and quantitatively determined by isotopic dilution liquid chromatography-mass spectrometry. The ricinine level in serum declined from 33 to 23 ng/mL between 10 and 29 h post-exposure. Three urine samples collected from 12 to 41 h after ricin intoxication showed ricinine concentrations in the range of 20-58 ng/mL. The creatinine corrected values (21-30 µg/g) indicated a concentration-time profile with a maximum ricinine level in urine between 12 and 29 h after exposure.
Full Text Available Atypical coronary artery disease (ACAD is characterized by atypical angina pectoris or silent myocardial ischemia. However, conventional diagnostic techniques are insufficient to identify this subtype of coronary atherosclerotic pathology, and specific and sensitive markers for diagnosing ACAD are still currently lacking. The aim of the present study is to identify a novel serum microRNA (miRNA expression profile of ACAD patients and evaluate its clinical diagnostic value.127 patients who were diagnosed with ACAD and 54 age-matched controls were enrolled in this study. An initial screen of miRNA expression was performed in serum samples from 35 patients and 20 controls using TaqMan Low Density Array. A stem-loop quantitative reverse-transcription PCR (RT-qPCR assay was conducted in the training and validation sets to confirm the levels of the altered miRNAs in 122 patients with ACAD and 68 controls. In addition, the potential target genes of the altered miRNAs were predicted using bioinformatics methods.The TaqMan low density array and RT-qPCR analysis identified four serum miRNAs including miR-487a, miR-502, miR-208 and miR-215 that were significantly increased, while one miRNA, miR-29b, that was significantly decreased in ACAD patients compared with normal controls (P<0.05. The area under the receiver-operating-characteristic (ROC curve (AUC for the combined 5 serum miRNAs were 0.850 (95% CI, 0.734-0.966, P<0.001 and 0.909 (95% CI, 0.858-0.960, P<0.001 for the training set and validation set, respectively. In addition, target gene prediction showed that these five altered miRNAs are involved in affecting various aspects of cardiac or vascular remodeling, especially in the pathway involving inflammation and fibrosis.Our findings indicate that the five altered serum miRNAs could be novel non-invasive biomarkers for ACAD and may also represent potential therapeutic targets for atherosclerosis and myocardial ischemia.
Jeffrey N Bryan
Full Text Available Serum biomarkers of canine lymphoma activity for diagnosis, prognosis, and therapy monitoring have been of clinical interest for more than a decade. Tumor products, biochemical enzymes, cytokines, metabolic profiling, leakage enzymes, as well as serum proteins have been studied as biomarkers for lymphoma. Multiple biomarkers combined have been shown to be most sensitive and specific. C-reactive protein, thymidine kinase 1, and haptoglobin have been most extensively studied and commercialized in diagnostic tests, the TK Canine Cancer Panel and the Canine Lymphoma Blood Test. These tests have been evaluated either in cohorts of diseased and healthy dogs or in prospective studies of ill dogs, respectively, for application to clinical decision making. Some evidence exists for application of these tests, but large-scale studies are lacking in a broad range of lymphoma forms. These biomarkers are commonly elevated at diagnosis and at relapse. Further study is necessary to determine if early intervention guided by biomarker elevation will improve quantity or quality of life for dogs with lymphoma.
Schreiber, Courtney A; Ratcliffe, Sarah J; Quinley, Kelly E; Miller, Carrie; Sammel, Mary D
In order to simplify management of early pregnancy loss, our goal was to elucidate predictors of successful medical management of miscarriage with a single dose of misoprostol. In this secondary analysis of data from a multicenter randomized controlled trial, candidate biomarkers were compared between 49 women with missed abortion who succeeded in passing their pregnancy with a single dose of misoprostol and 46 women who did not pass their pregnancy with a misoprostol single dose. We computed the precision of trophoblastic protein and hormone concentrations to discriminate between women who succeed or fail single dose misoprostol management. We also included demographic factors in our analyses. We found overlap in the concentrations of the individual markers between women who succeeded and failed single-dose misoprostol. However, hCG levels ≥ 4000 mIU/mL and ADAM-12 levels ≥ 2500 pg/mL were independently associated with complete uterine expulsion after one dose of misoprostol in our population. A multivariable logistic model for success included non-Hispanic ethnicity and parity <2 in addition to hCG ≥ 4000 mIU/mL and ADAM-12 ≥ 2500 pg/mL and had an area under the receiver operating characteristic (ROC) of 0.81 (95% confidence interval: 72-90%). Categorizing women with a predicted probability of ≥ 0.65 resulted in a sensitivity of 75.0%, specificity 77.1% and positive predictive value of 81.8%. While preliminary, our data suggest that serum biomarkers, especially when combined with demographic characteristics, may be helpful in guiding patient decision-making regarding the management of early pregnancy failure (EPF). Further study is warranted. Copyright © 2015 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.
Muto, Satoshi; Takagi, Hironori; Owada, Yuki; Inoue, Takuya; Watanabe, Yuzuru; Yamaura, Takumi; Fukuhara, Mitsuro; Okabe, Naoyuki; Matsumura, Yuki; Hasegawa, Takeo; Osugi, Jun; Hoshino, Mika; Higuchi, Mitsunori; Shio, Yutaka; Suzuki, Hiroyuki
Reportedly, hypertension tends to be associated with response to bevacizumab therapy, because bevacizumab suppresses vascular nitric oxide production. In this study we examined the predictive value of nitric oxide in bevacizumab-treated non-small cell lung cancer (NSCLC) patients. Fifteen patients with advanced or recurrent NSCLC treated with bevacizumab-based regimens were evaluated retrospectively. Serum NOx (NO 2 - /NO 3 - ) was assayed by the Griess method. Serum nitric oxide levels were decreased after two courses of bevacizumab treatment in our responder group (p=0.02). According to the change in nitric oxide levels after the second course of treatment, median progression-free survival was 11.0 months in the group with decreased serum nitric oxide and 7.6 months in the group with increased serum nitric oxide (p=0.08). Serum nitric oxide levels could be a predictive biomarker for response to bevacizumab in NSCLC patients. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
Rahimi Sharbaf F
Full Text Available "nBackground: Maternal zinc deficiency during pregnancy has been related to adverse pregnancy outcomes. Most studies in which pregnant women have been supplemented with zinc to examine its effects on the outcome of the pregnancy have been carried out in industrialized countries and the results have been inconclusive. It has been shown that women with gestational diabetes (GDM have lower serum zinc levels than healthy pregnant women, and higher rates of macrosomia. Zinc is required for normal glucose metabolism, and strengthens the insulin-induced transportation of glucose into cells by its effect on the insulin signaling pathway. The purpose of this study was to assess the serum zinc levels of GDM patients and evaluate the effect of zinc supplementation. "nMethods: In the first stage of this prospective controlled study, we enrolled 70 women who were 24-28 weeks pregnant at the Prenatal Care Center of Mirza Kochak Khan Hospital, Tehran, Iran. The serum zinc level of each subject was determined. In the second stage, among these 70 subjects, the diabetics receiving insulin were divided into two groups, only one of which received a zinc supplement and the other group was the control group. Birth weight of neonates and insulin dosages were recorded. "nResults: The mean serum zinc level in the GDM group was lower than that of the control group (94.83 vs. 103.49mg/dl, respectively and the mean birth weight of neonates from the GDM women who received the zinc supplement was lower than that of the control group (3849g vs. 4136g. The rate of macrosomia was lower in the zinc supplemented group (20% vs. 53%. The mean of increase of insulin after receiving the zinc supplement was lower (8.4u vs. 13.53. "nConclusion: Maternal insulin resistance is associated with the accumulation of maternal fat tissue during early stages of pregnancy and greater fetoplacental nutrient availability in later stages, when 70% of fetal growth occurs, resulting in macrosomia. In
Bhosale, Santosh D; Moulder, Robert; Kouvonen, Petri; Lahesmaa, Riitta; Goodlett, David R
Blood protein measurements are used frequently in the clinic in the assessment of patient health. Nevertheless, there remains the need for new biomarkers with better diagnostic specificities. With the advent of improved technology for bioanalysis and the growth of biobanks including collections from specific disease risk cohorts, the plasma proteome has remained a target of proteomics research toward the characterization of disease-related biomarkers. The following protocol presents a workflow for serum/plasma proteomics including details of sample preparation both with and without immunoaffinity depletion of the most abundant plasma proteins and methodology for selected reaction monitoring mass spectrometry validation.
Zeng, Xuemei; Hood, Brian L.; Zhao, Ting; Conrads, Thomas P.; Sun, Mai; Gopalakrishnan, Vanathi; Grover, Himanshu; Day, Roger S.; Weissfeld, Joel L.; Wilson, David O.; Siegfried, Jill M.; Bigbee, William L.
Introduction Lung cancer remains the leading cause of cancer-related death with poor survival due to the late stage at which lung cancer is typically diagnosed. Given the clinical burden from lung cancer, and the relatively favorable survival associated with early stage lung cancer, biomarkers for early detection of lung cancer are of important potential clinical benefit. Methods We performed a global lung cancer serum biomarker discovery study using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in a set of pooled non-small cell lung cancer (NSCLC) case sera and matched controls. Immunoaffinity subtraction was used to deplete the top most abundant serum proteins; the remaining serum proteins were subjected to trypsin digestion and analyzed in triplicate by LC-MS/MS. The tandem mass spectrum data were searched against the human proteome database and the resultant spectral counting data were used to estimate the relative abundance of proteins across the case/control serum pools. The spectral counting derived abundances of some candidate biomarker proteins were confirmed with multiple reaction monitoring MS assays. Results A list of 49 differentially abundant candidate proteins was compiled by applying a negative binomial regression model to the spectral counting data (pbiomarkers with statistically significant differential abundance across the lung cancer case/control pools which, when validated, could improve lung cancer early detection. PMID:21304412
Friedman Erica B
Full Text Available Abstract Background Identification of melanoma patients at high risk for recurrence and monitoring for recurrence are critical for informed management decisions. We hypothesized that serum microRNAs (miRNAs could provide prognostic information at the time of diagnosis unaccounted for by the current staging system and could be useful in detecting recurrence after resection. Methods We screened 355 miRNAs in sera from 80 melanoma patients at primary diagnosis (discovery cohort using a unique quantitative reverse transcription-PCR (qRT-PCR panel. Cox proportional hazard models and Kaplan-Meier recurrence-free survival (RFS curves were used to identify a miRNA signature with prognostic potential adjusting for stage. We then tested the miRNA signature in an independent cohort of 50 primary melanoma patients (validation cohort. Logistic regression analysis was performed to determine if the miRNA signature can determine risk of recurrence in both cohorts. Selected miRNAs were measured longitudinally in subsets of patients pre-/post-operatively and pre-/post-recurrence. Results A signature of 5 miRNAs successfully classified melanoma patients into high and low recurrence risk groups with significant separation of RFS in both discovery and validation cohorts (p = 0.0036, p = 0.0093, respectively. Significant separation of RFS was maintained when a logistic model containing the same signature set was used to predict recurrence risk in both discovery and validation cohorts (p Conclusion Our data demonstrate that serum miRNAs can improve accuracy in identifying primary melanoma patients with high recurrence risk and in monitoring melanoma tumor burden over time.
Pang, Li; Wang, Da-Wei; Zhang, Nan; Xu, Da-Hai; Meng, Xiang-Wei
Matrix metalloproteinase 11 (MMP11) has been shown to play a key role in human tumor progression and indicates poor clinical outcome in cancer patients. The current study aimed to evaluate the relationship between serum levels of MMP-11 and prognosis in colon cancer patients. Serum levels of MMP-11 were determined in 92 colon cancer patients and 92 healthy individuals using an enzyme-linked immunosorbent assay (ELISA). Associations between serum MMP-11 levels and clinicopathological characteristics of the patients and their outcomes were investigated. Survival analyses were performed to measure the 5-year overall survival (OS) and disease-free survival (DFS). Serum MMP-11 levels were substantially higher in colon cancer patients than in healthy controls. Moreover, serum MMP-11 levels were significantly higher in patients with advanced T status, lymph node metastasis, distant metastasis, and a higher TNM stage. Elevated serum levels of MMP-11 were identified as an independent prognostic factor for 5-year mortality and adverse events associated with colon cancer. Multivariate Cox regression analysis identified the serum MMP-11 level as an independent predictor of OS and DFS. Our study established that high serum levels of MMP-11 are associated with poor clinical outcome and may serve as a prognostic biomarker in colon cancer patients.
Full Text Available Background: Polycystic ovary syndrome (PCOS, the most common endocrinopathy in women of reproductive age, is characterized by polycystic ovaries, chronic anovulation, hyperandrogenism and insulin resistance. Despite the high prevalence of hyperandrogenemia, a definitive endocrine marker for PCOS has so far not been identified. Circulating miRNAs have recently been shown to serve as diagnostic/prognostic biomarkers in patients with cancers. Our current study focused on the altered expression of serum miRNAs and their correlation with PCOS. Method and Results: We systematically used the TaqMan Low Density Array followed by individual quantitative reverse transcription polymerase chain reaction assays to identify and validate the expression of serum miRNAs of PCOS patients. The expression levels of three miRNAs (miR-222, miR-146a and miR-30c were significantly increased in PCOS patients with respect to the controls in our discovery evaluation and followed validation. The area under the receiver operating characteristic (ROC curve (AUC is 0.799, 0.706, and 0.688, respectively. The combination of the three miRNAs using multiple logistic regression analysis showed a larger AUC (0.852 that was more efficient for the diagnosis of PCOS. In addition, logistic binary regression analyses show miR-222 is positively associated with serum insulin, while miR-146a is negatively associated with serum testosterone. Furthermore, bioinformatics analysis indicated that the predicted targets function of the three miRNAs mainly involved in the metastasis, cell cycle, apoptosis and endocrine. Conclusion: Serum miRNAs are differentially expressed between PCOS patients and controls. We identified and validated a class of three serum miRNAs that could act as novel non-invasive biomarkers for diagnosis of PCOS. These miRNAs may be involved in the pathogenesis of PCOS.
Full Text Available Lung cancer is one of the most common causes of cancer death, for which no validated tumor biomarker is sufficiently accurate to be useful for diagnosis. Additionally, the metabolic alterations associated with the disease are unclear. In this study, we investigated the construction, interaction, and pathways of potential lung cancer biomarkers using metabolomics pathway analysis based on the Kyoto Encyclopedia of Genes and Genomes database and the Human Metabolome Database to identify the top altered pathways for analysis and visualization. We constructed a diagnostic model using potential serum biomarkers from patients with lung cancer. We assessed their specificity and sensitivity according to the area under the curve of the receiver operator characteristic (ROC curves, which could be used to distinguish patients with lung cancer from normal subjects. The pathway analysis indicated that sphingolipid metabolism was the top altered pathway in lung cancer. ROC curve analysis indicated that glycerophospho-N-arachidonoyl ethanolamine (GpAEA and sphingosine were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis. Compared with the traditional lung cancer diagnostic biomarkers carcinoembryonic antigen and cytokeratin 19 fragment, GpAEA and sphingosine were as good or more appropriate for detecting lung cancer. We report our identification of potential metabolic diagnostic and prognostic biomarkers of lung cancer and clarify the metabolic alterations in lung cancer.
Galliera, Emanuela; Lombardi, Giovanni; Marazzi, Monica G; Grasso, Dalila; Vianello, Elena; Pozzoni, Roberto; Banfi, Giuseppe; Corsi Romanelli, Massimiliano M
Intense training can lead to a pathophysiological change in serum concentration of a variety of biomarkers. Traditional biomarkers of cardiac injury are very useful in monitoring CVD patients, but in healthy subjects or athletes they cannot be informative enough about the cardiovascular risk, because in these cases their serum levels do not increase over the pathological limit. Therefore novel cardiovascular biomarkers are required in order to allow a better monitoring of sport performance, prediction of overtraining and diagnosis of sport-related cardiac injuries. Growth differentiation factor-15 (GDF-15) is emerging as a powerful cardiovascular injury risk indicator. In this study we investigate the effect of intense physical training of on the circulating levels of GDF-15 in rugby professional players. Serum GDF-15, Erythropoietin, IL-6, the cardiovascular parameter ST-2, NT-proBNP and routine hematological parameters were measured in a group of 30 rugby players before and after a session of intense training. While ST-2, IL-6 and hsCRP displayed no significant changes after intense training, NT-proBNP and GDF-15 showed a significant increase, even without reaching the pathological level. The measure of GDF-15 in professional rugby players could be a useful tool to monitoring their cardiovascular status during training and competition session in order to prevent the onset of collateral cardiovascular adverse event due to the intense training and, in the case of cardiac injury, it could possibly allow a very early diagnosis at the beginning of the pathogenic process.
Ressom, Habtom W.; Xiao, Jun Feng; Tuli, Leepika; Varghese, Rency S.; Zhou, Bin; Tsai, Tsung-Heng; Nezami Ranjbar, Mohammad R.; Zhao, Yi; Wang, Jinlian; Di Poto, Cristina; Cheema, Amrita K.; Tadesse, Mahlet G.; Goldman, Radoslav; Shetty, Kirti
Characterizing the metabolic changes pertaining to hepatocellular carcinoma (HCC) in patients with liver cirrhosis is believed to contribute towards early detection, treatment, and understanding of the molecular mechanisms of HCC. In this study, we compare metabolite levels in sera of 78 HCC cases with 184 cirrhotic controls by using ultra performance liquid chromatography coupled with a hybrid quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS). Following data preprocessing, the most relevant ions in distinguishing HCC cases from patients with cirrhosis are selected by parametric and non-parametric statistical methods. Putative metabolite identifications for these ions are obtained through mass-based database search. Verification of the identities of selected metabolites is conducted by comparing their MS/MS fragmentation patterns and retention time with those from authentic compounds. Quantitation of these metabolites is performed in a subset of the serum samples (10 HCC and 10 cirrhosis) using isotope dilution by selected reaction monitoring (SRM) on triple quadrupole linear ion trap (QqQLIT) and triple quadrupole (QqQ) mass spectrometers. The results of this analysis confirm that metabolites involved in sphingolipid metabolism and phospholipid catabolism such as sphingosine-1-phosphate (S-1-P) and lysophosphatidylcholine (lysoPC 17:0) are up-regulated in sera of HCC vs. those with liver cirrhosis. Down-regulated metabolites include those involved in bile acid biosynthesis (specifically cholesterol metabolism) such as glycochenodeoxycholic acid 3-sulfate (3-sulfo-GCDCA), glycocholic acid (GCA), glycodeoxycholic acid (GDCA), taurocholic acid (TCA), and taurochenodeoxycholate (TCDCA). These results provide useful insights into HCC biomarker discovery utilizing metabolomics as an efficient and cost-effective platform. Our work shows that metabolomic profiling is a promising tool to identify candidate metabolic biomarkers for early detection of HCC cases in
Karimi-Zarchi, Mojgan; Dehshiri-Zadeh, Najmeh; Sekhavat, Leili; Nosouhi, Fahime
Cancer antigen 125 (CA-125) is a glycoprotein biomarker that is used in women with pelvic masses such as endometriosis and maybe is useful in practice of patients suspicious to endometriosis. The aim of this study was to evaluate the association between preoperative serum CA-125 levels and clinic pathological characteristic in women with endometriosis, and find out the best serum CA-125 levels cut-off in pre and post menopause women. Serum CA-125 levels in 87 women aged 21-54 years suspected to endometriosis with pelvic pain, dysmenorrhea, or dyspareunia were measured preoperatively. Also the association between clinic pathological characteristic and serum CA-125 level were analyzed. The mean age of women was 32.22±6.91. The mean serum CA-125 level was 49.93±4.30 U/mL. There was a significant correlation between the endometriosis stage, lesion size, adhesion score and preoperative CA-125 plasma concentration. However, we did not found significant differences in age, marital status, patient's complaints, and pelvic pain associated to Ca125 serum level. The suggested preoperative serum cut-off levels in premenopausal and postmenopausal patients were 37 U/ml and 35 U/ml, respectively. According to the results, preoperative serum CA-125 is an important predictor for patients with endometriosis and it should be taken into consideration when surgical management is suspected, especially if stage of disease, lesion size and adhesion score are undertaken.
Full Text Available Abstract Background The diagnosis of sarcoidosis is still a significant challenge in China because of the need to exclude other diseases including granulomatous infections and malignancies that may be clinically and radiographically similar. The specific aim of the study is to search for serum protein biomarkers of sarcoidosis and to validate their clinical usefulness in differential diagnosis. Methods Serum samples were collected from patients with sarcoidosis (n = 37, and compared to those from patients with tuberculosis (n = 20, other pulmonary diseases (n = 20, and healthy volunteers (n = 20 for determination of sarcoidosis-specific or -associated protein expression profiles. The first part of this study focused on proteomic analysis of serum from patients with sarcoidosis to identify a pattern of peptides capable of differentiating the studied populations using the ClinProt profiling technology based on mass spectrometry. Enzyme Linked Immunosorbent Assay (ELISA was then used to verify corresponding elevation of the serum protein concentration of the potential biomarkers in the same patients sets. Receiver operating characteristic curve (ROC analyses was performed to determine the optimal cutoff value for diagnosis. Immunohistochemistry was carried out to further confirm the protein expression patterns of the biomarkers in lung tissue. Results An unique protein peak of M/Z 3,210 Daltons (Da was found to be differentially expressed between the sarcoidosis and control groups and was identified as the N-terminal peptide of 29 amino acids (94-122 of serum amyloid A (SAA. ELISA confirmed that the serum SAA level was significantly higher in the sarcoidosis group than that of the other 3 control groups (p p Conclusion This is the first study to investigate serum protein markers in Chinese subjects with sarcoidosis. This study shows that the serum SAA expression profiles were different between the sarcoidosis and non
Schiødt, F V; Bondesen, S; Petersen, I
Gc-globulin scavenges actin released from necrotic hepatocytes to the extracellular space. In 77 patients with fulminant hepatic failure (FHF) (excluding patients treated with liver transplantation), admission levels of serum Gc-globulin and degree of complexing with monomeric actin (complex ratio......) were determined to evaluate their predictive values in relation to survival/nonsurvival. Gc-globulin levels were significantly reduced in 47 nonsurvivors, compared with 30 survivors (96 +/- 71 mg/L vs. 169 +/- 101 mg/L, P ... of patients with non-acetaminophen-induced FHF, whereas a higher value predicted survival in 60 percent. In patients with acetaminophen-induced FHF, nonsurvival was correctly predicted in 100 percent of patients and survival in 53 percent. In comparison, the King's College Hospital (KCH) criteria correctly...
Sørensen, Grith Lykke; Hjelmborg, Jacob v. B.; Kyvik, Kirsten Ohm
The collectin surfactant protein D (SP-D) is an important component of the pulmonary innate immune system, but SP-D is also present on extrapulmonary epithelial surfaces and in serum, where it has been used as a biomarker for pulmonary disease states. In this study, we investigate the mechanisms...
Sorensen, G.L.; Hjelmborg, J.V.; Kyvik, K.O.
The collectin surfactant protein D (SP-D) is an important component of the pulmonary innate immune system, but SP-D is also present on extrapulmonary epithelial surfaces and in serum, where it has been used as a biomarker for pulmonary disease states. In this study, we investigate the mechanisms ...
Eguchi, Akifumi; Sakurai, Kenichi; Watanabe, Masahiro; Mori, Chisato
Polychlorinated biphenyls (PCBs) have been associated with adverse human reproductive and fetal developmental measures or outcomes because of their endocrine-disrupting effects; however, the biological mechanisms of adverse effects of PCB exposure in humans are not currently well established. In this study, we aimed to identify the biological pathways and potential biomarkers of PCB exposure in maternal and umbilical cord serum using a hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS/MS) metabolomics platform. The median concentration of total PCBs in maternal (n=93) and cord serum (n=93) were 350 and 70pgg -1 wet wt, respectively. PCB levels in maternal and fetal serum from the Chiba Study of Mother and Children's Health (C-MACH) cohort are comparable to those of earlier cohort studies conducted in Japan, the USA, and European countries. We used the random forest model with the metabolome profile to predict exposure levels of PCB (first quartile [Q1] and fourth quartile [Q4]) for pregnant women and fetuses. In the prediction model for classification of Q1 versus Q4 (area-under-curve [AUC]: pregnant women=0.812 and fetuses=0.919), citraconic acid level in maternal serum and ethanolamine, p-hydroxybenzoate, and purine levels in cord serum had >0.70 AUC values. These candidate biomarkers and metabolite included in composited models were related to glutathione and amino acid metabolism in maternal serum and the amino acid metabolism and ubiquinone and other terpenoid-quinone biosynthesis in cord serum (FDR PCB exposure in pregnant women and fetuses. These results showed that metabolome analysis might be useful to explore potential biomarkers and related biological pathways for PCB exposure. Thus, more detailed studies are needed to verify sensitivity of the biomarkers and clarify the biochemical changes resulting from PCB exposure. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Full Text Available Current knowledge on the pathogenesis of diastolic heart failure predominantly rests on case-control studies involving symptomatic patients with preserved ejection fraction and relying on invasive diagnostic procedures including endomyocardial biopsy. Our objective was to gain insight in serum and urinary biomarkers reflecting collagen turnover and associated with asymptomatic diastolic LV dysfunction. We randomly recruited 782 Flemish (51.3% women; 50.5 years. We assessed diastolic LV function from the early and late diastolic peak velocities of the transmitral blood flow and of the mitral annulus. By sequencing urinary peptides, we identified 70 urinary collagen fragments. In serum, we measured carboxyterminal propeptide of procollagen type 1 (PICP as marker of collagen I synthesis and tissue inhibitor of matrix metalloproteinase type 1 (TIMP-1, an inhibitor of collagen-degrading enzymes. In multivariable-adjusted analyses with Bonferroni correction, we expressed effect sizes per 1-SD in urinary collagen I (uCI or collagen III (uCIII fragments. In relation to uCI fragments, e' decreased by 0.183 cm/s (95% confidence interval, 0.017 to 0.350; p = 0.025, whereas E/e' increased by 0.210 (0.067 to 0.353; p = 0.0012. E/e' decreased with uCIII by 0.168 (0.021 to 0.316; p = 0.018. Based on age-specific echocardiographic criteria, 182 participants (23.3% had subclinical diastolic LV dysfunction. Partial least squares discriminant analysis contrasting normal vs. diastolic LV dysfunction confirmed the aforementioned associations with the uCI and uCIII fragments. PICP and TIMP-1 increased in relation to uCI (p<0.0001, whereas these serum markers decreased with uCIII (p≤0.0006. Diastolic LV dysfunction was associated with higher levels of TIMP-1 (653 vs. 696 ng/mL; p = 0.013. In a general population, the non-invasively assessed diastolic LV function correlated inversely with uCI and serum markers of collagen I deposition, but positively with u
Ramsey, Jordan M; Cooper, Jason D; Penninx, Brenda W J H; Bahn, Sabine
Few serum biomarker tests are implemented in clinical practice and recent reports raise concerns about poor reproducibility of biomarker studies. Here, we investigated the potential role of sex and female hormonal status in this widespread irreproducibility. We examined 171 serum proteins and small molecules measured in 1,676 participants from the Netherlands Study of Depression and Anxiety. Concentrations of 96 molecules varied with sex and 66 molecules varied between oral contraceptive pill users, postmenopausal females, and females in the follicular and luteal phases of the menstrual cycle (FDR-adjusted p-value oral contraceptive pill use. High accuracy (over 90%) classification tools were developed to label samples with sex and female hormonal status where this information was not collected.
Zhang, Hongtai; Sun, Zhaogang; Wei, Wenjing; Liu, Zhonghui; Fleming, Joy; Zhang, Shuai; Lin, Nan; Wang, Ming; Chen, Maoshan; Xu, Yuhui; Zhou, Jie; Li, Chuanyou; Bi, Lijun; Zhou, Guangming
Tuberculosis (TB) remains a significant human health issue. More effective biomarkers for use in tuberculosis prevention, diagnosis, and treatment, including markers that can discriminate between healthy individuals and those with latent infection, are urgently needed. To identify a set of such markers, we used Solexa sequencing to examine microRNA expression in the serum of patients with active disease, healthy individuals with latent TB, and those with or without prior BCG inoculation. We i...
Delfani, P; Sturfelt, G; Gullstrand, B; Carlsson, A; Kassandra, M; Borrebaeck, C A K; Bengtsson, A A; Wingren, C
Systemic lupus erythematosus (SLE) is a severe chronic inflammatory autoimmune connective tissue disease. Despite major efforts, SLE remains a poorly understood disease with unpredictable course, unknown etiology and complex pathogenesis. Apoptosis combined with deficiency in clearing apoptotic cells is an important etiopathogenic event in SLE, which could contribute to the increased load of potential autoantigen(s); however, the lack of disease-specific protein signatures deciphering SLE and the underlying biological processes is striking and represents a key limitation. In this retrospective pilot study, we explored the immune system as a specific sensor for disease, in order to advance our understanding of SLE. To this end, we determined multiplexed serum protein expression profiles of crude SLE serum samples, using antibody microarrays. The aim was to identify differential immunoprofiles, or snapshots of the immune response modulated by the disease, reflecting apoptosis, a key process in the etiology of SLE and disease activity. The results showed that multiplexed panels of SLE-associated serum biomarkers could be decoded, in particular reflecting disease activity, but potentially the apoptosis process as well. While the former biomarkers could display a potential future use for prognosis, the latter biomarkers might help shed further light on the apoptosis process taking place in SLE.
Pianta, Timothy J; Peake, Philip W; Pickering, John W; Kelleher, Michaela; Buckley, Nicholas A; Endre, Zoltan H
Current methods for rapid detection of delayed graft function (DGF) after kidney transplantation are unreliable. Urinary clusterin is a biomarker of kidney injury but its utility for prediction of graft dysfunction is unknown. In a single-center, prospective cohort study of renal transplant recipients (N=81), urinary clusterin was measured serially between 4 hr and 7 days after transplantation. The utility of clusterin for prediction of DGF (hemodialysis within 7 days of transplantation) was compared with urinary interleukin (IL)-18, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1, serum creatinine, and clinical variables. At 4 hr after reperfusion, anuria was highly specific, but of low sensitivity for detection of DGF. At 4 hr, receiver operating characteristic analysis suggested that urinary clusterin, IL-18, kidney injury molecule-1, and NGAL concentration were predictive of DGF. After adjusting for preoperative clinical variables and anuria, clusterin and IL-18 independently enhanced the clinical model for prediction of DGF. Kidney injury molecule-1 only modestly improved the prediction of DGF, whereas NGAL, serum creatinine, and the creatinine reduction ratio did not improve on the clinical model. At 12 hr, the creatinine reduction ratio independently predicted DGF. Both urinary clusterin and IL-18 are useful biomarkers and may allow triaging of patients with DGF within 4 hr of transplantation. Relative performance of biomarkers for prediction of graft function is time-dependant. Early and frequent measurements of serum creatinine and calculation of the creatinine reduction ratio also predict DGF within 12 hr of reperfusion.
Finn, Anja; Hao, Jingxia; Wellfelt, Katrin; Josephson, Anna; Svensson, Camilla I.; Wiesenfeld-Hallin, Zsuzsanna; Eriksson, Ulf; Abrams, Mathew
Abstract With no currently available drug treatment for spinal cord injury, there is a need for additional therapeutic candidates. We took the approach of repositioning existing pharmacological agents to serve as acute treatments for spinal cord injury and previously found imatinib to have positive effects on locomotor and bladder function in experimental spinal cord injury when administered immediately after the injury. However, for imatinib to have translational value, it needs to have sustained beneficial effects with delayed initiation of treatment, as well. Here, we show that imatinib improves hind limb locomotion and bladder recovery when initiation of treatment was delayed until 4 h after injury and that bladder function was improved with a delay of up to 24 h. The treatment did not induce hypersensitivity. Instead, imatinib-treated animals were generally less hypersensitive to either thermal or mechanical stimuli, compared with controls. In an effort to provide potential biomarkers, we found serum levels of three cytokines/chemokines—monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-3α, and keratinocyte chemoattractant/growth-regulated oncogene (interleukin 8)—to increase over time with imatinib treatment and to be significantly higher in injured imatinib-treated animals than in controls during the early treatment period. This correlated to macrophage activation and autofluorescence in lymphoid organs. At the site of injury in the spinal cord, macrophage activation was instead reduced by imatinib treatment. Our data strengthen the case for clinical trials of imatinib by showing that initiation of treatment can be delayed and by identifying serum cytokines that may serve as candidate markers of effective imatinib doses. PMID:25914996
assess the severity of fibrosis according to METAVIR classification. Afterward, 15 samples from healthy controls were .... liver fibrosis animal model as compared to healthy controls (Liu et al., 2011). Moreover, the levels .... ethanol abuse, viral infection, cholestasis or metabolic syndrome; these four cytokines were confirmed ...
Full Text Available Background Dengue fever (DF and dengue hemorrhagic fever (DHF are differentiated by the occurrence in DHF of plasma leakage into the interstitial space as shown by pleural and peritoneal effusion, hemoconcentration, and intravascular hypovolemia. Perfusion dysfunction causes anaerobic metabolism, which leads to increased serum lactate. This study was to determine serum lactate as prognostic predictor and diagnostic biomarker of plasma leakage in adult dengue patients. Methods A cross-sectional retrospective cohort study was conducted on 57 adult dengue patients hospitalized in the internal medicine ward of Cipto Mangunkusumo Hospital and Persahabatan Hospital in Jakarta. Serum lactate was examined to determine its mean difference between DF and DHF. The data was analyzed by independent t-test and the cut-off points were identified for presence as well as absence of plasma leakage, then the receiver operating characteristics (ROC curve was used to determine sensitivity and specificity. Results Mean serum lactate was significantly higher in DHF than in DF. From the ROC curve, the cut-off point for serum lactate as prognostic predictor on day 3 of fever was ³2.65 mmol/L with AUC of 0.626 (95% CI 0.480-0.772; p=0.108. The cut-off point for diagnostic biomarker of plasma leakage on day 5 of fever was ³2.55 mmol/L with sensitivity 66.6%, specificity 54.2%, and AUC 0.668 (95% CI 0.550-0.826; p=0.016. Conclusion There was a significant difference in serum lactate between DF and DHF. In the critical phase, serum lactate of ³2.55 mmol/L could be used as plasma leakage diagnostic marker of low accuracy.
Full Text Available FDA-cleared ovarian cancer biomarkers are limited to CA-125 and HE4 for monitoring and recurrence and OVA1, a multivariate panel consisting of CA-125 and four additional biomarkers, for referring patients to a specialist. Due to relatively poor performance of these tests, more accurate and broadly applicable biomarkers are needed. We evaluated the dysregulation of 259 candidate cancer markers in serum samples from 499 patients. Sera were collected prospectively at 11 monitored sites under a single well-defined protocol. All stages of ovarian cancer and common benign gynecological conditions were represented. To ensure consistency and comparability of biomarker comparisons, all measurements were performed on a single platform, at a single site, using a panel of rigorously calibrated, qualified, high-throughput, multiplexed immunoassays and all analyses were conducted using the same software. Each marker was evaluated independently for its ability to differentiate ovarian cancer from benign conditions. A total of 175 markers were dysregulated in the cancer samples. HE4 (AUC=0.933 and CA-125 (AUC=0.907 were the most informative biomarkers, followed by IL-2 receptor α, α1-antitrypsin, C-reactive protein, YKL-40, cellular fibronectin, CA-72-4 and prostasin (AUC>0.800. To improve the discrimination between cancer and benign conditions, a simple multivariate combination of markers was explored using logistic regression. When combined into a single panel, the nine most informative individual biomarkers yielded an AUC value of 0.950, significantly higher than obtained when combining the markers in the OVA1 panel (AUC 0.912. Additionally, at a threshold sensitivity of 90%, the combination of the top 9 markers gave 88.9% specificity compared to 63.4% specificity for the OVA1 markers. Although a blinded validation study has not yet been performed, these results indicate that alternative biomarker combinations might lead to significant improvements in the
Donfrancesco, Renato; Parisi, Pasquale; Vanacore, Nicola; Martines, Francesca; Sargentini, Vittorio; Cortese, Samuele
Objective: (a) To compare serum ferritin levels in a sample of stimulant-naive children with ADHD and matched controls and (b) to assess the association of serum ferritin to ADHD symptoms severity, ADHD subtypes, and IQ. Method: The ADHD and the control groups included 101 and 93 children, respectively. Serum ferritin levels were determined with…
There is an ongoing debate on the role of serum uric acid as an independent risk factor for hypertension and renal disease. This study determined the serum uric acid levels of Nigerians with essential hypertension and also evaluated the association between serum uric acid levels and blood pressure of these patients.
May A Beydoun
Full Text Available The associations between nutritional biomarkers and measures of sleep quantity and quality remain unclear.Cross-sectional data from the National Health and Nutrition Examination Surveys (NHANES 2005-2006 were used. We selected 2,459 adults aged 20-85, with complete data on key variables. Five sleep measures were constructed as primary outcomes: (A Sleep duration; (B Sleep disorder; (C Three factors obtained from factor analysis of 15 items and labeled as "Poor sleep-related daytime dysfunction" (Factor 1, "Sleepiness" (Factor 2 and "Sleep disturbance" (Factor 3. Main exposures were serum concentrations of key nutrients, namely retinol, retinyl esters, carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lutein+zeaxanthin, lycopene, folate, vitamin B-12, total homocysteine (tHcy, vitamin C, 25-hydroxyvitamin D (25(OHD and vitamin E. Main analyses consisted of multiple linear, logistic and multinomial logit models.Among key findings, independent inverse associations were found between serum vitamin B-12 and sleep duration, 25(OHD and sleepiness (as well as insomnia, and between folate and sleep disturbance. Serum total carotenoids concentration was linked to higher odds of short sleep duration (i.e. 5-6 h per night compared to normal sleep duration (7-8 h per night.A few of the selected serum nutritional biomarkers were associated with sleep quantity and quality. Longitudinal studies are needed to ascertain temporality and assess putative causal relationships.
OBJECTIVES: To evaluate synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression during biological therapy for rheumatoid arthritis (RA). METHODS: Patients with active RA entered a randomised study of anakinra 100 mg\\/day, administered as monotherapy or in combination with pegsunercept 800 microg\\/kg twice a week. Arthroscopic synovial tissue biopsies were obtained at baseline and two further time points. Following immunohistochemical staining, selected mediators of RA pathophysiology were quantified using digital image analysis. Selected mediators were also measured in the serum. RESULTS: Twenty-two patients were randomly assigned: 11 received monotherapy and 11 combination therapy. American College of Rheumatology 20, 50 and 70 response rates were 64%, 64% and 46% with combination therapy and 36%, 9% and 0% with monotherapy, respectively. In synovial tissue, T-cell infiltration, vascularity and transforming growth factor beta (TGFbeta) expression demonstrated significant utility as biomarkers of disease activity and therapeutic response. In serum, interleukin 6 (IL-6), matrix metalloproteinase (MMP) 1, MMP-3 and tissue inhibitor of metalloproteinase 1 (TIMP-1) were most useful in this regard. An early decrease in serum levels of TIMP-1 was predictive of the later therapeutic outcome. Pretreatment tissue levels of T-cell infiltration and the growth factors vascular endothelial growth factor\\/TGFbeta, and serum levels of IL-6, IL-8, MMP-1, TIMP-1, soluble tumour necrosis factor receptor types I and II and IL-18 correlated with radiographic progression. CONCLUSIONS: Synovial tissue analysis identified biomarkers of disease activity, therapeutic response and radiographic progression. Biomarker expression in tissue was independent of the levels measured in the serum.
Gottschalk, M G; Cooper, J D; Chan, M K; Bot, M; Penninx, B W J H; Bahn, S
Although social anxiety disorder (SAD) is strongly associated with the subsequent development of a depressive disorder (major depressive disorder or dysthymia), no underlying biological risk factors are known. We aimed to identify biomarkers which predict depressive episodes in SAD patients over a 2-year follow-up period. One hundred sixty-five multiplexed immunoassay analytes were investigated in blood serum of 143 SAD patients without co-morbid depressive disorders, recruited within the Netherlands Study of Depression and Anxiety (NESDA). Predictive performance of identified biomarkers, clinical variables and self-report inventories was assessed using receiver operating characteristics curves (ROC) and represented by the area under the ROC curve (AUC). Stepwise logistic regression resulted in the selection of four serum analytes (AXL receptor tyrosine kinase, vascular cell adhesion molecule 1, vitronectin, collagen IV) and four additional variables (Inventory of Depressive Symptomatology, Beck Anxiety Inventory somatic subscale, depressive disorder lifetime diagnosis, BMI) as optimal set of patient parameters. When combined, an AUC of 0.86 was achieved for the identification of SAD individuals who later developed a depressive disorder. Throughout our analyses, biomarkers yielded superior discriminative performance compared to clinical variables and self-report inventories alone. We report the discovery of a serum marker panel with good predictive performance to identify SAD individuals prone to develop subsequent depressive episodes in a naturalistic cohort design. Furthermore, we emphasise the importance to combine biological markers, clinical variables and self-report inventories for disease course predictions in psychiatry. Following replication in independent cohorts, validated biomarkers could help to identify SAD patients at risk of developing a depressive disorder, thus facilitating early intervention. Copyright © 2015 Elsevier Inc. All rights reserved.
Di Sabatino, Antonio; Biagi, Federico; Lenzi, Marco; Frulloni, Luca; Lenti, Marco Vincenzo; Giuffrida, Paolo; Corazza, Gino Roberto
The progressively growing knowledge of the pathophysiology of a number of immune-mediated gastrointestinal and liver disorders, including autoimmune atrophic gastritis, coeliac disease, autoimmune enteropathy, inflammatory bowel disease, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis and autoimmune pancreatitis, together with the improvement of their detection methods have increased the diagnostic power of serum antibodies. In some cases - coeliac disease and autoimmune atrophic gastritis - they have radically changed gastroenterologists' diagnostic ability, while in others - autoimmune hepatitis, inflammatory bowel disease and autoimmune pancreatitis - their diagnostic performance is still inadequate. Of note, serum antibody misuse in clinical practice has raised a number of controversies, which may generate confusion in the diagnostic management of the aforementioned disorders. In this review, we critically re-evaluate the usefulness of serum antibodies as biomarkers of immune-mediated gastrointestinal and liver disorders, and discuss their pitfalls and merits. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Stavrinou, L C; Kalamatianos, T; Stavrinou, P; Papasilekas, T; Psachoulia, C; Tzavara, C; Stranjalis, G
Recreational scuba diving is a sport of increasing popularity. Previous studies indicating subtle brain injury in asymptomatic divers imply a cumulative effect of minor neural insults in association with diving for professional and/or recreational purposes, over the long-term. This is the first study to investigate putative neural tissue burden during recreational scuba diving by measuring circulating levels of S-100B, a sensitive biomarker of brain injury. 5 male divers performed 3 consecutive dives under conservative recreational diving settings (maximum depth 15 m, duration of dive 56 min, ascend rate 1.15 m/min) with an interval of 12 h between each session. Although a small increase in serum S-100B levels after each dive was apparent, this increase did not quite reach statistical significance (p=0.057). Moreover, no abnormal S-100B values were recorded (mean baseline: 0.06 μg/L, mean post-dive: 0.086 μg/L) and no effect of the 3 consecutive dives on changes in S-100B levels was detected. These results suggest that under the experimental conditions tested, diving does not seem to have a discernible and/or cumulative impact on central nervous system integrity. The extent to which variable diving settings and practices as well as individual susceptibility factors underlie putative neural tissue burden in asymptomatic divers, remains to be established. © Georg Thieme Verlag KG Stuttgart · New York.
Dai, Yufei; Ren, Dianzhi; Bassig, Bryan A; Vermeulen, Roel; Hu, Wei; Niu, Yong; Duan, Huawei; Ye, Meng; Meng, Tao; Xu, Jun; Bin, Ping; Shen, Meili; Yang, Jufang; Fu, Wei; Meliefste, Kees; Silverman, Debra; Rothman, Nathaniel; Lan, Qing; Zheng, Yuxin
The International Agency for Research on Cancer has classified diesel engine exhaust (DEE) as a human lung carcinogen. Given that inflammation is suspected to be an important underlying mechanism of lung carcinogenesis, we evaluated the relationship between DEE exposure and the inflammatory response using data from a cross-sectional molecular epidemiology study of 41 diesel engine testing workers and 46 unexposed controls. Repeated personal exposure measurements of PM 2.5 and other DEE constituents were taken for the diesel engine testing workers before blood collection. Serum levels of six inflammatory biomarkers including interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor (TNF)-α, macrophage inflammatory protein (MIP)-1β, and monocyte chemotactic protein (MCP)-1 were analyzed in all subjects. Compared to unexposed controls, concentrations of MIP-1β were significantly reduced by ∼37% in DEE exposed workers (P 397 µg/m 3 ) compared to unexposed controls. Further, significant inverse exposure-response relationships for IL-8 and MCP-1 were also found in relation to increasing PM 2.5 levels among the DEE exposed workers. Given that IL-8, MIP-1β, and MCP-1 are chemokines that play important roles in recruitment of immunocompetent cells for immune defense and tumor cell clearance, the observed lower levels of these markers with increasing PM 2.5 exposure may provide insight into the mechanism by which DEE promotes lung cancer. Environ. Mol. Mutagen. 59:144-150, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Felix, Joana; Cassinat, Bruno; Porcher, Raphael; Schlageter, Marie-Hélène; Maubec, Eve; Pages, Cécile; Baroudjian, Barouyr; Homyrda, Laurence; Boukouaci, Wahid; Tamouza, Ryad; Bagot, Martine; Caignard, Anne; Toubert, Antoine; Lebbé, Céleste; Moins-Teisserenc, Hélène
Metastatic melanoma is a rapidly spreading cancer whose prognosis remains poor although important therapy advances in recent years. Ipilimumab, an anti-CTLA-4 immunotherapy used in advanced melanoma, is an effective immunotherapy alone or combined with other agents but with few predictive biomarkers of response. Here, we sought to analyze the potential of S100B, MIA, soluble MICA, anti-MICA antibodies and LDH as serum biomarkers of response and survival in a cohort of 77 advanced melanoma patients subjected to ipilimumab. Lower levels of S100B, and LDH at baseline and at weeks 3 and 6 correlated to a better response and survival. After multivariate analysis LDH maintained its independence at baseline and week 6, whereas S100B might be a useful tool for anti-CTLA-4 treatment monitoring after the first two doses of ipilimumab (W6). In addition, higher sMICA serum levels at baseline were associated with less frequency of irAEs. Copyright © 2016 Elsevier B.V. All rights reserved.
Malin Elisabet Persson
Full Text Available The protein S-100B is a biomarker increasingly used within neurosurgery and neurointensive care. As a relatively sensitive, yet unspecific, indicator of CNS pathology, potential sources of error must be clearly understood when interpreting serum S-100B levels. This case report studied the course of a 46-year-old gentleman with a chronic subdural haemorrhage, serum S-100B levels of 22 μg/L and a history of malignant melanoma. Both intra- and extra-cranial sources of S-100B are evaluated and imply an unclear contribution of several sources to the total serum concentration. Potential sources of error when interpreting serum concentrations of S-100B are discussed
Full Text Available Morten Nørgaard Andersen,1–3,* Maja Ludvigsen,1,3,* Niels Abildgaard,4 Irma Petruskevicius,3 Rikke Hjortebjerg,5 Mette Bjerre,5 Bent Honoré,1 Holger J Møller,2 Niels F Andersen31Department of Biomedicine, Faculty of Health, Aarhus University, 2Department of Clinical Biochemistry, 3Department of Hematology, Aarhus University Hospital, Aarhus, 4Department of Hematology, Odense University Hospital, Odense, 5Medical Research Laboratory, Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark*These authors contributed equally to this workAbstract: Galectin-1 (Gal-1 is known to regulate cell signaling within the immune system and may be a target for new anticancer immune therapy. In patients with chronic lymphocytic leukemia (CLL and classical Hodgkin lymphoma (cHL, high levels of Gal-1 within the tumor microenvironment were associated with worse disease state or poor outcome. Gal-1 can be secreted from cells by an unknown mechanism, and levels in blood samples were associated with high tumor burden and worse disease state in cHL and CLL patients. However, serum levels of Gal-1 have never been investigated in patients with multiple myeloma (MM. We measured serum Gal-1 levels in samples from patients with treatment demanding MM at the time of diagnosis (n=102 and after treatment (n=24 and examined associations of serum Gal-1 with clinicopathological information obtained from patient medical records, as well as data on bone marrow angiogenesis and the macrophage activation biomarkers soluble CD163 (sCD163 and soluble mannose receptor. Serum Gal-1 levels were not elevated in patients with MM at diagnosis compared with healthy donors (median values 8.48 vs 11.93 ng/mL, P=0.05, which is in contrast to results in cHL and CLL. Furthermore, Gal-1 levels did not show association with bone marrow angiogenesis, clinicopathological parameters, overall survival, or response to treatment. There was a statically significant
Abdallah I Ali Kelani
Conclusion This study supports a significant association between deficient serum Se concentration with cut-off value of up to 84 ng/ml and MI. Strikingly, the most predictor of MI is serum Se, followed by total cholesterol, diabetes mellitus, low-density lipoprotein, and hypertension.
Full Text Available Retinol, α-tocopherol, and γ-tocopherol are fat-soluble vitamins acting as antioxidants via the prevention of lipid oxidation. Little is known about circulatory levels in healthy individuals. The present cross-sectional study aimed at elucidating the relationship between these antioxidants and clinical biomarkers in 206 male (median age 41 years, range 23–67 employees from companies located in the Okayama Prefecture, Japan. Subjects younger than 40 years (n = 94 showed a positive association of the frequency of alcohol consumption with the circulating retinol (β = 0.344, p = 0.001 and γ-tocopherol levels (β = 0.219, p = 0.041, and an inverse association of fast insulin with serum retinol (β = −0.301, p = 0.009. In participants older than 40 years (n = 112 we found that an inverse association of HOMA-R with serum retinol (β = −0.262, p = 0.021, α-tocopherol (β = −0.236, p = 0.035, and γ-tocopherol levels (β = −0.224, p = 0.052; and cigarette smoking was inversely associated with the levels of serum α-tocopherol (β = −0.286, p = 0.008 and γ-tocopherol (β = −0.229, p = 0.040. We further found negative relationships between serum ferritin and the retinol (β = −0.211, p = 0.032 and α-tocopherol levels (β = −0.223, p = 0.022 in men over 40 years of age. The present study suggests that the circulatory levels of antioxidant vitamins may modulate the action of insulin and that higher levels of iron might decrease the levels of antioxidant vitamins in the blood.
de Araújo, Thádia Evelyn; Coelho-Dos-Reis, Jordana Grazziela; Béla, Samantha Ribeiro; Carneiro, Ana Carolina Aguiar Vasconcelos; Machado, Anderson Silva; Cardoso, Ludmila Melo; Ribeiro, Ágata Lopes; Dias, Michelle Hallais França; Queiroz Andrade, Gláucia Manzan; Vasconcelos-Santos, Daniel Vitor; Januário, José Nélio; Teixeira-Carvalho, Andréa; Vitor, Ricardo Wagner Almeida; Ferro, Eloisa Amália Vieira; Martins-Filho, Olindo Assis
The present study characterized the early changes in the serum chemokines/cytokine signatures and networks in infants with congenital-toxoplasmosis/(TOXO) as compared to non-infected-controls/(NI). TOXO were subgrouped according to the retinochoroidal lesion status as no-lesion/(NL), active-lesion/(ARL), active/cicatricial-lesion/(ACRL) and cicatricial-lesion/(CRL). The results showed that TOXO display prominent chemokine production mediated by IL-8/CXCL8, MIG/CXCL9, IP-10/CXCL10 and RANTES/CCL5. Additionally, TOXO is accompanied by mixed proinflammatory/regulatory cytokine pattern mediated by IL-6, IFN-γ, IL-4, IL-5 and IL-10. While TNF appears as a putative biomarker for NL and IFN-γ/IL-5 as immunological features for ARL, IL-10 emerges as a relevant mediator in ACRL/CRL. IL-8/CXCL8 and IP-10/CXCL10 are broad-spectrum indicators of ocular disease, whereas TNF is a NL biomarker, IFN-γ and MIG/CXCL9 point out to ARL; and IL-10 is highlighted as a genuine serum biomarker of ACRL/CRL. The network analysis demonstrated a broad chemokine/cytokine crosstalk with divergences in the molecular signatures in patients with different ocular lesions during congenital toxoplasmosis. Copyright © 2017 Elsevier Ltd. All rights reserved.
Full Text Available Secondary hyperparathyroidism (SHPT is a common, important, and treatable complication of end-stage renal disease. This study was conducted to investigate the role of serum magnesium (Mg in regulating the secretion of parathyroid hormone (PTH by the parathyroid gland in patients on maintenance hemodialysis (HD. Pre-dialysis serum levels of calcium (Ca, phosphorus (P, Mg, alkaline phosphatase (ALP, intact serum PTH (iPTH, serum 25-hydroxy Vitamin D (25-OH Vit D and plasma bicarbonate (HCO3 were measured. The Urea Reduction Rate as well as duration and dosage of HD treatment were noted. Our study did not show any significant correlation between serum Mg levels and duration of HD treatment, levels of serum ALP, and plasma HCO3, Ca and P. An inverse correlation, albeit insignificant, was found between the serum Mg levels and iPTH (r=-0.30 p=0.079; also, a significant positive correlation was found between serum Mg levels and serum 25-OH Vit D levels (r= 0.40 p= 0.009. Our findings are in agreement with previous data, which suggest that factors other than serum Mg are more important in the regulation of PTH secretion in HD patients. A positive and strong association between serum Mg with 25-OH Vit D needs to be studied in greater detail.
Full Text Available INTRODUCTION: Former studies have investigated the potential of serum biomarkers for diseases affecting the human brain. In particular the glial protein S100B, a neuro- and gliotrophin inducing plasticity, seems to be involved in the pathogenesis and treatment of psychiatric diseases such as major depression and schizophrenia. Neuron-specific enolase (NSE is a specific serum marker for neuronal damage. However, the specificity of these biomarkers for cell type and brain region has not been investigated in vivo until now. METHODS: We acquired two magnetic resonance imaging parameters sensitive to changes in gray and white matter (T(1-weighted/diffusion tensor imaging and obtained serum S100B and NSE levels of 41 healthy subjects. Additionally, we analyzed whole brain gene expressions of S100B in another male cohort of three subjects using the Allen Brain Atlas. Furthermore, a female post mortal brain was investigated using double immunofluorescence labelling with oligodendrocyte markers. RESULTS: We show that S100B is specifically related to white matter structures, namely the corpus callosum, anterior forceps and superior longitudinal fasciculus in female subjects. This effect was observed in fractional anisotropy and radial diffusivity - the latest an indicator of myelin changes. Histological data confirmed a co-localization of S100B with oligodendrocyte markers in the human corpus callosum. S100B was most abundantly expressed in the corpus callosum according to the whole genome Allen Human Brain Atlas. In addition, NSE was related to gray matter structures, namely the amygdala. This effect was detected across sexes. CONCLUSION: Our data demonstrates a very high S100B expression in white matter tracts, in particular in human corpus callosum. Our study is the first in vivo study validating the specificity of the glial marker S100B for the human brain, and supporting the assumption that radial diffusivity represents a myelin marker. Our results
Streitbürger, Daniel-Paolo; Arelin, Katrin; Kratzsch, Jürgen; Thiery, Joachim; Steiner, Johann; Villringer, Arno
Introduction Former studies have investigated the potential of serum biomarkers for diseases affecting the human brain. In particular the glial protein S100B, a neuro- and gliotrophin inducing plasticity, seems to be involved in the pathogenesis and treatment of psychiatric diseases such as major depression and schizophrenia. Neuron-specific enolase (NSE) is a specific serum marker for neuronal damage. However, the specificity of these biomarkers for cell type and brain region has not been investigated in vivo until now. Methods We acquired two magnetic resonance imaging parameters sensitive to changes in gray and white matter (T1-weighted/diffusion tensor imaging) and obtained serum S100B and NSE levels of 41 healthy subjects. Additionally, we analyzed whole brain gene expressions of S100B in another male cohort of three subjects using the Allen Brain Atlas. Furthermore, a female post mortal brain was investigated using double immunofluorescence labelling with oligodendrocyte markers. Results We show that S100B is specifically related to white matter structures, namely the corpus callosum, anterior forceps and superior longitudinal fasciculus in female subjects. This effect was observed in fractional anisotropy and radial diffusivity – the latest an indicator of myelin changes. Histological data confirmed a co-localization of S100B with oligodendrocyte markers in the human corpus callosum. S100B was most abundantly expressed in the corpus callosum according to the whole genome Allen Human Brain Atlas. In addition, NSE was related to gray matter structures, namely the amygdala. This effect was detected across sexes. Conclusion Our data demonstrates a very high S100B expression in white matter tracts, in particular in human corpus callosum. Our study is the first in vivo study validating the specificity of the glial marker S100B for the human brain, and supporting the assumption that radial diffusivity represents a myelin marker. Our results open a new perspective
Al-Abri, Suad A; Anderson, Ilene B; Pedram, Fatehi; Colby, Jennifer M; Olson, Kent R
Massive naproxen overdose is not commonly reported. Severe metabolic acidosis and seizure have been described, but the use of renal replacement therapy has not been studied in the context of overdose. A 28-year-old man ingested 70 g of naproxen along with an unknown amount of alcohol in a suicidal attempt. On examination in the emergency department 90 min later, he was drowsy but had normal vital signs apart from sinus tachycardia. Serum naproxen level 90 min after ingestion was 1,580 mg/L (therapeutic range 25-75 mg/L). He developed metabolic acidosis requiring renal replacement therapy using sustained low efficiency dialysis (SLED) and continuous venovenous hemofiltration (CVVH) and had recurrent seizure activity requiring intubation within 4 h from ingestion. He recovered after 48 h. Massive naproxen overdose can present with serious toxicity including seizures, altered mental status, and metabolic acidosis. Hemodialysis and renal replacement therapy may correct the acid base disturbance and provide support in cases of renal impairment in context of naproxen overdose, but further studies are needed to determine the extraction of naproxen.
Naoko Aminaka; Tiffany Fohey; Attila Kovacs; Roksana Zak
Background: Delayed-onset muscle soreness (DOMS) causes muscle damage and edema that can hinder performance and increase risks for secondary injuries. Kinesiology Tape (KT) may be an effective modality for aiding in recovery, however, no study has investigated the effects of KT on the physiological biomarkers such as serum creatine kinase (CK) level, concurrently with measures of performance and function, during recovery from DOMS. Objective: Investigate the effects of KT on serum CK level, e...
Ahn, Song Vogue; Koh, Sang-Baek; Lee, Kwang-Sik; Bong, Yeon-Sik; Park, Jong-Ku
Stable isotope ratios have been reported to be potential biomarkers of dietary intake and nutritional status. High serum levels of leptin, a hormone which regulates energy metabolism and food intake, are associated with insulin resistance and metabolic syndrome. However, little is known about the association between stable isotope ratios and the metabolic risk in humans. We investigated whether the carbon and nitrogen stable isotope ratios in hair are associated with serum leptin levels. Hair samples were collected from 399 healthy adults (233 men and 166 women) aged 40 to 70 years of a community-based cohort in Korea and the bulk stable isotope ratios of carbon (δ 13 C) and nitrogen (δ 15 N) were measured for all hair samples. Serum leptin levels were analyzed by radioimmunoassay. δ 15 N showed positive correlations with serum leptin levels. In multivariate models, increasing δ 15 N were associated with elevated serum leptin levels (defined as ≥ the median values), whereas δ 13 C were not significantly associated with serum leptin levels. The odds ratio (95% confidence interval) per 1‰ increase in δ 15 N for an elevated serum leptin level was 1.58 (1.11-2.26). In participants with high body mass index, δ 15 N showed positive associations with serum leptin levels, whereas these associations were not seen in participants with low body mass index. The nitrogen stable isotopic ratio in hair is positively associated with serum leptin levels. The hair δ 15 N could be used as a clinical marker to estimate metabolic risk.
Zhou, Na; Wang, Jie; Yu, Yaqin; Shi, Jieping; Li, Xiaokun; Xu, Bin; Yu, Qiong
Diagnosis of schizophrenia does not have a clear objective test at present, so we aimed to identify the potential biomarkers for the diagnosis of schizophrenia by comparison of serum protein profiling between first-episode schizophrenia patients and healthy controls. The combination of a magnetic bead separation system with matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF-MS) was used to analyze the serum protein spectra of 286 first-episode patients with schizophrenia, 41 chronic disease patients and 304 healthy controls. FlexAnlysis 3.0 and ClinProTools(TM) 2.1 software was used to establish a diagnostic model for schizophrenia. The results demonstrated that 10 fragmented peptides demonstrated an optimal discriminatory performance. Among these fragmented peptides, the peptide with m/z 1206.58 was identified as a fragment of fibrinopeptide A. Receiver operating characteristic analysis for m/z 1206.58 showed that the area under the curve was 0.981 for schizophrenia vs healthy controls, and 0.999 for schizophrenia vs other chronic disease controls. From our result, we consider that the analysis of serum protein spectrum using the magnetic bead separation system and MALDI-TOF/TOF-MS is an objective diagnostic tool. We conclude that fibrinopeptide A has the potential to be a biomarker for diagnosis of schizophrenia. This protein may also help to elucidate schizophrenia disease pathogenesis. Copyright © 2013 John Wiley & Sons, Ltd.
Full Text Available Background: Diabetic retinopathy (DR is a retinopathy resulting from diabetes mellitus (DM which was classified into non-proliferative DR (NPDR and proliferative DR (PDR. Without an early screening and effective diagnosis, patients with PDR will develop serious complications. Therefore, we sought to identify special serum microRNAs (miRNAs that can serve as a novel non-invasive screening signature of PDR and test its specificity and sensitivity in the early diagnosis of PDR. Methods: In total, we obtained serum samples from 90 PDR cases, 90 matched NPDR patients and 20 controls. An initial screening of miRNA expression was performed through TaqMan Low Density Array (TLDA. The candidate miRNAs were validated by individual reverse transcription quantitative real-time PCR (RT-qPCR arranged in an initial and a two-stage validation sets. Moreover, additional double-blind testing was performed in 20 patients clinically suspected of having DR to evaluate the diagnostic value and accuracy of the serum miRNA profiling system in predicting PDR. Results: Three miRNAs were significantly increased in patients with PDR compared with NPDR after the multiple stages. The areas under the receiver operating characteristic (ROC curves of the validated three-serum miRNAs signature were 0.830, 0.803 and 0.873 in the initial and two validation sets, respectively. Combination of miR-21, miR-181c, and miR-1179 possessed a moderate ability to discrimination between PDR and NPDR with an area under ROC value of 0.89. The accuracy rate of the three-miRNA profile as PDR signature was 82.6%. Conclusions: These data provide evidence that serum miRNAs have the potential to be sensitive, cost-effective biomarkers for the early detection of PDR. These biomarkers could serve as a dynamic monitoring factor for detecting the progression of PDR from NPDR.
Ressom, Habtom W., E-mail: email@example.com [Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057 (United States); Xiao, Jun Feng; Tuli, Leepika; Varghese, Rency S.; Zhou Bin; Tsai, Tsung-Heng; Nezami Ranjbar, Mohammad R.; Zhao Yi; Wang Jinlian; Di Poto, Cristina; Cheema, Amrita K. [Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057 (United States); Tadesse, Mahlet G. [Department of Mathematics and Statistics, Georgetown University, Washington, DC 20057 (United States); Goldman, Radoslav [Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057 (United States); Shetty, Kirti [Department of Surgery, Georgetown University Medical Center, Washington, DC 20057 (United States); Georgetown University Hospital, Washington, DC 20057 (United States)
Highlights: Black-Right-Pointing-Pointer We analyzed sera from HCC and cirrhotic patients by LC-MS in three experiments. Black-Right-Pointing-Pointer Metabolites with significant and consistent changes in HCC vs. cirrhosis were selected. Black-Right-Pointing-Pointer Verification of the identities of selected metabolites was performed by MS/MS. Black-Right-Pointing-Pointer Quantitation of candidate metabolites was conducted using isotope dilution by SRM. - Abstract: Characterizing the metabolic changes pertaining to hepatocellular carcinoma (HCC) in patients with liver cirrhosis is believed to contribute towards early detection, treatment, and understanding of the molecular mechanisms of HCC. In this study, we compare metabolite levels in sera of 78 HCC cases with 184 cirrhotic controls by using ultra performance liquid chromatography coupled with a hybrid quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS). Following data preprocessing, the most relevant ions in distinguishing HCC cases from patients with cirrhosis are selected by parametric and non-parametric statistical methods. Putative metabolite identifications for these ions are obtained through mass-based database search. Verification of the identities of selected metabolites is conducted by comparing their MS/MS fragmentation patterns and retention time with those from authentic compounds. Quantitation of these metabolites is performed in a subset of the serum samples (10 HCC and 10 cirrhosis) using isotope dilution by selected reaction monitoring (SRM) on triple quadrupole linear ion trap (QqQLIT) and triple quadrupole (QqQ) mass spectrometers. The results of this analysis confirm that metabolites involved in sphingolipid metabolism and phospholipid catabolism such as sphingosine-1-phosphate (S-1-P) and lysophosphatidylcholine (lysoPC 17:0) are up-regulated in sera of HCC vs. those with liver cirrhosis. Down-regulated metabolites include those involved in bile acid biosynthesis (specifically
Baumann, R; Gube, M; Markert, A; Davatgarbenam, S; Kossack, V; Gerhards, B; Kraus, T; Brand, P
Zinc- and copper-containing welding fumes increase systemic C-reactive protein (CRP). The aim of this study was to investigate the performance of the biomarkers serum amyloid A (SAA) and soluble vascular cell adhesion molecule-1 (VCAM-1) in this regard. Fifteen male subjects were exposed under controlled conditions to welding fumes containing either zinc, or copper, or copper and zinc for 6 h. Plasma samples were collected before, 6 and 24 h after start of exposure and biomarkers therein were measured by electrochemiluminescent assay. For each exposure, systemic concentrations of systemic SAA, but not VCAM-1, increased significantly at 24 h after exposure start compared with baseline ("copper only": P=0.0005, "zinc only": P=0.027, "copper and zinc": P=0.001). SAA showed a wider range of concentrations than did CRP and its levels increased up to 19-fold after welding fume exposure. The recognition of copper as a potential harmful component in welding fumes, also independent from zinc, deserves further consideration. SAA might represent a new sensitive biomarker for potential subclinical sterile inflammation after inhalation of copper- and/or zinc-containing welding fumes. As elevations of CRP and SAA protein have both been linked to a higher risk for cardiovascular disease, these findings might particularly be important for long-term welders.
Paola ede Candia
Full Text Available Induction of the adaptive immune system is evaluated mostly by assessment of serum antibody titers and T lymphocyte responses in peripheral blood, although T and B cell activation occurs in lymphoid tissues. In recent years, the release of microRNAs (miRNAs in the extra-cellular environment has been exploited to assess cell functions at distance via measurement of serum miRNAs. Also activated lymphocytes release a large amount of nano-sized vesicles (exosomes, containing miRNA, but there are still few data on whether this phenomenon is reflected in modulation of serum miRNAs. Interestingly, miRNA signatures of CD4+ T cell-derived exosomes are substantially different from intracellular miRNA signatures of the same cells. We have recently identified serum circulating miR-150 as a sensor of general lymphocyte activation and we strongly believe that the identification of miRNAs differentially released by specific CD4+ effector T cell subsets (Th1, Th2, Th17 and Treg may work as serum biomarkers of their elicitation in lymphoid tissues but also in damaged tissues, thus providing pivotal information about the nature of immune responses occurring in health and disease.
Filippini, Tommaso; Michalke, Bernhard; Malagoli, Carlotta; Grill, Peter; Bottecchi, Ilaria; Malavolti, Marcella; Vescovi, Luciano; Sieri, Sabina; Krogh, Vittorio; Cherubini, Andrea; Maffeis, Giuseppe; Modenesi, Marina; Castiglia, Paolo; Vinceti, Marco
Introduction: Cadmium (Cd) is a heavy metal and a serious environmental hazard to humans. Some uncertainties still exist about major sources of Cd exposure in non-occupationally exposed subjects in addition to cigarette smoking, such as diet and outdoor air pollution. We sought to determine the influence of these sources on a biomarker of exposure, serum Cd concentration. Methods: We recruited 51 randomly selected residents from an Italian urban community, from whom we obtained detailed information about dietary habits and smoking habits, and a blood sample for serum Cd determination. We also assessed outdoor air Cd exposure, by modeling outdoor air levels of particulate matter ≤10 µm (PM 10 ) from motorized traffic at geocoded subjects’ residence. Results: In crude analysis, regression beta coefficients for dietary Cd, smoking and PM10 on serum Cd levels were 0.03 (95% CI -0.83 to 0.88), 6.96 (95% CI -0.02 to 13.95) and 0.62 (95% CI -0.19 to 1.43), respectively. In the adjusted analysis, regression beta coefficients were -0.34 (95% CI -1-40 to 0.71), 5.81 (95% CI -1.43 to 13.04) and 0.47 (95% CI -0.35 to 1.29), respectively. Conclusion: Cigarette smoking was the most important factor influencing serum Cd in our non-occupationally exposed population, as expected, while dietary Cd was not associated with this biomarker. Outdoor air pollution, as assessed through exposure to particulate matter generated by motorized traffic, was an additional source of Cd exposure. - Highlights: • Smoking markedly increases serum Cd levels in non-occupationally exposed individuals. • Overall dietary Cd intake shows little association with serum Cd levels. • Air pollution from motorized traffic increases serum Cd levels.
Hayashi, K; Yanagihara, T; Hata, T
To evaluate alterations in maternal circulating angiogenin levels with advancing gestation and to assess the effect of labor stress on serum angiogenin levels in neonates delivered vaginally and by cesarean section. The maternal circulating angiogenin concentrations were compared in 37 normotensive nonpregnant women, in 60 normotensive pregnant women from 7 to 41 weeks of gestation, and in 12 normotensive postpartum women on the 3rd puerperal day. The serum angiogenin concentrations were also measured in 12 patients with threatened premature labor. Moreover, maternal and fetal serum angiogenin samples before and after delivery were used to determine differences in 12 neonates delivered vaginally and in 11 neonates delivered by elective cesarean section. The serum angiogenin level was measured using an enzyme-linked immunosorbent assay. There was no significant difference in serum angiogenin levels during each phase of the menstrual cycle. The serum angiogenin levels were decreasing until 15 weeks of gestation and increasing thereafter. There was no significant difference in serum angiogenin levels between normal pregnant women and in patients with threatened premature labor. Labor stress did not affect either maternal or fetal serum angiogenin concentrations. The serum angiogenin levels of the neonates were significantly lower than those in maternal serum after both vaginal delivery and delivery by cesarean section. These results suggest that regulatory mechanisms of angiogenin may exist during pregnancy. Copyright 2000 S. Karger AG, Basel
Yuan, Tong-Ling; Chen, Jin; Tong, Yan-Li; Zhang, Yan; Liu, Yuan-Yuan; Wei, James Cheng-Chung; Liu, Yi; Zhao, Yi; Herrmann, Martin
Backgrounds. Heme oxygenase-1 (HO-1) has been reported to play a regulatory role in osteoclastogenesis. Bone morphogenetic protein (BMP) pathways induce osteoblastic differentiation and bone remodeling. Aims. To identify serum levels of HO-1, BMP-7, and Runt related-transcription factor 2 (Runx2) in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and to investigate the relationships between HO-1, BMP-7, Runx2, and other common biomarkers for bone metabolism. Results. Serum levels of HO-1 and BMP-7 were revealed to be significantly higher in patients with RA or AS than in healthy controls (p pathways in the two types of arthritis.
Zhang, Hongtai; Sun, Zhaogang; Wei, Wenjing; Liu, Zhonghui; Fleming, Joy; Zhang, Shuai; Lin, Nan; Wang, Ming; Chen, Maoshan; Xu, Yuhui; Zhou, Jie; Li, Chuanyou; Bi, Lijun; Zhou, Guangming
Tuberculosis (TB) remains a significant human health issue. More effective biomarkers for use in tuberculosis prevention, diagnosis, and treatment, including markers that can discriminate between healthy individuals and those with latent infection, are urgently needed. To identify a set of such markers, we used Solexa sequencing to examine microRNA expression in the serum of patients with active disease, healthy individuals with latent TB, and those with or without prior BCG inoculation. We identified 24 microRNAs that are up-regulated (2.85-1285.93 fold) and 6 microRNAs that are down-regulated (0.003-0.11 fold) (PmicroRNAs were up-regulated (2.05-2454.58 fold) and 11 were down-regulated (0.001-0.42 fold) (PmicroRNAs were differentially-expressed in BCG-inoculated relative to un-inoculated individuals (18 up-regulated 2.9-499.29 fold, 116 down-regulated 0.0002-0.5 fold), providing insights into the effects of BCG inoculation at the microRNA level. Target prediction of differentially-expressed microRNAs by microRNA-Gene Network analysis and analysis of pathways affected suggest that regulation of the host immune system by microRNAs is likely to be one of the main factors in the pathogenesis of tuberculosis. qRT-PCR validation indicated that hsa-miR-196b and hsa-miR-376c have potential as markers for active TB disease. The microRNA differential-expression profiles generated in this study provide a good foundation for the development of markers for TB diagnosis, and for investigations on the role of microRNAs in BCG-inoculated and latent-infected individuals.
Salem, E.S.; Abdel-Messeih, Ph.L.; Mansour, H.H.
The fact that bone mass density (BMD) is not useful for assessing fracture risk in diabetic patients (DM) seems problematic, because those populations are increasing in every country. Osteocalcin (OC) is synthesized by osteoblasts and is considered to be a marker of bone formation. The present study was carried out to evaluate the usefulness of OC as noninvasive biomarker of bone formation in diabetes mellitus type 2 (uncomplicated) and diabetic nephropathy. Immunoradiometric assay(IRMA) was used for the quantitative measurement of human intact OC both N-terminal and C-terminal fragments in the serum of the control and the studied groups. OC levels in the uncomplicated diabetic group were significantly lower while in the diabetic nephropathy group was significantly higher compared to control values . There was a weak negative correlation between OC and both fasting blood glucose and glycated Hb% in the diabetic group. In diabetic nephropathy patients, a weak positive correlation was observed between OC and protein creatinine ratio. The results concluded that changes in bone remodelling marker OC are present in both DM type 2 and diabetic nephropathy explaining osteopenia and osteoporosis observed in both cases.Therefore, an effective glycaemic control should be the hallmark of prevention and treatment of diabetes mellitus induced osteoporosis
Wilting, Ingeborg; Fase, Sandra; Martens, Edwin P.; Heerdink, Eibert R.; Nolen, Willem A.; Egberts, Antoine C. G.
Objectives: Three studies have reported a seasonal variation in lithium serum levels, with higher levels during summer. Our objective was to investigate the impact of actual environmental temperature on lithium serum levels. Methods: A retrospective study was conducted using available records of
Zhang, Yuan; Chen, Xianqiu; Hu, Yang; Du, Shanshan; Shen, Li; He, Yifan; Zhang, Yuxuan; Zhang, Xia; Li, Huiping; Yung, Rex C
The diagnosis of sarcoidosis is still a significant challenge in China because of the need to exclude other diseases including granulomatous infections and malignancies that may be clinically and radiographically similar. The specific aim of the study is to search for serum protein biomarkers of sarcoidosis and to validate their clinical usefulness in differential diagnosis. Serum samples were collected from patients with sarcoidosis (n = 37), and compared to those from patients with tuberculosis (n = 20), other pulmonary diseases (n = 20), and healthy volunteers (n = 20) for determination of sarcoidosis-specific or -associated protein expression profiles. The first part of this study focused on proteomic analysis of serum from patients with sarcoidosis to identify a pattern of peptides capable of differentiating the studied populations using the ClinProt profiling technology based on mass spectrometry. Enzyme Linked Immunosorbent Assay (ELISA) was then used to verify corresponding elevation of the serum protein concentration of the potential biomarkers in the same patients sets. Receiver operating characteristic curve (ROC) analyses was performed to determine the optimal cutoff value for diagnosis. Immunohistochemistry was carried out to further confirm the protein expression patterns of the biomarkers in lung tissue. An unique protein peak of M/Z 3,210 Daltons (Da) was found to be differentially expressed between the sarcoidosis and control groups and was identified as the N-terminal peptide of 29 amino acids (94-122) of serum amyloid A (SAA). ELISA confirmed that the serum SAA level was significantly higher in the sarcoidosis group than that of the other 3 control groups (p biomarker for ruling-out the diagnosis of sarcoidosis in Chinese subjects.
Wang-Johanning, Feng; Li, Ming; Esteva, Francisco J; Hess, Kenneth R; Yin, Bingnan; Rycaj, Kiera; Plummer, Joshua B; Garza, Jeremy G; Ambs, Stefan; Johanning, Gary L
A simple and accurate test to detect early-stage breast cancer has not been developed. Previous studies indicate that the level of human endogenous retrovirus type K (group HERV-K(HML-2)) transcription may be increased in human breast tumors. We hypothesized that HERV-K(HML-2) reactivation can serve as a biomarker for early detection of breast cancer. Serum samples were collected from women without cancer (controls) and patients with ductal carcinoma in situ (DCIS) and invasive breast cancer. ELISA assays were used to detect serum anti-HERV-K(HML-2) antibody titers. RNA was extracted from sera and analyzed by real-time RT-PCR to quantitate the level of HERV-K(HML-2) mRNA. We measured significantly higher serum mRNA and serum antibody titers against HERV-K(HML-2) proteins in women with DCIS and stage I disease than in women without cancer. At optimized cutoffs for the antibody titers, the assay produced an area under the receiver operating characteristic curve (AUC) of 0.89 (95% confidence interval 0.77-1.00) for DCIS and of 0.95 (95% confidence interval 0.89-1.00) for invasive breast cancer. These AUCs are comparable to those observed for mammograms. We also found that serum HERV-K(HML-2) mRNA tended to be higher in breast cancer patients with a primary tumor who later on developed the metastatic disease than in patients who did not develop cancer metastasis. Our results show that HERV-K(HML-2) antibodies and mRNA are already elevated in the blood at an early stage of breast cancer, and further increase in patients who are at risk of developing a metastatic disease. © 2013 UICC.
Full Text Available The COQ2 gene encodes an essential enzyme for biogenesis, coenzyme Q10 (CoQ10. Recessive mutations in this gene have recently been identified in families with multiple system atrophy (MSA. Moreover, specific heterozygous variants in the COQ2 gene have also been reported to confer susceptibility to sporadic MSA in Japanese cohorts. These findings have suggested the potential usefulness of CoQ10 as a blood-based biomarker for diagnosing MSA. This study measured serum levels of CoQ10 in 18 patients with MSA, 20 patients with Parkinson's disease and 18 control participants. Although differences in total CoQ10 (i.e., total levels of serum CoQ10 and its reduced form among the three groups were not significant, total CoQ10 level corrected by serum cholesterol was significantly lower in the MSA group than in the Control group. Our findings suggest that serum CoQ10 can be used as a biomarker in the diagnosis of MSA and to provide supportive evidence for the hypothesis that decreased levels of CoQ10 in brain tissue lead to an increased risk of MSA.
Kim, Dong Young; Kim, Jeong Hong; Lee, Keun-Hwa; Hong, Seong-Chul; Lee, Hye-Sook; Kang, Ju Wan
Periostin is a matricellular protein, synthesized in the airway epithelium and induced by interleukin (IL)-4 and IL-13. The significance of periostin as a biomarker of T helper type 2 cell (Th2)-induced airway inflammation, and as a measure of the response to Th2-targeted therapy, has recently been highlighted. We explored the relationship between serum periostin and allergic rhinitis in Korean children. Data for fifth and sixth grade children from six randomly selected elementary schools located in Jeju and Seogwipo City, Korea, were investigated. Serum periostin levels were determined by enzyme-linked immunosorbent assay. Sex, school grade, body mass index, and presence of allergic nasal symptoms were obtained via a self-reported survey and skin prick testing was performed. There were no significant differences between groups, when stratification was applied according to sex, grade, presence of atopy, and presence of allergic nasal symptoms. Sex and body mass index were significantly associated with serum periostin levels in multivariate linear regression analysis. However, allergic rhinitis was not associated with serum periostin levels. Allergic rhinitis or allergic sensitization in Korean children did not influence serum periostin levels. Further studies are required to investigate the significance of serum periostin levels in pediatric allergic rhinitis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Full Text Available Background. Alzheimer's disease (AD is the most common cause of dementia in the elderly. AD is characterized by the accumulation of amyloid plaques and neurofibrillary tangles and by massive neuronal loss in the brain. There is epidemiologic and pathologic evidence that AD is associated with vascular risk factors and vascular diseases, contributing to cerebral hypoperfusion with consecutive stimulation of angiogenesis and upregulation of proangiogenic factors such as Angiopoietin-1 (Ang-1. Methods. In the present study, we measured Ang-1 serum levels in 42 patients with AD, 20 patients with mild cognitive impairment (MCI, and in 40 healthy elderly controls by ELISA. Results. We found significantly increased Ang-1 serum levels in patients with AD compared to control subjects (P=0.003. There was no significant difference between MCI patients and healthy controls (P=0.553 or between AD and MCI patients (P=0.054. The degree of cognitive impairment as measured by the mini-mental status examination (MMSE score was significantly correlated with the Ang-1 serum levels in all patients and healthy controls. Conclusions. We found significantly increased Ang-1 serum levels in AD patients. We could also show an association between Ang-1 serum levels and the cognitive status in all patients and healthy controls. Thus, serum Ang-1 could be a potential candidate for a biomarker panel for AD diagnosis.
Damera, Sriharsha; Raphael, Kalani L.; Baird, Bradley C.; Cheung, Alfred K.; Greene, Tom; Beddhu, Srinivasan
High serum alkaline phosphatase concentrations are associated with elevated serum C-reactive protein (CRP) levels in the general population. To examine whether this association is independent of serum vitamin D levels or modified in chronic kidney disease (CKD), we determined if such associations exist using data from the National Health and Nutrition Examination Survey III of 14,420 adult participants in which 5.7% had CKD (defined as estimated glomerular filtration rate < 60 ml/min per 1.73...
Lu, Zhao-Lian; Chen, Ying-Jian; Jing, Xin-Yan; Wang, Na-Na; Zhang, Ting; Hu, Cheng-Jin
BACKGROUND Papillary thyroid cancer (PTC) is currently the most commonly diagnosed endocrine malignancy. In addition, the sex- and age-adjusted incidence of PTC has exhibited a greater increase over the last 2 decades than in many other malignancies. Thus, discovering noninvasive specific serum biomarker to distinguish PTC from cancer-free controls in its early stages remains an important goal. MATERIAL AND METHODS Serum samples from 88 PTC patients and 80 cancer-free controls were randomly allocated into training or validation sets. Serum peptide profiling was performed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) after using weak cation exchange magnetic beads (WCX-MB), and the results were evaluated by use of ClinProTools™ Software. To distinguish PTC from cancer-free controls, quick classifier (QC), supervised neural network (SNN), and genetic algorithm (GA) models were established. The models were blindly validated to verify their diagnostic capabilities. The most discriminative peaks were subsequently identified with a nano-liquid chromatography-electrospray ionization-tandem mass spectrometry system. RESULTS Six peptide ions were identified as the most discriminative peaks between the PTC and cancer-free control samples. The QC model exhibited satisfactory sensitivity and specificity among the 3 models that were validated. Two peaks, at m/z 2671.17 and m/z 1464.68, were identified as fragments of the alpha chain of fibrinogen, while a peak at m/z 1738.92 was a fragment of complement component 4A/B. CONCLUSIONS MS combined with ClinProTools™ software was able to detect peptide biomarkers in PTC patients. In addition, the constructed classification models provided a serum peptidome pattern for distinguishing PTC from cancer-free controls. Both fibrinogen a and complement C4A/B were identified as potential markers for diagnosis of PTC.
Full Text Available Background. Survivin is an inhibitor of apoptosis protein involved in the regulation of cell proliferation that could be used as a marker for cancer diagnosis or prognosis. Our aim was to evaluate whether serum survivin levels influence the outcome of cisplatin-based chemotherapy in patients with malignant mesothelioma (MM. Methods. Serum survivin levels were determined using human survivin enzyme-linked immunosorbent assay in 78 MM patients before chemotherapy, after chemotherapy, and at disease progression. The influence on tumor response and survival was evaluated using nonparametric tests and Cox regression. Results. A median serum survivin level at diagnosis was 4.1 (0–217.5 pg/mL. Patients with a progressive disease had significantly higher survivin levels before chemotherapy (p = 0.041. A median serum survivin level after chemotherapy was 73.1 (0–346.2 pg/mL. If survivin levels increased after chemotherapy, patients had, conversely, better response (p = 0.001, OR = 5.40, 95% CI = 1.98–14.72. Unexpectedly, patients with increased survivin levels after chemotherapy also had longer progression-free (p < 0.001, HR = 0.33, 95% CI = 0.20–0.57 and overall survival (p = 0.001, HR = 0.29, 95% CI = 0.14–0.58. Conclusions. These results suggest that serum survivin levels before and during chemotherapy could serve as a biomarker predicting MM treatment response.
Gangemi, Sebastiano; Ricciardi, Luisa; Minciullo, Paola Lucia; Cristani, Mariateresa; Saitta, Salvatore; Chirafisi, Joselita; Spatari, Giovanna; Santoro, Giusy; Saija, Antonella
Nickel sensitization can not only induce allergic contact dermatitis (ACD), but also can induce an overlapping disease referred to as "systemic nickel allergy syndrome" (SNAS), characterized by urticaria/angioedema and gastrointestinal symptoms correlated to the ingestion of nickel-containing foods. This study was designed to determine if oxidative stress occurs in patients with nickel allergy. Thirty-one female patients (mean age 31.26 + 13.04 years, range 16-64 years) with confirmed nickel CD underwent oral nickel challenge because of clinically suspected SNAS; serum concentrations of protein carbonyl groups (PCGs) and nitrosylated proteins (NPs; biomarkers of oxidative stress) were measured before and after oral nickel challenge as well as in healthy female controls. Twenty-three of these 31 patients were diagnosed with SNAS because they had a positive reaction to the oral nickel challenge, and 8 patients had no reaction and therefore were classified as patients with contact nickel allergy only. Although both nickel-allergic patients and controls presented similar serum levels of PCGs, NP values in nickel-allergic patients appeared higher than in controls and tended to decrease after the challenge; furthermore, serum levels of NPs in patients affected by SNAS were higher (although not significantly) than in patients with nickel ACD only. The involvement of specific biomarkers of oxidative stress such as NPs and the lack of involvement of other biomarkers such as PCGs may help to better understand the alteration of the redox homeostasis occurring in nickel ACD and particularly in SNAS.
Hao, Yuan; Yu, Yingyan; Wang, Lishun; Yan, Min; Ji, Jun; Qu, Ying; Zhang, Jun; Liu, Bingya; Zhu, Zhenggang
Gastric cancer is one of the most common malignancies in China. So far, there are few reliable serum biomarkers for diagnosis. The available biomarkers of CEA, CA19-9 and CA72-4 are not sufficiently sensitive and specific for gastric cancer. In this study, a high density antibody microarray was used for identifying new biomarkers from serum samples of gastric cancer. Serum samples from colorectal cancer, pancreatic cancer, hepatocellular cancer, and breast cancer were also screened for comparative study. As result, some candidate biomarkers were identified. IPO-38, an up-regulated serum protein in gastric cancer was selected for subsequent validation including serum IPO-38 expression by ELISA and IPO-38 protein expression by immunohistochemistry. The immunoprecipitation by IPO-38 for gastric cancer cell line and MALDI-TOF/TOF mass spectrometer suggested that pull-down of IPO-38 belongs to H2B histone, which was supported by co-localization study of laser scanning confocal microscope. A follow-up study showed that the survival rate of IPO-38 negative group was better than that in IPO-38 positive group. The study first clarified the property of IPO-38 proliferating marker, and proposed that IPO-38 protein is a promising biomarker both for diagnosis and for predicting prognosis of gastric cancer.
Boosalis, M G; Solem, L D; Ahrenholz, D H; McCall, J T; McClain, C J
Information concerning selenium status in thermal injury patients is limited. Therefore, both serum selenium concentration and 24 h urinary excretion of selenium were evaluated throughout the hospital course for 23 patients with partial and full skin thickness thermal burns. Serum selenium levels were depressed throughout the hospital course in the majority of patients, and only two patients' serum selenium levels had reached the normal range by discharge. Urinary selenium losses were essentially within normal range throughout the same period and thus were not responsible for the observed depression in serum selenium levels. A possible antagonistic relationship between selenium and silver is discussed.
Serum urea and creatinine levels were determined in malaria patients infected with P. falciparum. Serum urea levels decreased significantly (P<0.05) in both mild (4.10 ±1.10 mmol/L) and moderate (4.40 ±1.40 mmol/L) parasitaemia when compared to control subjects (5.50 ±1.40 mmol/L). On the other hand, serum ...
Ziganshin, R Kh; Arapidi, G P; Azarkin, I V; Balmasova, I P; Timchenko, O L; Fed'kina, Iu A; Morozova, E A; Piradov, M A; Suponeva, N A; Iushchuk, N D; Govorun, V M
Time-of-flight MALDI mass spectrometry (MALDI-TOF-MS) profiling of blood serum of patients with Guillain-Barré syndrome (GBS, 36 samples), chronic inflammatory demyelinating polyneuropathy (CIDP, 24 samples) and practically healthy donors (HD) (35 samples) was carried out in order to identify potential biomarkers of autoimmune demyelinating polyneuropathies (ADP). To simplify the peptide-protein mixture of serum prior to MALDI-TOF-MS analysis samples were pre-fractionated on magnetic microparticles with a weak cation-exchange (MB-WCX) surface. Comparative analysis of mass spectrometric data using the classification algorithms (genetic and neural network-controlled) revealed a characteristic set of peaks, agreed change area with a high specificity and sensitivity of the differentiated mass spectrometry profiles of the blood serum of patients with DPNP and healthy donors (for GBS values of these characteristics reached 100 and 100, and for CIDP 94.1 and 100% respectively). Comparative analysis of mass spectrometric profiles of serum samples obtained from patients with GBS and CIDP, allowed to build a classification model to differentiate these diseases from each other, with a specificity of 88.9 and a sensitivity of 80%.
Liu, Wentao; Gao, Xiang; Cai, Qu; Li, Jianfang; Zhu, Zhenglun; Li, Chen; Yao, Xuexin; Yang, Qiumeng; Xiang, Ming; Yan, Min; Zhu, Zhenggang
Early diagnosis and early treatment is known to improve prognosis for gastric cancer. Magnetic affinity beads can be used to extract peptides from un-fractionated serum samples. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) can detect the presence and the molecular mass of peptides. MALDI-TOF-MS mass spectra of peptides and proteins were generated after WCX CLINPROT bead fractionation of 62 gastric cancer serum samples. The discovery set consisted of 44 samples while the validation set was 18 serum samples. The spectra were analyzed statistically using flexAnalysisTM and Clin-ProtTM bioinformatic software. The six most significant peaks were selected out by ClinProTool software and utilized to train a Supervised Neural Network to identify gastric cancer sera from control sera. The sensitivity and specificity of the model when tested on the validation set were 100% and 75%, respectively. A set of 6 peptides that can be used to distinguish serum from gastric cancer patients with good sensitivity and specificity were identified, and these peptides may be useful biomarkers to distinguish cancer individuals who may benefit from radiologic or endoscopic examination.
Full Text Available Objective. To explore the correlation between matrix metalloproteinase- (MMP- 3 and histological synovitis in rheumatoid arthritis (RA. Methods. Serum MMP-3 of 62 patients with active RA was detected by ELISA. Serial synovial tissue sections from all RA patients, 13 osteoarthritis, and 10 orthopedic arthropathies patients were stained with hematoxylin and eosin and immunohistochemically for MMP-3, CD3, CD20, CD38, CD68, and CD15. Results. The percentage of lining MMP3+ cells was significantly higher in RA patients especially with high grade synovitis and it was significantly correlated with Krenn’s synovitis score r=0.574, P<0.001 and sublining inflammatory cells. Multivariate stepwise linear regression analysis revealed that the association of the percentage of lining MMP3+ cells with activation of synovial stroma, sublining CD68+ macrophages, and CD15+ neutrophils was stronger than other histological indicators. The percentage of lining MMP3+ cells was significantly correlated with serum MMP-3 in RA r=0.656, P<0.001. Serum MMP-3 was higher in RA patients with high grade synovitis than that of low grade synovitis and significantly correlated with synovitis score and activation of synovial stroma subscore (all P<0.05. Conclusion. Serum MMP-3 may be an alternative noninvasive biomarker of histological synovitis and RA diagnosis.
Ozturk, C F; Karakelleoglu, C; Orbak, Z; Yildiz, L
An inadequate and imbalanced intake of protein and energy results in protein-energy malnutrition (PEM). It is known that bone mineral density and serum magnesium levels are low in malnourished children. However, the roles of serum magnesium and endothelin-1 (ET-1) levels in the pathophysiology of bone mineralization are obscure. Thus, the relationships between serum magnesium and ET-1 levels and the changes in bone mineral density were investigated in this study. There was a total of 32 subjects, 25 of them had PEM and seven were controls. While mean serum ET-1 levels of the children with kwashiorkor and marasmus showed no statistically significant difference, mean serum ET-1 levels of both groups were significantly higher than that of the control group. Serum magnesium levels were lower than normal value in 9 (36%) of 25 malnourished children. Malnourished children included in this study were divided into two subgroups according to their serum magnesium levels. While mean serum ET-1 levels in the group with low magnesium levels were significantly higher than that of the group with normal magnesium levels (p malnutrition. Our study suggested that lower magnesium levels and higher ET-1 levels might be important factors in changes of bone mineral density in malnutrition. We recommend that the malnourished patients, especially with hypomagnesaemia, should be treated with magnesium early.
Rai, Narendra Prakash; Anekar, Jayaprasad; Shivaraja Shankara, Y M; Divakar, Darshan Devang; Al Kheraif, Abdulaziz Abdullah; Ramakrishnaiah, Ravikumar; Sebastian, Roopa; Raj, A C; Al-Hazmi, Ali; Mustafa, Shabil Mohamed
Tumor markers, designated as a broad group of substances produced by malignancies, could be in the form of biochemical substances, immunological substances, cell surface changes and genetic alterations. Cancer, a disorder of cellular behavior is characterized by alteration of serum glycoproteins. L-fucose, a hexose, which is the terminal sugar in most of the plasma glycoproteins, may be useful as a tumor marker for the detection, monitoring and prognostic assessment of malignancies. The aim of the study was to ascertain the role of serum fucose as a biomarker for early detection of oral cancer and to compare serum fucose levels in healthy controls, leukoplakia and oral cancer patients. The study included 60 (100.0%) subjects, who were grouped as 20 (33.3%) control subjects, 20 (33.3%) squamous cell carcinoma patients and 20 (33.3%) leukoplakia patients. Fucose estimation was done using UV-visible spectrophotometry based on the method as adopted by Winzler using cysteine reagent. The results were analyzed statistically using ANOVA with Bonferroni post hoc tests. Results showed a high significance in serum fucose in oral squamous cell carcinoma (OSCC) and leukoplakia subjects compared to normal controls. There was a gradual increase in the values noted from control to leukoplakia and to squamous cell carcinoma. Estimation of serum fucose may be a reliable marker and can be used as an effective diagnostic biomarker in oral squamous cell carcinoma patients.
The use of biomarkers is considered a promising alternative, or complement, to traditional ecotoxicological assays. Toxic effects are often initially manifested at the molecular or biochemical level, biomarkers are therefore used as sensitive indicators of toxic exposure. Ideally, biomarkers would also indicate reduced fitness and possible later effects at the individual or population levels. However, implementing biomarkers in ecotoxicology is challenging and few biomarkers have an establish...
Haque, Z.; Rahman, M.A.
Objective: To compare serum leptin levels of diabetic and non-diabetic female subjects and also assess the relationship of hyperglycemia with serum insulin, C-peptide and leptin levels. Results: Serum leptin levels of obese diabetic and non-diabetic subjects were significantly higher as compared with lean diabetic patients and non-diabetic subjects (P<0.05). Leptin levels were positively correlated with serum insulin and C-peptide levels. Serum leptin increased with increase in body mass index and waist hip ratio was strongly related with insulin resistance in NIDDM. Conclusion: Leptin levels are increased in obesity and may play a role in development of insulin resistance and NIDDM. (author)
Chen, Tingting; He, Ping; Tan, Yong; Xu, Dongying
Preeclampsia presents serious risk of both maternal and fetal morbidity and mortality. Biomarkers for the detection of preeclampsia are critical for risk assessment and targeted intervention. The goal of this study is to screen potential biomarkers for the diagnosis of preeclampsia and to illuminate the pathogenesis of preeclampsia development based on the differential expression network. Two groups of subjects, including healthy pregnant women, subjects with preeclampsia, were recruited for this study. The metabolic profiles of all of the subjects' serum were obtained by liquid chromatography quadruple time-of-flight mass spectrometry. Correlation between metabolites was analyzed by bioinformatics technique. Results showed that the PC(14:0/00), proline betaine and proline were potential sensitive and specific biomarkers for preeclampsia diagnosis and prognosis. Perturbation of corresponding biological pathways, such as iNOS signaling, nitric oxide signaling in the cardiovascular system, mitochondrial dysfunction were responsible for the pathogenesis of preeclampsia. This study indicated that the metabolic profiling had a good clinical significance in the diagnosis of preeclampsia as well as in the study of its pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.
Antunes, Paula; Watterson, Daniel; Parmvi, Mattias; Burger, Robert; Boisen, Anja; Young, Paul; Cooper, Matthew A.; Hansen, Mikkel F.; Ranzoni, Andrea; Donolato, Marco
Dengue is a tropical vector-borne disease without cure or vaccine that progressively spreads into regions with temperate climates. Diagnostic tools amenable to resource-limited settings would be highly valuable for epidemiologic control and containment during outbreaks. Here, we present a novel low-cost automated biosensing platform for detection of dengue fever biomarker NS1 and demonstrate it on NS1 spiked in human serum. Magnetic nanoparticles (MNPs) are coated with high-affinity monoclonal antibodies against NS1 via bio-orthogonal Cu-free ‘click’ chemistry on an anti-fouling surface molecular architecture. The presence of the target antigen NS1 triggers MNP agglutination and the formation of nanoclusters with rapid kinetics enhanced by external magnetic actuation. The amount and size of the nanoclusters correlate with the target concentration and can be quantified using an optomagnetic readout method. The resulting automated dengue fever assay takes just 8 minutes, requires 6 μL of serum sample and shows a limit of detection of 25 ng/mL with an upper detection range of 20000 ng/mL. The technology holds a great potential to be applied to NS1 detection in patient samples. As the assay is implemented on a low-cost microfluidic disc the platform is suited for further expansion to multiplexed detection of a wide panel of biomarkers.
Zhang, Guo-Jun; Chai, Kevin Tshun Chuan; Luo, Henry Zhan Hong; Huang, Joon Min; Tay, Ignatius Guang Kai; Lim, Andy Eu-Jin; Je, Minkyu
Early detection of cardiac biomarkers for diagnosis of heart attack is the key to saving lives. Conventional method of detection like the enzyme-linked immunosorbent assay (ELISA) is time consuming and low in sensitivity. Here, we present a label-free detection system consisting of an array of silicon nanowire sensors and an interface readout application specific integrated circuit (ASIC). This system provides a rapid solution that is highly sensitive and is able to perform direct simultaneous-multiplexed detection of cardiac biomarkers in serum. Nanowire sensor arrays were demonstrated to have the required selectivity and sensitivity to perform multiplexed detection of 100 fg/ml troponin T, creatine kinase MM, and creatine kinase MB in serum. A good correlation between measurements from a probe station and the readout ASIC was obtained. Our detection system is expected to address the existing limitations in cardiac health management that are currently imposed by the conventional testing platform, and opens up possibilities in the development of a miniaturized device for point-of-care diagnostic applications. Copyright © 2012 Elsevier B.V. All rights reserved.
Marcelletti, John F; Evans, Cindy L; Saxena, Manju; Lopez, Adriana E
It is often necessary to adjust for detectable endogenous biomarker levels in spiked validation samples (VS) and in selectivity determinations during bioanalytical method validation for ligand-binding assays (LBA) with a matrix like normal human serum (NHS). Described herein are case studies of biomarker analyses using multiplex LBA which highlight the challenges associated with such adjustments when calculating percent analytical recovery (%AR). The LBA test methods were the Meso Scale Discovery V-PLEX® proinflammatory and cytokine panels with NHS as test matrix. The NHS matrix blank exhibited varied endogenous content of the 20 individual cytokines before spiking, ranging from undetectable to readily quantifiable. Addition and subtraction methods for adjusting endogenous cytokine levels in %AR calculations are both used in the bioanalytical field. The two methods were compared in %AR calculations following spiking and analysis of VS for cytokines having detectable endogenous levels in NHS. Calculations for %AR obtained by subtracting quantifiable endogenous biomarker concentrations from the respective total analytical VS values yielded reproducible and credible conclusions. The addition method, in contrast, yielded %AR conclusions that were frequently unreliable and discordant with values obtained with the subtraction adjustment method. It is shown that subtraction of assay signal attributable to matrix is a feasible alternative when endogenous biomarkers levels are below the limit of quantitation, but above the limit of detection. These analyses confirm that the subtraction method is preferable over that using addition to adjust for detectable endogenous biomarker levels when calculating %AR for biomarker LBA.
The effects of marijuana and cigarette use on serum levels of testosterone, the principal androgen in man has been a matter of serious controversy; and there is a paucity of reports on the subject in Nigeria in West Africa south of Sahara. We therefore investigated the effects of the use of these substances on serum levels of ...
Biggar, R.J.; Johansen, J.S.; Smedby, K.E.
PURPOSE: Serum levels of the inflammatory markers YKL-40 and interleukin 6 (IL-6) are increased in many conditions, including cancers. We examined serum YKL-40 and IL-6 levels in patients with Hodgkin lymphoma, a tumor with strong immunologic reaction to relatively few tumor cells, especially...
This study examined the level of total serum proteins and globulins in HIV infected Nigerians. 64 patients with HIV infection and 10 apparently healthy subjects were recruited from 3 hospitals in Lagos Metropolis. They were examined for the presence of TB and malaria. Serum total protein, albumin and creatinine levels ...
The objective of this study was to compare the serum magnesium levels in normal pregnancy and pregnancy complicated by pre-eclampsia since magnesium has been implicated in the pathogenesis of vascular dysfunction. We measured serum magnesium levels in patients with pre-eclampsia (n=36), patients with normal ...
Objectives: It is hypothesized that soccer players with periodontal disease exhibit raised serum creatine kinase (CK) levels as compared to those without periodontal disease. We assessed the clinical gingival status and serum CK levels among young soccer players. Materials and Methods: Demographic data were ...
There have been several reports on the role of macronutrients in the pathogenesis of high blood pressure (HBP), however, reports on the relationship between micronutrients and trace metals are few, especially in blacks. This study aim to determine the serum levels of trace metals and correlate same with serum levels of ...
Elzanaty, Saad; Rezanezhad, Babak; Borgquist, Rasmus
This study was aimed to determine the association between PSA levels and biomarkers of subclinical systemic inflammation based on data from 119 middle-aged healthy men from the general population. Serum levels of PSA and biomarkers of systemic inflammation (CRP and fibrinogen) were measured. Demographic data were also collected. Subjects were divided into two groups according to PSA levels; PSA and fibrinogen levels (r = 0.20, p = 0.04), and between CRP and fibrinogen levels (r = 0.60, p = 0.01). On the other hand, no significant correlation between PSA and CRP levels was found. Men with PSA values ≥ 2 ng/ml had significantly higher levels of fibrinogen as compared to those with PSA PSA as a dependent variable, serum level of fibrinogen predicted higher PSA-values (odds ratio = 3.30, 95% CI = 1.05-10.20, p = 0.042). The present results indicate that serum fibrinogen is a biomarker of subclinical systemic inflammation associated with PSA elevation among middle-aged healthy men from the general population.
Sanaei Dashti, Anahita; Alizadeh, Shekoofan; Karimi, Abdullah; Khalifeh, Masoomeh; Shoja, Seyed Abdolmajid
Abstract There are many difficulties distinguishing bacterial from viral meningitis that could be reasonably solved using biomarkers. The aim of this study was to evaluate lactate, procalcitonin (PCT), ferritin, serum-CRP (C-reactive protein), and other known biomarkers in differentiating bacterial meningitis from viral meningitis in children. All children aged 28 days to 14 years with suspected meningitis who were admitted to Mofid Children's Hospital, Tehran, between October 2012 and Novemb...
Huang, Yi-Jhih; Huang, Tsai-Wang; Chao, Tsu-Yi; Sun, Yu-Shan; Chen, Shyi-Jou; Chu, Der-Ming; Chen, Wei-Liang; Wu, Li-Wei
Tartrate-resistant phosphatase isoform 5a is expressed in tumor-associated macrophages and is a biomarker of chronic inflammation. Herein, we correlated serum tartrate-resistant phosphatase isoform 5a levels with metabolic syndrome status and made comparisons with traditional markers of inflammation, including c-reactive protein and interleukin-6. One hundred healthy volunteers were randomly selected, and cut-off points for metabolic syndrome related inflammatory biomarkers were determined using receiver operating characteristic curves. Linear and logistic regression models were subsequently used to correlate inflammatory markers with the risk of metabolic syndrome. Twenty-two participants met the criteria for metabolic syndrome, and serum tartrate-resistant phosphatase isoform 5a levels of >5.8 μg/L were associated with metabolic syndrome (c-statistics, 0.730; p = 0.001; 95% confidence interval, 0.618-0.842). In addition, 1 μg/L increases in tartrate-resistant phosphatase isoform 5a levels were indicative of a 1.860 fold increase in the risk of metabolic syndrome (p = 0.012). Elevated serum tartrate-resistant phosphatase isoform 5a levels are associated with the risk of metabolic syndrome, with a cut-off level of 5.8 μg/L.
Sheng, Jonathan; Wang, Yi; Turesky, Robert J; Kluetzman, Kerri; Zhang, Qing-Yu; Ding, Xinxin
Albumin is a commonly used serum protein for studying human exposure to xenobiotic compounds, including therapeutics and environmental pollutants. Often, the reactivity of albumin with xenobiotic compounds is studied ex vivo with human albumin or plasma/serum samples. Some studies have characterized the reactivity of albumin with chemicals in rodent models; however, differences between the orthologous peptide sequences of human and rodent albumins can result in the formation of different types of chemical-protein adducts with different interaction sites or peptide sequences. Our goal is to generate a human albumin transgenic mouse model that can be used to establish human protein biomarkers of exposure to hazardous xenobiotics for human risk assessment via animal studies. We have developed a human albumin transgenic mouse model and characterized the genotype and phenotype of the transgenic mice. The presence of the human albumin gene in the genome of the model mouse was confirmed by genomic PCR analysis, whereas liver-specific expression of the transgenic human albumin mRNA was validated by RT-PCR analysis. Further immunoblot and mass spectrometry analyses indicated that the transgenic human albumin protein is a full-length, mature protein, which is less abundant than the endogenous mouse albumin that coexists in the serum of the transgenic mouse. The transgenic protein was able to form ex vivo adducts with a genotoxic metabolite of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, a procarcinogenic heterocyclic aromatic amine formed in cooked meat. This novel human albumin transgenic mouse model will facilitate the development and validation of albumin-carcinogen adducts as biomarkers of xenobiotic exposure and/or toxicity in humans.
Full Text Available Background: The focus of this study was to compare serum biomarkers: interleukin-6 (IL-6, tumor necrosis factor-alpha (TNF-α, matrix-metalloproteinase-2 (MMP-2 and vascular endothelial growth factor (VEGF in endometriosis stage I-II and stage III-IV. Methods: This is a cross-sectional study. Forty endometriosis patients were diagnosed using laparoscopy procedure. Serum sample was taken before the surgery. The serum biomarkers (IL-6, TNF-α, MMP-2, and VEGF were analyzed with ELISA method at the end of research. Mean of serum biomarkers in endometrosis stage I-II and stage III-IV were compared using unpaired t-test. Variables that show significant mean difference were tested using ROC measurement and the optimal cut-off point was determined. Results: There was no significant difference in mean serum biomarkers level of IL-6, TNF-α, and MMP-2 between endometriosis stage I-II and stage III-IV (1.58 ± 0.78 vs 1.55 ± 0.98 pg/mL, 1.5 ± 0.47 vs 1.49 ± 0.29 pg/mL, and 152.04 ± 27.32 vs 140.98 ± 28.08 ng/mL, respectively. On the other hand, the comparison of VEGF level in endometriosis stage I-II and stage III-IV demonstrated significant difference (289.76 ± 188.13 vs 581.29 ± 512.85 pg/mL (p < 0.05. Mean difference of VEGF had AUC of 74.5%. Optimal cut-off point for VEGF was ≥ 314.75 pg/mL with sensitivity 78.6% and specificity 69.2%. Conclusion: This study showed that serum biomarkers of VEGF level (but not IL-6, TNF-α, and MMP-2 can be used to measure the degree of severity in endometriosis. VEGF level of 314.75 pg/mL represents the cut-off point between lower and higher stage of severity. (Med J Indones. 2013;22:76-82Keywords: Endometriosis, interleukin-6, matrix-metalloproteinase-2, TNF-α, vascular endhothelial growth factor
Full Text Available Tissue damage or pathological alterations are not detectable in the majority of people with whiplash associated disorders (WAD. Widespread hyperalgisa, morphological muscle changes and psychological distress are common features of WAD. However little is known about the presence of inflammation and its association with symptom persistence or the clinical presentation of WAD. This study aimed to prospectively investigate changes in serum inflammatory biomarker levels from the acute (3 months stages of whiplash injury. It also aimed to determine relationships between biomarker levels and hyperalgesia, fatty muscle infiltrates of the cervical extensors identified on MRI and psychological factors. 40 volunteers with acute WAD and 18 healthy controls participated. Participants with WAD were classified at 3 months as recovered/mild disability or having moderate/severe disability using the Neck Disability Index. At baseline both WAD groups showed elevated serum levels of CRP but by 3 months levels remained elevated only in the moderate/severe group. The recovered/mild disability WAD group had higher levels of TNF-α at both time points than both the moderate/severe WAD group and healthy controls. There were no differences found in serum IL-1β. Moderate relationships were found between hyperalgesia and CRP at both time points and between hyperalgesia and IL-1β 3 months post injury. There was a moderate negative correlation between TNF-α and amount of fatty muscle infiltrate and pain intensity at 3 months. Only a weak relationship was found between CRP and pain catastrophising and no relationship between biomarker levels and posttraumatic stress symptoms. The results of the study indicate that inflammatory biomarkers may play a role in outcomes following whiplash injury as well as being associated with hyperalgesia and fatty muscle infiltrate in the cervical extensors.
Darusman, Huda Shalahudin; Sajuthi, D; Kalliokoski, O
In an attempt to explore cynomolgus monkeys as an animal model for Alzheimer's disease, the present study focused on the Alzheimer's biomarkers beta amyloid 1-42 (Aβ42 ) in serum, and total tau (t-tau) and phosphorylated tau (p-tau) levels in cerebrospinal fluid....
Yang, Cheng-Zhe; Ma, Jie; Luo, Qing-Qiong; Neskey, David M; Zhu, Dong-Wang; Liu, Ying; Myers, Jeffrey N; Zhang, Chen-Ping; Zhang, Zhi-Yuan; Zhong, Lai-Ping
Although molecular mechanism of growth differentiation factor 15 (GDF15) in tumorigenesis of oral squamous cell carcinoma (OSCC) is not clear, the diagnostic and prognostic value of serum GDF15 detection has been noticed. However, serum GDF15 levels in patients with oral leukoplakia and GDF15 as a potential predictive biomarker for response to induction chemotherapy in patients with OSCC have not been reported. Pretreatment serum GDF15 concentration was detected using an enzyme-linked immunosorbent assay in 30 healthy persons, 24 patients with oral leukoplakia, and 60 patients with OSCC. Serum GDF15 concentration was significantly higher in patients with oral leukoplakia and OSCC, compared with healthy controls (F = 13.701, df = 2, P oral leukoplakia, but also a prognostic/predictive biomarker associated with decreased survival and diminished response to induction chemotherapy for patients with OSCC. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Kotze, Paulo Gustavo; Martinez, Carlos Augusto Real; Camargo, Michel Gardere; Guadagnini, Dioze; Calixto, Antonio Ramos; Vasques, Ana Carolina Junqueira; Ayrizono, Maria de Lourdes Setsuko; Geloneze, Bruno; Pareja, José Carlos; Saad, Mario José; Coy, Claudio Saddy Rodrigues
Background/Aims Lipopolysaccharide (LPS) is a molecule formed by lipids and polysaccharides and is the major cell wall component of gram-negative bacteria. High LPS levels are known to block CD26 expression by activating Toll-like receptor 4. The aim of this study was to correlate the serum levels of LPS and CD26 in Crohn's disease (CD) patients with serum levels of C-reactive protein (CRP), interleukins, CD activity index, and tumor necrosis factor-α (TNF-α). Methods Serum samples were collected from 27 individuals (10 with active CD, 10 with inactive CD, and 7 controls) and the levels of LPS, CD26, TNF-α, interleukin-1β (IL-1β), IL-6, IL-17, and CRP were determined by enzyme-linked immunosorbent assay. The levels of LPS and CD26 were then tested for correlation with TNF-α, IL-1β, IL-6, IL-17, and CRP. Results Serum levels of LPS were significantly elevated in the active CD group (P=0.003). Levels of IL-1β (P=0.002), IL-6 (P=0.003), and IL-17 (P<0.001) were lower in the CD groups. Serum TNF-α levels were increased in the active CD group. The CRP levels were elevated in the CD groups when compared to controls (P<0.001). The CD26 levels were lower in the CD groups than in the control group (P<0.001). Among the variables analyzed, there was a correlation between LPS and CRP (r=−0.53, P=0.016) in the CD groups. Conclusions Individuals with CD exhibited higher serum levels of LPS varying from a 2- to 6-fold increase depending on disease activity, when compared with healthy controls. CD26 levels were lower in the CD groups. Both LPS and CD26 correlated with disease severity and serve as potential CD biomarkers. PMID:28670232
Daniéla Oliveira Magro
Full Text Available Background/Aims: Lipopolysaccharide (LPS is a molecule formed by lipids and polysaccharides and is the major cell wall component of gram-negative bacteria. High LPS levels are known to block CD26 expression by activating Toll-like receptor 4. The aim of this study was to correlate the serum levels of LPS and CD26 in Crohn's disease (CD patients with serum levels of C-reactive protein (CRP, interleukins, CD activity index, and tumor necrosis factor-α (TNF-α.Methods: Serum samples were collected from 27 individuals (10 with active CD, 10 with inactive CD, and 7 controls and the levels of LPS, CD26, TNF-α, interleukin-1β (IL-1β, IL-6, IL-17, and CRP were determined by enzyme-linked immunosorbent assay. The levels of LPS and CD26 were then tested for correlation with TNF-α, IL-1β, IL-6, IL-17, and CRP.Results: Serum levels of LPS were significantly elevated in the active CD group (P=0.003. Levels of IL-1β (P=0.002, IL-6 (P=0.003, and IL-17 (P<0.001 were lower in the CD groups. Serum TNF-α levels were increased in the active CD group. The CRP levels were elevated in the CD groups when compared to controls (P<0.001. The CD26 levels were lower in the CD groups than in the control group (P<0.001. Among the variables analyzed, there was a correlation between LPS and CRP (r=−0.53, P=0.016 in the CD groups.Conclusions: Individuals with CD exhibited higher serum levels of LPS varying from a 2- to 6-fold increase depending on disease activity, when compared with healthy controls. CD26 levels were lower in the CD groups. Both LPS and CD26 correlated with disease severity and serve as potential CD biomarkers.
Goy, Burhan; Atmaca, Murat; Aslan, Mehmet; Ucler, Rıfkı; Alay, Murat; Seven, Ismet; Demir, Halit; Ozturk, Mustafa
Menopause is a natural step in the process of aging. Postmenopausal women have decreased levels of antioxidants and increased oxidative stress, the latter of which plays an important role in atherogenesis. The aim of the present study was to evaluate the relationship of the body mass index (BMI) with serum catalase activity, malondialdehyde (MDA), and dehydroepiandrosterone sulfate (DHEAS) levels in healthy postmenopausal women and estimate whether the MDA/DHEAS ratio is a possible marker of oxidative stress for determining cardiovascular risk in these women. We investigated serum catalase activity, MDA, and DHEAS levels, parity history, age, and BMI in 96 healthy postmenopausal women aged 50-82 years. The serum MDA levels and catalase activity were measured spectrophotometrically. The serum DHEAS levels were measured using an enzyme-linked immunosorbent assay. The ratio percentage of the serum DHEAS levels to serum MDA levels was designated as a biomarker for oxidative stress. The mean BMI of the patients was 31.72 ± 6.16 kg/m(2) (range = 20.5-47.94). The MDA/DHEAS ratio was significantly decreased in patients with a BMI over 30 compared to that of patients with a BMI between 25 and 30 (P = 0.025). Moreover, BMI was positively correlated with serum DHEAS levels (r = 0.285, P < 0.01) and negatively correlated with the MDA/DHEAS ratio (r = -0.241, P < 0.05) in postmenopausal women. Furthermore, BMI was observed to be a potential predictor of the MDA/DHEAS ratio based on covariance analysis (P = 0.039). Our results indicate that healthy, obese, postmenopausal women have a decreased MDA/DHEAS ratio. Additionally, BMI was observed to be a potential predictor of the MDA/DHEAS ratio.
Full Text Available Osteoprotegerin (OPG wird in der entzündeten Synovialis bei chronischer Polyarthritis von Makrophagen, dendritischen Zellen und B-Zellen produziert. OPG hemmt die Differenzierung von Osteoklasten und ihre Aktivierung durch die Bindung an RANKL (receptor activator of NFkappaBbeta ligand. OPG könnte daher eine wichtige Rolle in der Verhinderung des Auftretens von Erosionen bei chronischer Polyarthritis spielen. In der vorliegenden Studie wurde untersucht, ob die Serumspiegel von Osteoprotegerin mit Entzündungsparametern oder der Gelenksdestruktion bei chronischer Polyarthritiskorrelieren. Patienten und Methoden: In 85 Sera von 68 Patienten mit chronischer Polyarthritis wurden die Serumspiegel von OPG untersucht und mit klinischen Parametern, Laborbefunden und dem Larsen-Score verglichen. Zur OPG-Bestimmung wurde ein Sandwich-ELISA (enzyme-linked-im-munosorbent-assay mit zwei spezifischen OPG-Antikörpern verwendet. Mit dem bindenden Antikörper wurde eine Mikrotiterplatte beladen, der zweite Biotin-konjugierte Antikörper wurde durch Streptavidin-Peroxidase und TMB gemessen. Der Immunoassay mißt sowohl freies als auch an RANKL gebundenes OPG. Zur statistischen Auswertung wurde ein SAS-Programm verwendet, als Tests wurden der Mann-Whitney-Test, die Spearman-Korrelation und die Varianzanalyse (ANOVA angewandt. Ergebnisse: Verglichen mit einer gesunden Kontrollgruppe (Alter 56-76 Jahre lagen die Mittelwerte von Serum-OPG bei chronischer Polyarthritis höher. Wenn man den Mittelwert der Gesunden für die Einteilung in höhere oder niedrigere Serum-OPG-Werte bei Patienten mit chronischer Polyarthritis verwendet, zeigt sich im Mann-Whitney-Test eine signifikante Korrelation nicht nur mit BSG und Rheumafaktor, sondern auch mit dem Larsen-Score. Die OPG-Spiegel korrelierten mit dem Rheumafaktor, der BSG und dem Serum-CRP (C-reaktives Protein signifikant positiv, der Larsen-Score zeigte nur einen statistischen Trend. Diskussion: OPG blockiert die
Majid Rostami Mogaddam
Full Text Available Introduction : Vitiligo is an acquired, idiopathic disorder characterized by circumscribed depigmented macules and patches, which affects approximately 0.1–2% of the general population worldwide. Zinc is an essential trace element that is necessary for growth and development at all stages of life. Some studies have reported an association between serum zinc levels and vitiligo. Aim : To measure the serum zinc level in patients with vitiligo compared to healthy subjects. Material and methods : One hundred patients with vitiligo and 100 healthy controls were referred to our clinic. The two groups were matched for age and sex. Atomic absorption spectrophotometry was used to measure serum zinc levels. The statistical analysis was performed using SPSS software. Results : The mean serum level of zinc in vitiligo patients and controls was 80.11 ±17.10 µg/dl and 96.10 ±16.16 µg/dl, respectively. The serum zinc level in patients with vitiligo was significantly lower than in healthy controls (p = 0.0001. Conclusions : The results of our study revealed a significant association between vitiligo and serum zinc levels. A relative decrease in the serum zinc level in vitiligo patients can highlight the role of zinc in the pathogenesis of vitiligo, and large-scale studies need to be conducted to confirm these findings and assess the effect of oral zinc supplements in patients with low zinc levels.
Kim, Hyung-Keun; Jang, Eun-Chul; Yeom, Ju-Ok; Kim, Sun-Young; Cho, Hyunjung; Kim, Sung Soo; Chae, Hiun-Suk; Cho, Young-Seok
Background/Aim. Hepcidin, an iron regulatory hormone, is increased in response to inflammation and some infections. We investigated the relationships among serum prohepcidin, iron status, Helicobacter pylori infection status, and the presence of gastric mucosal atrophy. Methods. Seventy subjects undergoing esophagogastroduodenoscopy underwent multiple gastric biopsies, and the possibility of H. pylori infection and the degree of endoscopic and histologic gastritis were investigated. In all subjects, serum prohepcidin and iron parameters were evaluated. Results. No correlations were observed between serum prohepcidin levels and the other markers of anemia, such as hemoglobin, serum iron, ferritin, and total iron binding capacity. Serum prohepcidin levels were not significantly different between the H. pylori-positive group and the H. pylori-negative group. Serum prohepcidin levels in atrophic gastritis patients were significantly lower than those in subjects without atrophic gastritis irrespective of H. pylori infection. Conclusion. Serum prohepcidin levels were not altered by H. pylori infection. Serum prohepcidin levels decrease in patients with atrophic gastritis, irrespective of H. pylori infection. It suggests that hepcidin may decrease due to gastric atrophy, a condition that causes a loss of hepcidin-producing parietal cells. Further investigations with a larger number of patients are necessary to substantiate this point. PMID:23533385
Full Text Available Background/Aim. Hepcidin, an iron regulatory hormone, is increased in response to inflammation and some infections. We investigated the relationships among serum prohepcidin, iron status, Helicobacter pylori infection status, and the presence of gastric mucosal atrophy. Methods. Seventy subjects undergoing esophagogastroduodenoscopy underwent multiple gastric biopsies, and the possibility of H. pylori infection and the degree of endoscopic and histologic gastritis were investigated. In all subjects, serum prohepcidin and iron parameters were evaluated. Results. No correlations were observed between serum prohepcidin levels and the other markers of anemia, such as hemoglobin, serum iron, ferritin, and total iron binding capacity. Serum prohepcidin levels were not significantly different between the H. pylori-positive group and the H. pylori-negative group. Serum prohepcidin levels in atrophic gastritis patients were significantly lower than those in subjects without atrophic gastritis irrespective of H. pylori infection. Conclusion. Serum prohepcidin levels were not altered by H. pylori infection. Serum prohepcidin levels decrease in patients with atrophic gastritis, irrespective of H. pylori infection. It suggests that hepcidin may decrease due to gastric atrophy, a condition that causes a loss of hepcidin-producing parietal cells. Further investigations with a larger number of patients are necessary to substantiate this point.
Full Text Available Yuelong Jin,* Lianping He,* Quanhai Wang, Yan Chen, Xiaohua Ren, Hui Tang, Xiuli Song, Lingling Ding, Qin Qi, Zhiwei Huang, Jiegen Yu, Yingshui Yao Department of Preventive Medicine, Wannan Medical College, Wuhu, People's Republic of China *These authors contributed equally to this work Background: Numerous studies have reported that low calcium intake is related to a higher prevalence of cardiovascular disease. However, the relationship between serum calcium and coronary heart disease is unclear. The purpose of this study was to compare serum calcium levels in patients with coronary heart disease and those in healthy individuals. Methods: This retrospective, case-control study conducted in the People's Republic of China comprised 380 cases and 379 controls. Serum calcium levels, blood lipids, and anthropometric measurements were measured in both groups. The Student's unpaired t-test or Chi-square test was used to compare differences between cases and controls. Pearson's partial correlation coefficient was used to determine the association between serum calcium, blood lipids, and blood pressure in both groups. Results: Our results indicate that the average level of serum calcium in cases was higher than in controls. Serum calcium levels showed no correlation with any parameter except for triglycerides in either group. Conclusion: Overall, these data suggest that serum calcium has no influence on coronary heart disease or triglyceride levels in the general population. Keywords: serum calcium, hypertension, blood lipids
Larsen, J T; Kumar, S K; Dispenzieri, A; Kyle, R A; Katzmann, J A; Rajkumar, S V
A markedly elevated serum free light chain (FLC) ratio may serve as a biomarker for malignant transformation in high-risk smoldering multiple myeloma (SMM) and identify patients who are at imminent risk of progression. We retrospectively studied the predictive value of the serum (FLC) assay in 586 patients with SMM diagnosed between 1970 to 2010. A serum involved/uninvolved FLC ratio ≥ 100 was used to define high-risk SMM, which included 15% (n=90) of the total cohort. Receiver operating characteristics analysis determined the optimal FLC ratio cut-point to predict progression to symptomatic multiple myeloma (MM) within 2 years of diagnosis, which resulted in a specificity of 97% and sensitivity of 16%. Fifty-six percent of patients developed progressive disease during median follow-up of 52 months, but this increased to 98% in the subgroup of patients with FLC ratio ≥ 100. The median time to progression in the FLC ratio ≥ 100 group was 15 months versus 55 months in the FLC <100 group (P<0.0001). The risk of progression to MM within the first 2 years in patients with an FLC ratio ≥ 100 was 72%; the risk of progression to MM or light chain amyloidosis in 2 years was 79%. We conclude that a high FLC ratio ≥ 100 is a predictor of imminent progression in SMM, and such patients may be considered candidates for early treatment intervention.
Massarrat, Sadegh; Haj-Sheykholeslami, Arghavan
Serum pepsinogen I and II are considered as indicators of changes in gastric morphology. Important publications from the last decades are reviewed with regard to the serum level of these biomarkers for the diagnosis of normal gastric mucosa, diffuse gastritis and its change to atrophic gastritis and intestinal metaplasia as well as gastric cancer. Due to the low sensitivity of serum biomarkers for diagnosis of gastric cancer, especially at its early stage and the poor prognosis of the tumor at the time of diagnosis, its prevention by eradication of H. pylori remains the mandatory strategy. On the other hand, the severity of regression and non-reversibility of precancerous lesions and intestinal metaplasia in gastric mucosa through eradication of H. pylori make it necessary to diagnose diffuse gastritis at its early stage. Increased serum pepsinogen II compared to normal serum pepsinogen I seems to indicate the presence of diffuse gastritis without precancerous lesions suitable for eradication of H. pylori infection, when it is serologically positive. A diagram illustrates the strategy of this therapeutic measure depending on the age of people and the level of serum biomarkers in areas with high gastric cancer prevalence.
Full Text Available Hepcidin is the key mediator of renal anemia, and reliable measurement of serum hepcidin levels has been made possible by the ProteinChip system. We therefore investigated the iron status and serum hepcidin levels of peritoneal dialysis (PD patients who had not received frequent doses of an erythrocytosis-stimulating agent (ESA and had not received iron therapy. In addition to the usual iron parameters, the iron status of erythrocytes can be determined by measuring reticulocyte hemoglobin (RET-He. The mean serum hepcidin level of the PD patients (n=52 was 80.7 ng/mL. Their serum hepcidin levels were significantly positively correlated with their serum ferritin levels and transferrin saturation (TSAT levels, but no correlations were found between their serum hepcidin levels and RET-He levels, thereby suggesting that hepcidin has no effect on the iron dynamics of reticulocytes. Since low serum levels of CRP and IL-6, biomarkers of inflammation, were not correlated with the serum hepcidin levels, there is likely to be a threshold for induction of hepcidin expression by inflammation.
Watson, Chris J
BACKGROUND: Heart failure (HF) prevention strategies require biomarkers that identify disease manifestation. Increases in B-type natriuretic peptide (BNP) correlate with increased risk of cardiovascular events and HF development. We hypothesize that coronary sinus serum from a high BNP hypertensive population reflects an active pathological process and can be used for biomarker exploration. Our aim was to discover differentially expressed disease-associated proteins that identify patients with ventricular dysfunction and HF. METHODS AND RESULTS: Coronary sinus serum from 11 asymptomatic, hypertensive patients underwent quantitative differential protein expression analysis by 2-dimensional difference gel electrophoresis. Proteins were identified using mass spectrometry and then studied by enzyme-linked immunosorbent assay in sera from 40 asymptomatic, hypertensive patients and 105 patients across the spectrum of ventricular dysfunction (32 asymptomatic left ventricular diastolic dysfunction, 26 diastolic HF, and 47 systolic HF patients). Leucine-rich alpha2-glycoprotein (LRG) was consistently overexpressed in high BNP serum. LRG levels correlate significantly with BNP in hypertensive, asymptomatic left ventricular diastolic dysfunction, diastolic HF, and systolic HF patient groups (P<\\/=0.05). LRG levels were able to identify HF independent of BNP. LRG correlates with coronary sinus serum levels of tumor necrosis factor-alpha (P=0.009) and interleukin-6 (P=0.021). LRG is expressed in myocardial tissue and correlates with transforming growth factor-betaR1 (P<0.001) and alpha-smooth muscle actin (P=0.025) expression. CONCLUSIONS: LRG was identified as a serum biomarker that accurately identifies patients with HF. Multivariable modeling confirmed that LRG is a stronger identifier of HF than BNP and this is independent of age, sex, creatinine, ischemia, beta-blocker therapy, and BNP.
Tajiri, T; Matsumoto, H; Gon, Y; Ito, R; Hashimoto, S; Izuhara, K; Suzukawa, M; Ohta, K; Ono, J; Ohta, S; Ito, I; Oguma, T; Inoue, H; Iwata, T; Kanemitsu, Y; Nagasaki, T; Niimi, A; Mishima, M
Omalizumab, a humanized anti-IgE monoclonal antibody, has demonstrated efficacy in patients with severe allergic asthma. However, treatment responses vary widely among individuals. Despite a lack of data, free serum IgE levels following omalizumab treatment have been proposed as a marker of treatment responsiveness. In this prospective, observational study, we assessed the utility of biomarkers of type 2 inflammation in predicting omalizumab treatment responses, as determined by the absence of asthma exacerbation during the first year of treatment. Free serum IgE levels were monitored for 2 years to examine their association with baseline biomarker levels and the number of exacerbations. We enrolled thirty patients who had been treated with omalizumab for at least 1 year, of whom 27 were treated for 2 years. Baseline serum periostin levels and blood eosinophil counts were significantly higher in patients without exacerbations during the first year of treatment than in patients with exacerbations. Baseline serum periostin levels, but not eosinophil counts, were negatively associated with free serum IgE levels after 16 or 32 weeks of treatment. Reduced free serum IgE levels during treatment from those at baseline were associated with reduced exacerbation numbers at 2 years. In 14 patients who continued to have exacerbations during the first year of treatment, exacerbation numbers gradually and significantly decreased over the 2-year study period, with concurrent significant reductions in free serum IgE levels. Baseline serum periostin levels and serum free IgE levels during treatment follow-up may be useful in evaluating responses to omalizumab treatment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
renal disease. This study determined the serum uric acid levels of Nigerians with essential hypertension and also evaluated .... Table 1: Blood Pressure, Serum Uric Acid, Lipid profile in patients with essential hypertension and control subjects. (Mean+ SEM) .... where rats developed high blood pressure in about 3 to 5 weeks ...
This study was conducted to examine if there is a relationship between serum lipid and vitamin E levels and unexplained infertility and recurrent miscarriages. Eighty-two (82) healthy Nigerian Women volunteers were recruited for this study. The mean serum cholesterol and triglyceride were slightly higher in the women with ...
Background: Alternative methods for stress monitoring and evaluation prove very useful in proper dealing with it. Thus, establishing a link between stress exposure and serum antioxidant vitamins' levels would certainly provide a clue towards stress management. Aim : The study aimed at evaluating the status of serum ...
Background: Low libido is considered to be the most prominent symptomatic reflection of low serum testosterone and it is unclear how frequent an individual who reported to the clinic with low libido indicates low serum testosterone levels. Objective: This study seeks to know how many of the self reported patients with low ...
Perheentupa, A; Mäkinen, J; Laatikainen, T
To investigate whether a population-level decline in serum testosterone exists in Finnish men. In comparison with other European populations, Finnish men have compared well in the studies of reproductive health (i.e. semen quality, incidence of cryptorchidism and testicular cancer); thus, we...... expected no significant cohort-dependent decrease in serum testosterone....
Dr. J. T. Ekanem
chronic disease, like malaria2. Serum ferritin concentrations of less than 12 µg/L are highly predictive of iron deficiency, defined by the absence of iron stores3. Alteration in serum ferritin levels are important not only in the classical diseases of iron acquisition, transport, and haemochromatosis, but also in diseases ...
Andries, Alin; Niemeier, Andreas; Støving, Rene K
Objective. Recent data suggest that fetal antigen (FA1) is linked to disorders of body weight. Thus, we measured FA1 serum levels in two extreme nutritional states of morbid obesity (MO) and anorexia nervosa (AN) and monitored its response to weight changes. Design. FA1 and insulin serum...
Methods: Fifty-nine children aged two years to 16 years with no evidence of overt kidney disease were recruited from the Paediatric Clinics of the Lagos University Teaching Hospital. Serum cystatin C levels were measured using ELISA method while serum creatinine was measured by a rateblanked and compensated Jaffe ...
Full Text Available Tuberculosis (TB remains a significant human health issue. More effective biomarkers for use in tuberculosis prevention, diagnosis, and treatment, including markers that can discriminate between healthy individuals and those with latent infection, are urgently needed. To identify a set of such markers, we used Solexa sequencing to examine microRNA expression in the serum of patients with active disease, healthy individuals with latent TB, and those with or without prior BCG inoculation. We identified 24 microRNAs that are up-regulated (2.85-1285.93 fold and 6 microRNAs that are down-regulated (0.003-0.11 fold (P<0.05 in patients with active TB relative to the three groups of healthy controls. In addition, 75 microRNAs were up-regulated (2.05-2454.58 fold and 11 were down-regulated (0.001-0.42 fold (P<0.05 in latent-TB infected individuals relative to BCG- inoculated individuals. Of interest, 134 microRNAs were differentially-expressed in BCG-inoculated relative to un-inoculated individuals (18 up-regulated 2.9-499.29 fold, 116 down-regulated 0.0002-0.5 fold, providing insights into the effects of BCG inoculation at the microRNA level. Target prediction of differentially-expressed microRNAs by microRNA-Gene Network analysis and analysis of pathways affected suggest that regulation of the host immune system by microRNAs is likely to be one of the main factors in the pathogenesis of tuberculosis. qRT-PCR validation indicated that hsa-miR-196b and hsa-miR-376c have potential as markers for active TB disease. The microRNA differential-expression profiles generated in this study provide a good foundation for the development of markers for TB diagnosis, and for investigations on the role of microRNAs in BCG-inoculated and latent-infected individuals.
Kulkarni, Shilpa [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Koller, Antonius [Proteomics Center, Stony Brook University School of Medicine, Stony Brook, New York (United States); Proteomics Shared Resource, Herbert Irving Comprehensive Cancer Center, New York, New York (United States); Mani, Kartik M. [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Wen, Ruofeng [Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York (United States); Alfieri, Alan; Saha, Subhrajit [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Wang, Jian [Center for Computational Mass Spectrometry, University of California, San Diego, California (United States); Department of Computer Science and Engineering, University of California, San Diego, California (United States); Patel, Purvi [Proteomics Shared Resource, Herbert Irving Comprehensive Cancer Center, New York, New York (United States); Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York (United States); Bandeira, Nuno [Center for Computational Mass Spectrometry, University of California, San Diego, California (United States); Department of Computer Science and Engineering, University of California, San Diego, California (United States); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, California (United States); Guha, Chandan, E-mail: firstname.lastname@example.org [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); and others
Purpose: Early and accurate assessment of radiation injury by radiation-responsive biomarkers is critical for triage and early intervention. Biofluids such as urine and serum are convenient for such analysis. Recent research has also suggested that exosomes are a reliable source of biomarkers in disease progression. In the present study, we analyzed total urine proteome and exosomes isolated from urine or serum for potential biomarkers of acute and persistent radiation injury in mice exposed to lethal whole body irradiation (WBI). Methods and Materials: For feasibility studies, the mice were irradiated at 10.4 Gy WBI, and urine and serum samples were collected 24 and 72 hours after irradiation. Exosomes were isolated and analyzed using liquid chromatography mass spectrometry/mass spectrometry-based workflow for radiation exposure signatures. A data dependent acquisition and SWATH-MS combined workflow approach was used to identify significantly exosome biomarkers indicative of acute or persistent radiation-induced responses. For the validation studies, mice were exposed to 3, 6, 8, or 10 Gy WBI, and samples were analyzed for comparison. Results: A comparison between total urine proteomics and urine exosome proteomics demonstrated that exosome proteomic analysis was superior in identifying radiation signatures. Feasibility studies identified 23 biomarkers from urine and 24 biomarkers from serum exosomes after WBI. Urinary exosome signatures identified different physiological parameters than the ones obtained in serum exosomes. Exosome signatures from urine indicated injury to the liver, gastrointestinal, and genitourinary tracts. In contrast, serum showed vascular injuries and acute inflammation in response to radiation. Selected urinary exosomal biomarkers also showed changes at lower radiation doses in validation studies. Conclusions: Exosome proteomics revealed radiation- and time-dependent protein signatures after WBI. A total of 47 differentially secreted
Kulkarni, Shilpa; Koller, Antonius; Mani, Kartik M.; Wen, Ruofeng; Alfieri, Alan; Saha, Subhrajit; Wang, Jian; Patel, Purvi; Bandeira, Nuno; Guha, Chandan
Purpose: Early and accurate assessment of radiation injury by radiation-responsive biomarkers is critical for triage and early intervention. Biofluids such as urine and serum are convenient for such analysis. Recent research has also suggested that exosomes are a reliable source of biomarkers in disease progression. In the present study, we analyzed total urine proteome and exosomes isolated from urine or serum for potential biomarkers of acute and persistent radiation injury in mice exposed to lethal whole body irradiation (WBI). Methods and Materials: For feasibility studies, the mice were irradiated at 10.4 Gy WBI, and urine and serum samples were collected 24 and 72 hours after irradiation. Exosomes were isolated and analyzed using liquid chromatography mass spectrometry/mass spectrometry-based workflow for radiation exposure signatures. A data dependent acquisition and SWATH-MS combined workflow approach was used to identify significantly exosome biomarkers indicative of acute or persistent radiation-induced responses. For the validation studies, mice were exposed to 3, 6, 8, or 10 Gy WBI, and samples were analyzed for comparison. Results: A comparison between total urine proteomics and urine exosome proteomics demonstrated that exosome proteomic analysis was superior in identifying radiation signatures. Feasibility studies identified 23 biomarkers from urine and 24 biomarkers from serum exosomes after WBI. Urinary exosome signatures identified different physiological parameters than the ones obtained in serum exosomes. Exosome signatures from urine indicated injury to the liver, gastrointestinal, and genitourinary tracts. In contrast, serum showed vascular injuries and acute inflammation in response to radiation. Selected urinary exosomal biomarkers also showed changes at lower radiation doses in validation studies. Conclusions: Exosome proteomics revealed radiation- and time-dependent protein signatures after WBI. A total of 47 differentially secreted
Tian, Chun-Fang; Lv, Fa-Hui; Wang, Min; Gu, Xiao-Shan
Chorioamnionitis is common in females with prematurely ruptured fetal membranes (PROM). The current diagnosis of PROM and preterm PROM (PPROM) is based on vaginal fluid analysis. The present study investigated the value of serum β-human chorionic gonadotropin (β-hCG) and interleukin-1 (IL-1) levels in diagnosing chorioamnionitis. In total, 150 term-pregnancy patients were included in the prospective study. A total of 50 females had normal pregnancies (control group) and 100 had PROM. One hour before delivery, 3 ml venous blood was collected and analyzed. Fetal membrane and placental tissue underwent histopathological analyses. Of the 100 term-pregnancy females, 56 had PROM and 44 had PROM combined with chorioamnionitis (PROM + C). The serum β-hCG levels for the control, PROM and PROM + C groups were 7,557.86±2,922.06, 636.96±14,379.10 and 50,310.34±22,874.82 IU/l, respectively. The receiver operating characteristic (ROC) for PROM and PROM + C groups (β-hCG ≥23,900.50 IU/l) had a sensitivity of 77.5% and a specificity of 78.6%. The level of IL-1 in the PROM + C group was higher compared to the control and PROM groups (0.58±0.05, 0.12±0.04 and 0.13±0.03 ng/ml, respectively). In conclusion, ROC for the PROM and PROM + C groups (IL-1 ≥0.38 ng/ml) had a sensitivity of 76.5% and a specificity of 72.6%. Therefore, serum β-hCG and IL-1 are potential biomarkers for diagnosing PROM and PROM + C, respectively.
Biggar, R.J.; Johansen, J.S.; Smedby, K.E.
PURPOSE: Serum levels of the inflammatory markers YKL-40 and interleukin 6 (IL-6) are increased in many conditions, including cancers. We examined serum YKL-40 and IL-6 levels in patients with Hodgkin lymphoma, a tumor with strong immunologic reaction to relatively few tumor cells, especially...... in nodular sclerosis Hodgkin lymphoma. EXPERIMENTAL DESIGN: We analyzed Danish and Swedish patients with incident Hodgkin lymphoma (N=470) and population controls from Denmark (n=245 for YKL-40; n=348 for IL-6). Serum YKL-40 and IL-6 levels were determined by ELISA, and log-transformed data were analyzed...... by linear regression, adjusting for age and sex. RESULTS: Serum levels of YKL-40 and IL-6 increased in Hodgkin lymphoma patients compared with controls (YKL-40, 3.6-fold; IL-6, 8.3-fold; both, PHodgkin lymphoma patients (n=176), levels were correlated...
Ahluwalia, Tarunveer Singh; Allin, Kristine Højgaard; Sandholt, Camilla Helene; Sparsø, Thomas Hempel; Jørgensen, Marit Eika; Rowe, Michael; Christensen, Cramer; Brandslund, Ivan; Lauritzen, Torsten; Linneberg, Allan; Husemoen, Lise Lotte; Jørgensen, Torben; Hansen, Torben; Grarup, Niels; Pedersen, Oluf
Type 2 diabetes (T2D) prevalence is spiraling globally, and knowledge of its pathophysiological signatures is crucial for a better understanding and treatment of the disease. We aimed to discover underlying coding genetic variants influencing fasting serum levels of nine biomarkers associated with T2D: adiponectin, C-reactive protein, ferritin, heat shock 70-kDa protein 1B, IGF binding protein 1 and IGF binding protein 2, IL-18, IL-2 receptor-α, and leptin. A population-based sample of 6215 adult Danes was genotyped for 16 340 coding single-nucleotide polymorphisms and were tested for association with each biomarker. Identified loci were tested for association with T2D through a large-scale meta-analysis involving up to 17 024 T2D cases and up to 64 186 controls. We discovered 11 associations between single-nucleotide polymorphisms and five distinct biomarkers at a study-wide P < 3.4 × 10(-7). Nine associations were novel: IL18: BIRC6, RAD17, MARVELD2; ferritin: F5; IGF binding protein 1: SERPING1, KLKB, GCKR, CELSR2, and heat shock 70-kDa protein 1B: CFH. Three of the identified loci (CELSR2, HNF1A, and GCKR) were significantly associated with T2D, of which the association with the CELSR2 locus has not been shown previously. The identified loci influence processes related to insulin signaling, cell communication, immune function, apoptosis, DNA repair, and oxidative stress, all of which could provide a rationale for novel diabetes therapeutic strategies.
Pulin, A A; Brovko, M Iu; Kustova, T Iu; Kozlovskaia, L V; Fomin, V V; Mukhin, N A
To determine the nature and magnitude of changes in the detectable serum and urinary biomarkers of water-salt metabolism in patients with proteinuric forms of chronic glomerulonephritis (CGN), their importance for assessing the activity and prognosis of the disease. Forty-seven patients with CGN were examined. Group 1 included 10 patients with nephrotic syndrome (NS) and decreased renal function; Group 2 comprised 16 patients with persistent NS and normal renal function; Group 3 consisted of 10 patients with partial remission of NS; Group 4 included 11 patients with active hematuric CGN. A control group consisted of 9 healthy individuals matched for gender and age with the patients with CGN. The serum level of copeptin and the urinary excretion of aquaporine-2 (AQP-2) and kidney injury molecule-1 (KIM-1) were determined by indirect enzyme-linked immunosorbent assay (ELISA). In the NS patients with and without renal dysfunction, the serum copeptin concentration was significantly higher than that in those with partial remission of NS or hematuric CGN and in the controls. In the patients with hematuric CGN, this indicator was virtually different from that in the control group. Urinary AQP-2 excretion was significantly similar in 3 NS groups. In the patients with hematuric CGN, the urinary AQP-2 concentration was higher than that in those with NS, but it was significantly lower than in the control group. The highest urinary excretion of KIM-1 was found in the patients with NS and diminished renal function while its excretion was significantly lower in the patients with NS and stable renal function, as in those with partial remission of NS. The lowest values were seen in the patients with hematuric CGN and in the control group; the differences between these groups were statistically insignificant. Correlation analysis showed that there was an inverse correlation between serum copeptin and urinary AQP-2 levels and between urinary AQP- 2 and KIM-1 levels. Serum copeptin
Vogelzang, Nicolas [Nevada Cancer Inst., Las Vegas, NV (United States); Fink, Louis [Nevada Cancer Inst., Las Vegas, NV (United States)
The discovery of genetic or biochemical markers to discriminate malignant cancers from normal or benign disease states, markers to stage cancer or monitor disease progression and markers that provide an early indication of an individual’s response to chemotherapy have become a major research objectives of the oncology community over the past few years. The goal of the project is to create a patient specimen bank of serum, plasma, urine and tissues from approximately 1500 individuals. The collection of samples from individuals on a longitudinal basis provided proteomic and biochemical data to be correlated with clinical endpoints. This greatly enhanced our ability to identify biomarkers for staging different cancers and to detect patient responsiveness to therapy at an early state in the treatment process.
Patel, Mira C; Shirey, Kari Ann; Boukhvalova, Marina S; Vogel, Stefanie N; Blanco, Jorge C G
modality for influenza virus infection. Recently, host-derived DAMPs, such as oxidized phospholipids and HMGB1, were shown to be generated during influenza virus infection and cause ALI. To establish a clear link between influenza virus infection and HMGB1 as a biomarker, we have systematically analyzed temporal patterns of serum HMGB1 release in cotton rats infected with nonadapted strains of influenza A and B viruses and compared these patterns with a live attenuated influenza vaccine and infection by other respiratory viruses. Towards development of a new therapeutic modality, we show herein that blocking serum HMGB1 levels by Eritoran improves lung pathology in influenza B virus-infected cotton rats. Our study is the first report of systemic HMGB1 as a potential biomarker of severity in respiratory virus infections and confirms that drugs that block virus-induced HMGB1 ameliorate ALI. Copyright © 2018 Patel et al.
Full Text Available Serum proteins are routinely used to diagnose diseases, but are hard to find due to low sensitivity in screening the serum proteome. Public repositories of microarray data, such as the Gene Expression Omnibus (GEO, contain RNA expression profiles for more than 16,000 biological conditions, covering more than 30% of United States mortality. We hypothesized that genes coding for serum- and urine-detectable proteins, and showing differential expression of RNA in disease-damaged tissues would make ideal diagnostic protein biomarkers for those diseases. We showed that predicted protein biomarkers are significantly enriched for known diagnostic protein biomarkers in 22 diseases, with enrichment significantly higher in diseases for which at least three datasets are available. We then used this strategy to search for new biomarkers indicating acute rejection (AR across different types of transplanted solid organs. We integrated three biopsy-based microarray studies of AR from pediatric renal, adult renal and adult cardiac transplantation and identified 45 genes upregulated in all three. From this set, we chose 10 proteins for serum ELISA assays in 39 renal transplant patients, and discovered three that were significantly higher in AR. Interestingly, all three proteins were also significantly higher during AR in the 63 cardiac transplant recipients studied. Our best marker, serum PECAM1, identified renal AR with 89% sensitivity and 75% specificity, and also showed increased expression in AR by immunohistochemistry in renal, hepatic and cardiac transplant biopsies. Our results demonstrate that integrating gene expression microarray measurements from disease samples and even publicly-available data sets can be a powerful, fast, and cost-effective strategy for the discovery of new diagnostic serum protein biomarkers.
Heidegger, Isabel; Höfer, Julia; Luger, Markus; Pichler, Renate; Klocker, Helmut; Horninger, Wolfgang; Steiner, Eberhard; Jochberger, Stefan; Culig, Zoran
Eotaxin-1 (CCL11) is a protein expressed in various tissues influencing immunoregulatory processes by acting as selective eosinophil chemo-attractant. In prostate cancer (PCa), the expression and functional role of CCL11 have not been intensively investigated so far. Therefore, the aim of the present study was to investigate the diagnostic or prognostic potential of Eotaxin-1 in PCa patients. We analyzed serum from 140 patients who have undergone prostate biopsy due to elevated prostate-specific antigen (PSA) levels as well as serum of 20 individuals with PSA levels 112.2 pg/ml) Eotaxin-1 serum levels. Although this study has not established a prognostic role of Eotaxin-1 in PCa patients, this chemokine may serve as a diagnostic marker to distinguish between disease-free prostate and cancer. © 2015 Wiley Periodicals, Inc.
Srinivasan, A; Rusia, U; Anand, N K; Sood, S K
Serum and CSF ferritin were estimated in 35 consecutive patients of acute leukaemia at the time of admission and on induction of remission. Serum ferritin levels were significantly raised in 94 per cent patients of acute leukaemia. The mean (+/- SD) serum ferritin (314.36 +/- 158.4 micrograms/1) was significantly higher when compared with control values (P less than 0.001). Remission induction resulted in significant fall in serum ferritin values to a mean of 149 (+/- 98.7) micrograms/l (P less than 0.05). Serum ferritin is thus of value in assessing the state of remission and is a sensitive indicator of the leukaemic cell mass and the state of activity of the disease. CSF ferritin levels in acute leukaemia were comparable to normal control values. CSF ferritin did not reflect CNS involvement in acute leukaemia and therefore its value as a tumour marker of CNS infiltration is doubtful.
There is a lack of consensus on the pathophysiology of bladder pain syndrome/interstitial cystitis. The chronic pain symptoms of bladder pain syndrome/interstitial cystitis refractory to local treatment could be a result of central nervous system sensitization and persisting abnormalities in the bladder wall, which activate the afferent sensory system. Evidence also shows that bladder pain syndrome/interstitial cystitis is a heterogeneous syndrome and that the two subtypes, the ulcerative (classic) and non-ulcerative types, represent different disease entities. There is a need for non-invasive markers for the differential diagnoses of the subtypes of bladder pain syndrome/interstitial cystitis, and between bladder pain syndrome/interstitial cystitis and bladder sensory disorders, such as hypersensitive bladder syndrome or overactive bladder. Bladder pain syndrome/interstitial cystitis, but not overactive bladder, involves an aberrant differentiation program in the bladder urothelium that leads to altered synthesis of several proteoglycans, cell adhesion and tight junction proteins, and bacterial defense molecules. These findings have led to the rationale for identifying urinary biomarkers to detect bladder pain syndrome/interstitial cystitis in patients with frequency urgency syndrome. Recently, the markers that have been the focus of the most research are antiproliferative factor, epidermal growth factor, heparin-binding epidermal growth factor, glycosaminoglycans and bladder nitric oxide. In addition, inflammatory proteins in the urine and serum play important roles in the pathogenesis of bladder pain syndrome/interstitial cystitis. The urinary proteome is an easily accessible source of biomarkers for differentiation between inflammatory bladder disorders. Analysis of multiple urinary proteins and serum cytokines could provide a diagnostic basis for bladder pain syndrome/interstitial cystitis, and could be a tool for the differential diagnosis of bladder pain
Laske, Christoph; Fallgatter, Andreas J; Stransky, Elke; Hagen, Katja; Berg, Daniela; Maetzler, Walter
Detection and differentiation of neurodegenerative dementias, such as dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), with blood-based biomarkers would facilitate diagnosis and treatment. By use of a commercially available ELISA kit, we measured α-synuclein levels in the serum of 40 DLB patients and controls, and of 80 AD patients. We found significantly reduced α-synuclein serum levels in DLB compared to both AD (p = 0.006) and control subjects (p = 0.001), reaching an area under the curve of >0.70. Although these results do not justify a definition of serum α-synuclein as a potential single biomarker, results may contribute to a multimarker strategy in DLB diagnosis. Copyright © 2011 S. Karger AG, Basel.
Rehan, Ibrahim F; Ueda, Koichiro; Mitani, Tomohiro; Amano, Maho; Hinou, Hiroshi; Ohashi, Tetsu; Kondo, Seiji; Nishimura, Shin-Ichiro
Because various stresses strongly influence the food productivity of livestock, biomarkers to indicate unmeasurable environmental stress in domestic animals are of increasing importance. Thermal comfort is one of the basic principles of dairy cow welfare that enhances productivity. To discover sensitive biomarkers that monitor such environmental stresses in dairy cows, we herein performed, for the first time, large-scale glycomics on 336 lactating Holstein cow serum samples over 9 months between February and October. Glycoblotting combined with MALDI-TOF/MS and DMB/HPLC allowed for comprehensive glycomics of whole serum glycoproteins. The results obtained revealed seasonal alterations in serum N-glycan levels and their structural characteristics, such as an increase in high-mannose type N-glycans in spring, the occurrence of di/triantennary complex type N-glycans terminating with two or three Neu5Gc residues in summer and autumn, and N-glycans in winter dominantly displaying Neu5Ac. A multivariate analysis revealed a correlation between the serum expression levels of these season-specific glycoforms and productivity.
control hospital-based descriptive study carried out at the Institute of Child. Health (ICH) Banzazzau, Zaria. Systematic sampling method was adopted to select undernourished children aged 6-59 months for the study. Serum vitamin A level was.
4. The recommended ... tics and Nutrition Examination Survey (NHANES) used serum zinc level below 10.71mmol/l as a cut .... demanded increased intake in childhood, adolescence and pregnancy. This may explain the low ...
Full Text Available Objective This study measured serum and follicular fluid (FF levels of biopterin, neopterin, vascular endothelial growth factor (VEGF, and macrophage colony-stimulating factor (M-CSF in patients receiving mild ovarian stimulation for oocyte retrieval. Patients and Methods Infertile patients who underwent ovarian stimulation were divided into the following: Group 1, no oocyte retrieval ( n = 12, and Group 2, retrieval of more than four oocytes ( n = 13. Median total gonadotropin dose in both groups was 150 IU. Biopterin and neopterin levels were measured using high-performance liquid chromatography. VEGF and M-CSF levels were measured by enzyme-linked immunosorbent assay. Results Compared to Group 2, serum and FF levels of neopterin and VEGF and serum levels of M-CSF were significantly increased, and serum and FF levels of biopterin were significantly decreased in Group 1 ( P < 0.05 each. Conclusion Biopterin and neopterin levels showed similar differences in FF and serum of patients with empty follicles. Decreased biopterin and increased neopterin in serum could predict poor oocyte retrieval.
Diamandis, EP; Scorilas, A; Fracchioli, S; van Gramberen, M; de Bruijn, H; Henrik, A; Soosaipillai, A; Grass, L; Yousef, GM; Stenman, UH; Massobrio, M; van der Zee, AGJ; Vergote, [No Value; Katsaros, D
Purpose : The discovery of new ovarian cancer biomarkers that are suitable for early disease diagnosis and prognosis may ultimately lead to improved patient management and outcomes. Patients and Methods: We measured, by immunoassay, human kallikrein 6 (hK6) concentration in serum of 97 apparently
Soendergaard, Christoffer; Nielsen, Ole Haagen; Seidelin, Jakob Benedict
-stimulating factor produced a predictive model with an AUC of 0.72 when differentiating mild and moderate UC, and an AUC of 0.96 when differentiating moderate and severe UC, the latter being as reliable as CRP. CONCLUSIONS: Alpha-1 antitrypsin is identified as a potential serum biomarker of mild-to-moderate disease...
Full Text Available Background: Migraine is common worldwide. In recent years, vitamin D deficiency has been determined as a global health problem. A few studies have shown inverse relationship between serum vitamin D levels and headache. Thus, in this study, we assessed relationship between serum vitamin D levels with migraine. Materials and Methods: The present study was a cross-sectional. Seventy-six migraine patients aged 10-61 years were included. The multiple linear regression was used to show association between serum 25-0H-D3 and migraine. Adjustments were performed for age, sex, waist circumference, body mass index (BMI, number of chronic diseases, and education level . Results: The positive weak relationship was observed between serum vitamin D and headache diary result (P = 0.042, r = 0.19. But, no significant relationship was observed between serum vitamin D and migraine severity (P = 0.741. Conclusion: High levels of serum 25-OH-D3 was related to higher headache diary result. After adjustment for confounding variables, this significant association remained. No significant relationship was shown between serum vitamin D and migraine severity.
Andersson, A M; Skakkebaek, N E
Inhibin B is a testicular peptide hormone that regulates FSH secretion in a negative feedback loop. In males serum levels of inhibin B are detectable throughout life with prominent changes in the first year of life and during puberty. Serum inhibin B is normally detectable throughout childhood...... normal or near-normal levels are seen in cryptorchidism and disorders with preserved Sertoli cell function in spite of absence of germ cells or impaired androgen biosynthesis or action. During puberty a developmental change in the regulation of serum inhibin B occurs. In contrast to childhood inhibin B...
Full Text Available Abstract Background Chronic kidney disease (CKD is a newly recognized high-risk condition for cardiovascular disease (CVD, and previous studies reported the changes in inflammation and oxidative stress in advanced stages of CKD. We compared the levels of serum biomarkers for inflammation and oxidative stress between subjects with normal and mildly reduced glomerular filtration rate (GFR. Methods The subjects were 182 participants of a health check-up program including those with normal (≥ 90 mL/min/1.73 m2, N = 79 and mildly reduced eGFR (60-89 mL/min/1.73 m2, N = 103 which was calculated based on serum creatinine, age and sex. We excluded those with reduced eGFR 2. No one had proteinuria. We measured serum levels of C-reactive protein (CRP and thioredoxin (TRX as the markers of inflammation and oxidative stress, respectively. Results As compared with subjects with normal eGFR, those with mildly reduced eGFR had increased levels of both CRP and TRX. Also, eGFR was inversely correlated with these biomarkers. The associations of eGFR with these biomarkers remained significant after adjustment for age and sex. When adjustment was done for eight possible confounders, CRP showed significant association with systolic blood pressure, high density lipoprotein cholesterol (HDL-C and non-HDL-C, whereas TRX was associated with sex significantly, and with eGFR and systolic blood pressure at borderline significance. Conclusions We showed the increased levels of CRP and TRX in subjects with mildly reduced eGFR. The eGFR-CRP link and the eGFR-TRX link appeared to be mediated, at least partly, by the alterations in blood pressure and plasma lipids in these subjects.
Background: The relationship between body iron levels and malaria presents a complex interaction that provide variable and contradicting results. We designed a study to investigate associations between concentrations of biomarkers of body iron and malaria recurrence among children. Methods: We conducted a ...
Full Text Available Lupus nephritis (LN is among the most serious complications of systemic lupus erythematosus (SLE, which causes significant morbidity and mortality. Renalase is a novel, kidney-secreted cytokine-like protein that promotes cell survival. Here, we aimed to investigate the relationship of serum renalase levels with LN and its role in the disease progression of LN.For this cross-sectional study, 67 LN patients and 35 healthy controls were enrolled. Seventeen active LN patients who received standard therapies were followed up for six months. Disease activity was determined by the SLE Disease Activity-2000 (SLEDAI-2K scoring system and serum renalase amounts were determined by ELISA. Predictive value of renalase for disease activity was assessed. Furthermore, the expression of renalase in the kidneys of patients and macrophage infiltration was assessed by immunohistochemistry.Serum renalase amounts were significantly higher in LN patients than in healthy controls. Moreover, patients with proliferative LN had more elevated serum renalase levels than Class V LN patients. In proliferative LN patients, serum renalase levels were significantly higher in patients with active LN than those with inactive LN. Serum renalase levels were positively correlated with SLEDAI-2K, 24-h urine protein excretion, ds-DNA and ESR but inversely correlated with serum albumin and C3. Renalase amounts decreased significantly after six-months of standard therapy. The performance of renalase as a marker for diagnosis of active LN was 0.906 with a cutoff value of 66.67 μg/ml. We also observed that the amount of renalase was significantly higher in glomerular of proliferative LN along with the co-expression of macrophages.Serum renalase levels were correlated with disease activity in LN. Serum renalase might serve as a potential indicator for disease activity in LN. The marked increase of glomerular renalase and its association with macrophages suggest that it might play an
Full Text Available We evaluated the tendency of the plasma concentration and procalcitonin (PCT clearance (PCTc to act as biomarkers of prognosis in patients with severe sepsis and septic shock. From 2011 to 2013, we prospectively analyzed patients with sepsis admitted to the intensive care unit (ICU. The serum PCT was evaluated at the time of sepsis diagnosis and again after 48 h (day 3 and 96 h (day 5. PCTc after 48 h (PCTc-day 3 and 96 h (PCTc-day 5 was also calculated to evaluate the prognostic value for survival in patients with sepsis. A total of 48 patients were included. Overall mortality was 16.7% (8 patients. PCTc was higher in survivors than in nonsurvivors, with significant differences on day 3 and day 5 (p=0.033; p=0.002, resp.; however, serum PCT levels on day 1, day 3, and day 5 were not significant prognostic factors for survival. The prognosis of patients with severe sepsis and septic shock may be associated with PCTc. Dynamic changes of PCT reflected as PCTc at 48 h (day 3 and 96 h (day 5 after admission to the ICU may serve as a predictor of survival in critically ill patients with severe sepsis.
Ibrahim, I.M.; Alkady, M.M.; Saif-Elnasr, M.
High blood pressure is very prevalent worldwide, as well as vitamin D deficiency. There are several observation data that support the concept that vitamin D is involved in the pathogenesis of hypertension. Also some clinical data demonstrate positive effect of vitamin D therapy on hypertension. We studied serum levels of vitamin D and its association with blood pressure in 30 hypertensive patients and 20 age and socioeconomic status matched healthy controls. There was no statistically significant difference in serum vitamin D levels in the group of patients compared with controls. In patients group, patients with body mass index (BMI) > 30 kg/m 2 showed statistically significant decrease in serum vitamin D levels as compared to those with BMI ≤ 30 kg/m 2 (P = 0.021). There was no significant association between serum vitamin D levels and age, systolic and diastolic blood pressure in the group of patients. A negative correlation between serum vitamin D levels and BMI was found in patients group (P = 0.045). In conclusion, no association between serum levels of vitamin D and blood pressure in hypertensive patients, but it is statistically associated with BMI. Further large scale studies are needed putting in consideration the effect of genetic factor
Baran, Anna; Myśliwiec, Hanna; Szterling-Jaworowska, Malgorzata; Kiluk, Paulina; Świderska, Magdalena; Flisiak, Iwona
YKL-40 is an inflammatory glycoprotein associated with atherosclerosis, cardiovascular disease, diabetes or metabolic syndrome which are common comorbidities in psoriasis. The aim of the study was to assess serum YKL-40 level in psoriasis and elucidate possible associations with disease activity, inflammatory or metabolic parameters and treatment. A total of 37 individuals with active plaque-type psoriasis and 15 healthy controls were enrolled. Blood samples were collected before and after 2 weeks of therapy. Serum YKL-40 concentrations were evaluated by enzyme-linked immunosorbent assay (ELISA). The results were correlated with Psoriasis Area and Severity Index (PASI), body mass index (BMI), inflammatory and biochemical markers, lipid profile and topical therapy. Median YKL-40 serum levels were significantly increased in psoriatic patients in comparison to the controls (p psoriasis and inflammation in psoriatic patients, but not a reliable indicator of metabolic conditions, severity of psoriasis nor efficacy of the treatment.
Heikkinen, Anna Maria; Sorsa, Timo; Pitkäniemi, Janne; Tervahartiala, Taina; Kari, Kirsti; Broms, Ulla; Koskenvuo, Markku; Meurman, Jukka H
The effects of smoking on periodontal biomarkers in adolescents are unknown. This study investigates matrix metalloproteinase (MMP)-8 and polymorphonuclear leukocyte elastase levels in saliva together with periodontal health indices accounting for body mass index and smoking in a birth cohort from Finland. The oral health of boys (n = 258) and girls (n = 243) aged 15 to 16 years was examined clinically. Health habits were assessed by questionnaire. Saliva samples were collected and analyzed by immunofluorometric and peptide assays for MMP-8 levels and polymorphonuclear leukocyte elastase activities, and investigated statistically with the background factors. Median MMP-8 values of male smokers were 112.03 microg/l compared to 176.89 microg/l of non-smokers (P = 0.05). For female smokers corresponding values were 170.88 microg/l versus 177.92 microg/l in non-smokers (not statistically significant). Elastase values in male smokers were 5.88 x 10(-3) Delta OD(405)/h versus 11.0 x 10(-3) Delta OD(405)/h in non-smokers (P = 0.02), and in female smokers 9.16 x 10(-3) Delta OD(405)/h versus 10.88 x 10(-3) Delta OD(405)/h in non-smokers (P = 0.72). The effect was strengthened by high pack-years of smoking (MMP-8, P = 0.04; elastase, P = 0.01). Both biomarkers increased with gingival bleeding. However, statistically significant associations were observed with bleeding on probing and MMP-8 (P = 0.04); MMP-8 was suggestively associated with probing depth (P = 0.09) in non-smoking boys. In smokers with calculus, MMP-8 increased after adjusting with body mass index (P = 0.03). No corresponding differences were seen in girls. Smoking significantly decreased both biomarkers studied. Compared to girls, boys seem to have enhanced susceptibility for periodontitis as reflected in salivary MMP-8 values.
Bartels, E M; Henrotin, Y; Bliddal, H
OBJECTIVE: To explore effects of weight loss and maintenance on serum cartilage biomarkers denaturation neoepitope for Collagen2 (Coll2-1) and Fibulin3 fragment (Fib3-2), as well as correlations between Coll2-1 and Fib3-2 and symptomatic improvement, in a knee osteoarthritis (KOA) population....... DESIGN: 192 obese KOA patients followed a 16 week weight loss intervention and 52 weeks weight maintenance (ClinicalTrials.gov identifier: NCT00655941). Assessments were at 0, 8, 16 and 68 weeks. Serum Coll2-1 and Fib3-2 were determined with ELISA, and symptoms by the Knee Osteoarthritis Outcome Score......-points there were significant positive correlations between changes from baseline in Coll2-1 and in KOOSSports/Recreation (week 8, 16, 68: r = 0.17; P = 0.03; r = 0.16; P = 0.04; and r = 0.17; P = 0.04, respectively). CONCLUSION: The clinical improvement after a substantial weight loss and weight maintenance in KOA...
Antunes, Paula Soares Martins; Watterson, Daniel; Parmvi, Mattias
Dengue is a tropical vector-borne disease without cure or vaccine that progressively spreads into regions with temperate climates. Diagnostic tools amenable to resource-limited settings would be highly valuable for epidemiologic control and containment during outbreaks. Here, we present a novel low......-cost automated biosensing platform for detection of dengue fever biomarker NS1 and demonstrate it on NS1 spiked in human serum. Magnetic nanoparticles (MNPs) are coated with high-affinity monoclonal antibodies against NS1 via bio-orthogonal Cu-free 'click' chemistry on an anti-fouling surface molecular...... method. The resulting automated dengue fever assay takes just 8 minutes, requires 6 μL of serum sample and shows a limit of detection of 25 ng/mL with an upper detection range of 20000 ng/mL. The technology holds a great potential to be applied to NS1 detection in patient samples. As the assay...
Moledina, Dennis G; Hall, Isaac E; Thiessen-Philbrook, Heather; Reese, Peter P; Weng, Francis L; Schröppel, Bernd; Doshi, Mona D; Wilson, F Perry; Coca, Steven G; Parikh, Chirag R
The diagnosis of acute kidney injury (AKI), which is currently defined as an increase in serum creatinine (Scr) concentration, provides little information on the condition's actual cause. To improve phenotyping of AKI, many urinary biomarkers of tubular injury are being investigated. Because AKI cases are not frequently biopsied, the diagnostic accuracy of concentrations of Scr and urinary biomarkers for histologic acute tubular injury is unknown. Cross-sectional analysis from multicenter prospective cohort. Hospitalized deceased kidney donors on whom kidney biopsies were performed at the time of organ procurement for histologic evaluation. (1) AKI diagnosed by change in Scr concentration during donor hospitalization and (2) concentrations of urinary biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], liver-type fatty acid-binding protein [L-FABP], interleukin 18 [IL-18], and kidney injury molecule 1 [KIM-1]) measured at organ procurement. Histologic acute tubular injury. Of 581 donors, 98 (17%) had mild acute tubular injury and 57 (10%) had severe acute tubular injury. Overall, Scr-based AKI had poor diagnostic performance for identifying histologic acute tubular injury and 49% of donors with severe acute tubular injury did not have AKI. The area under the receiver operating characteristic curve (AUROC) of change in Scr concentration for diagnosing severe acute tubular injury was 0.58 (95% CI, 0.49-0.67) and for any acute tubular injury was 0.52 (95% CI, 0.45-0.58). Compared with Scr concentration, NGAL concentration demonstrated higher AUROC for diagnosing both severe acute tubular injury (0.67; 95% CI, 0.60-0.74; P=0.03) and any acute tubular injury (0.60; 95% CI, 0.55-0.66; P=0.005). In donors who did not have Scr-based AKI, NGAL concentrations were higher with increasing severities of acute tubular injury (subclinical AKI). However, compared with Scr concentration, AUROCs for acute tubular injury diagnosis were not significantly higher for urinary L
Arpaci, Dilek; Karakas Celik, Sevim; Can, Murat; Ermiş, Esra; Kuzu, Fatih; Kokturk, Furuzan; Hamamcioglu, Ayse Ceylan; Dursun, Ahmet; Bayraktaroglu, Taner
Acromegalic patients have increased cardiometabolic risk factors due to an elevation of growth hormone (GH) levels. Human serum paraoxonase (PON), a high-density lipoprotein (HDL)-related enzyme, is one of the major bioscavengers and decreases the oxidation of low-density lipoprotein (LDL), a key regulator in the pathogenesis of atherosclerosis. In this study, we investigated a potential relationship between serum PON levels or PON polymorphisms and acromegaly. A total of 48 acromegalic patients and 44 healthy controls were included in this study. Serum GH levels, insulin-like growth factor-1 levels and lipid profiles were measured. Serum PON levels, as well as PON 1 L55M and Q192R gene polymorphisms, were examined. No significant differences were found in terms of age, gender, presence of diabetes, serum LDL cholesterol (LDL-C), HDL-C, or triglyceride levels between the case and control groups (P > 0.05). A statistically significant difference was found in serum PON levels between the cases and controls (P = 0.007). The median serum PON level was 101 ± 63.36 U/l in the case group and 63 ± 60.50 U/l in the control group. There was a significant correlation between serum PON levels and IGF-1 levels (P = 0.004, r = 0.319); however, no significant differences were found in PON1 L55M and PON Q192R polymorphisms between the patients and controls (P = 0.607 and P = 0.308, respectively). In addition, no significant differences were found in serum PON levels in acromegalic patients who were and were not in remission (P = 0.385), nor between those with PON1 L55M and Q192R polymorphisms (P = 0.161 and P = 0.336, respectively). Elevated serum PON levels were detected in acromegalic patients, independently of their remission status. This suggests protective effects for cardiometabolic risk parameters.
Maria P. H. Koster
Full Text Available Objective. To expand the search for preeclampsia (PE metabolomics biomarkers through the analysis of acylcarnitines in first-trimester maternal serum. Methods. This was a nested case-control study using serum from pregnant women, drawn between 8 and 14 weeks of gestational age. Metabolites were measured using an UPLC-MS/MS based method. Concentrations were compared between controls (n=500 and early-onset- (EO- PE (n=68 or late-onset- (LO- PE (n=99 women. Metabolites with a false discovery rate <10% for both EO-PE and LO-PE were selected and added to prediction models based on maternal characteristics (MC, mean arterial pressure (MAP, and previously established biomarkers (PAPPA, PLGF, and taurine. Results. Twelve metabolites were significantly different between EO-PE women and controls, with effect levels between −18% and 29%. For LO-PE, 11 metabolites were significantly different with effect sizes between −8% and 24%. Nine metabolites were significantly different for both comparisons. The best prediction model for EO-PE consisted of MC, MAP, PAPPA, PLGF, taurine, and stearoylcarnitine (AUC = 0.784. The best prediction model for LO-PE consisted of MC, MAP, PAPPA, PLGF, and stearoylcarnitine (AUC = 0.700. Conclusion. This study identified stearoylcarnitine as a novel metabolomics biomarker for EO-PE and LO-PE. Nevertheless, metabolomics-based assays for predicting PE are not yet suitable for clinical implementation.
David R Boulware
Full Text Available Although antiretroviral therapy (ART improves survival in persons with cryptococcal meningitis (CM and AIDS, ART frequently elicits HIV immune reconstitution inflammatory syndrome (IRIS, an exaggerated and frequently deadly inflammatory reaction that complicates recovery from immunodeficiency. The pathogenesis of IRIS is poorly understood and prediction of IRIS is not possible.We prospectively followed 101 ART-naïve Ugandans with AIDS and recent CM for one year after initiating ART, and used Luminex multiplex assays to compare serum cytokine levels in participants who did or did not develop IRIS. IRIS occurred in 45% of participants with recent CM on ART, including 30% with central nervous system (CNS manifestations. The median time to CM-IRIS was 8.8 wk on ART. Overall mortality on ART was 36% with IRIS and 21% without IRIS. CM-IRIS was independently associated with death (HR = 2.3, 95% CI 1.1-5.1, p = 0.04. Patients experiencing subsequent CM-IRIS had 4-fold higher median serum cryptococcal antigen (CRAG levels pre-ART (p = 0.006. Higher pre-ART levels of interleukin (IL-4 and IL-17 as well as lower tumor necrosis factor (TNF-α, granulocyte colony-stimulating factor (G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF, and vascular endothelial growth factor (VEGF predicted future IRIS in multivariate analyses (area under the curve [AUC] = 0.82. An algorithm based on seven pre-ART serum biomarkers was a robust tool for stratifying high (83%, moderate (48%, and low risk (23% for IRIS in the cohort. After ART was initiated, increasing levels of C-reactive protein (CRP, D-dimer, IL-6, IL-7, IL-13, G-CSF, or IL-1RA were associated with increasing hazard of IRIS by time-to-event analysis (each p≤0.001. At the time of IRIS onset, multiple proinflammatory cytokine responses were present, including CRP and IL-6. Mortality was predicted by pre-ART increasing IL-17, decreasing GM-CSF, and CRP level >32 mg/l (highest quartile. Pre-ART CRP
Mirzaii-Dizgah, Iraj; Riahi, Esmail
Coronary artery disease (CAD) is the major cause of death nearly all over the world, and accurate and rapid diagnosis of CAD is of major medical and economic importance. The aim of this study was to evaluate the serum and saliva levels of cathepsin L in patients with acute coronary syndrome (ACS). In a cross-sectional study, 39 patients with ACS and 28 with controls were recruited to the study, and cathepsin L levels were measured in serum, resting saliva, and stimulated saliva obtained 12 and 24 h after the onset of ACS by ELISA method. Statistical analyses of Fisher's exact test, the Student's t-test or Kruskal-Wallis test were performed. Stimulated saliva cathepsin L levels in patients with ACS 12 hours but not 24 hours after admission showed significant decrease compared with that in control subjects. However, there were no significant differences in serum and unstimulated saliva cathepsin L levels between groups. Serum and saliva levels of cathepsin L remain unchanged in patients with ACS and hence may not be a promising factor in CAD risk assessment. It seems that serum and saliva cathepsin L may not be a good biomarker for CHD. CAD: Coronary artery disease, ACS: Acute coronary syndrome, CHD: Coronary heart disease, EU: Emergency unit, MI: Myocardial infarction. Cathepsin L, Acute coronary syndrome, Resting saliva, Stimulated saliva. How to cite this article: Mirzaii-Dizgah I, Riahi E. Serum and Saliva Levels of Cathepsin L in Patients with Acute Coronary Syndrome. J Contemp Dent Pract 2011;12(2):114-119.
Full Text Available Depression is a serious and potentially life-threatening mental disorder with unknown etiology. Emerging evidence shows that brain-derived neurotrophic factor (BDNF and microRNAs (miRNAs play critical roles in the etiology of depression. Here this study was aimed to identify and characterize the roles of BDNF and its putative regulatory miRNAs in depression. First, we identified that miR-182 may be a putative miRNA that regulates BDNF levels by bioinformatic studies, and characterized the effects of miR-182 on the BDNF levels using cell-based studies, side by side with miR-132 (a known miRNA that regulates BDNF expression. We showed that treatment of miR-132 and miR-182 respectively decreased the BDNF protein levels in a human neuronal cell model, supporting the regulatory roles of miR-132 and miR-182 on the BDNF expression. Furthermore, we explored the roles of miR-132 and miR-182 on the BDNF levels in depression using human subjects by assessing their serum levels. Compared with the healthy controls, patients with depression showed lower serum BDNF levels (via the enzyme-linked immunosorbent assays and higher serum miR-132 and miR-182 levels (via the real-time PCR. Finally, the Pearson's (or Spearman's correlation coefficient was calculated to study whether there was a relationship among the Self-Rating Depression Scale score, the serum BDNF levels, and serum BDNF-related miRNA levels. Our results revealed that there was a significant negative correlation between the SDS scores and the serum BDNF levels, and a positive correlation between the SDS scores and miR-132 levels. In addition, we found a reverse relationship between the serum BDNF levels and the miR-132/miR-182 levels in depression. Collectively, we provided evidence supporting that miR-182 is a putative BDNF-regulatory miRNA, and suggested that the serum BDNF and its related miRNAs may be utilized as important biomarkers in the diagnosis or as therapeutic targets of depression.
Redman, R S; Kerr, G S; Payne, J B; Mikuls, T R; Huang, J; Sayles, H R; Becker, K L; Nylén, E S
Serum procalcitonin (ProCT) is elevated in response to bacterial infections, whereas high sensitivity C-reactive protein (hsCRP) is a nonspecific inflammatory marker that is increased by excess adipose tissue. We examined the efficacy of ProCT and hsCRP as biomarkers of periodontitis in the saliva and serum of patients with arthritis, which is characterized by variable levels of systemic inflammation that potentially can confound the interpretation of inflammatory biomarkers. Blood and unstimulated whole saliva were collected from 33 patients with rheumatoid arthritis (RA) and 50 with osteoarthritis (OA). Periodontal status was assessed by full mouth examination and patients were categorized as having no/mild, moderate or severe periodontitis by standard parameters. Salivary and serum ProCT and hsCRP concentrations were compared. BMI, diabetes, anti-inflammatory medications and smoking status were ascertained from the patient records. Differences between OA and RA in proportionate numbers of patients were compared for race, gender, diabetes, adiposity and smoking status. Serum ProCT was significantly higher in arthritis patients with moderate to severe and severe periodontitis compared with no/mild periodontitis patients. There were no significant differences in salivary ProCT or salivary or serum hsCRP in RA patients related to periodontitis category. Most of the OA and RA patients were middle aged or older, 28.9% were diabetic, 78.3% were overweight or obese, and slightly more than half were either current or past smokers. The OA and RA groups differed by race, but not gender; blacks and males were predominant in both groups. The OA and RA groups did not differ in terms of controlled or uncontrolled diabetes, smoking status or BMI. The RA patients had been prescribed more anti-inflammatory medication than the OA patients. Our results demonstrate that circulating ProCT is a more discriminative biomarker for periodontitis than serum hsCRP in patients with
Skrinjar, Ivana; Brailo, Vlaho; Vidovic-Juras, Danica; Vucicevic-Boras, Vanja; Milenovic, Aleksandar
Oral squamous cell carcinoma (OSCC) constitutes 3 percent of all cancers with predominant occurrence in middle aged and elderly males. Tumour recurrence worsens disease prognosis and decreases quality of life in patients with OSCC. Proinflammatory cytokines such as interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α) have been suggested to play a certain role in variety of tumours. The aim of this study was to investigate the relationship of pretreatment serum IL-6 and TNF-α levels on tumour recurrence in patients with OSCC in order to identify potential biomarkers for the early detection of disease recurrence. The patients with newly diagnosed OSCC were treated and followed from the first visit from November 2006 until January 2008. Serum IL-6 and TNF-α concentrations were measured. The records of the patients were re-examined in July 2012 and data were recorded about cancer characteristics and tumour recurrence. Disease free survival was analyzed by Kaplan-Meier survival curves, log rank test and Cox proportional hazards regression. Serum IL-6 was shown as an independent risk factor for tumour recurrence. Pretreatment serum IL-6 concentration may be a useful biomarker for identification of OSCC patients with increased risk of the disease recurrence.
Full Text Available Abstract Background Oxidative stress play a main role in the initiation and progression of the OA disease and leads to the degeneration of mitochondria. To prevent this, the chondrocytes possess a well-coordinated enzymatic antioxidant system. Besides, the mitochondrial DNA (mtDNA haplogroups are associated with the OA disease. Thus, the main goal of this work is to assess the incidence of the mtDNA haplogroups on serum levels of two of the main antioxidant enzymes, Manganese Superoxide Dismutase (Mn-SOD or SOD2 and catalase, and to test the suitability of these two proteins for potential OA-related biomarkers. Methods We analyzed the serum levels of SOD2 and catalase in 73 OA patients and 77 healthy controls carrying the haplogroups J, U and H, by ELISA assay. Knee and hip radiographs were classified according to Kellgren and Lawrence (K/L scoring from Grade 0 to Grade IV. Appropriate statistical analyses were performed to test the effects of clinical variables, including gender, body mass index (BMI, age, smoking status, diagnosis, haplogroups and radiologic K/L grade on serum levels of these enzymes. Results Serum levels of SOD2 appeared statistically increased in OA patients when compared with healthy controls (p Conclusions The increased levels of SOD2 in OA patients indicate an increased oxidative stress OA-related, therefore this antioxidant enzyme could be a suitable candidate biomarker for diagnosis of OA. Mitochondrial haplogroups significantly correlates with serum levels of catalase
Full Text Available Regarding the high prevalence of hyperlipidaemia, which is one of the major risk factors of cardiovascular disease, and uncertain reports about the relation between periodontal disease and serum lipid profile, this study was conducted to assess this relation. The historical cohort study was conducted on 52 cases including 26 persons with chronic periodontitis as case group, and 26 healthy subjects as control group. Both groups had the same age and weight ranges, sex, and diet, without any periodontal treatment history in the past six months, underling systemic disease such as diabetes, anti-hyperlipidemic drugs or active tobacco smoking history. Low Density Lipoprotein (LDL, High Density Lipoprotein (HDL, Triglyceride (TG and Total Cholesterol (CHOL were measured by direct enzymatic assay. TG level was 128.4±71.1 mg/dl in control group and 165.2± 83.7 in case group indicating a significantly higher level in case group (P<0.05. In control group, 30.8 percent and in case group, 61.5 percent had abnormal serum cholesterol levels, which presents a significantly higher level in case group (P<0.03. Other serum level indices did not show any significant difference. Although it seems that patients with chronic periodontal disease are more susceptible to hyperlipidemia, it is doubtful that the former causes an increase in serum lipid levels, so we suggest studying the effects of treating chronic periodontitis on serum lipid level.
George A Alexiou
Full Text Available Aim: Several epidemiological studies have shown an inverse correlation between allergy and brain cancer. The purpose of this study was to compare the serum IgE levels between patients with gliomas and nonglial tumors and their possible prognostic role. Methods: A total of 84 patients with intracranial tumors were included in this study. At clinical presentation, estimation of serum IgE levels was assessed by nephelometry. Detailed information regarding the history of allergies was collected by interview. Results: Of the 84 cases, 42 were gliomas, 23 were meningiomas, 16 were metastases and 3 were primary central nervous system lymphomas. Patients with high-grade glioma had lower IgE levels than patients with low-grade glioma. Patients with glioma and meningioma had statistical significant lower serum IgE levels than patients with metastases. Patients with glioblastoma with serum IgE levels greater than 24 U/mL had a better survival. Conclusion: Patients with glioma and meningioma had lower IgE levels than patients with metastatic lesions. A prognostic role of serum IgE levels was found in glioblastoma. Further studies in larger patient series are required in order to verify our preliminary observations.
Full Text Available Introduction : Systemic sclerosis (SSc is achronic connective tissue disease characterized by microangiopathy with inadequate angiogenesis. Angiostatin (AS is a potent antiangiogenic factor specifically inhibiting proliferation and inducing apoptosis of vascular endothelial cells. Aim : To evaluate the level of angiostatin in the serum of patients with SSc. Material and methods : Serum levels of AS were measured in 20 SSc patients and 12 healthy controls. Results : A statistically significant difference in the serum levels of AS in SSc patients was observed compared to the control group (636.51 vs. 869.20 ng/ml; p = 0.012. Significant correlations between limited and disseminated SSc (lSSc/dSSc were not found, however, a difference between lSSc and the control group was demonstrated (620.00 vs. 869.20 ng/ml; p = 0.011. The serum level of AS was not associated positively with organ changes caused by SSc. However, a statistically significant lower serum level of AS was observed in patients with SSc and no esophageal (p = 0.008 or pulmonary changes (p = 0.007 compared to the control group. Conclusions : Our results reveal significant differences in AS level in SSc patients compared to the healthy controls, and suggest that a low level of AS may occur as a result of impaired angiogenesis.
Fisher, G.L. (Battelle Columbus Labs., OH); Spitler, L.E.; McNeill, K.L.; Rosenblatt, L.S.
Serum copper levels (SCL) and serum zinc levels (SZL) were evaluated in malignant melanoma patients at various clinical stages. Copper levels were generally found to be elevated, reflecting the degree and extent of tumor activity. Zinc levels and, hence, SCL:SZL ratios did not reflect tumor activity. SCL appeared to prognosticate disease progression in that all patients whose values never declined below 150 ..mu..g/100 ml died during the course of the study. However, not all patients who died from tumor metastases displayed persistent elevations of SCL. Patients receiving BCG immunotherapy appeared to have higher SCL than untreated patients.
Brown, Joseph N.; Brewer, Heather M.; Nicora, Carrie D.; Weitz, Karl K.; Morris, Michael J.; Skabelund, Andrew J.; Adkins, Joshua N.; Smith, Richard D.; Cho, Ji-Hoon; Gelinas, Richard
Background: We have identified candidate protein and microRNA (miRNA) biomarkers for dyspnea by studying serum, lavage fluid, and urine from military personnel who reported serious respiratory symptoms after they were deployed to Iraq or Afghanistan. Methods: Forty-seven soldiers with the complaint of dyspnea who enrolled in the STudy of Active Duty Military Personnel for Environmental Dust Exposure (STAMPEDE) underwent comprehensive pulmonary evaluations at the San Antonio Military Medical Center. The evaluation included fiber-optic bronchoscopy with bronchoalveolar lavage. The clinical findings from the STAMPEDE subjects pointed to seven general underlying diagnoses or findings including airway hyperreactivity, asthma, low diffusivity of carbon monoxide, and abnormal cell counts. The largest category was undiagnosed. As an exploratory study, not a classification study, we profiled proteins or miRNAs in lavage fluid, serum, or urine in this group to look for any underlying molecular patterns that might lead to biomarkers. Proteins in lavage fluid and urine were identified by accurate mass tag (database-driven) proteomics methods while miRNAs were profiled by a hybridization assay applied to serum, urine, and lavage fluid. Results: Over seventy differentially expressed proteins were reliably identified both from lavage and from urine in forty-eight dyspnea subjects compared to fifteen controls with no known lung disorder. Six of these proteins were detected both in urine and lavage. One group of subjects was distinguished from controls by expressing a characteristic group of proteins. A related group of dyspnea subjects expressed a unique group of miRNAs that included one miRNA that was differentially overexpressed in all three fluids studied. The levels of several miRNAs also showed modest but direct associations with several standard clinical measures of lung health such as forced vital capacity or gas exchange efficiency. Conclusions: Candidate proteins and mi
Silva, M B; Silva, M G; Shinjo, S K
Polymyositis (PM) is a rare systemic idiopathic inflammatory myopathy. Hyaluronic acid (HA) is closely linked to inflammatory cellular reactions and disease activity. Increased serum levels of HA have been reported in several inflammatory diseases, but currently, there are no studies analysing the HA in PM. Thus, clinical association of HA with PM in patients was determined in the present study. The present cross-sectional study was performed at one centre from 2012 to 2013 and included 35 consecutive adult patients with PM (Bohan and Peter criteria, 1975) and 38 adult healthy volunteers. The serum HA was assessed with anti-HA antibody, using the specific ELISA/EIA kits according to the manufacturer's protocol. The average age, distribution of females and ethnicity were comparable in patients with PM and the control group. Regarding disease status, patients with PM had a median patient visual analogue score (VAS) of 2 [0-6], physician VAS of 1 [0-3], MMT-8 of 74 [68-80] and HAQ of 0.48 [0.00-1.14]. The serum levels of HA were also significantly increased in patients with PM (390±412 ng/mL) compared to healthy subjects (129±119 ng/mL), p=0.001. In an additional analysis, the serum levels of HA did not correlate with PM demographic data (gender and ethnicity), current organ involvement or autoantibodies and were not been influenced by the use of prednisolone and/or immunosuppressives by the PM patients. However, there was a positive correlation between serum levels of HA and VAS (patient and physician), and a negative correlation between serum levels of HA and MMT-8. High serum levels of HA were observed in patients with PM and tended to correlate with PM disease activity. Additional studies are needed to assess this correlation, as well as to understand the mechanism involved in the pathogenesis of PM by HA.
Saeki, Harumi; Hashizume, Akane; Izumi, Hiroshi; Suzuki, Fujihiko; Ishi, Kazuhisa; Nojima, Michio; Maeda, Masahiro; Hino, Okio
Ovarian carcinoma has been difficult to diagnose at an early stage. Recently, it has been recognized that the measurement of blood N-ERC/mesothelin levels aids early detection in and postoperative therapeutic monitoring of patients with mesothelioma, who have been exposed to asbestos. ERC/mesothelin has also been reported to be expressed in ovarian carcinoma. We determined serum N-ERC/mesothelin levels in patients with ovarian carcinoma using an enzyme-linked immunosorbent assay (ELISA). In addition, we immunohistochemically evaluated surgically resected specimens for C-ERC/mesothelin expression. As a result, of the 32 patients with ovarian tumors (18 carcinoma, 2 borderline tumors), one patient with serous adenocarcinoma showed increased N-ERC/ mesothelin levels. Immunohistochemically, of the 20 ovarian tumor (carcinoma and borderline tumor) specimens evaluated for serum N-ERC/mesothelin, 9 (45.0%) were positive for C-ERC/mesothelin. The C-ERC/mesothelin-positive specimens were found to be serous and clear cell adenocarcinomas. If serum N-ERC/mesothelin, which is considered useful for early detection in and therapeutic monitoring of patients with mesothelioma, may also be used for ovarian carcinoma monitoring, it may be a valuable serum tumor marker for the early detection of ovarian carcinoma.
Amin, Saleh; El Amrousy, Doaa; Elrifaey, Shaymaa; Gamal, Rasha; Hodeib, Hossam
The aim of the study was to investigate the relationship between osteocalcin and nonalcoholic fatty liver disease (NAFLD) in children with obesity. 60 obese children with NAFLD were taken as a patient group and 60 obese children and normal liver with matching age, sex, and body mass index were taken as a control group. Anthropometric measurements, abdominal ultrasonography for diagnosis and grading of NAFLD, and laboratory investigations in the form of liver function tests, lipid profile, fasting serum glucose and insulin, and serum osteocalcin levels were done for all children. Patients with NAFLD were further divided into patients with metabolic syndrome (MS) and patients without MS. Age of NAFLD children was (10.55 ± 2.71), 20 boys and 40 girls, whereas age of children in control group was (10.05 ± 3.51), 24 boys and 36 girls (P > 0.05). Patients with NAFLD showed significant increase in waist and hip circumference, alanine aminotransferase, alkaline phosphatase, total cholesterol, triglycerides, insulin resistance (IR), fasting serum glucose, and insulin, but lower serum osteocalcin level than control group. Serum osteocalcin level is inversely correlated with waist circumference, triglyceride, liver enzymes, fasting serum insulin, fasting serum glucose, IR, and grades of fatty liver. Increase in alanine aminotransferase, total cholesterol, triglycerides, fasting insulin, and IR went with increase in degree of hepatic steatosis. Serum osteocalcin level <44.5 ng/mL is a good predictor for severity of hepatic steatosis with sensitivity and specificity of 80%. Osteocalcin plays an important role in glucose and lipid metabolism for protection against NAFLD occurrence and progression. Moreover, it could be a useful marker for progression of NAFLD in children with obesity.
Niu, Qian; Huang, Zhuochun; Shi, Yunying; Wang, Lanlan; Pan, Xiaofu; Hu, Chaojun
To identify novel serum protein biomarkers and establish diagnostic pattern for rheumatoid arthritis (RA) by using proteomic technology. Serum proteomic spectra were generated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) combined with weak cationic exchange magnetic beads. A training set of spectra, derived from analyzing sera from 22 patients with RA, 26 patients with other autoimmune diseases and 25 age- and sex-matched healthy volunteers, was used to train and develop a decision tree model with a machine learning algorithm called decision boosting. A blinded testing set, including 21 patients with RA, 24 patients with other autoimmune diseases and 25 healthy people, was used to examine the accuracy of the model. A decision tree model was established, consisting of four potential protein biomarkers whose m/z values were 4966.88, 5065.3, 5636.97 and 7766.87, respectively. In validation test, the decision tree model could differentiate RA from other autoimmune diseases and healthy people with the sensitivity of 85.71% and specificity of 87.76%, respectively. The present data suggested that MALDI-TOF-MS combined with magnetic beads could screen and identify some novel serum protein biomarkers related to RA. The proteomic pattern based on the four candidate biomarkers is of value for laboratory diagnosis of RA.
Ericksen Mielle Borba
Full Text Available Background/Aims: Hippocampal atrophy is a recognized biomarker of Alzheimer disease (AD pathology. Serum brain-derived neurotrophic factor (BDNF reduction has been associated with neurodegeneration. We aimed to evaluate BDNF serum levels and hippocampal volume in clinical AD (dementia and mild cognitive impairment [MCI]. Methods: Participants were 10 patients with MCI and 13 with dementia due to AD as well as 10 healthy controls. BDNF serum levels were determined by ELISA and volumetric measures with NeuroQuant®. Results: MCI and dementia patients presented lower BDNF serum levels than healthy participants; dementia patients presented a smaller hippocampal volume than MCI patients and healthy participants. Discussion: The findings support that the decrease in BDNF might start before the establishment of neuronal injury expressed by the hippocampal reduction.
Borba, Ericksen Mielle; Duarte, Juliana Avila; Bristot, Giovana; Scotton, Ellen; Camozzato, Ana Luiza; Chaves, Márcia Lorena Fagundes
Hippocampal atrophy is a recognized biomarker of Alzheimer disease (AD) pathology. Serum brain-derived neurotrophic factor (BDNF) reduction has been associated with neurodegeneration. We aimed to evaluate BDNF serum levels and hippocampal volume in clinical AD (dementia and mild cognitive impairment [MCI]). Participants were 10 patients with MCI and 13 with dementia due to AD as well as 10 healthy controls. BDNF serum levels were determined by ELISA and volumetric measures with NeuroQuant®. MCI and dementia patients presented lower BDNF serum levels than healthy participants; dementia patients presented a smaller hippocampal volume than MCI patients and healthy participants. The findings support that the decrease in BDNF might start before the establishment of neuronal injury expressed by the hippocampal reduction.
Kathleen M Schieffer
Full Text Available Chronic inflammation associated with inflammatory bowel disease (IBD results in increased oxidative stress that damages the colonic microenvironment. Low levels of serum bilirubin, an endogenous antioxidant, have been associated with increased risk for Crohn's disease (CD. Therefore, the aim of this study was to examine whether total serum bilirubin levels are associated with ulcerative colitis (UC. We identified a retrospective case-control population (n = 6,649 from a single tertiary care center, Penn State Hershey Medical Center (PSU and a validation cohort (n = 1,996 from Virginia Commonwealth University Medical Center (VCU. Cases were age- and sex-matched to controls (PSU: CD n = 254, UC n = 187; VCU: CD n = 233, UC n = 124. Total serum bilirubin levels were obtained from de-identified medical records and segregated into quartiles. Logistic regression analysis was performed on each quartile of total serum bilirubin compared to the last quartile (highest bilirubin levels to determine the association of total serum bilirubin with UC. Similar to CD patients, UC patients demonstrated reduced levels of total serum bilirubin compared to controls at PSU and VCU. The lowest quartile of total serum bilirubin was independently associated with UC for the PSU (OR: 1.98 [95% CI: 1.09-3.63] and VCU cohorts (OR: 6.07 [95% CI: 3.01-12.75]. Lower levels of the antioxidant bilirubin may reduce the capability of UC patients to remove reactive oxygen species leading to an increase in intestinal injury. Therapeutics that reduce oxidative stress may be beneficial for these patients.
Nass, Flávia R; Skare, Thelma L; Goeldner, Isabela; Nisihara, Renato; Messias-Reason, Iara T; Utiyama, Shirley R R
To evaluate the frequency of four serum biomarkers in RA patients and their relatives and identify possible associations with clinical findings of the disease. This was a transversal analytical study. Anti-cyclic citrullinated peptide (anti-CCP), anti-mutated citrullinated vimentin (anti-MCV) and IgA-rheumatoid factor (RF) were determined by ELISA and IgM-RF by latex agglutination in 210 RA patients, 198 relatives and 92 healthy controls from Southern Brazil. Clinical and demographic data were obtained through charts review and questionnaires. A higher positivity for all antibodies was observed in RA patients when compared to relatives and controls (p<0.0001). IgA-RF was more frequent in relatives compared to controls (14.6% vs. 5.4%, p=0.03, OR=2.98; 95% CI=1.11-7.98) whereas anti-CCP was the most common biomarker among RA patients (75.6%). Concomitant positivity for the four biomarkers was more common in patients (46.2%, p<0.0001). Relatives and controls were mostly positive for just one biomarker (20.2%, p<0.0001 and 15.2%, p=0.016, respectively). No association was observed between the number of positive biomarkers and age of disease onset, functional class or tobacco exposure. In seronegative patients predominate absence of extra articular manifestations (EAMs) (p=0.01; OR=3.25; 95% CI=1.16-10.66). Arthralgia was present in positive relatives, regardless the type of biomarker. A higher number of biomarkers was present in RA patients with EAMs. Positivity of biomarkers was related to arthralgia in relatives. These findings reinforce the link between distinct biomarkers and the pathophysiologic mechanisms of AR. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.
Boulware, David R; Meya, David B; Bergemann, Tracy L; Wiesner, Darin L; Rhein, Joshua; Musubire, Abdu; Lee, Sarah J; Kambugu, Andrew; Janoff, Edward N; Bohjanen, Paul R
Although antiretroviral therapy (ART) improves survival in persons with cryptococcal meningitis (CM) and AIDS, ART frequently elicits HIV immune reconstitution inflammatory syndrome (IRIS), an exaggerated and frequently deadly inflammatory reaction that complicates recovery from immunodeficiency. The pathogenesis of IRIS is poorly understood and prediction of IRIS is not possible. We prospectively followed 101 ART-naïve Ugandans with AIDS and recent CM for one year after initiating ART, and used Luminex multiplex assays to compare serum cytokine levels in participants who did or did not develop IRIS. IRIS occurred in 45% of participants with recent CM on ART, including 30% with central nervous system (CNS) manifestations. The median time to CM-IRIS was 8.8 wk on ART. Overall mortality on ART was 36% with IRIS and 21% without IRIS. CM-IRIS was independently associated with death (HR = 2.3, 95% CI 1.1-5.1, p = 0.04). Patients experiencing subsequent CM-IRIS had 4-fold higher median serum cryptococcal antigen (CRAG) levels pre-ART (p = 0.006). Higher pre-ART levels of interleukin (IL)-4 and IL-17 as well as lower tumor necrosis factor (TNF)-α, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF) predicted future IRIS in multivariate analyses (area under the curve [AUC] = 0.82). An algorithm based on seven pre-ART serum biomarkers was a robust tool for stratifying high (83%), moderate (48%), and low risk (23%) for IRIS in the cohort. After ART was initiated, increasing levels of C-reactive protein (CRP), D-dimer, IL-6, IL-7, IL-13, G-CSF, or IL-1RA were associated with increasing hazard of IRIS by time-to-event analysis (each p≤0.001). At the time of IRIS onset, multiple proinflammatory cytokine responses were present, including CRP and IL-6. Mortality was predicted by pre-ART increasing IL-17, decreasing GM-CSF, and CRP level >32 mg/l (highest quartile). Pre-ART CRP
Patrick, J.; Marpaung, B.; Ginting, Y.
Differentiate bacterial infections from flare in SLE patients is difficult to do because clinical symptoms of infection is similar to flare. SLE patients with infection require antibiotic therapy with decreased doses of immunosuppressant while in flare diseases require increased immunosuppressant. Procalcitonin (PCT), a biological marker, increased in serum patients with bacterial infections and expected to be a solution of problem. The aim of this study was to examine the function of PCT serum as marker to differentiate bacterial infection and flare in SLE patients. This cross-sectional study was conducted in Adam Malik Hospital from January-July 2017. We examined 80 patients SLE flare (MEX-SLEDAI>5), screen PCT and culture according to focal infection. Data were statistically analyzed. 80 SLE patients divided into 2 groups: bacterial infection group (31 patients) and non-infection/flare group (49 patients). Median PCT levels of bacterial infection group was 1.66 (0.04-8.45)ng/ml while flare group was 0.12 (0.02-0.81)ng/ml. There was significant difference of serum Procalcitonin level between bacterial infection and flare group in SLE patients (p=0.001). Procalcitonin serum levels can be used as a biomarker to differentiate bacterial infections and flare in SLE patients.
Sabitha; Suneetha; Mohanty, Shruti; Rao, Pragna
Breast cancer is a hormone dependent neoplasm. Conflicting results regarding the clinical correlation between breast cancer and thyroid diseases have been reported. The objective of this study was to determine the association of anti - TPO levels in patients having complaints of a lump in breast. Serum samples and Fine needle aspiration cytology (FNAC) samples were collected from 31 female patients with a lump in breast between the age group of 20-75 years. 31 age matched normal healthy controls were also examined for the same parameters. Serum samples were analyzed for its anti - TPO levels. FNAC reports confirmed patients as having duct cell carcinoma. They had raised serum anti - TPO levels compared to controls. FNAC results of others (n=26) were reported as fibroadenoma whose anti - TPO levels were less than the controls.
Suadicani, P; Hein, H O; Gyntelberg, F
Serum selenium has been implicated as a risk factor for lung cancer, but the issue remains unsettled. We tested in a cohort of 3,333 males aged 53 to 74 years the hypothesis that a low serum selenium would be associated with an increased risk of lung cancer mortality.During 16 years, 167 subjects(5.......1%) died from lung cancer; 48 males (5.0%) among males with low serum selenium, 0.4-1.0 μmol·l(-1), n=965, 57 males (5.1%) among males with medium serum selenium, 1.1-1.2 μmol·l(-1), n=1,141, and 62 males (5.1%) among males with high serum selenium, 1.3-3.0 μmol·l(-1), n=1,227. After adjustment for age...... (chronic bronchitis and peak flow), referencing the lowest level of serum selenium HRs were 1.17(0.79-1.75), and 1.43(0.96-2.14), respectively. Among heavy smokers a high serum selenium was associated with a significantly increased risk of lung cancer mortality after taking into account all potential...
Petersen, P M; Andersson, A M; Rørth, M
A group of men treated with testicular irradiation for carcinoma in situ in the remaining testis after orchidectomy for unilateral testicular germ cell cancer was used as a model to study of the effect of selective eradication of germ cells on the levels of serum inhibin B in the human male....... Thirteen men with verified spermatogenesis and detectable preirradiation levels of serum inhibin B (median, 55; range, 23-193 pg/mL) were investigated before and after testicular irradiation (14-20 Gy). All patients had undetectable levels of inhibin B 2-12 months (median, 5 months) after radiotherapy (...
Jawed, S.; Khawaja, T.F.; Sultan, M.A.; Ahmad, S.
Patient with arterial hypertension and no definable cause are said to have essential, primary or idiopathic hypertension. A total of 100 patients suffering from essential hypertension and 100 control subjects with almost same mean age and sex distribution were enrolled in this study. Levels of serum uric acid, total cholesterol, TG, and HDL-c were determined by enzymatic colorimetric method. Serum LDL-c and VLDL-c was calculated by using Friedewald and Wilson's formulae. The study was aimed to find out the levels of serum uric acid and lipid profile in patients with essential hypertension and to compare them with levels of normal healthy individuals. Results show increased level of serum uric acid and lipid parameters except for HDL-c, which was significantly, decreased in patients with essential hypertension as compared to the control subjects. Variations in aforementioned parameters were also observed on comparing the obese and the non-obese patients. It can be concluded from the present study that the essential hypertension is associated with abnormalities in the levels of serum uric acid and lipid profile. (author)
Kapoor, Aneel; Zuberi, Nudrat Anwar; Rathore, M. Imran; Baig, Mukhtiar
Objectives: The aim of present study was to investigate serum homocysteine levels in apparently healthy vegetarians and ominvores in Mithi, district Tharparker, Sindh, Pakistan. Methods: This study was conducted in the Department of Biochemistry, Basic Medical Sciences Institute (BMSI), Jinnah Postgraduate Medical Center (JPMC), Karachi and blood samples were collected from Mithi, district Tharparker, Sindh, Pakistan, in 2012. One hundred vegetarian and one hundred omnivores (age ranging from 20-40 years) were enrolled for this study. Serum homocysteine levels were measured by the chemiluminescence enzyme immunoassay method. Results: Serum homocysteine (Hcy) level was considerably higher (p15µmol/L compared to omnivores 6%, (p15µmol/L serum Hcy level in vegetarian group and 6.9% male and 3.5% females had >15µmol/L serum Hcy level in omnivores group, but the difference was not significant in any group. Conclusion: Vegetarians are more prone to develop hyperhomocysteinemia, so they are at high risk to develop cardiovascular disease. PMID:25878628
Seifi S, Mokhtari A
Full Text Available "nBackground: The annual amount of mortality in ESRD exceeds the expectation and represents the recent evidences of the inflammation as its etiology. The etiology of inflammation is not clearly known. Chronic inflammation is a dominant occurrence of ESRD which increases the risk of atherosclerosis, malnutrition and peripheral vascular disease. Inflammatory responses are orchestrated by cytokines. Some of the proinflammatory cytokines like IL-6 have a crucial role in this phenomenon. The IL-6 and its receptor activity is up regulated in ESRD patients and the increased level of IL-6 predicts cardiovascular mortality and morbidity in normal and CRF patients. This study devotes itself to determining the serum level of IL-6 and factors affecting it in patients undergoing chronic hemodialysis in Imam Khomeini Hospital which can represent the Iranian Society. By identifying factors affecting the serum level of IL-6 and high-risk patients we can provide treatment possibilities, a decrease in mortality and an improvement in its prognosis. "n"nMethods: In this study 42 patients in Imam Dialysis Center were chosen and their serum IL-6 levels were measured at 2 times at three month interval and at the same time blood sample analysis were done for the following: Alb CPR, Ca, P, PTH, TIBC, Ferritin, TG, Chol, LDL, HDL, Uric Acid, Hb, WBC and urea."n"nResults: The mean serum level of IL-6 in hemodialysis patients was 6.35±4.47pg/ml (minimum: 0.55, maximum: 18.25 with the normal range of 1.3±3.2pg/ml."n"nConclusions: The IL-6 level was higher than normal range in the 52% of the patients. The serum IL-6 level had a significant correlations with CPR, Ferritin, TIBC, WBC and their serum IL-6 level was significantly higher in patients with hypertension, but no significant correlation was observed between other parameters and IL-6
Hirayama, Tatsuro; Takazono, Takahiro; Iwata, Kazuma; Senju, Hiroaki; Shimazaki, Takaharu; Tashiro, Masato; Saijo, Tomomi; Tanaka, Takeshi; Nakamura, Shigeki; Imamura, Yoshifumi; Kojiro, Maiko; Miyazaki, Taiga; Tsukamoto, Misuzu; Furumoto, Akitsugu; Morimoto, Konosuke; Muraosa, Yasunori; Matsubara, Yuichi; Yanagihara, Katsunori; Mukae, Hiroshi; Kamei, Katsuhiko; Kohno, Shigeru; Izumikawa, Koichi
Histoplasmosis is a common endemic mycosis that is usually asymptomatic but occasionally results in severe illness. Histoplasmosis and its causative agent, Histoplasma capsulatum, are found worldwide but rarely in Japan. In recent years, however, the number of histoplasmosis patients in Japan has increased. In addition, to our knowledge, there are no previous reports of increased serum soluble interleukin-2 receptor (sIL-2R) levels in patients with histoplasmosis. We report a case series of histoplasmosis in three Japanese temporary workers in Manzanillo, Mexico. All three patients developed a persistent high fever and general fatigue. Laboratory tests showed increased C-reactive protein levels and mild liver dysfunction. All patients also showed increased soluble interleukin-2 receptor (sIL-2R) levels. Chest computed tomography revealed multiple nodules in both lung fields. All patients were positive for serum anti-Histoplasma antibodies, and two patients were positive for Histoplasma on polymerase chain reaction tests. After treatment that included antifungals, their conditions gradually improved and laboratory data normalized. Although one patient developed respiratory failure, this patient recovered with antifungal therapy in combination with methylprednisolone. Serum sIL-2R levels in all patients gradually declined to normal levels, indicating their recovery from Histoplasma infection. From our experience with these patients, sIL-2R levels may be a useful biomarker for patients with histoplasmosis. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Bliddal, Henning; Møller, H J; Schaadt, M
OBJECTIVE: To investigate the levels of hyaluronic acid (HA) in Danish patients with fibromyalgia (FM). METHODS: Serum levels of HA were determined in 53 patients with established FM and 55 control samples using a radiometric assay. Values were correlated to clinical disease severity variables...
Full Text Available Background. Serum ghrelin levels may be related to metabolic and clinical changes in patients with psoriasis. Objective. This study was performed to determine the possible effects of serum ghrelin in patients with psoriasis. Methods. The study population consisted of 25 patients with plaque psoriasis. The patients were questioned with regard to age, gender, age of onset, duration of disease, height, weight, and body mass index (BMI. In addition, fasting blood sugar, triglyceride, cholesterol levels, insulin, and ghrelin levels were measured. Results. The mean serum ghrelin level was 45.41 ± 22.41 in the psoriasis group and 29.92 ± 14.65 in the healthy control group. Serum ghrelin level was significantly higher in the psoriasis group compared with the controls (P=0.01. The mean ghrelin level in patients with a lower PASI score was significantly higher than in those with a higher PASI score (P=0.02. Conclusion. The present study was performed to determine the effects of ghrelin in psoriasis patients. We found a negative correlation between severity of psoriasis and ghrelin level. Larger and especially experimental studies focusing on correlation of immune system-ghrelin levels and severity of psoriasis may be valuable to clarify the etiopathogenesis of the disease.
Full Text Available Background Leptin is a multifunctional hormone plays an important role in regulating lipid, energy, homeostasis, angiogenesis, inflammation, hematopoiesis and cell cycle. This polypeptide is effective in growth and differentiation of leukemic cells through an Ob-R receptor expressed by them. Objectives The purpose of this study was to evaluate serum leptin levels in patients with acute leukemia and compare it in lymphoid and myeloid groups. Patients and Methods This analytical case-control study, conducted on 60 children in age ranged from 6 months to 16 years in two case and control groups in Ali ibn Abi Talib hospital, Zahedan. They matched based on age and gender and examined after their parent’s satisfaction according to the parental consent forms. None of patients had heart disease, digestive, glandular and metabolic problems, iron deficiency anemia and chronic kidney disease. After collecting the samples, leptin levels of both groups were measured with ELISA kit. Then, the gathered data were analyzed in SPSS-20 software, using independent t-test in considering of 95% confidence interval. Results Leptin serum levels in patients with acute leukemia and controls showed significant difference (P < 0.05. Leptin serum levels in patients with acute lymphoblastic leukemia and acute myeloblastic leukemia showed significant difference (P < 0.05. Leptin serum level in relation to age and gender groups was not statistically significant. Conclusions The findings of this study showed that in patients with acute leukemia, leptin serum levels increase independently of age and gender. In addition, leptin serum levels in acute lymphoid leukemia were higher than acute myeloid leukemia in this study.
Full Text Available Low serum albumin levels are associated with aging and medical conditions such as cancer, liver dysfunction, inflammation, and malnutrition and might be an independent predictor of long-term mortality in healthy older populations. We tested the hypothesis that economic status is associated with serum albumin levels and explained by nutritional and health status in Japanese older adults.We performed a cross-sectional analysis using data from the Japan Gerontological Evaluation study (JAGES. The study participants were 6528 functionally independent residents (3189 men and 3339 women aged ≥65 years living in four municipalities in Aichi prefecture. We used household income as an indicator of economic status. Multiple linear regression was used to compare serum albumin levels in relation to household income, which was classified as low, middle, and high. Additionally, mediation by nutritional and health-related factors was analyzed in multivariable models.With the middle-income group as reference, participants with low incomes had a significantly lower serum albumin level, even after adjustment for sex, age, residential area, education, marital status, and household structure. The estimated mean difference was -0.17 g/L (95% confidence interval, -0.33 to -0.01 g/L. The relation between serum albumin level and low income became statistically insignificant when "body mass index", "consumption of meat or fish", "self-rated health", "presence of medical conditions", "hyperlipidemia", or "respiratory disease "was included in the model.Serum albumin levels were lower in Japanese older adults with low economic status. The decrease in albumin levels appears to be mediated by nutrition and health-related factors with low household incomes. Future studies are needed to reveal the existence of other pathways.
Ota, Asami; Kondo, Naoki; Murayama, Nobuko; Tanabe, Naohito; Shobugawa, Yugo; Kondo, Katsunori
Low serum albumin levels are associated with aging and medical conditions such as cancer, liver dysfunction, inflammation, and malnutrition and might be an independent predictor of long-term mortality in healthy older populations. We tested the hypothesis that economic status is associated with serum albumin levels and explained by nutritional and health status in Japanese older adults. We performed a cross-sectional analysis using data from the Japan Gerontological Evaluation study (JAGES). The study participants were 6528 functionally independent residents (3189 men and 3339 women) aged ≥65 years living in four municipalities in Aichi prefecture. We used household income as an indicator of economic status. Multiple linear regression was used to compare serum albumin levels in relation to household income, which was classified as low, middle, and high. Additionally, mediation by nutritional and health-related factors was analyzed in multivariable models. With the middle-income group as reference, participants with low incomes had a significantly lower serum albumin level, even after adjustment for sex, age, residential area, education, marital status, and household structure. The estimated mean difference was -0.17 g/L (95% confidence interval, -0.33 to -0.01 g/L). The relation between serum albumin level and low income became statistically insignificant when "body mass index", "consumption of meat or fish", "self-rated health", "presence of medical conditions", "hyperlipidemia", or "respiratory disease "was included in the model. Serum albumin levels were lower in Japanese older adults with low economic status. The decrease in albumin levels appears to be mediated by nutrition and health-related factors with low household incomes. Future studies are needed to reveal the existence of other pathways.
Kubota, Takuo; Wang, Wei; Miura, Kohji; Nakayama, Hirofumi; Yamamoto, Keiko; Fujiwara, Makoto; Ohata, Yasuhisa; Tachibana, Makiko; Kitaoka, Taichi; Takakuwa, Satoshi; Miyoshi, Yoko; Namba, Noriyuki; Ozono, Keiichi
Serum amino-terminal propeptide of C-type natriuretic peptide (NT-proCNP) levels have been proposed as a biomarker of linear growth in healthy children. The usefulness of NT-proCNP in patients with achondroplasia (ACH)/hypochondroplasia (HCH) remains to be elucidated. The objective was to study whether serum NT-proCNP level is a good biomarker for growth in ACH/HCH and other patients of short stature. This was a longitudinal cohort study. Sixteen children with ACH (aged 0·4-4·3 years), six children with HCH (2·7-6·3 years), 23 children with idiopathic short stature (ISS) (2·2-9·0 years), eight short children with GH deficiency (GHD) (2·9-6·8 years) and five short children born small for gestational age (SGA) (2·0-6·6 years). Patients with ACH/HCH received GH treatment for 1 year. Serum NT-proCNP levels and height were measured. NT-proCNP levels positively correlated with height velocity in these short children (P < 0·05, r = 0·27). NT-proCNP levels inversely correlated with age in children with ISS alone (P < 0·01, r = -0·55). Serum NT-proCNP levels in patients with ACH/HCH were increased 3 months following the initiation of GH treatment (P < 0·05). Height SDS gain during GH treatment for 1 year was positively correlated with the changes in NT-proCNP levels after the initiation of GH (P < 0·01, r = 0·72). Serum NT-proCNP levels may be a good biomarker to indicate the effect of GH treatment on growth in patients with ACH/HCH at least in the first year and height velocity in short stature patients. © 2016 John Wiley & Sons Ltd.
Smit Henriette A
Full Text Available Abstract Background There is mounting evidence that estimates of intakes of a range of dietary nutrients are related to both lung function level and rate of decline, but far less evidence on the relation between lung function and objective measures of serum levels of individual nutrients. The aim of this study was to conduct a comprehensive examination of the independent associations of a wide range of serum markers of nutritional status with lung function, measured as the one-second forced expiratory volume (FEV1. Methods Using data from the Third National Health and Nutrition Examination Survey, a US population-based cross-sectional study, we investigated the relation between 21 serum markers of potentially relevant nutrients and FEV1, with adjustment for potential confounding factors. Systematic approaches were used to guide the analysis. Results In a mutually adjusted model, higher serum levels of antioxidant vitamins (vitamin A, beta-cryptoxanthin, vitamin C, vitamin E, selenium, normalized calcium, chloride, and iron were independently associated with higher levels of FEV1. Higher concentrations of potassium and sodium were associated with lower FEV1. Conclusion Maintaining higher serum concentrations of dietary antioxidant vitamins and selenium is potentially beneficial to lung health. In addition other novel associations found in this study merit further investigation.
Full Text Available Background: The etiology of multiple sclerosis (MS, a chronic demyelinative disease-is unknown. The damage of blood–brain barrier (BBB vasculature is a characteristic of MS and Homocystein (Hcy can damage BBB, then increase in total Hcy may be important in MS pathogenesis. The aim of this study was to compare the serum level of total Hcy in MS patients with control group. Methods: In a case control study, serum level of total Hcy measured in 35 MS patient and compared with 30 healthy matched controls. All patients had definitive MS according to Poser criteria, without history of myocardial infarction, stroke, neuropathy, transient ischemic attack, homocystinuria or renal failure. Results: The serum concentration of total homocystein was significantly higher in multiple sclerosis patients than healthy controls. The mean total Hcy level was 17.92± 6.9 mmol/lit in cases and 14.6±2.92 mmol/lit in controls (P=0.013. Conclusion: Serum total Homocystein may have a role in MS pathogenesis and reduction of it should be studied moreover. Key words: Multiple Sclerosis, Homocystein, Serum level
Full Text Available Introduction: Noise exposure may have anatomical, nonauditory, and auditory influences. Considering nonauditory impacts, noise exposure can cause alterations in the automatic nervous system, including increased pulse rates, heightened blood pressure, and abnormal secretion of hormones. The present study aimed at examining the effect of various sound pressure levels (SPLs on the serum aldosterone level among rats. Materials and Methods: A total of 45 adult male rats with an age range of 3 to 4 months and a weight of 200 ± 50 g were randomly divided into 15 groups of three. Three groups were considered as the control groups and the rest (i.e., 12 groups as the case groups. Rats of the case groups were exposed to SPLs of 85, 95, and 105 dBA. White noise was used as the noise to which the rats were exposed. To measure the level of rats’ serum aldosterone, 3 mL of each rat’s sample blood was directly taken from the heart of anesthetized animals by using syringes. The taken blood samples were put in labeled test tubes that contained anticoagulant Ethylenediaminetetraacetic acid. In the laboratory, the level of aldosterone was assessed through Enzyme-linked immunosorbent assay protocol. The collected data were analyzed by the use of Statistical Package for Social Sciences (SPSS version 18. Results: The results revealed that there was no significant change in the level of rats’ serum aldosterone as a result of exposure to SPLs of 65, 85, and 95 dBA. However, the level of serum aldosterone experienced a remarkable increase after exposure to the SPL of 105 dBA (P < 0.001. Thus, the SPL had a significant impact on the serum aldosterone level (P < 0.001. In contrast, the exposure time and the level of potassium in the used water did not have any measurable influence on the level of serum aldosterone (P = 0.25 and 0.39. Conclusion: The findings of this study demonstrated that serum aldosterone can be used as a biomarker in the face of sound
Lopalco, Giuseppe; Lucherini, Orso Maria; Vitale, Antonio; Talarico, Rosaria; Lopalco, Antonio; Galeazzi, Mauro; Lapadula, Giovanni; Cantarini, Luca; Iannone, Florenzo
Abstract Behcet's disease (BD) is a multisystemic disorder of unknown etiology characterized by relapsing oral–genital ulcers, uveitis, and involvement of vascular, gastrointestinal, neurological, and musculoskeletal system. Although disease pathogenesis is still unclear, both innate and adaptive immunity have shown to play a pivotal role, and multiple proinflammatory cytokines seem to be involved in different pathogenic pathways that eventually lead to tissue damage. The aims of our study were to evaluate serum cytokines levels of IL-8, IL-18, IFN-α2a, IL-6, IFN-γ, CXCL10, CXCL11, CXCL9, and SAA levels in patients with BD, in comparison to healthy controls (HC), and to correlate their levels to disease activity. We included 78 serum samples obtained from 58 BD patients and analyzed a set of proinflammatory cytokines including IL-8, IL-18, IFN-α2a, IL-6, IFN-γ, CXCL10, CXCL11, and CXCL9 by multiplex bead analysis as well as SAA by enzyme-linked immunosorbent assay. Compared to HC, BD patients showed elevated cytokine levels of IL-8, IL-18, IFN-α2a, and IL-6, and low levels of CXCL11. BD patients with SAA serum levels >20 mg/L showed higher levels of proinflammatory markers than HC or group with SAA ≤20 mg/L. IL-18, IFN-α2a, and IL-6 were higher in BD group with SAA >20 mg/L than HC, while IL-8 and CXCL9 levels were higher than in patients with SAA ≤20 mg/L and HC. Active BD patients with SAA >20 mg/L exhibited elevated levels of inflammatory mediators, suggesting that may exist a relationship between SAA and proinflammatory cytokines in the intricate scenario of BD pathogenesis. PMID:26496336
Lopalco, Giuseppe; Lucherini, Orso Maria; Vitale, Antonio; Talarico, Rosaria; Lopalco, Antonio; Galeazzi, Mauro; Lapadula, Giovanni; Cantarini, Luca; Iannone, Florenzo
Behcet's disease (BD) is a multisystemic disorder of unknown etiology characterized by relapsing oral-genital ulcers, uveitis, and involvement of vascular, gastrointestinal, neurological, and musculoskeletal system. Although disease pathogenesis is still unclear, both innate and adaptive immunity have shown to play a pivotal role, and multiple proinflammatory cytokines seem to be involved in different pathogenic pathways that eventually lead to tissue damage.The aims of our study were to evaluate serum cytokines levels of IL-8, IL-18, IFN-α2a, IL-6, IFN-γ, CXCL10, CXCL11, CXCL9, and SAA levels in patients with BD, in comparison to healthy controls (HC), and to correlate their levels to disease activity.We included 78 serum samples obtained from 58 BD patients and analyzed a set of proinflammatory cytokines including IL-8, IL-18, IFN-α2a, IL-6, IFN-γ, CXCL10, CXCL11, and CXCL9 by multiplex bead analysis as well as SAA by enzyme-linked immunosorbent assay.Compared to HC, BD patients showed elevated cytokine levels of IL-8, IL-18, IFN-α2a, and IL-6, and low levels of CXCL11. BD patients with SAA serum levels >20 mg/L showed higher levels of proinflammatory markers than HC or group with SAA ≤20 mg/L. IL-18, IFN-α2a, and IL-6 were higher in BD group with SAA >20 mg/L than HC, while IL-8 and CXCL9 levels were higher than in patients with SAA ≤20 mg/L and HC.Active BD patients with SAA >20 mg/L exhibited elevated levels of inflammatory mediators, suggesting that may exist a relationship between SAA and proinflammatory cytokines in the intricate scenario of BD pathogenesis.
Bagni, B.; Feggi, L.M.; Prandini, N.; Pasini, S.; Mollica, G.
The tumor marker CA-125 is an embrional glycoprotein detectable in tissues derived from celomatic epitelium. Serum Ca-125 was determined by RIA in 66 patients with various ovarian pathologies (16 malignant at stage III-IV and 50 benign). Six patients with ovarian carcinoma were monitored during the first week after surgery and chemiotherapy for a total of 150 days of treatment. It has been observed that CA-125 serum level is consistently above the normal range (>35 U/ml) in all malignant diseases. In benign pathology, levels above the normal were found to be represented almost exclusively by ovarian endometriosis. Furthermore, the results demonstrate that chemiotherapy alone is capable of lowering CA-125 serum levels. This tumor marker may be of great advantage in diagnosis and follow-up of ovarian malignancy
Full Text Available Introduction: The use of tobacco and its products has increased in the population over the past two decades, resulting in considerable systemic exposure to nicotine. Aims and Objectives: To estimate and compare the serum nicotine levels among smokers and gutkha chewers, along with the effect of nicotine replacement therapy on serum nicotine levels between them. Materials and Methods: Forty individuals were selected and divided into two groups with 20 individuals in each group. First group included individuals with a smoking habit, whereas the second group included individuals with the habit of chewing gutkha exclusively. Four blood samples were collected from all the participants in both the groups and subjected to serum nicotine estimation. Two blood samples were obtained (first sample after 30 min and the next sample after 60 min following smoking/chewing on the first day, and the other two were obtained after 24 h of tobacco abstinence (after 24 h all the participants were asked to chew nicotine chewing gums each containing 2 mg of nicotine. Statistical Analysis Used: The particulars of age, frequency of habit (smoking and chewing gutkha, and serum nicotine levels before and after replacement therapy (nicotine chewing gum were recorded and analyzed statistically by cross-tabulation for calculation of mean and frequency. Results: The serum concentration of nicotine in smokers at 30 min after smoking ranged 120-309 ng/ml and at 60 min ranged 29-77 ng/ml. In group 1, individuals′ serum nicotine concentration after replacement therapy with nicotine chewing gum ranged 29-77 ng/ml at 30 min and 1-6 ng/ml at 60 min. Serum concentration of nicotine at 30 min after chewing gutkha ranged 86-200 ng/ml and at 60 min ranged 61-102 ng/ml. The serum nicotine concentration in group 2 individuals at 30 min following chewing nicotine gum ranged 24-55 ng/ml and at 60 min ranged 0-3 ng/ml. Conclusion: Serum nicotine concentration in chewers was less at 30 min
Yousefi, Maryam; Mozafari, Nikoo; Hosseini, Mahboobeh Sadat; Gholamin, Sharareh; Razavi, Seyed-Mostafa; Namazi, Mohammad Reza; Younespour, Shima
Altered levels of sex hormones have been observed in many autoimmune disorders, but there is no considerable data about pemphigus. The aim of this study is to compare serum total and free prolactin and dehydroepiandrosterone sulfate (DHEAS) levels between patients with pemphigus and healthy controls and to determine the correlation of these hormones with disease severity. This study included 52 newly diagnosed cases of pemphigus and 57 healthy controls. Serum prolactin (total and free) and DHEAS were measured in all subjects. Data analyses were performed using JMP, Version 7. Pemphigus patients had significantly higher levels of total and free serum prolactin (both P = 0.01) and lower levels of DHEAS (P = 0.005) than healthy controls. A significant association was found between severity of pemphigus and total prolactin levels (r = 0.40, P = 0.003). The patients with pemphigus had higher total and free prolactin and lower DHEAS concentrations, and patients with more severe disease had higher levels of serum total prolactin. These new data may suggest a potential role for sex hormones in the pathogenesis of pemphigus disease and provide new insights for the better management of this chronic and life-threatening disease. © 2016 The International Society of Dermatology.
Full Text Available BACKGROUND : Acute myocardial infarction (AMI is one of the major causes of mortality and morbidity in the world. Serum albumin levels are inversely related with age, smoking, blood pressure and obesity. It is not clear whether low serum albumin level is a nonspecific , prognostic variable, a marker of subclinical disease, or whether it is a part of causal mechanism leading to death due to cardiovascular disease. Some studies have reported an inverse association between serum albumin and cardiovascular mortality but oth ers have not . 1 The association between serum albumin and cardiovascular mortality remains controversial. This study was done to evaluate the serum albumin levels in patients with ST segment elevation Myocardial infarction (STEMI over a period of three days from the date of admission and whether the changes had any relationship with the prognosis of the patient. AIM: to associate changes in serum albumin levels in AMI patients over a period of three days i.e., day zero - at the time of admission, day+1 - the following day(12 to 30hrs after collecting first sample, day +2(32 to 54 hrs after collecting first sample with the clinical prognosis of the patient. SETTINGS AND DESIGN : Prospective follow up study in patents admitted with AMI in a tertiary care hospital. METHODS: 30 pati ents admitted with STEMI were included in the study and serum albumin levels were estimated in them on admission and for two days thereafter. Statistical analysis used. The data was analysed using SPSS 15.0, STATA 8.0, MEDLAC 9.0.1, And SYSTAT 11 softwares. Repeated measures analysis of variance and student t test was used to find the significance in changes of serum albumin levels and prognosis of the patient on different days. RESULTS AND CONCLUSION: This study found that there was fall in serum albumin le vels in patients with AMI in the course of three days compared with the day of admission and it was significantly associated with bad prognosis.
Ludwicki, Jan K; Góralczyk, Katarzyna; Struciński, Paweł
Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) blood levels are commonly used as biomarkers of human environmental exposure to these compounds. Many biomonitoring studies indicate 100% detection for PFOS and PFOA thus justifying a concern of possible risk for the most exposed...... individuals. This study addresses the predictive value of hazard quotients (HQs) calculated on the basis of serum PFOS and PFOA in male and female populations of reproductive age in Greenland, Poland and Ukraine. Overall, 2026 results of PFOS and PFOA serum concentrations (589 males, 1437 females) were...... obtained from the INUENDO database. HQs were calculated from the actual biomonitoring results and literature-based animal data linking toxicological outcomes and critical PFOS/PFOA serum levels. HQs for serum PFOS were calculated based on Points of Departure (PoD) at 13μgmL(-1) (cynomolgus monkeys, 183days...
Mayerhofer, K; Hefler, L; Zeisler, H; Tempfer, C; Bodner, K; Stöckler-Ipsiroglu, S; Mühl, A; Kaider, A; Schatten, C; Leodolter, S; Husslein, P; Kainz, C
Endothelial dysfunction has been described as the final common pathophysiological pathway in the development of preeclampsia. Since it has been suggested that homocyst(e)ine damages endothelial cells, we measured serum homocyst(e)ine levels in women with preeclampsia and in healthy pregnant women in order to find a new prognostic parameter for women with preeclampsia. Forty-five women with preeclampsia and 45 healthy women with uncomplicated pregnancies, matched for age and parity, were entered into the study. Serum homocyst(e)ine levels were measured by gas chromatography-mass spectrometry analysis and correlated to clinical data. Logistic regression models were used to analyse the influence of serum homocyst(e)ine levels on the presence of preeclampsia versus healthy pregnant women and on the risk of premature termination of pregnancy due to preeclampsia. Median serum homocyst(e)ine levels in women with preeclampsia and healthy pregnant women were 14.2 (range 5.7-38.1) mumol/L and 15.1 (range 5.2-23.1) mumol/L, respectively (Mann-Whitney U-test, p = 0.8). In univariate logistic regression models, serum homocyst(e)ine levels had no significant influence on the odds of presenting with preeclampsia versus healthy pregnant women (univariate logistic regression model, p = 0.8) and on the odds of premature termination of pregnancy due to preeclampsia (univariate logistic regression model, p = 0.3). Serum homocyst(e)ine levels are not elevated in women with preeclampsia and are not associated with clinical outcome in women with preeclampsia.
Haen, Sebastian P; Gouttefangeas, Cécile; Schmidt, Diethard; Boss, Andreas; Clasen, Stephan; von Herbay, Alexandra; Kosan, Bora; Aebert, Hermann; Pereira, Philippe L; Rammensee, Hans-Georg
Due to their adjuvant effect and their ability to chaperone tumor-associated peptides, heat shock proteins constitute a potent alarm signal for the immune system and can lead to activation of anti-tumor T-cell immunity. Radiofrequency ablation has been reported to induce heat shock protein expression especially that of heat shock protein 70 in sublethally damaged tumor cells. In this study, we evaluated the release of heat shock protein 70 into the serum of cancer-bearing patients directly after radiofrequency ablation. Sera of 22 patients undergoing radiofrequency ablation for the treatment of primary and secondary malignancies of the liver, kidney, and lung, as well as control sera of 20 patients undergoing diagnostic liver biopsy were analyzed using a manufactured heat shock protein 70 ELISA. A significant increase in serum levels of heat shock protein 70 was detectable in the patient cohort 1 day after radiofrequency ablation. More than a twofold increase was observed in nine out of 22 patients, which tended to correlate with favorable clinical outcome. No patient of the control group revealed a comparable increase. Radiofrequency ablation can lead to a release of heat shock protein 70 into the serum, which is transiently detectable 1 day after treatment. Elevated heat shock protein 70 serum levels may constitute a biomarker for favorable clinical outcome.
Full Text Available IgG4-related disease is a new disease entity involving IgG4 in its clinical presentation and having 6 characteristic features: (1 systemic involvement; (2 solitary or multiple lesions showing diffuse or localized swelling, masses, nodules, and/or wall thickening on imaging; (3 high serum IgG4 concentration >135 mg/dL; (4 abundant infiltration of lymphoplasmacytes and IgG4-bearing plasma cells; (5 a positive response to corticosteroid therapy; and (6 complications of other IgG4-related diseases. To date, most IgG4-related diseases have been recognized as extrapancreatic lesions of autoimmune pancreatitis. This paper will discuss the utility of IgG4 as a biomarker of IgG4-related diseases, including in the diagnosis of autoimmune pancreatitis and its differentiation from pancreatic cancer, in the prediction of relapse, in the long-term follow-up of patients with autoimmune pancreatitis and normal or elevated IgG4 concentrations, and in patients with autoimmune pancreatitis and extrapancreatic lesions, as well as the role of IgG4 in the pathogenesis of IgG4-related disease.
Ouwens, D Margriet; van Duinkerken, Eelco; Schoonenboom, S Niki M; Herzfeld de Wiza, Daniella; Klein, Martin; van Golen, Larissa; Pouwels, Petra J W; Barkhof, Frederik; Moll, Annette C; Snoek, Frank J; Teunissen, Charlotte E; Scheltens, Philip; Diamant, Michaela
Type 1 diabetes is associated with moderate cognitive decline and cerebral alterations and may lead to an increased risk of dementia, including Alzheimer's disease. This study aimed to investigate the levels of risk markers for Alzheimer's disease in middle-aged patients with type 1 diabetes and controls, and their potential associations with cognitive and cerebral measures. Levels of β-amyloid (Aβ) 42, Tau, phosphorylated Tau (pTau), the soluble form of low-density lipoprotein receptor-related protein 1 (sLRP1) and macrophage colony-stimulating factor (MCSF) were quantified by ELISA in serum and cerebrospinal fluid (CSF) collected from 37 patients with type 1 diabetes and 15 controls. Associations between biomarkers and determinants of cognitive function and white matter integrity were assessed using hierarchical regression analysis controlling for age, HbA1c and estimated intelligence quotient (IQ). CSF levels of pTau, Aβ42 and LRP1 were higher in patients with type 1 diabetes than in controls (all p < 0.05). There was a trend towards increased Tau levels in patients with type 1 diabetes (p = 0.056), while CSF levels of MCSF were similar between patients with type 1 diabetes and controls. Regression analysis showed that elevated CSF sLRP1 levels were associated with better attention (β = 0.518; p = 0.002) and a better speed of information-processing (β = 0.368; p = 0.034), as well as increased integrity of the white matter of the right inferior fronto-occipital tract (β = 0.395; p = 0.022). Furthermore, elevated Tau levels were associated with decreased integrity of the white matter of right inferior fronto-occipital tract (β = -0.584; p = 0.002). CSF levels of biomarkers for Alzheimer's disease are altered in patients with type 1 diabetes compared with controls, but the observed profile does not match the profile characterising pre-Alzheimer's disease patients.
Full Text Available S100B, established as prevalent protein of the central nervous system, is a peripheral biomarker for blood-brain barrier disruption and often also a marker of brain injury. However, reports of extracranial sources of S100B, especially from adipose tissue, may confound its interpretation in the clinical setting. The objective of this study was to characterize the tissue specificity of S100B and assess how extracranial sources of S100B affect serum levels. The extracranial sources of S100B were determined by analyzing nine different types of human tissues by ELISA and Western blot. In addition, brain and adipose tissue were further analyzed by mass spectrometry. A study of 200 subjects was undertaken to determine the relationship between body mass index (BMI and S100B serum levels. We also measured the levels of S100B homo- and heterodimers in serum quantitatively after blood-brain barrier disruption. Analysis of human tissues by ELISA and Western blot revealed variable levels of S100B expression. By ELISA, brain tissue expressed the highest S100B levels. Similarly, Western blot measurements revealed that brain tissue expressed high levels of S100B but comparable levels were found in skeletal muscle. Mass spectrometry of brain and adipose tissue confirmed the presence of S100B but also revealed the presence of S100A1. The analysis of 200 subjects revealed no statistically significant relationship between BMI and S100B levels. The main species of S100B released from the brain was the B-B homodimer. Our results show that extracranial sources of S100B do not affect serum levels. Thus, the diagnostic value of S100B and its negative predictive value in neurological diseases in intact subjects (without traumatic brain or bodily injury from accident or surgery are not compromised in the clinical setting.
Khan, Abdul Rehman; Awan, Fazli Rabbi; Najam, Syeda Sadia; Islam, Mehboob; Siddique, Tehmina; Zain, Maryam
To investigate a correlation between serum alkaline phosphatase level and body mass index in human subjects. The comparative cross-sectional study was carried out at the National Institute for Biotechnology and Genetic Engineering, Faisalabad, Pakistan, from April 2012 to June 2013. Blood serum alkaline phosphatase levels were estimated and the subjects were divided into three sub-groups on the basis of their body mass. normal weight (27kg/m2) subjects. The serum samples were used for the estimation of clinically important biochemical parameters, using commercial kits on clinical chemistry analyser. Of the 197 subjects, 97(49%) were obese and 100(51%) were non-obese. The serum alkaline phosphatase level increased in obese (214±6.4 IU/L) compared to the non-obese subjects (184.5±5 IU/L). Furthermore, a significant linear relationship (r=0.3;p-0.0001) was found between serum alkaline phosphatase and body mass index. Other biochemical variables were not correlated to the body mass index. Over activity and higher amounts of alkaline phosphatase were linked to the development of obesity.
Khan, A. R.; Awan, F. R.; Najam, S. S.; Islam, M.; Siddique, T.; Zain, M.
Objective: To investigate a correlation between serum alkaline phosphatase level and body mass index in human subjects. Methods: The comparative cross-sectional study was carried out at the National Institute for Biotechnology and Genetic Engineering, Faisalabad, Pakistan, from April 2012 to June 2013. Blood serum alkaline phosphatase levels were estimated and the subjects were divided into three sub-groups on the basis of their body mass index: normal weight (<25kg/m2), overweight (25-27kg/m2) and obese (>27kg/m2) subjects. The serum samples were used for the estimation of clinically important biochemical parameters, using commercial kits on clinical chemistry analyser. Results: Of the 197 subjects, 97(49 percent) were obese and 100(51 percent) were non-obese. The serum alkaline phosphatase level increased in obese (214±6.4 IU/L) compared to the non-obese subjects (184.5±5 IU/L). Furthermore, a significant linear relationship (r=0.3;p-0.0001) was found between serum alkaline phosphatase and body mass index. Other biochemical variables were not correlated to the body mass index. Conclusion: Over activity and higher amounts of alkaline phosphatase were linked to the development of obesity. (author)
Full Text Available Adipose tissue produces a wide range of proteins that may influence the immune system. In this study, we assessed the serum levels of leptin, adiponectin, and ghrelin, in association with the measurements of body composition, in 15 female patients with various autoimmune diseases (systemic lupus erythematosus, primary Sjögren's syndrome, sarcoidosis, mixed connective tissue disease, vasculitis, CREST syndrome, and polymyositis and in 15 healthy female controls. There were no statistically significant differences between the patients and controls with regard to serum leptin, serum ghrelin, global fat mass, adiposity, and fat mass in the android or gynoid regions, whereas serum adiponectin levels were higher in patients than controls (16.3±1.6 μg/mL versus 9.7±0.6 μg/mL; =.01. As adiponectin is known to exhibit potent anti-inflammatory properties, a high adiponectinemia in patients with systemic autoimmune disease may mitigate the inflammatory response. However, the precise consequences of these elevated serum adiponectin levels on the metabolic syndrome development and atherosclerotic cardiovascular risk in this patient population still needs to be determined.
Full Text Available The measurement of serum tumor markers levels in breast cancer (BC patients is an economic and noninvasive diagnostic assay frequently requested by clinical oncologists to get information about the presence or absence of disease as well as its evolution. Despite their wide use in clinical practice, there is still an intense debate between scientific organizations about the real usefulness for patient monitoring during followup as well as response to therapy evaluation in case of advanced BC. In this review, we want to highlight the current recommendations published by scientific organizations about the use of “established” BC serum markers (CEA, TPA, TPS, CIFRA-21, CA15-3, and s-HER2 in clinical oncology practice. Moreover, we will focus on recent papers evidencing the usefulness of tumor markers levels measurement as a guide for the prescription and diagnostic integration of molecular imaging exams such as those performed by hybrid 18-fluorofeoxyglucose-positron emission tomography with integrated computed tomography. This technology is nowadays able to detect early cancer lesions undetectable by conventional morphological imaging investigation and most likely responsible for increasing of serum tumor markers levels.
Full Text Available Background and Aims. Dysregulation of miR-223 was recently linked to various diseases associated with systemic inflammatory responses such as type 2 diabetes, cancer, and bacterial infections. However, contradictory results are available on potential alterations of miR-223 serum levels during sepsis. We thus aimed to evaluate the diagnostic and prognostic value of miR-223 serum concentrations in patients with critical illness and sepsis. Methods. We used i.v. injection of lipopolysaccharide (LPS as well as cecal pole ligation and puncture (CLP for induction of polymicrobial sepsis in mice and measured alterations in serum levels of miR-223. These results from mice were translated into a large and well-characterized cohort of critically ill patients admitted to the medical intensive care unit (ICU. Finally, results from analysis in patients were correlated with clinical data and extensive sets of routine and experimental biomarkers. Results. Although LPS injection induced moderately elevated serum miR-223 levels in mice, no significant alterations in miR-223 serum levels were found in mice after CLP-induced sepsis. In accordance with these results from animal models, serum miR-223 levels did not differ between critically ill patients and healthy controls. However, ICU patients with more severe disease (APACHE-II score showed moderately reduced circulating miR-223. Strikingly, no differences in miR-223 levels were found in critically ill patients with or without sepsis, and serum levels of miR-223 did not correlate with classical markers of inflammation or bacterial infection. Finally, low miR-223 serum levels were moderately associated with an unfavorable prognosis of patients during the ICU treatment but did not predict long-term mortality. Conclusion. Recent reports on alterations in miR-223 serum levels during sepsis revealed contradictory results, preventing a potential use of this miRNA in clinical routine. We clearly show that miR-223 serum
Full Text Available Background. Few studies have shown that self-reported secondhand smoke exposure in never smokers is associated with high blood pressure. However, there are no studies investigating the relationship between secondhand smoke exposure, measured objectively by serum cotinine levels, and high blood pressure in never smokers. Methods. We examined never smokers (n=2027 from the National Health and Nutrition Examination Survey 2005–2008. Our exposure of interest was the secondhand smoke exposure estimated by serum cotinine level and our outcome was prehypertension (n=734, defined as a systolic blood pressure of 120–139 mmHg or diastolic blood pressure of 80–89 mmHg. Results. We found that, in never smokers, serum cotinine levels were positively associated with prehypertension. Compared to those with cotinine levels in the lowest quartile (≤0.024 ng/mL, the multivariable odds ratio (95% confidence interval of prehypertension among those with cotinine levels in the highest quartile (≥0.224 ng/mL was 1.45(1.00, 2.11; P trend =0.0451. In subsequent subgroup analyses, the positive association was found to be stronger among men, non-Whites, and non-obese subjects. Conclusion. Higher secondhand smoke exposure measured objectively by serum cotinine levels was found to be associated with prehypertension in certain subgroups of a representative sample of the US population.
Asilsoy, Suna; Bekem, Ozlem; Karaman, Ozkan; Uzuner, Nevin; Kavukçu, Salih
Serum carnitine is decreased in recurrent pulmonary infections. We aimed to evaluate serum carnitine levels in asthmatic children. Study group consisted of children with stable asthma and those with acute asthma attacks, while control group included healthy children. Attack severity was determined by the pulmonary score system. Total and free carnitine levels were studied in one blood sample from the control group and stable asthmatics and in two samples from children with acute asthma exacerbation during and after the attack. All the 40 patients in the study group had moderate asthma including 30 with acute attack (13 mild and 17 moderate) and 10 with stable asthma. Carnitine levels were significantly lower in acute attack asthmatics than in the stable asthmatics and controls, while there was no significant difference between the latter two groups. Carnitine levels were not different between asthmatics with mild and moderate attack, and were similar during and after an acute attack. Serum carnitine levels decrease in children with moderate asthma during exacerbation of asthma and shortly thereafter. Further studies are needed to evaluate the effect of carnitine treatment on serum carnitine level.
Demir, Betul; Ucak, Haydar; Cicek, Demet; Aydin, Suleyman; Erden, Ilker; Dertlioglu, Selma Bakar
Androgens and insulin may contribute to increased sebum production in the pathogenesis of acne vulgaris. We investigated the association between serum desnutrin levels and acne vulgaris in the pathogenesis of insulin resistance. 25 patients presenting with acne vulgaris and 25 control subjects participated in this study. Fasting blood glucose, triglycerides, LDL, VLDL, HDL, total cholesterol, insulin, C-peptide and thyroid function tests were measured. The homeostasis model assessment of insulin resistance (HOMA-IR) was used to calculate insulin resistance. Desnutrin levels were determined by enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's protocol. Patients with acne vulgaris had a mean serum desnutrin level of (8.83 ± 1.13 μIU/mL), which was statistically significantly lower in the control group (10:58 ± 3.43 μIU/mL). In patients with acne vulgaris the serum glucose levels, insulin levels and HOMA-IR values (87.92 ± 7:46 mg/dL, 11.33 ± 5.93 μIU/mL, 2.49 ± 1.40, respectively) were significantly higher than the control group (77.36 ± 9.83 mg/dL, 5.82 ± 2.68 μIU/mL, 1.11 ± 0.51, respectively) (p = 0.01, pacne vulgaris, as a result of increased levels of serum glucose and insulin, the function of desnutrin was suppressed, perhaps contributing to insulin resistance.
Full Text Available The κ/λ hybrid antibodies in normal human serum were reported recently, but their clinical relevance has not yet been explored. Rheumatoid arthritis (RA is one of the major joint diseases, and the early diagnosis and treatment of RA remain a challenge. Here, we developed a double-sandwich enzyme-linked immunosorbent assay system to quantify relative serum κ/λ hybrid antibody levels in RA patients, osteoarthritis (OA patients, and healthy controls (HC in order to assess their potential use as a serological biomarker of early disease and clinical activity and to preliminarily investigate their immunomodulatory roles in RA. Surprisingly, we found that κ/λ hybrid antibody was markedly increased in both early and established RA. Serum κ/λ hybrid antibody levels were significantly correlated with clinical indexes and inflammatory markers in RA. Further analysis showed a positive correlation between κ/λ hybrid antibody levels and the 28-joint disease activity score (DAS28. In conclusion, serum κ/λ hybrid antibodies in RA were identified for the first time. High levels of κ/λ hybrid antibody may be a useful tool in distinguishing early RA from OA and HC. We suggest κ/λ hybrid antibody as a marker for disease activity. The increased κ/λ hybrid antibodies were associated with inflammatory conditions in RA.
Full Text Available Wenjing Ruan,1 Minliang Wu,2 Liuhong Shi,1 Fengying Li,3 Liangliang Dong,1 Yuanhua Qiu,1 Xiaohong Wu,1 Kejing Ying1 1Department of Respiratory Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 2Department of Laboratory, The Second Affiliated Hospital of Zhejiang University, School of Medicine, 3Department of Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Hangzhou, China Objective: The purpose of this study was to explore the insulin-like growth factor binding protein 7 (IGFBP7 level in the serum of chronic obstructive pulmonary disease (COPD patients during acute exacerbation (AE.Methods: The study population consisted of 47 AECOPD patients, including 25 patients enrolled between January 2011 and February 2011 (the first group and 22 patients enrolled from December 2011 to August 2012 (the second group and 29 healthy controls. Chemiluminescence–linked immunoassay was used to detect serum IGFBP7 levels. For the second group patients, IGFBP7 and C-reactive protein (CRP levels were measured both on the admission day and on the discharge day.Results: Among the first group AECOPD patients, serum IGFBP7 levels were significantly elevated in AECOPD patients in the intensive care unit (ICU; 52.92±16.32 ng/mL, and in hospitalized AECOPD patients not in ICU (40.66±13.9, compared to healthy subjects (30.3±7.09 ng/mL; P<0.01. For the second group AECOPD patients, the increased IGFBP7 levels reduced after the patients had recovered (34.42±11.88 vs 27.24±7.2 ng/mL; P<0.01. During AE, the correlation coefficient between IGFBP7 and CRP was 0.357. In receiver operating characteristic analysis, the area under the curve was 0.799 for CRP, and 0.663 for IGFBP7 in distinguishing patients with AECOPD on the admission day from the discharge day.Conclusion: Serum IGFBP7 levels were raised during AECOPD. Similar to the expression pattern of CRP, the IGFBP7 levels reduced after convalescence, suggesting that IGFBP7
Petersen, Kasper Meidahl; Eplov, Kasper; Nielsen, Torben Kjær
allocations within sealed opaque envelopes. Participants and all staff were kept blinded to treatment allocations during the trial. Serum folate was measured at baseline and at end of trial. In the 58 participants analyzed (30 in the trimethoprim group and 28 in the placebo group), 8 had folate deficiency......Trimethoprim antagonize the actions of folate by inhibition of dihydrofolate reductase. This could diminish serum folate levels in humans and causes folate deficiency in some patients. We conducted a randomized, double-blind, placebo-controlled trial, to investigate the effect of trimethoprim...... on serum folate levels in healthy participants after a 7-day trial period. Thirty young, healthy males were randomly allocated to receive trimethoprim, 200 mg twice daily, and 30 were randomly allocated to placebo. Before trial initiation, participant numbers were given randomly generated treatment...
Full Text Available Florin Petrescu1, Sebastian Cosmin Voican1, Isabela Silosi21Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, Craiova, Romania; 2Department of Immunology, University of Medicine and Pharmacy of Craiova, Craiova, RomaniaBackground: Tobacco smoking is the most important risk factor for chronic obstructive pulmonary disease (COPD development. Inhaled cigarette smoke can induce tumor necrosis factor-a (TNF-a production by alveolar macrophages, which in turn may enhance the production of metalloproteinases (MMPs. MMPs have been involved in mediating airway inflammation and lung destruction.Objectives: We aimed to measure the TNF-a serum levels in healthy heavy smokers and healthy nonsmokers to determine the dose-response relationship based on the cigarette smoke exposure.Subjects and methods: We included in our study 43 healthy heavy smokers and 19 healthy nonsmokers (the control group. The smokers group was classified as less than one pack, one pack, and more than one pack per day. A clinical and paraclinical evaluation was performed in both groups, without any evidence of infection or COPD. The serum levels of TNF-a were assessed by ELISA.Results: The TNF-a serum levels were significantly higher for the group of smokers compared to the group of nonsmokers (P < 0.004. We also noticed an increased TNF-a concentration in the serum of smokers with more than one pack per day compared with those with less than one pack per day (P < 0.03. There was a positive correlation between the serum level of TNF-a and tobacco smoke exposure.Conclusions: The high levels of TNF-a in the serum of smokers suggest an imbalance between the proinflammatory and anti-inflammatory factors as a result of tobacco smoke exposure. The concentration of TNF-a is elevated in the serum of healthy heavy smokers in a cigarette dose-dependent manner. We speculate that the serum level of TNF-a might be a useful biomarker for the selection of heavy smokers
Moore, Richard G; Plante, Beth; Hartnett, Erin; Mitchel, Jessica; Raker, Christine A; Vitek, Wendy; Eklund, Elizabeth; Lambert-Messerlian, Geralyn
Human epididymis protein 4 is a serum biomarker to aid in differentiating benign and malignant disease in women with a pelvic mass. Interpretation of human epididymis protein 4 results relies on robust normative data. The purpose of this study was to evaluate whether human epididymis protein 4 levels are variable in women during the normal menstrual cycle. Healthy women, 18-45 years old, with regular menstrual cycles were recruited from community gynecologic practices in Rhode Island. Women consented to enroll and to participate by the donation of blood and urine samples at 5 specific times over the course of each cycle. Levels of reproductive hormones and human epididymis protein 4 were determined. Data were analyzed with the use of linear regression after log transformation. Among 74 enrolled cycles, 53 women had confirmed ovulation during the menstrual cycle and completed all 5 sample collections. Levels of estradiol, progesterone, and luteinizing hormone displayed the expected menstrual cycle patterns. Levels of human epididymis protein 4 in serum were relatively stable across the menstrual cycle, except for a small ovulatory (median, 37.0 pM) increase. Levels of human epididymis protein 4 in urine, after correction for creatinine, displayed the same pattern of secretion observed in serum. Serum human epididymis protein 4 levels are relatively stable across the menstrual cycle of reproductive-aged women and can be determined on any day to evaluate risk of ovarian malignancy. A slight increase is expected at ovulation; but even with this higher human epididymis protein 4 level, results are well within the healthy reference range for women (<120 pM). Levels of human epididymis protein 4 in urine warrant further investigation for use in clinical practice as a simple and convenient sample. Copyright © 2017 Elsevier Inc. All rights reserved.
Chang, Yu-Tang; Huang, Ming-Yii; Yeh, Yung-Sung; Huang, Ching-Wen; Tsai, Hsiang-Lin; Cheng, Tian-Lu; Wang, Jaw-Yuan
Circulating biomarkers can predict clinical outcomes in colorectal cancer patients. The aim of the study was to evaluate the feasibility of our multigene biomarker chip for detecting circulating tumor cells for postoperative surveillance of stage I-III colorectal cancer patients. In total, 298 stage I-III colorectal cancer patients were analyzed after curative resection between June 2010 and October 2014. During each follow-up, a postoperative surveillance strategy, including ESMO Guidelines Working Group recommendations and the biochip, was used. After a 28.4-month median follow-up, 48 (16.1%) patients had postoperative relapse. Univariate analysis revealed that the postoperative relapse risk factors were rectal tumor, perineural invasion, elevated preoperative and postoperative serum carcinoembryonic antigen levels, and positive biochip results (all P carcinoembryonic antigen levels (odds ratio = 4.136, P = 0.008) and positive biochip results (odds ratio = 66.878, P carcinoembryonic antigen levels. Moreover, the median lead time between positive biochip result and postoperative relapse detection was significantly earlier than that between elevated postoperative serum carcinoembryonic antigen level and postoperative relapse detection (10.7 vs. 2.8 months, P carcinoembryonic antigen detection, our multigene chip aided more accurate and earlier prediction of postoperative relapse during stage I-III colorectal cancer patient surveillance. In clinical practice, this biochip may facilitate early postoperative relapse diagnosis in colorectal cancer patients.
Chai Yanlan; Wang Juan; Gao Ying
Radiation-induced acute intestinal symptoms (RIAISs) are the most frequent complication of radiotherapy that causes great pain and limits the treatment efficacy. The aim of this study was to identify serum biomarkers of RIAISs in cervical cancer patients by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Serum samples were collected from 66 cervical cancer patients prior to pelvic radiotherapy. In our study, RIAISs occurred in 11 patients. An additional 11 patients without RIAISs were selected as controls, whose age, stage, histological type and treatment methods were matched to RIAISs patients. The 22 sera were subsequently analyzed by SELDI-TOF MS, and the resulting protein profiles were evaluated to identify biomarkers using appropriate bioinformatics tools. Comparing the protein profiles of serum samples from the RIAIS group and the control group, it was found that 22 protein peaks were significantly different (P < 0.05), and six of these peaks with mass-to-charge (m/z) ratios of 7514.9, 4603.94, 6887.41, 2769.21, 3839.72 and 4215.7 were successfully identified. A decision tree model of biomarkers was constructed based on three biomarkers (m/z 1270.88, 1503.23 and 7514.90), which separated RIAIS-affected patients from the control group with an accuracy of 81%. This study suggests that serum proteomic analysis by SELDI-TOF MS can identify cervical cancer patients that are susceptible to RIAISs prior to pelvic radiotherapy. (author)
Wiener, Carolina David; de Mello Ferreira, Sharon; Pedrotti Moreira, Fernanda; Bittencourt, Guilherme; de Oliveira, Jacqueline Flores; Lopez Molina, Mariane; Jansen, Karen; de Mattos Souza, Luciano Dias; Rizzato Lara, Diogo; Portela, Luiz Valmor; da Silva, Ricardo Azevedo; Oses, Jean Pierre
Nerve growth factor (NGF) is an important member of the neurotrophins group and their involvement in the pathophysiology of major depression disorder (MDD) and suicide risk (SR) has been recently suggested. The aim of this study is to evaluate the changes in NGF serum levels in individuals with MDD and with or without risk of suicide, in subjects from a young population-based sample. This is a paired cross-sectional study nested in a population-based study. Individuals were rated for MDD and SR by a diagnostic interview--Mini International Neuropsychiatric Interview (M.I.N.I). The total population of the sample was comprised of 141 subjects distributed in three groups: 47 healthy controls, 47 subjects with current depressive episode without SR (MDD) and 47 subjects with current depressive episode and with SR (MDD + SR). NGF serum levels were significantly reduced in the MDD and MDD + SR groups when compared with controls (p ≤ 0.001). However, there were no differences in NGF levels between the MDD and MDD + SR groups (p = 1.000). These results suggest that reduced NGF serum levels can be a possible biomarker of MDD. Copyright © 2015 Elsevier B.V. All rights reserved.
Toros, Sema Zer; Ozel, Leyla; Yekrek, Mehmet Murat; Toros, Ahmet Burak; Naiboglu, Baris; Kara, Melih; Erdoğdu, Erdal; Egeli, Erol; Titiz, Izzet
The goal of this study was to investigate the effects of routine thyroid gland palpation on serum thyroid hormone levels. Prospective study at Haydarpaşa Numune Research and Education Hospital, Istanbul, Turkey. This study was carried out in two groups with a total of 50 consecutive adults. Group I consisted of 20 patients (12 female and 8 male, aged 20-48 years) with a diagnosis of nodular thyroid disease confirmed by ultrasound imaging techniques. The second group consisted of 30 otherwise healthy subjects (17 female and 13 male, aged 18-50 years) referred for neck and thyroid ultrasound and with no thyroid pathology detected. Thyroid gland palpations were performed by the same physician. Blood samples were obtained before and 2 hours after thyroid gland palpation. Serum total T3 (TT3), total T4 (TT4), free T3 (FT3), free T4 (FT4), thyroid stimulating hormone (TSH), and thyroglobulin (TG) measurements were made. We found that routine palpation in the first group caused a significant increase in serum TT3 (P .05). Preliminary data proposing a possible effect of routine thyroid gland palpation on serum thyroid hormone levels suggest that serum thyroid hormone measurements should be performed before any manipulation of the gland, including palpation, to avoid misdiagnosis.
Tran, Lara; Palmiere, Cristian
The first aim of this study was to assess whether non-allergic deaths in non-atopic individuals with increasing postmortem intervals are characterized by progressively greater concentrations of total IgE in postmortem serum from femoral blood. Our second goal was to determine whether traumatic deaths with different survival times, septic deaths, and deaths in individuals suffering from diseases with significant systemic inflammation are systematically characterized by increased concentrations of total IgE in postmortem serum from femoral blood. Four study groups were prospectively and retrospectively formed (non-allergic deaths in non-atopic individuals with increasing postmortem intervals, traumatic deaths in non-atopic individuals with different survival times, deaths possibly related to sepsis in non-atopic individuals, and deaths occurring in non-atopic individuals with disseminated malignancies at autopsy). Unenhanced computed tomography, autopsy, histology, and biochemistry were performed in all cases. First results indicate that increasing postmortem intervals are not associated with progressively increasing postmortem serum IgE levels. Moreover, the obtained results do not reveal that severe trauma, bacterial sepsis, and disseminated malignancies are systematically associated with increased postmortem serum IgE levels, irrespective of survival time duration. Though the usefulness of increased total IgE concentrations in postmortem samples to assess any underlying atopic disposition or death preceded by acute IgE-mediated allergic reaction remains questionable, measurements of total IgE are possible in postmortem serum samples.
Dunn, Michael E; Manfredi, Thomas G; Agostinucci, Kevin; Engle, Steven K; Powe, Josh; King, Nicholas M P; Rodriguez, Luis A; Gropp, Kathryn E; Gallacher, Matthew; Vetter, Frederick J; More, Vijay; Shimpi, Prajakta; Serra, David; Colton, Heidi M
Given the proven utility of natriuretic peptides as serum biomarkers of cardiovascular maladaptation and dysfunction in humans and the high cross-species sequence conservation of atrial natriuretic peptides, natriuretic peptides have the potential to serve as translational biomarkers for the identification of cardiotoxic compounds during multiple phases of drug development. This work evaluated and compared the response of N-terminal proatrial natriuretic peptide (NT-proANP) and N-terminal probrain natriuretic peptide (NT-proBNP) in rats during exercise-induced and drug-induced increases in cardiac mass after chronic swimming or daily oral dosing with a peroxisome proliferator-activated receptor γ agonist. Male Sprague-Dawley rats aged 8 to 10 weeks were assigned to control, active control, swimming, or drug-induced cardiac hypertrophy groups. While the relative heart weights from both the swimming and drug-induced cardiac hypertrophy groups were increased 15% after 28 days of dosing, the serum NT-proANP and NT-proBNP values were only increased in association with cardiac hypertrophy caused by compound administration. Serum natriuretic peptide concentrations did not change in response to adaptive physiologic cardiac hypertrophy induced by a 28-day swimming protocol. These data support the use of natriuretic peptides as fluid biomarkers for the distinction between physiological and drug-induced cardiac hypertrophy.
Full Text Available Background. It has been reported that several microRNAs (miRNAs, such as miR-141, miR-9, and miR-122, are involved in the regulation of pancreatitis-related proteins or that their levels change in acute pancreatitis (AP animal models. However, the serum levels, as well as the clinical diagnostic and prognostic values, of these miRNAs in AP patients remain unclear. Furthermore, as a pancreas- (islet enriched miRNA, miR-7 was reported to be downregulated in AP patients, which requires further verification. Methods. The levels of miR-7, miR-9, miR-122, and miR-141 were examined and compared using qRT-PCR among 80 severe AP patients, 80 mild AP patients, and 74 healthy controls. Results. The serum levels of these four miRNAs were increased markedly in the AP patients compared with the controls, and these levels decreased significantly after effective therapy. Particularly, the level of miR-7 was higher in severe AP patients than in mild AP patients. ROC curve analysis demonstrated that four miRNAs could be used as potential biomarkers for AP. Moreover, these miRNAs showed strong positive correlations with CRP, which may be associated with inflammation. Conclusions. The serum miR-7, miR-9, miR-122, and miR-141 levels were increased in AP patients. These 4 miRNAs may represent diagnostic and prognostic biomarkers for AP.
Full Text Available To investigate the serum levels of Brain Derived Neurotrophic Factor (BDNF and Nerve Growth Factor (NGF in patients affected by primary open angle glaucoma with a wide spectrum of disease severity compared to healthy controls and to explore their relationship with morphological and functional glaucoma parameters.45 patients affected by glaucoma at different stages and 15 age-matched healthy control subjects underwent visual field testing, peripapillary retinal nerve fibre layer thickness measurement using Spectral Domain Optical Coherence Tomography and blood collection for both neurotrophins detection by Enzyme-Linked Immunosorbent Assay. Statistical analysis and association between biostrumental and biochemical data were investigated.Serum levels of BDNF in glaucoma patients were significantly lower than those measured in healthy controls (261.2±75.0 pg/ml vs 313.6±79.6 pg/ml, p = 0.03. Subgroups analysis showed that serum levels of BDNF were significantly lower in early (253.8±40.7 pg/ml, p = 0.019 and moderate glaucoma (231.3±54.3 pg/ml, p = 0.04 but not in advanced glaucoma (296.2±103.1 pg/ml, p = 0.06 compared to healthy controls. Serum levels of NGF in glaucoma patients were significantly lower than those measured in the healthy controls (4.1±1 pg/mL vs 5.5±1.2 pg/mL, p = 0.01. Subgroups analysis showed that serum levels of NGF were significantly lower in early (3.5±0.9 pg/mL, p = 0.0008 and moderate glaucoma (3.8±0.7 pg/ml, p<0.0001 but not in advanced glaucoma (5.0±0.7 pg/ml, p = 0.32 compared to healthy controls. BDNF serum levels were not related to age, visual field mean deviation or retinal nerve fibre layer thickness either in glaucoma or in controls while NGF levels were significantly related to visual field mean deviation in the glaucoma group (r2 = 0.26, p = 0.004.BDNF and NGF serum levels are reduced in the early and moderate glaucoma stages, suggesting the possibility that both factors could be further investigated
Full Text Available Asli Gorek Dilektasli,1 Ezgi Demirdogen Cetinoglu,1 Esra Uzaslan,1 Ferah Budak,2 Funda Coskun,1 Ahmet Ursavas,1 Ilker Ercan,3 Ercument Ege1 1Department of Pulmonary Disesaes, 2Department of Immunology, 3Department of Biostatistics, Uludag University Faculty of Medicine, Bursa, Turkey Introduction: Chemokine (C-C motif ligand 18 (CCL-18 has been shown to be elevated in chronic obstructive pulmonary disease (COPD patients. This study primarily aimed to evaluate whether the serum CCL-18 level differentiates the frequent exacerbator COPD phenotype from infrequent exacerbators. The secondary aim was to investigate whether serum CCL-18 level is a risk factor for exacerbations requiring hospitalization. Materials and methods: Clinically stable COPD patients and participants with smoking history but normal spirometry (NSp were recruited for the study. Modified Medical Research Council Dyspnea Scale, COPD Assessment Test, spirometry, and 6-min walking test were performed. Serum CCL-18 levels were measured with a commercial ELISA Kit. Results: Sixty COPD patients and 20 NSp patients were recruited. Serum CCL-18 levels were higher in COPD patients than those in NSp patients (169 vs 94 ng/mL, P<0.0001. CCL-18 level was significantly correlated with the number of exacerbations (r=0.30, P=0.026, although a difference in CCL-18 values between infrequent and frequent exacerbator COPD (168 vs 196 ng/mL subgroups did not achieve statistical significance (P=0.09. Serum CCL-18 levels were significantly higher in COPD patients who had experienced at least one exacerbation during the previous 12 months. Overall, ROC analysis revealed that a serum CCL-18 level of 181.71 ng/mL could differentiate COPD patients with hospitalized exacerbations from those who were not hospitalized with a 88% sensitivity and 88.2% specificity (area under curve: 0.92. Serum CCL-18 level had a strong correlation with the frequency of exacerbations requiring hospitalization (r=0.68, P<0
Full Text Available Aim To compare plasma IL-10 concentrations in patients with Acute Coronary Syndrome (ACS with those in Coronary Artery Disease (CAD.Methods ACS patients hospitalized in intensive coronary care unit (ICCU of Cipto Mangunkusumo Hospital/Faculty of Medicine University of Indonesia (CMH/FMUI, Persahabatan Hospital, MMC Hospital, and Medistra Hospital, Jakarta, between May 2005 and May 2006, were included in this study. The ambulatory CAD patients were taken as comparator. The serum IL-10 level was measured by immunoassay method, and compared by using Independent Student’s t-test. To investigate whether IL-10 serum level could predict ACS, the sensitivity and specificity of this parameter towards ACS in various IL-10 serum levels were calculated as well.Results In this observational study, as many as 146 subjects were analyzed, consisting of 84 ACS patients, and 62 coronary artery disease (CAD. The IL-10 level was higher in the group of ACS patients (7.37 pg/mL + 7.81, CI 95% 5.68-9.07 than that in CAD patients (1.59 pg/mL + 1.55, CI 95% 1.2-1.98. The optimal cut-off point for serum IL-10level is >1.95 pg/mL, with 79.76 % sensitivity and 77.42 % specificity.Conclusion The IL-10 level was higher in the ACS patients compared to that in CAD patients. Serum IL-10 measurement is a quite superior method to distinguish acute and stable condition, eventhough it is not as good as hsCRP for the same purpose. (Med J Indones 2009;18:165-9Key words: Interleukin-10, acute coronary syndrome
Lee, Ju-Mi; Kim, Hyeon Chang; Cho, Hye Min; Oh, Sun Min; Choi, Dong Phil; Suh, Il
Serum uric acid levels have been reported to be associated with a variety of cardiovascular conditions. However, the direct association between uric acid levels and metabolic syndrome remains controversial. Thus, we evaluated the association of serum uric acid levels and metabolic syndrome in a community-based cohort study in Korea. We performed cross-sectional analysis of baseline data of 889 males and 1491 females (aged 38 to 87) who participated in baseline examinations of the Korean Genome and Epidemiology Study: Kanghwa study. Blood samples were collected after at least an 8 hour fast. Uric acid quartiles were defined as follows: Metabolic syndrome was defined by the National Cholesterol Education Program Adult Treatment Panel III Criteria with adjusted waist circumference cutoffs (90 cm for males; 80 cm for females). The association between serum uric acid quartiles and metabolic syndrome was assessed using multivariate logistic regression. The odds ratio for having metabolic syndrome in the highest versus lowest quartiles of serum uric acid levels was 2.67 (95% confidence interval [CI], 1.60 to 4.46) in males and 2.14 (95% CI, 1.50 to 3.05) in females after adjusting for age, smoking, alcohol intake, body mass index, total cholesterol, HbA1c, albumin, γ-glutamyltransferase, blood urea nitrogen, and log C-reactive protein. The number of metabolic abnormalities also increased gradually with increasing serum uric acid levels (adjusted p for trend uric acid levels are positively associated with the presence of metabolic syndrome in Korean males and females.
Vasavada, P.; Chen, I.; Maxon, H.; Barnes, E.; Sperling, M.
The diagnosis of borderline hyperthyroidism is difficult. A sensitive radioimmunoassay capable of detecting subnormal levels of serum TSH may be of value in confirming this diagnosis because of the suppressed pituitary function in this disease state. This sensitive assay may also be useful in monitoring the suppression of pituitary function in thyroid cancer patients receiving thyroid hormone therapy. A sensitive radioimmunoassay capable of detecting serum TSH levels as low as 0.25 μU/m1 with coefficients of variation less than 17.2% was used to measure serum TSH levels in 80 healthy subjects, 44 hyperthyroid patients, and 25 athyrotic thyroid cancer patients on daily suppressive doses of thyroxine. All healthy subjects had detectable TSH levels with a mean value of 1.17 and two standard deviation ranges of 0.41 - 2.70 μU/m1 (lognormal distribution). Although the mean +-1 SEM value of 0.63 +- 0.003 μUm1 for hyperthyroid patients and 0.76 +- 0.08 μU/ml for thyroid cancer patients were significantly lower than that of healthy subjects (t-test, p<0.05), subnormal levels of serum TSH were found in only 28.6% (12/42) and 24% (6/25) of hyperthyroid and thyroid cancer patients, respectively. TSH stimulation tests performed in 6 of the cancer patients all gave suppressed responses. Because of considerable overlap, serum TSH levels alone cannot distinguish hyperthyroidsm from euthyroidism. However, a sensitive TSH radioimmunoassay such as the one described here may be of value in evaluating the extent of pituitary suppression in thyroid cancer therapy
Aim : This study was performed to compare the serum lipid levels of pregnant normotensive and pre-eclamptic women. Methods: It was a case control study involving 50 normotensive and 50 preeclamptic women at the University College Hospital, Ibadan, making a total of 100 participants. Their venous blood (5mls) was ...
Full Text Available Background/Aims: Hyperuricemia has been reported to affect renal hemodynamics in rat models. We evaluate the relationship between serum uric acid and intrarenal hemodynamic parameters in humans, utilizing the plasma clearance of para-aminohippurate (CPAH and inulin (Cin. Methods: Renal and glomerular hemodynamics were assessed by simultaneous measurement of CPAH and Cin in 58 subjects. Of these, 19 subjects were planned to provide a kidney for transplantation; 26 had diabetes without proteinuria; and 13 had mild proteinuria. Renal and glomerular hemodynamics were calculated using Gomez`s formulae. Results: Cin was more than 60 ml/min/1.73m2 in all subjects. Serum uric acid levels correlated significantly with vascular resistance at the afferent arteriole (Ra (r = 0.354, p = 0.006 but not with that of the efferent arteriole (Re. Serum uric acid levels (β = 0.581, p = a after adjustment for several confounders (R2 = 0.518, p = Conclusions: These findings suggest, for the first time in humans, that higher serum uric acid levels are associated significantly with Ra in subjects with Cin > 60 ml/min/1.73m2. The increase in Ra in subjects with higher uric acid levels may be related to dysfunction of glomerular perfusion.
Dec 21, 2013 ... However, in one study, clinical factors may have influenced serum bilirubin levels. Bilirubin suppresses ... of inducible nitric oxide, as well as, the secretion of phospholipase A2 and NO; therefore, ... hypoxia, severe hemodynamic instability and/or possible brain death were excluded. Blood samples were ...
The Cochrane. Library2012. 5. Shazia Q, Mohammad ZH, Rahman T, Shekhar HU. Correlation of oxidative stress with serum trace element levels and antioxidant enzyme status in Beta thalassemia major patients: a review of the literature. Anemia2012, 2012:270923. 6. Powell SR. The antioxidant properties of zinc. The.
Summary: Serum levels of the immunoglobulins: IgG, IgA and IgM were determined by the single radial immunodiffusion technique of Mancini in a total of 122 apparently healthy subjects consisting of 43 children (20 males; 23 females) aged 5-12 years and 79 adults (39 males; 40 females) aged 18-65 years resident in Port ...
Methods. An analysis of 8 453 adults aged .20 years was performed. Every subject completed a household interview and a questionnaire regarding personal health, and their BMI and serum C-reactive protein (CRP) level were measured. The BMI data were divided into quintiles, using multiple linear regression to estimate ...
Serum levels of the immunoglobulins: IgG, IgA and IgM were determined by the single radial immunodiffusion technique of Mancini in a total of 122 apparently healthy subjects consisting of 43 children (20 males; 23 females) aged 5-12 years and 79 adults (39 males; 40 females) aged 18-65 years resident in Port Harcourt, ...
Apr 18, 2011 ... pathogenesis of several other diseases, including rheumatoid arthritis (Katrib et al., 2003; Yoshihara et al.,. 2000), which share several features with periodontitis, including the chronic nature of the inflammatory reaction and tissue destruction activity. In the present study, TIMP-1 serum levels were increa-.
A study was conducted to evaluate the haematology and serum indices of broiler starter fed graded levels of raw pride of Barbados (Caesalpina pulcherima) seedmeal. Seventy two day old Marshal broiler chicks obtained from Obasanjo Farms, Igboora, Oyo state, Nigeria were randomly assigned into four treatments, each ...
Pregnant women in developing countries have been reported to consume diets with low density of minerals and essential trace elements. Therefore, this study aims to assess the serum levels of magnesium and manganese and its trimester correlates among pregnant women in Ika community of Delta state, Nigeria.
... between two groups was statistically significant. Conclusion: Our study is probably the first study in India comparing serum resistin levels of CKD patients vis-à-vis control subjects. Further cellular research may be needed to explore this relation. Key words: Chronic kidney disease, HOMA-IR, insulin resistance, resistin ...
Malekahmadi, Mohammad; Farrahi, Fereydoun; Tajdini, Afshin
Chalazion is a chronic, localized lipogranulomatous inflammation of the sebaceous glands of the lids. Chalazion occurs often secondary to blockage of the sebaceous gland ducts. Some studies have reported vitamin A deficiency as a risk factor for chalazion. In this study, we determined the serum levels of vitamin A in patients with chalazion. The study involved a total of 107 subjects (52 patients with chalazion and 55 control healthy subjects). The study was conducted at the Ophthalmology Clinics of Imam Khomeini Hospital, Ahwaz Jundishapur University of Medical Sciences, Ahwaz, Iran between September 2014 and February 2015. The subjects were divided into three groups according to age: 7-12 years old, 13-19 years old, and more than 19 years old. Patients were further divided into four subgroups based on the type of chalazion: single, multiple, primary, and recurrent. Blood samples were collected and the serum was tested for levels of vitamin A using high-performance liquid chromatography (HPLC). The average serum vitamin A levels in patients with chalazion in the age groups of 7-12 and 13-19 years were significantly lower than in their control counterparts. Serum vitamin A levels in patients with recurrent, multiple chalazia were significantly lower than in patients with primary, multiple chalazia (P = 0.026) and patients with a recurrent, single chalazion (P = 0.029). In conclusion, chalazion could be one of the ocular presentations of vitamin A deficiency.
The serum levels of the thyroid hormones (T4 and T3) and thyrotropin (TSH) were measured by radio-immunoassay (RIA) in the steady state of 10 homozygous sickle cell anaemia patients and 10 normal subjects of the same age group in years (15-25) who were the control group. The results showed that sickle cell disease ...
... (p<0.05) than those of the control samples. Serum aminotransferases and bilirubin levels should therefore be routinely monitored in malaria patients since Plasmodium parasites invasion could produce liver and blood complications, even when least suspected. International Journal of Natural and Applied Sciences Vol.
Background: Vitamin A deficiency (VAD) affects an estimated 6 million pre-school children in Nigeria and 20 million in Africa. When associated with severe malnutrition, it significantly increases morbidity and mortality. Objectives: To determine serum vitamin A levels in children with Protein Energy Malnutrition and age and ...
Pulmonary tuberculosis (PTB) is still a very common cause of morbidity and mortality around the globe and the disorder of calcium and inorganic phosphate metabolism has been poorly associated with the infection. This study was aimed at assessing the total serum calcium and inorganic phosphate levels in PTB patients in ...
The haematological profiles and serum lead levels of male fuel station attendants in Calabar metropolis were determined. The haematological parameters assessed included haemoglobin concentration (Hb), haematocrit (HCT), total white blood cell count (WBC), differential white cell counts and platelet count. Age range of ...
Background: Autism is a behaviorally defined neurodevelopmental disorder of unknown etiology. Objective: To assess serum copper and ceruloplasmin levels in Egyptian autistic children patients. Subjects and methods: 40 participants have been subjected to thorough history taking, complete clinical examination, ...
Background: Vitamin D is a steroid hormone that plays essential roles in calcium and phosphorus metabolism, bone formation and mineralization homeostasis, also has a role in the maintenance of immune-homeostasis. Objective: We aimed to investigate seasonal serum vitamin D levels and seasonal disease activity in ...
Conclusion: The results of this study showed that higher serum levels of obestatin were associated with macro albuminuria suggesting that obestatin may have a role in underlying pathogenic mechanisms that leads to diabetic nephropathy. Key words: Diabetes mellitus type 2, diabetic nephropathy, obestatin, omentin ...
Kellum, John A; Sileanu, Florentina E; Murugan, Raghavan; Lucko, Nicole; Shaw, Andrew D; Clermont, Gilles
Severity of AKI is determined by the magnitude of increase in serum creatinine level or decrease in urine output. However, patients manifesting both oliguria and azotemia and those in which these impairments are persistent are more likely to have worse disease. Thus, we investigated the relationship of AKI severity and duration across creatinine and urine output domains with the risk for RRT and likelihood of renal recovery and survival using a large, academic medical center database of critically ill patients. We analyzed electronic records from 32,045 patients treated between 2000 and 2008, of which 23,866 (74.5%) developed AKI. We classified patients by levels of serum creatinine and/or urine output according to Kidney Disease Improving Global Outcomes staging criteria for AKI. In-hospital mortality and RRT rates increased from 4.3% and 0%, respectively, for no AKI to 51.1% and 55.3%, respectively, when serum creatinine level and urine output both indicated stage 3 AKI. Both short- and long-term outcomes were worse when patients had any stage of AKI defined by both criteria. Duration of AKI was also a significant predictor of long-term outcomes irrespective of severity. We conclude that short- and long-term risk of death or RRT is greatest when patients meet both the serum creatinine level and urine output criteria for AKI and when these abnormalities persist. Copyright © 2015 by the American Society of Nephrology.
Typhoid fever is a systemic infection caused by the bacterium Salmonella enterica, subspecies enterica, serotype Typhi, which is mostly contracted through the ingestion of food or water contaminated by the faeces of an infected person. Serum sodium, potassium, chloride, and bicarbonate levels were determined in sixty ...
Pulmonary function tests are routinely used to assess the pulmonary functional status of workers exposed to cement dust in cement factories. There is a no biochemical marker as yet employed for this. A comparison of the serum bicarbonate levels of workers in the production line against those in the administration is under ...
Lowered Serum Triglyceride Levels among Chronic Hepatitis B-Infected Patients in Ghana. JK Kwarteng, L Owusu, M Afihene, E Mica, O Opare-Sem, FKN Arthur. Abstract. Dyslipidemia is a common finding in most studies of liver diseases. Little is however known about the effect of the two pathological stages of chronic ...
Detection of serum midkine levels in cancer patients using rabbit anti-human midkine monoclonal antibodies. X Yao, FC Qian, LC Dai, LS Min. Abstract. Midkine (MK) is a heparin-binding growth factor and was found to be highly expressed in many types of human carcinomas. MK may become a novel tumor marker. In this ...
Context: Bilirubin has been shown to influence the mechanisms of both apoptosis and inflammation. Aims: The aim of the following study is to investigate the relationship between the serum bilirubin level with sepsis progression. Settings and Design: A total of 20 patients from intensive care unit were included for this study.
Relationship between Serum Testosterone Levels and Features of the Metabolic Syndrome Defining Criteria in Patients with Type 2 Diabetes Mellitus. ... West African Journal of Medicine ... Methods: A total of 203 men with type 2 DM aged 30–86 years were evaluated for the testosterone deficiency syndrome (TDS).
Wang, Yanmao; Dai, Jiezhi; Zhong, Wanrun; Hu, Chengfang; Lu, Shengdi; Chai, Yimin
Previous epidemiological studies have found an association between serum cholesterol level and bone mineral density. However, epidemiological studies evaluating the association between serum cholesterol level and the incidence of osteoporotic fracture are scant. Therefore, the objective of this study was to investigate whether serum cholesterol levels in Chinese participants aged 55 years or older was associated with an increased risk of osteoporotic fracture. We performed a cross-sectional study, including 1,791 participants (62.1% postmenopausal women and 213 fractures). Standardized self-administered questionnaires, physical examination, laboratory tests, and dual-energy X-ray absorptiometry examination were performed. Multivariate-adjusted logistic regression models were used to evaluate associations between serum cholesterol [total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C)] levels and the osteoporotic fracture risk. After adjusting for potential confounding factors, there were no associations between per SD increase in TC and LDL level and an increased risk of osteoporotic fracture in total participants, and in men and women as individual groups. There was a significant association between per SD increase in HDL-C level and an increased risk of osteoporotic fracture in total participants [odds ratios (OR) 1.20, 95% confidence interval (CI) 1.03, 1.40, P = 0.023] and in women (OR 1.37, 95% CI 1.12, 1.68, P = 0.003), whereas no association was observed in men (OR 1.01, 95% CI 0.73, 1.40, P = 0.951). Additionally, we found a significant association between per SD increase in TG level and an increased risk of osteoporotic fracture in total participants (OR 1.20, 95% CI 1.04, 1.38, P = 0.015). In women, a nonlinear relationship was observed between per SD increase in TG level and an increased risk of osteoporotic fracture. The risk of osteoporotic fracture in women increased
Emma Louise Beckett
General significance: This study demonstrates that serum miR-21 expression correlates with folate status and related genetic status. This may have consequences for the proposed use of miR-21 as a colorectal cancer biomarker.
García-Pascual, Luis; Barahona, María José; Perea, Verónica; Simó, Rafael
Hypercalciuria is an adverse event of postsurgical hypoparathyroidism treatment that can lead to renal complications. The collection of 24-hour urine to detect hypercalciuria is often considered unreliable. The purpose of this study was to find useful predictive biomarkers of hypercalciuria in patients with permanent postsurgical hypoparathyroidism receiving treatment with oral calcium and calcitriol supplements. The investigation was designed as a prospective cross-sectional study. An outpatient hospital clinic served as the study setting. Fifty-four consecutive observations were made of 34 stable outpatients with postsurgical hypoparathyroidism taking oral calcium and calcitriol supplements, and 17 adult controls without hypoparathyroidism. There were no interventions. Hypercalciuria was defined as 24-hour urine calcium >300 mg. Patients without hypercalciuria (n = 21) vs those with hypercalciuria (n = 33) had lower levels of serum 1,25-dihydroxyvitamin D (33.5 ± 11.9 pg/mL vs 45.8 ± 9.5 pg/mL; P hypoparathyroidism who are receiving treatment with oral calcium and calcitriol supplements. Copyright © 2017 by the Endocrine Society
Sanaei Dashti, Anahita; Alizadeh, Shekoofan; Karimi, Abdullah; Khalifeh, Masoomeh; Shoja, Seyed Abdolmajid
Abstract There are many difficulties distinguishing bacterial from viral meningitis that could be reasonably solved using biomarkers. The aim of this study was to evaluate lactate, procalcitonin (PCT), ferritin, serum-CRP (C-reactive protein), and other known biomarkers in differentiating bacterial meningitis from viral meningitis in children. All children aged 28 days to 14 years with suspected meningitis who were admitted to Mofid Children's Hospital, Tehran, between October 2012 and November 2013, were enrolled in this prospective cross-sectional study. Children were divided into 2 groups of bacterial and viral meningitis, based on the results of cerebrospinal fluid (CSF) culture, polymerase chain reaction, and cytochemical profile. Diagnostic values of CSF parameters (ferritin, PCT, absolute neutrophil count [ANC], white blood cell count, and lactate) and serum parameters (PCT, ferritin, CRP, and erythrocyte sedimentation rate [ESR]) were evaluated. Among 50 patients with meningitis, 12 were diagnosed with bacterial meningitis. Concentrations of all markers were significantly different between bacterial and viral meningitis, except for serum (P = .389) and CSF (P = .136) PCT. The best rates of area under the receiver operating characteristic (ROC) curve (AUC) were achieved by lactate (AUC = 0.923) and serum-CRP (AUC = 0.889). The best negative predictive values (NPV) for bacterial meningitis were attained by ANC (100%) and lactate (97.1%). The results of our study suggest that ferritin and PCT are not strong predictive biomarkers. A combination of low CSF lactate, ANC, ESR, and serum-CRP could reasonably rule out the bacterial meningitis. PMID:28858084
Rounge, Trine B; Lauritzen, Marianne; Langseth, Hilde; Enerly, Espen; Lyle, Robert; Gislefoss, Randi E
The impacts of long-term storage and varying preanalytical factors on the quality and quantity of DNA and miRNA from archived serum have not been fully assessed. Preanalytical and analytical variations and degradation may introduce bias in representation of DNA and miRNA and may result in loss or corruption of quantitative data. We have evaluated DNA and miRNA quantity, quality, and variability in samples stored up to 40 years using one of the oldest prospective serum collections in the world, the Janus Serumbank, a biorepository dedicated to cancer research. miRNAs are present and stable in archived serum samples frozen at -25°C for at least 40 years. Long-time storage did not reduce miRNA yields; however, varying preanalytical conditions had a significant effect and should be taken into consideration during project design. Of note, 500 μL serum yielded sufficient miRNA for qPCR and small RNA sequencing and on average 650 unique miRNAs were detected in samples from presumably healthy donors. Of note, 500 μL serum yielded sufficient DNA for whole-genome sequencing and subsequent SNP calling, giving a uniform representation of the genomes. DNA and miRNA are stable during long-term storage, making large prospectively collected serum repositories an invaluable source for miRNA and DNA biomarker discovery. Large-scale biomarker studies with long follow-up time are possible utilizing biorepositories with archived serum and state-of-the-art technology. ©2015 American Association for Cancer Research.
Costa, C; Angi, M R; De Carli, M; Vanzan, S; Allegri, G
In order to clarify the role of tryptophan in the patogenesis of senile cataract, we have studied the serum total and free levels of tryptophan in cataract patients as compared with age and sex-matched controls, and the urinary excretion of 10 metabolites after oral load of the amino acid. This excretion increases in the cataract group both as total per cent and as kynurenine. No difference has been found in the free and total serum tryptophan between normal subjects and cataract patients. A possible role of the kynurenines in the pathogenesis of senile cataract is suggested.
Kang, Seung Joo; Kim, Donghee; Park, Hyo Eun; Chung, Goh Eun; Choi, Seung Ho; Choi, Su-Yeon; Lee, Whal; Kim, Joo Sung; Cho, Sang-Heon
Inverse correlations of high serum bilirubin with metabolic and cardiovascular disease have been suggested. However, anti-atherogenic effects of bilirubin have not been well-established in terms of the presence of plaques and stenosis identified in coronary computed tomography (CT). A cross-sectional study was conducted on 2862 men who were free of cardiovascular disease and underwent coronary CT as part of a routine medical screening examination. Coronary stenotic lesions were considered to be incidences of coronary atherosclerosis, and stenosis was classified as stenosis atherosclerosis and stenosis ≥50% in subjects with elevated bilirubin levels (>1.2 mg/dL) were lower than those in subjects with normal bilirubin levels (≤1.2 mg/dL) (19.9% vs. 27.9%, p atherosclerosis (OR 0.73, 95% CI 0.56-0.94 in the 4th quartile vs. 1st quartile) and calcified plaque (OR 0.66, 95% CI 0.53-0.84) were inversely associated with the bilirubin grade in a dose-dependent manner. The serum bilirubin level was inversely associated with coronary atherosclerosis and calcified plaques in a dose-dependent manner. These results suggested that serum bilirubin could be used as a protective biomarker of coronary artery disease. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Full Text Available The clinical value of Serum alpha-fetoprotein (AFP to detect early hepatocellular carcinoma (HCC has been questioned due to its low sensitivity and specificity found in recent years. Other than AFP, several new serum biomarkers including the circulating AFP isoform AFP-L3, des-gamma-carboxy prothrombin (DCP and Golgi protein-73 (GP73 have been identified as useful HCC markers. In this investigation, we review the current knowledge about these HCC-related biomarkers, and sum up the results of our meta-analysis on studies that have addressed the utility of these biomarkers in early detection and prognostic prediction of HCC. A systematic search in PubMed, Web of Science, and the Cochrane Library was performed for articles published in English from 1999 to 2012, focusing on serum biomarkers for HCC detection. Data on sensitivity and specificity of tests were extracted from 40 articles that met the inclusion criteria, and the summary receiver operating characteristic curve (sROC was obtained. A meta-analysis was carried out in which the area under the curve (AUC for each biomarker or biomarker combinations (AFP, DCP, GP73, AFP-L3, AFP + DCP, AFP + AFP-L3, and AFP + GP73 was used to compare the diagnostic accuracy of different biomarker tests. The AUC of AFP, DCP, GP73, AFP-L3, AFP + DCP, AFP + AFP-L3, and AFP + GP73 are 0.835, 0.797, 0.914, 0.710, 0.874, 0.748, and 0.932 respectively. A combination of AFP + GP73 is superior to AFP in detecting HCC and differentiating HCC patients from non-HCC patients, and may prove to be a useful marker in the diagnosis and screening of HCC. In addition, the AUC of GP73, AFP + DCP and AFP + GP73 are better than that of AFP. The clinical value of GP73, AFP + DCP, or AFP + GP73 as serological markers for HCC diagnosis needs to be addressed further in future studies.
Kilic, Eser; Yazar, Süleyman; Saraymen, Recep; Ozbilge, Hatice
AIM: The aim of the study was to investigate the changes of serum malondialdehyde level, i.e; the oxidative stress hypothesis in patients infected with Ascaris lumbricoides. METHODS: Serum malondialdehyde activity was measured in 43 patients who were positive for intestinal parasite of Ascaris lumbricoides. Scores were obtained for the positives and their age-and sex-matched 60 Ascaris lumbricoides negative healthy controls. RESULTS: The difference between malondialdehyde levels of patients infected with Ascaris lumbricoides and control group was statistically significant both for females (P 0.05) both in females and in males. In addition, no significant correlation could be found between malondialdehyde levels of both females and males for patients and control groups (P > 0.05). CONCLUSION: Malondialdehyde levels clearly increase in patients infected with Ascaris lumbricoides. PMID:14562404
In 188 males FSH, LH, and prolactin serum levels determined by radioimmunoassay from a single blood sample were found to be closely correlated. No correlation appeared to testosterone levels. The same correlation is observed, if serum levels of FSH, LH, and prolactin are measured after stimulation with LH-RH and TRH. In order to explain the close correlation, in five young men hormone levels were measured at 2-min-intervals over a period of 2 hours. Peaks of prolactin often correspond to those of FSH and LH, and a statistical correlation was found in two cases between FSH and prolactin. Results suggest a common releasing mechanism, which is superposed to the main mediating mechanism. (author)
de Kom, J F; Dissels, H M; van der Voet, G B; de Wolff, F A
Aluminium is produced from the mineral bauxite. Occupational exposure is reported during the industrial processing of aluminium and is associated with pulmonary and neurotoxicity. However, data on exposure and toxicity of workers in the open bauxite mining industry do not exist. Therefore, a study was performed to explore aluminium exposure in employees involved in this bauxite mining process in a Surinam mine. A group of workers occupationally exposed to aluminium in an open bauxite mine were compared with a group of nonexposed wood processors. Serum aluminium was analyzed using atomic absorption spectrometry Data from the clinical chemistry of the blood and a questionnaire were used to explore determinants for aluminium exposure. No significant difference between serum aluminium in the exposed (4.4 +/- 2.0 micrograms/L, n = 27) and control group (5.1 +/- 1.5 micrograms/L, n = 27) was detected. For the serum concentration of the clinical chemical variables (calcium, citrate, and creatinine), a statistically significant difference was computed (p < or = 0.02) between the exposed and control group. All levels were slightly higher in the exposed group; no statistically significant correlations with serum aluminium were found. In this study, serum aluminium values were in the normal range, no significant difference between the groups could be detected despite long-term occupational exposure.
Kobayashi, H; Sun, G W; Tanaka, Y; Kondo, T; Terao, T
To study the changes in concentrations of serum hyaluronic acid in uncomplicated human pregnancies. We determined the concentrations of serum hyaluronic acid, using a specific enzyme-linked immunosorbent assay, in 70 nonpregnant women, 250 women during their pregnancies, and 68 women at the time of parturition. Results were analyzed for statistical significance with Scheffé test for multiple comparisons. During pregnancy, mean (+/- standard deviation) serum hyaluronic acid levels were 11.4 +/- 4.5, 13.6 +/- 2.8, 20.6 +/- 1.5, and 46.9 +/- 7.9 ng/mL at 5-14 (n = 47), 15-26 (n = 46), 27-37 (n = 58), and 38-40 (n = 99) weeks' gestation, respectively. Pregnant women in labor (n = 68) had significantly higher levels (100.4 +/- 11.3 ng/mL) than did women at term but not in labor (P hyaluronic acid concentrations increase as pregnancy progresses and serum levels increase significantly at term. Hyaluronic acid may be associated with cervical ripening during parturition.
Full Text Available SUMMARY The role of trace elements in dengue virulence is not yet known. The present study assessed the serum levels of two micronutrients, copper and iron, in cases of dengue fever. The study involved 96 patients of whom 48 had either severe or non-severe forms of dengue (with and without warning signs, and the remaining 48 were patients with other febrile illnesses (OFI, used as controls. Serum levels of copper and iron were evaluated at admission and by the time of defervescence using commercially available kits. At admission, no difference in the level of serum copper was observed between cases and controls. In the group of dengue cases, the copper level was found to be significantly decreased in severe and non-severe cases with warning signs, compared to non-severe cases without warning signs. In contrast, by the time of defervescence the copper level was found to be increased in all dengue cases compared to OFI controls, but no difference was observed among dengue cases. Unlike OFI controls, dengue cases showed an increasing pattern of copper levels from admission until defervescence. On the other hand, no such significant differences were observed in the serum level of iron in the clinical groups, except for a decreased iron level found in severe cases, compared to non-severe dengue without warning signs. The results show that copper is associated with dengue severity and this finding emphasizes the need to investigate the involvement of trace elements in disease severity so as to improve the prognosis of dengue.
Full Text Available The article presents the results of investigation of basal gastrin serum level and its relationships at chronic reflux gastritis. It has been established that gastrin level was increased in 100 % of patients. It was directly dependent on the biliary acid concentration in gastric acid, H.pylori-infection, stomach alkalization. Thus, duodenogastrical reflux causes hypergastrinemia that can result in chronic gastritis development.
Full Text Available Objective: To determine the role of hepcidin hormone levels in iron accumulation in patients with thalassemia major (TM and thalassemia intermedia (TI. Materials and Methods: Serum prohepcidin and ferritin levels were determined in 34 patient with TM, 10 patient with TI, who attended the Department of Pediatric Hematology Adnan Menderes University Medical Faculty and the Department of Pediatrics at Aydın Atatürk State Hospital between 1 September 2006 and 30 September 2007 and 40 control patients without infection/inflammation, hepatitis or liver failure. Serum prohepcidin levels were measured using a commercial enzyme-linked immunosorbent assay kit (DRG International, Inc. Marburg, Germany; ferritin was studied with chemiluminescence method (Immulite 2000 DPC. Results: Mean serum ferritin levels in TM, TI and control groups were 2347.97±1724.81 ng/mL (range: 144-8015 ng/mL, 1352.40±918.94 ng/mL (range: 311-3109 ng/mL, and 33.35±12.03 ng/mL (range: 20-69.1 ng/mL, respectively. Serum prohepcidin levels in the same groups were 221.78±74.38 ng/mL (range: 7l.14-446.57 ng/mL, 173.31±52.14 ng/mL (range: 100.83-267.69 ng/mL, and 218.20±50.37 ng/mL (range: 116.18-330.43 ng/mL, respectively. There was a statistically significant difference in prohepcidin levels between patients with TI and control group only (p=0.016. No correlation was found between prohepcidin and ferritin levels in all groups (r=-0.023, p=0.839. Conclusion: Low levels of prohepcidin in patients with TI may be related to increased erythropoietic activity. Prohepcidin can be an indicator of active erythropoiesis.
Full Text Available Multiplex serological immunoassays, such as implemented on microarray or microsphere-based platforms, provide greater information content and higher throughput, while lowering the cost and blood volume required. These features are particularly attractive in pediatric food allergy testing to facilitate high throughput multi-allergen analysis from finger- or heel-stick collected blood. However, the miniaturization and microfluidics necessary for creating multiplex assays make them highly susceptible to the "matrix effect" caused by interference from non-target agents in serum and other biofluids. Such interference can result in lower sensitivity, specificity, reproducibility and quantitative accuracy. These problems have in large part prevented wide-spread implementation of multiplex immunoassays in clinical laboratories. We report the development of a novel method to eliminate the matrix effect by utilizing photocleavable capture antibodies to purify and concentrate blood-based biomarkers (a process termed PC-PURE prior to detection in a multiplex immunoassay. To evaluate this approach, it was applied to blood-based allergy testing. Patient total IgE was purified and enriched using PC-PURE followed by multiplex microsphere-based detection of allergen-specific IgEs (termed the AllerBead assay. AllerBead was formatted to detect the eight most common pediatric food allergens: milk, soy, wheat, egg, peanuts, tree nuts, fin fish and shellfish, which account for >90% of all pediatric food allergies. 205 serum samples obtained from Boston Children's Hospital were evaluated. When PC-PURE was employed with AllerBead, excellent agreement was obtained with the standard, non-multiplex, ImmunoCAP® assay (average sensitivity above published negative predictive cutoffs = 96% and average Pearson r = 0.90; average specificity = 97%. In contrast, poor ImmunoCAP®-correlation was observed when PC-PURE was not utilized (average sensitivity above published negative
Naduparambil Korah Jacob
Full Text Available Exposure to ionizing radiation through environmental, occupational or a nuclear reactor accident such as the recent Fukushima Daiichi incident often results in major consequences to human health. The injury caused by radiation can manifest as acute radiation syndromes within weeks in organs with proliferating cells such as hematopoietic and gastrointestinal systems. Cancers, fibrosis and degenerative diseases are also reported in organs with differentiated cells, months or years later. Studies conducted on atom bomb survivors, nuclear reactor workers and animal models have shown a direct correlation of these effects with the absorbed dose. Physical dosimeters and the available radio-responsive biologics in body fluids, whose responses are rather indirect, have limitations to accurately evaluate the extent of post exposure damage. We have used an amplification-free, hybridization based quantitative assay utilizing the nCounter multiplex platform developed by nanoString Technologies to compare the levels of over 600 miRNAs in serum from mice irradiated at a range of 1 to 12 Gy at 24 and 48 hr time points. Development of a novel normalization strategy using multiple spike-in oligonucleotides allowed accurate measurement of radiation dose and time dependent changes in serum miRNAs. The response of several evolutionarily conserved miRNAs abundant in serum, were found to be robust and sensitive in the dose range relevant for medical triage and in patients who receive total body radiation as preparative regimen for bone marrow transplantation. Notably, miRNA-150, abundant in lymphocytes, exhibited a dose and time dependent decrease in serum, which we propose as a sensitive marker indicative of lymphocyte depletion and bone marrow damage. Our study has identified several markers useful for evaluation of an individual's response by minimally invasive methods, relevant to triage in case of a radiation accident and evaluation of toxicity and response
Bhattacharyya, Sudeepa; Siegel, Eric R; Achenbach, Sara J; Khosla, Sundeep; Suva, Larry J
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
Hong, Wen-Xu; Liu, Wei; Zhang, Yanfang; Huang, Peiwu; Yang, Xifei; Ren, Xiaohu; Ye, Jinbo; Huang, Haiyan; Tang, Haiyan; Zhou, Guifeng; Huang, Xinfeng; Zhuang, Zhixiong; Liu, Jianjun
Occupational medicamentosa-like dermatitis induced by trichloroethylene (OMLDT) is an autoimmune disease and it has become a serious occupational health hazard. In the present study, we collected fasting blood samples from patients with OMLDT (n = 18) and healthy volunteers (n = 33) to explore serum peptidome patterns. Peptides in sera were purified using weak cation exchange magnetic beads (MB-WCX), and analyzed by matrix-assisted laser desorption ionization time-of-flight-mass spectrometry (MALDI-TOF-MS) and ClinProTools bioinformatics software. The intensities of thirty protein/peptide peaks were significantly different between the healthy control and OMLDT patients. A pattern of three peaks (m/z 2106.3, 2134.5, and 3263.67) was selected for supervised neural network (SNN) model building to separate the OMLDT patients from the healthy controls with a sensitivity of 95.5% and a specificity of 73.8%. Furthermore, two peptide peaks of m/z 4091.61 and 4281.69 were identified as fragments of ATP-binding cassette transporter family A member 12 (ABCA12), and cationic trypsinogen (PRRS1), respectively. Our findings not only show that specific proteomic fingerprints in the sera of OMLDT patients can be served as a differentiated tool of OMLDT patients with high sensitivity and high specificity, but also reveal the novel correlation between OMLDT with ABC transports and PRRS1, which will be of potential value for clinical and mechanistic studies of OMLDT. - Highlights: • Identify 30 differential protein/peptide peaks between OMLDT and healthy control • The test sensitivity and test specificity were 95.5% and 73.8%, respectively. • ABCA12 and PRSS1 were identified as potential biomarkers in OMLDT patients
Hong, Wen-Xu; Liu, Wei [Key Laboratory of Modern Toxicology of Shenzhen, Medical Key Laboratory of Guangdong Province, Medical Key Laboratory of Health Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055 (China); Zhang, Yanfang [Shenzhen Prevention and Treatment Center for Occupational Disease, Shenzhen 518001 (China); Huang, Peiwu; Yang, Xifei; Ren, Xiaohu; Ye, Jinbo; Huang, Haiyan [Key Laboratory of Modern Toxicology of Shenzhen, Medical Key Laboratory of Guangdong Province, Medical Key Laboratory of Health Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055 (China); Tang, Haiyan [Shenzhen Prevention and Treatment Center for Occupational Disease, Shenzhen 518001 (China); Zhou, Guifeng [Medical School of Hunan Normal University, Changsha 410006 (China); Huang, Xinfeng; Zhuang, Zhixiong [Key Laboratory of Modern Toxicology of Shenzhen, Medical Key Laboratory of Guangdong Province, Medical Key Laboratory of Health Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055 (China); Liu, Jianjun, E-mail: email@example.com [Key Laboratory of Modern Toxicology of Shenzhen, Medical Key Laboratory of Guangdong Province, Medical Key Laboratory of Health Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055 (China)
Occupational medicamentosa-like dermatitis induced by trichloroethylene (OMLDT) is an autoimmune disease and it has become a serious occupational health hazard. In the present study, we collected fasting blood samples from patients with OMLDT (n = 18) and healthy volunteers (n = 33) to explore serum peptidome patterns. Peptides in sera were purified using weak cation exchange magnetic beads (MB-WCX), and analyzed by matrix-assisted laser desorption ionization time-of-flight-mass spectrometry (MALDI-TOF-MS) and ClinProTools bioinformatics software. The intensities of thirty protein/peptide peaks were significantly different between the healthy control and OMLDT patients. A pattern of three peaks (m/z 2106.3, 2134.5, and 3263.67) was selected for supervised neural network (SNN) model building to separate the OMLDT patients from the healthy controls with a sensitivity of 95.5% and a specificity of 73.8%. Furthermore, two peptide peaks of m/z 4091.61 and 4281.69 were identified as fragments of ATP-binding cassette transporter family A member 12 (ABCA12), and cationic trypsinogen (PRRS1), respectively. Our findings not only show that specific proteomic fingerprints in the sera of OMLDT patients can be served as a differentiated tool of OMLDT patients with high sensitivity and high specificity, but also reveal the novel correlation between OMLDT with ABC transports and PRRS1, which will be of potential value for clinical and mechanistic studies of OMLDT. - Highlights: • Identify 30 differential protein/peptide peaks between OMLDT and healthy control • The test sensitivity and test specificity were 95.5% and 73.8%, respectively. • ABCA12 and PRSS1 were identified as potential biomarkers in OMLDT patients.
Ain, Q. A.; Khan, D. A.; Ijaz, A.; Khan, F. A.; Latif, A.
Objective: To determine the serum 25-hydroxycalciferol levels [25(OH)D] in adults with pre-diabetes and normoglycaemia to examine a possible association of vitamin D deficiency with pre-diabetes. Study Design: Case control study. Place and Duration of Study: Armed Forces Institute of Pathology, Rawalpindi, from November 2012 to July 2013. Methodology: A total of 272 adults including 136 pre-diabetics and 136 normoglycaemics of either gender aged 20 years and above were consecutively inducted. Patients with diabetes mellitus, pregnancy, rickets and osteomalacia, ischemic heart disease, chronic kidney disease and chronic liver disease were excluded. Fasting Plasma Glucose (FPG) was estimated with hexokinase method on Modular p800 Roche chemistry analyzer while serum 25(OH)D was measured on Diasorin Liaison immunoassay analyzer using the chemiluminescent technique. Mean 25(OH)D levels in pre-diabetic and normoglycaemic groups were compared using Mann-Whitney U test. Spearman's correlation coefficient 'rs' was determined between serum 25(OH)D and FPG. Odds ratio for vitamin D deficiency was also calculated. Results: Mean serum 25(OH)D level was low in pre-diabetics (23.2 nmol/L) as compared to normoglycaemics (29 nmol/L; p=0.001). Serum 25(OH)D level had inverse correlation with FPG (rs = -0.448, p=0.000). There was also significant association of vitamin D deficiency with pre-diabetes compared with normoglycaemia (OR: 2.21, p= 0.016; 95 percentage CI: 1.15-4.27). Conclusion: Vitamin D deficiency with pre-diabetes suggested that vitamin D may have an important role in pathogenesis of pre-diabetes. (author)
For 101 hospitalized patients where clinical symptoms of a glucosidine intoxication as a consequence of oral digoxin treatment were noted, serum digoxin levels were determined using a RIA kit of the Boehringer company (I-125 tracer, solid phase tube separation technique) on a fasted stomach prior to oral drug administration. An ECG was performed simultaneously and in addition kidney function parameters and electrolyte levels were determined. An anamnesis and clinical examination of the patients were also conducted. Interferences in the RIA method and gastro-intestinal illness resulting in changes in resorption behaviour were excluded. The group of patients showed collectively an average serum digoxin level of 2.9 +- 0.9 ng/ml with a range from 1.8 to 6.8 ng/ml, which was statistically significantly higher than the average value for 101 patients receiving long-term oral medication but without symptoms of glycosidine intoxication. According to the manufacture's specifications for the RIA kit, values > 2.0 ng/ml are considered as toxic, with values between 1.6 and 2.0 ng/mg falling into a ''grey zone''. A correlation was found between toxic serum values with changes in ECG pattern and subjective clinical symptoms of intoxication. A limitation of kidney function was responsible for the high serum glycoside levels in 62% of the patients. It was shown that the differing response of patients towards digitalis medication, above all in the case of long-term therapy, warrants an RIA determination of serum glycoside values in order to adjust the digoxin dose to individual requirements. (orig./MG) [de
Rohini Bipin Bhadre
Full Text Available INTRODUCTION Gallstones are one of the most common problem associated with the gallbladder, affecting millions of people throughout the world. Bile is excreted from liver and gallbladder into Duodenum for digestion. After digestion, if the gallbladder is not emptied out completely, the Bile Juice that remains in the gallbladder can become too concentrated with cholesterol leading to gallstone formation. Cholesterol and calcium bilirubinate are the two main substances involved in gallstone formation. Gallstones derived from bile consists of mixture of cholesterol, bilirubin with or without calcium. Based on their chemical composition, gallstones found in the gallbladder are classified as cholesterol, pigmented or mixed stones. Iron deficiency has been shown to alter the activity of several hepatic enzymes, leading to increased gallbladder bile cholesterol saturation and promotion of cholesterol crystal formation. AIMS & OBJECTIVE Attempt to establish a correlation with gallstones and decreased serum iron levels. MATERIAL & METHODS This study was a prospective cohort study which included 100 consecutive patients with imaging studies suggestive of Cholelithiasis. The Gallstone surgically removed was crushed with mortar and pestle and then analysed for cholesterol, calcium, phosphate and bilirubin (pigment. Serum samples were analysed for Cholesterol, iron and iron binding capacity. RESULTS 86% patients had increased cholesterol levels (p=0.04 and 93% had decreased serum Iron levels (p=0.96. The most common type of gallstone was found to be Cholesterol type of gallstone followed by Mixed and Pigment gallstones. CONCLUSION Serum cholesterol levels were found to be raised in majority of the patients and serum iron was found to be low in these majority of the patients indicating iron deficiency may play a role in gallstone formation.
Paul, R.F.; Hassan, M.; Nazar, H.S.
Background: Leptin is product of ob gene, an adipose tissue derived hormone that plays a key role in the regulation of body fat mass by regulating appetite and metabolism while balancing energy intake and energy expenditure. The objective of the study was to evaluate possible association between serum leptin levels and Body Mass Index (BMI) of gender in adult age group. Methods: Two-hundred-seventy subjects aged 20-50 years were randomly selected from general population of Abbottabad. The subjects were grouped on the basis on BMI (89 normal, 92 overweight, and 89 obese). After complete evaluation, demographic data was recorded and BMI. Non-fasting venous blood samples were drawn to measure serum leptin and serum glucose levels. The data were analysed using SPSS-15 calculating mean, percentage, independent t-test and chi-square test. Correlation and regression curve analysis were obtained, and p and r values were calculated. Results: Serum leptin levels and differences between genders were significant in all body mass indices. For normal BMI group the mean values for leptin were 2.6+-1.5 gamma g/ml in men, and 17.3+9-10.2 gamma g/ml for women. For Group-2 mean leptin levels in men were 9.9+-6.8 gamma g/ml and in women were 34.8+-13.6 gamma g/ml. For Group-3 BMI comprising obese subjects mean values for men were 21.3+-14.2 gamma g/ml and for women were 48.21+-21.2 gamma g/ml (p<0.001). Conclusion: A progressive increase in serum leptin concentration was observed with an increase in BMI. Significant difference between leptin concentrations in either gender was found in normal, overweight and obese subjects. (author)
Full Text Available Aim: The aim of the present study is to compare body mass indexes (BMI and serum leptin levels of most frequently observed three chronic airway diseases; namely, Asthma, Chronic Obstructive Pulmonary Disease (COPD and bronchiectasis. Material and Method: The study included a total of 216 people, 78 asthma, 67 COPD, and 37 bronchiectasis patients who were in stable period and 34 healthy individuals all aged above 18. Control group consisted of non-smokers and non-corticosteroid users. Of all the participants, the blood samples were taken in order to determine serum leptin levels and BMI were calculated, and pulmonary function tests measured at rest. Results: The BMI levels of all the groups was above >25 kg/m2. There were no statistical differences between the control and patient groups with regard to BMI (p>0.05. Comparing patient groups, the BMI of asthma patients was higher than those with COPD and bronchiectasis (29.84±6.46, 25.78±4.96, 27.64±5.19, p=0.0001, p=0.20. FEV1 results of COPD patients were lower than those with asthma and bronchiectasis (63.25±19.26, 76.73±20.35, 72.75±20.17 and p=0.0001, p=0.06. Serum leptin levels of asthma patients were higher than the COPD, bronchiectasis patients, as well as that of the control group (12.36±11.16 ng/ml, 3.35±4.71 ng/ml, 8.49±7.85 ng/ml and 5.21±6.83 ng/ml, p=0.0001, p=0.09 and p=0.0001, respectively. Serum leptin level of COPD patients was lower than control group, but it was not statistically significant (p=0.71. Serum leptin levels of the patients with bronchiectasis were higher than healthy control group members; yet , not statistical significant (p=0.34. However serum leptin levels of the patients with bronchiectasis were higher than the patient COPD groups and this was statisticaly significant (p=0.01. Istatistically significant different emerge on comparing serum leptin levels and BMI of the asthma, COPD and bronchiectasis patients in the Lineear regression analysis made (beta
Brubel, Reka; Bokor, Attila; Pohl, Akos; Schilli, Gabriella Krisztina; Szereday, Laszlo; Bacher-Szamuel, Reka; Rigo, Janos; Polgar, Beata
To investigate the usefulness of soluble galectin-9 (Gal-9) in the noninvasive laboratory diagnosis of endometriosis and various gynecologic disorders. Prospective case-control study. University medical centers. A total of 135 women of reproductive age were involved in the study, 77 endometriosis patients, 28 gynecologic controls, and 30 healthy women. Diagnostic laparoscopy and collection of tissue biopsies, peritoneal cells, and native peripheral blood from different case groups of gynecology patients and healthy women. The expression of mRNA and serum concentration of Gal-9. Semiquantitative reverse transcription-polymerase chain reaction analysis and serum soluble Gal-9 ELISA were performed on three different cohorts of patients: those with endometriosis, those with benign gynecologic disorders, and healthy controls. Differences in the Gal-9 concentrations between the investigated groups and the stability of Gal-9 in the serum and diagnostic characteristics of Gal-9 ELISA were determined by statistical evaluation and receiver operating characteristic (ROC) curve analysis. Significantly elevated Gal-9 levels were found in both minimal-mild (I-II) and moderate-severe (III-IV) stages of endometriosis in comparison with healthy controls. At a cutoff of 132 pg/mL, ROC analysis revealed an excellent diagnostic value of Gal-9 ELISA in endometriosis (area under the curve = 0.973) with a sensitivity of 94% and specificity of 93.75%, indicating better diagnostic potential than that of other endometriosis biomarkers. Furthermore, various pelvic pain or infertility-associated benign gynecologic conditions were also associated with increased serum Gal-9 levels. Our results suggest that Gal-9 could be a promising noninvasive biomarker of endometriosis and a predictor of various infertility or pelvic pain-related gynecologic disorders. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Sara Soleimani Rad
Full Text Available Background: Infertility is defined as the inability to achieve the pregnancy within a year of unprotected intercourse. Infertility is a complex issue and different factors such as stress oxidative can be involved in this problem. So, any attempt to neutralize oxidative stress would be helpful in the treatment of infertility. Melatonin is a known scavenger of free radicals. Objective: The aim of our study was to evaluate the level of melatonin and its correlation with oxidative biomarkers in fertile and infertile women. Materials and Methods: The participants including fertile and infertile women were divided into two groups of 30 people. Blood sampling was performed and sera were collected. The level of Malondialdehyde (MDA, total antioxidant capacity (TAC and melatonin were detected. Data were analyzed using T-test and their correlation was assessed using Spearman test. Results: Serum melatonin from fertile women was higher than infertile women but the difference was not significant (p= 0.46. MDA level in fertile women was significantly lower than infertile women (p<0.001 and the level of TAC in fertile women was significantly higher than infertile women (p<0.001. Spearman test revealed a significant and direct correlation between melatonin and TAC in fertile and infertile women and a significant but reverse correlation between melatonin and MDA in infertile and fertile women. Conclusion: Differences in the level of oxidative stress biomarkers in fertile and infertile individuals have been reported. This study revealed a significant correlation between melatonin and oxidative stress biomarkers, concluding that melatonin level could be involved in infertility.
Full Text Available The prognostic value of serum cystatin-C (Cys-C in renal cell carcinoma (RCC remains unknown. The purpose of this study is to explore the prognostic value of Cys-C for RCC patients.The levels of preoperative Cys-C, creatinine (CRE and estimated glomerular filtration rate (e-GFR were retrospectively collected in 325 RCC patients undergoing surgery. The cutoff values of Cys-C, CRE and e-GFR were determined by the standardized Cutoff Finder algorithm. The receiver operating characteristic (ROC curve and pairwise comparison were performed to compare the three variables. Univariate and multivariate Cox regression analyses were performed to investigate the prognostic value of serum Cys-C in RCC.Based on the analysis of Cutoff Finder algorithm, ROC curve and pairwise comparison, the preoperative Cys-C was superior to CRE and e-GFR as a predictive factor in RCC. Multivariate Cox regression analyses showed that high preoperative Cys-C (>1.09 mg/L was significantly associated with shorter overall survival (OS in all RCC patients (hazard ratio [HR], 1.59; P = 0.012, patients at pT1-2 (P<0.001, pN0 (P<0.001 and pM0 stages (P<0.001. Moreover, Multivariate Cox regression analyses also showed that in the 306 patients without metastasis, high preoperative Cys-C was also associated with shorter disease-free survival (DFS (HR, 3.50; P = 0.013.An elevated preoperative Cys-C level was demonstrated to be related with worse survival in patients with RCC. Measuring preoperative serum Cys-C might be a simple way for finding poor prognostic patients and patients with elevated preoperative Cys-C level should be more closely followed up.
He, Xiaobo; Guo, Kunbin; Dong, Pei; Yao, Kai; Yang, Guangwei; Chen, Dong; Li, Zaishang; Li, Xiangdong; Qin, Zike; Liu, Zhuowei; Cheng, Wenjie; Guo, Chao; Zhang, Meng; Han, Hui; Zhou, Fangjian
Purpose The prognostic value of serum cystatin-C (Cys-C) in renal cell carcinoma (RCC) remains unknown. The purpose of this study is to explore the prognostic value of Cys-C for RCC patients. Patients and methods The levels of preoperative Cys-C, creatinine (CRE) and estimated glomerular filtration rate (e-GFR) were retrospectively collected in 325 RCC patients undergoing surgery. The cutoff values of Cys-C, CRE and e-GFR were determined by the standardized Cutoff Finder algorithm. The receiver operating characteristic (ROC) curve and pairwise comparison were performed to compare the three variables. Univariate and multivariate Cox regression analyses were performed to investigate the prognostic value of serum Cys-C in RCC. Results Based on the analysis of Cutoff Finder algorithm, ROC curve and pairwise comparison, the preoperative Cys-C was superior to CRE and e-GFR as a predictive factor in RCC. Multivariate Cox regression analyses showed that high preoperative Cys-C (>1.09 mg/L) was significantly associated with shorter overall survival (OS) in all RCC patients (hazard ratio [HR], 1.59; P = 0.012), patients at pT1-2 (Ppreoperative Cys-C was also associated with shorter disease-free survival (DFS) (HR, 3.50; P = 0.013). Conclusions An elevated preoperative Cys-C level was demonstrated to be related with worse survival in patients with RCC. Measuring preoperative serum Cys-C might be a simple way for finding poor prognostic patients and patients with elevated preoperative Cys-C level should be more closely followed up. PMID:28586363
Full Text Available The performance of serum biomarkers for the early detection of invasive aspergillosis expectedly depends on the timing of test results relative to the empirical administration of antifungal therapy during neutropenia, although a dynamic evaluation framework is lacking.We developed a multi-state model describing simultaneously the likelihood of empirical antifungal therapy and the risk of invasive aspergillosis during neutropenia. We evaluated whether the first positive test result with a biomarker is an independent predictor of invasive aspergillosis when both diagnostic information used to treat and risk factors of developing invasive aspergillosis are taken into account over time. We applied the multi-state model to a homogeneous cohort of 185 high-risk patients with acute myeloid leukemia. Patients were prospectively screened for galactomannan antigenemia twice a week for immediate treatment decision; 2,214 serum samples were collected on the same days and blindly assessed for (1->3- β-D-glucan antigenemia and a quantitative PCR assay targeting a mitochondrial locus.The usual evaluation framework of biomarker performance was unable to distinguish clinical benefits of β-glucan or PCR assays. The multi-state model evidenced that the risk of invasive aspergillosis is a complex time function of neutropenia duration and risk management. The quantitative PCR assay accelerated the early detection of invasive aspergillosis (P = .010, independently of other diagnostic information used to treat, while β-glucan assay did not (P = .53.The performance of serum biomarkers for the early detection of invasive aspergillosis is better apprehended by the evaluation of time-varying predictors in a multi-state model. Our results provide strong rationale for prospective studies testing a preemptive antifungal therapy, guided by clinical, radiological, and bi-weekly blood screening with galactomannan antigenemia and a standardized quantitative PCR assay.
Zmyslowska, Agnieszka; Ciborowski, Michal; Borowiec, Maciej; Fendler, Wojciech; Pietrowska, Karolina; Parfieniuk, Ewa; Antosik, Karolina; Pyziak, Aleksandra; Waszczykowska, Arleta; Kretowski, Adam; Mlynarski, Wojciech
Wolfram syndrome (WFS) is an example of a rare neurodegenerative disease with coexisting endocrine symptoms including diabetes mellitus as the first clinical symptom. Treatment of WFS is still only symptomatic and associated with poor prognosis. Potential markers of disease progression that could be useful for possible intervention trials are not available. Metabolomics has potential to identify such markers. In the present study, serum fingerprinting by LC-QTOF-MS was performed in patients with WFS (n = 13) and in patients with T1D (n = 27). On the basis of the obtained results, aminoheptadecanediol (17:0 sphinganine isomer) (+50%, p = 0.02), as the most discriminatory metabolite, was selected for validation. The 17:0 sphinganine isomer level was determined using the LC-QQQ method in the samples from WFS patients at two time points and compared with samples obtained from patients with T1D (n = 24) and healthy controls (n = 24). Validation analysis showed higher 17:0 sphinganine isomer level in patients with WFS compared to patients with T1D (p = 0.0097) and control group (p < 0.0001) with progressive reduction of its level after two-year follow-up period. Patients with WFS show a unique serum metabolic fingerprint, differentiating them from patients with T1D. Sphinganine derivate seems to be a marker of the ongoing process of neurodegeneration in WFS patients.
Paradowski, L.; Dolinska, G.; Knapik, Z.; Rynowiecka, M. (Akademia Medyczna, Wroclaw (Poland))
Iodine uptake by the thyroid and serum triiodothyronine (T/sub 3/) level in subjects aged from 65 to 93 years were determined. Low T/sub 3/ level and normal uptake of inorganic iodine by the thyroid were found. In the light of these results it is suggested that normal accumulation of inorganic iodine and low production of T/sub 3/ are characteristic features of euthyroidism in elderly subjects. It is believed that the function of the thyroid is expressed better by determination of the serum levels of thyroid hormones than determination of the uptake of radioactive iodine. Elaboration of standard normal values which would take into account abnormalities encountered in old age is postulated.
Kirvelä, O; Antila, H; Heinonen, O; Toivanen, A
This study investigated plasma carnitine levels in patients undergoing allogenic bone marrow transplantation. The patients received fat-based TPN (50% fat, 50% CHO; calorie: nitrogen ratio 125:1) for an average of 33 +/- 7.5 days. TPN was started before transplantation and stopped when patients were able to eat. Caloric needs were estimated using the Harris-Benedict equation; 150% of the estimated BEE was given for the first two weeks after transplantation. The amount of TPN was gradually decreased as patients resumed their oral intake. All patients had low-normal serum carnitine levels before transplantation. There was no significant change in total or free serum carnitine levels during the course of TPN. However, in patients who had symptoms of graft vs. host reaction (GVH), the highest carnitine values during GVH (total 72.3 +/- 6.5 and free 61.2 +/- 12.4 mumol/l) were significantly higher (p < 0.001) than the baseline values (total 27.1 +/- 9.3 and free 24.9 +/- 9.6 mumol/l) or the highest non GVH values after transplantation (total 32.0 +/- 10.7 and free 29.0 +/- 10.7 mumol/l, respectively). The serum triglyceride, total cholesterol, and HDL cholesterol remained within normal range. In conclusion, bone marrow transplant patients receiving fat-based TPN have normal circulating levels of carnitine. GVH reaction caused an increase in the carnitine levels, which was probably due to increased tissue catabolism.
Full Text Available Introduction : Vitiligo is a common acquired pigmentary skin disorder. Vitamin D is responsible for skin pigmentation, increases tyrosinase activity and melanogenesis, and exhibits immunoregulatory functions. Low levels of vitamin D are associated with many autoimmune diseases, including systemic lupus, diabetes mellitus, rheumatoid arthritis, multiple sclerosis and alopecia areata. Few reports have evaluated serum vitamin D levels in vitiligo patients, and their results are conflicting. Aim : To evaluate serum vitamin D levels of vitiligo patients and compare the results with controls. Material and methods : In total, 50 vitiligo patients and 47 controls were enrolled in the study. Vitamin D levels were measured from blood samples. Group comparisons were performed using appropriate statistical methods. Results : The patients had lower serum vitamin D levels than the controls, but this difference was not significant (p = 0.570. Conclusions : It remains unknown whether vitamin D deficiency causes vitiligo. Larger controlled studies are required to prove whether low circulating vitamin D is a causative factor in vitiligo.
Specht, Ina Olmer; Toft, Gunnar; Hougaard, Karin S
Phthalates which are widely used, are ubiquitous in the environment and in some human tissues. It is generally accepted that phthalates exert their toxic action by inhibiting Leydig cell synthesis of testosterone, but in vitro studies have also shown anti-androgenic effects at the receptor level....... Some cross-sectional studies have shown inverse associations between urinary levels of phthalates and reproductive hormones, but results are conflicting and the evidence base is limited. The aim of this study was to investigate if levels of di-2-ethylhexyl phthalate (DEHP) and diisononyl phthalate (Di...... and Ukraine were enrolled between 2002 and 2004. The men gave semen and blood samples and were interviewed. Six phthalate metabolites of DEHP and DiNP were measured by liquid chromatography tandem mass spectrometry in serum. The metabolites were summed according to their molar weight. We observed significant...
Biondi, Antonio; Malaguarnera, Giulia; Vacante, Marco; Berretta, Massimiliano; D'Agata, Velia; Malaguarnera, Michele; Basile, Francesco; Drago, Filippo; Bertino, Gaetano
During the past three decades, the incidence of hepatocellular carcinoma in the United States has tripled. The neuroendocrine character has been observed in some tumor cells within some hepatocellular carcinoma nodules and elevated serum chromogranin A also been reported in patients with hepatocellular carcinoma. The aim of this work was to investigate the role of serum concentration of chromogranin A in patients with hepatocellular carcinoma at different stages. The study population consisted of 96 patients (63 males and 33 females age range 52-84) at their first hospital admission for hepatocellular carcinoma. The control group consisted of 35 volunteers (20 males and 15 females age range 50-80). The hepatocellular carcinoma patients were stratified according the Barcelona-Clinic Liver Cancer classification. Venous blood samples were collected before treatment from each patients before surgery, centrifuged to obtain serum samples and stored at -80° C until assayed. The chromogranin A serum levels were elevated (> 100 ng/ml) in 72/96 patients with hepatocellular carcinoma. The serum levels of chromogranin A were significantly correlated (p<0.05) with alpha-fetoprotein. In comparison with controls, the hepatocellular carcinoma patients showed a significant increase (p<0.001) vs controls. The chromogranin A levels in the Barcelona staging of hepatocellular carcinoma was higher in stage D compared to stage C (p<0.01), to stage B (p<0.001), and to stage A (p<0.001). Molecular markers, such as chromogranin A, could be very useful tools for hepatocellular carcinoma diagnosis. However the molecular classification should be incorporated into a staging scheme, which effectively separated patients into groups with homogeneous prognosis and response to treatment, and thus serves to aid in the selection of appropriate therapy.
Harishchandra Venkata Yanamandala
Full Text Available BACKGROUND In developing countries, in both adults and children, tuberculosis is an important cause of morbidity and mortality. In 1993, it is declared as the first infectious disease by global health emergency.1 According to WHO report globally, there were an estimated 9.27 million ancient cases of TB in 2009. The cases reported were 8.3 million, the children covered an estimated percentage of 11 and it ranged from 3-25 percent.2 BCG vaccination was advocated for prevention of tuberculosis in children. The aim of the study is to estimate serum ADA levels in newborns before BCG vaccination, serum ADA levels in children with and without BCG scar, after receiving BCG vaccination, serum ADA levels in children without BCG vaccination and to find significance of serum ADA levels in BCG vaccinated children by comparing the above groups. MATERIALS AND METHODS This study was conducted at the Department of Paediatrics, Gitam Institute of Medical Sciences and Research Institute, October 2015 to September 2016. Babies who were in postnatal ward and infants of age of 12 weeks attending for BCG vaccination were included in the study. The total numbers of infants studied were 150. RESULTS In our study, out of 120 children included in the study before BCG vaccination comprising group-1, 61% were males and 39% were females. Out of 120 children received BCG vaccination, only 100 came for follow up comprising group-2, of which 67 (67% were males and 33 (33% were females. 15 children who did not receive BCG vaccination at 12 weeks of age were included in group 3 out of which 11 (73.33% were males and 4 (26.67% were females. Mean ADA levels at the age of 12 weeks in group-2 who were vaccinated at birth were 30.89 ± 5.27 U/L compared to mean ADA levels at the age of 12 weeks in group-3, which was 15.47 ± 1.85 U/L. This shows significant rise in mean ADA levels at 12 weeks of age in those who were vaccinated at birth comprising group-2 compared to their mean ADA
Full Text Available Backgrounds. Heme oxygenase-1 (HO-1 has been reported to play a regulatory role in osteoclastogenesis. Bone morphogenetic protein (BMP pathways induce osteoblastic differentiation and bone remodeling. Aims. To identify serum levels of HO-1, BMP-7, and Runt related-transcription factor 2 (Runx2 in patients with rheumatoid arthritis (RA and ankylosing spondylitis (AS and to investigate the relationships between HO-1, BMP-7, Runx2, and other common biomarkers for bone metabolism. Results. Serum levels of HO-1 and BMP-7 were revealed to be significantly higher in patients with RA or AS than in healthy controls (p<0.01. In RA group, HO-1 was positively correlated with BMP-7, Runx2, and tartrate-resistant acid phosphatase-5b (TRAP-5b (p<0.05, resp., BMP-7 was positively correlated with Runx2 and TRAP-5b (p<0.05, resp., and Runx2 was negatively correlated with N-terminal midfragment of osteocalcin (NMID (p<0.05. In AS group, we observed identical correlation between HO-1 and BMP-7, but opposite correlations between BMP-7 and TRAP-5b and between Runx2 and NMID, when comparing with the RA cohort. Conclusion. Our findings suggest that HO-1 and BMP-7 are potential biomarkers for bone metabolism in patients with RA and AS. The different correlations between the bone markers point to distinct differences in bone remodeling pathways in the two types of arthritis.
Moreira, Fernanda Pedrotti; Medeiros, João Ricardo Carvalho; Lhullier, Alfredo Cardoso; Souza, Luciano Dias de Mattos; Jansen, Karen; Portela, Luis Valmor; Lara, Diogo R; da Silva, Ricardo Azevedo; Wiener, Carolina David; Oses, Jean Pierre
Cocaine abuse is capable of activating the innate immune system in the CNS resulting in deregulation of homeostasis between pro and antiinflammatory cytokines. The aim of this study was to investigate serum levels of pro and antiinflammatory cytokines, IL-6 and IL-10 respectively, in cocaine users from a young population-based sample. This is a case-control study nested in a cross-sectional population-based survey, with individuals of 18 and 35 years old. Two groups were selected: 24 healthy controls and 12 subjects who reported cocaine use. Serum IL-6 and IL-10 were measured by ELISA using a commercial kit. There was a statistically significant increase in IL-6 (p=0.037) and decrease in IL-10 (p=0.007) serum levels, between cocaine users and the control group. There was also an increase in the ratio IL-6/IL-10 (p=0.013) among cocaine users individuals, when compared to the control group. Our results suggest that cocaine users showed an activation of the immune system when compared a control group, demonstrating a disruption in the balance of pro and antiinflammatory cytokines. Thus, peripheral cytokines may represent a putative biomarkers for cocaine users, contributing to the development of diagnosis and effective treatments. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Full Text Available OBJECTIVE: The role of mitochondrial function in the complex pathogenesis of type 2 diabetes is not yet completely understood. Therefore, the aim of this study was to investigate serum concentrations of short-, medium- and long-chain acylcarnitines as markers of mitochondrial function in volunteers with normal, impaired or diabetic glucose control. METHODS: Based on a 75 g oral glucose tolerance test, 1019 studied subjects were divided into a group with normal glucose tolerance (NGT; n = 636, isolated impaired fasting glycaemia (IFG; n = 184, impaired glucose tolerance (IGT; n = 87 or type 2 diabetes (T2D; n = 112. Serum concentrations of free carnitine and 24 acylcarnitines were measured by mass spectrometry. RESULTS: Serum levels of acetylcarnitine (C2, propionylcarnitine (C3, octanoylcarnitine (C8, malonylcarnitine/hydroxybutyrylcarnitine (C3DC+C4OH, hexanoylcarnitine (C6, octenoylcarnitine (C8:1, decanoylcarnitine (C10, decenoylcarnitine (C10:1, dodecanoylcarnitine (C12, tetradecenoylcarnitine (C14:1, tetradecadienylcarnitine (C14:2, hydroxytetradecanoylcarnitine (C14OH, hydroxyhexadecanoylcarnitine (C16OH and octadecenoylcarnitine (C18:1 were significantly different among the groups (all p<0.05 adjusted for age, gender and BMI. Between the prediabetic states C14:1, C14:2 and C18:1 showed significantly higher serum concentrations in persons with IGT (p<0.05. Compared to T2D the IFG and the IGT subjects showed lower serum concentrations of malonylcarnitine/hydroxybutyrylcarnitine (C3DC+C4OH (p<0.05. CONCLUSION: Alterations in serum concentrations of several acylcarnitines, in particular tetradecenoylcarnitine (C14:1, tetradecadienylcarnitine (C14:2, octadecenoylcarnitine (C18:1 and malonylcarnitine/hydroxybutyrylcarnitine (C3DC+C4OH are associated not only with T2D but also with prediabetic states.
Sallinen, Hanna; Heikura, Tommi; Koponen, Jonna; Kosma, Veli-Matti; Heinonen, Seppo; Ylä-Herttuala, Seppo; Anttila, Maarit
The aim of the study was to explore the serum levels of eight angiogenesis biomarkers in patients with benign, borderline or malignant epithelial ovarian neoplasms and to compare them to those of healthy controls. In addition, we aimed to study how those biomarkers predict the clinical course and survival of patients with epithelial ovarian cancer. We enrolled 132 patients with ovarian neoplasms and 32 unaffected women in this study. Serum samples were collected preoperatively at the time of diagnosis and the levels of angiogenesis biomarkers were measured with an ELISA. Levels of Ang-1, Ang-2, VEGF, VEGF-D, VEGF/sVEGFR-2 and Ang-2/ sVEGFR-2 ratios were elevated whereas sVEGFR-2 was lower in patients with ovarian carcinoma than in women with normal ovaries, benign and/or borderline ovarian neoplasms. In ROC analysis, the area under the curve for serum Ang-2/sVEGFR-2 ratio (0.76) was greater than Ang-2 (0.75) and VEGF (0.65) but lower than for CA 125 (0.90) to differentiate ovarian cancer from benign or borderline ovarian tumors. In ovarian cancer high Ang-2/sVEGFR-2 ratio was associated with the presence of ascites, high stage and grade of ovarian cancer, with the size of primary residual tumor>1 cm and with recurrence of disease. Elevated Ang-2, VEGF, VEGF/sVEGFR-2, Ang-2/VEGF and Ang-2/sVEGFR-2 ratios and low level of sVEGFR-2 were significant predictors of poor overall survival (OS) and recurrence free survival (RFS) in univariate survival analyses. Ovarian cancer patients had elevated levels of angiogenesis related growth factors in circulation reflecting increased angiogenesis and poor prognosis. The serum level of Ang-2 predicted most accurately poor OS and Ang-2/sVEGFR-2 ratio malignancy of ovarian neoplasms and short RFS.
Dauvilliers, Yves; Chenini, Sofiene; Vialaret, Jérôme; Delaby, Constance; Guiraud, Lily; Gabelle, Audrey; Lopez, Regis; Hirtz, Christophe; Jaussent, Isabelle; Lehmann, Sylvain
To better understand the role of iron homeostasis dysregulation in restless legs syndrome, we compared serum hepcidin and ferritin levels in drug-free patients with primary restless legs syndrome and healthy controls and studied the relationship between hepcidin level and restless legs syndrome severity. One hundred and eight drug-free patients with primary restless legs syndrome (65 women; median age, 61.5 years) and 45 controls (28 women; median age, 53.9 years) were enrolled. Inclusion criteria were: normal ferritin level (>50 ng/mL) and absence of iron disorders, chronic renal or liver failure, and inflammatory or neurological diseases. Each subject underwent a thorough clinical examination and a polysomnography assessment. Serum hepcidin-25 was quantified using a validated mass spectrometry method. Restless legs syndrome severity was evaluated according to the International Restless Legs Syndrome Study Group. Despite no group difference between normal ferritin levels and demographic features, serum hepcidin level and hepcidin/ferritin ratio were higher in patients than in controls. Hepcidin level and hepcidin/ferritin ratio, but not ferritin level, were positively correlated with periodic leg movements during sleep and wakefulness in the whole sample. Hepcidin level seem to be associated with restless legs syndrome severity in a complex U-shaped relationship, without relationship with age at restless legs syndrome onset, positive family history, sleep and depressive symptoms, genetic background, and polysomnographic measurements. No relationship was found between ferritin level and restless legs syndrome severity. In drug-free patients with primary restless legs syndrome, hepcidin level is higher than in controls and may be associated with restless legs syndrome clinical severity. This result emphasizes the complex peripheral iron metabolism deregulation in restless legs syndrome, opening potential perspectives for a personalized approach with a hepcidin
Gulec, U K; Paydas, S; Guzel, A B; Vardar, M A; Urunsak, I F; Cetin, M T
The aim of this study was to investigate the relationship between ovarian volume and serum CA-125 levels. Serum CA-125 levels and ovarian volume were compared among the cases with benign ovarian neoplasms, primary epithelial ovarian cancer (EOC), controlled ovarian hyperstimulation, and ovarian hyperstimulation syndrome (OHSS). Also, the correlation between CA-125 levels and ovarian volume were evaluated in the presence of peritoneal fluid and/or peritoneal carcinomatosis. Although ovarian volume was not different among the groups, CA-125 levels were higher in the cases with EOC than with benign ovarian tumors (p = 0.001). Baseline CA-125 levels were not found to have increased while ovarian volume went up with controlled hyperstimulation in the infertile group (p = 0.555). However, uncontrolled hyperstimulation of the ovaries and the presence of peritoneal fluid caused an increase in the levels of CA-125 (p = 0.001). There was no correlation between ovarian volume and CA-125 levels in the cases with malignant ovarian tumors (r = 0.083). The results of this study have confirmed that CA-125 is a peritoneal marker and increased ovarian volume with benign ovarian neoplasms or controlled hyperstimulation does not increase CA-125 levels in the same way. The presence of peritoneal carcinomatosis and/or peritoneal fluid seems to be an important factor for high CA-125 levels in patients with epithelial ovarian cancer (EOC).
Kim, Y. H.; Choi, K. A.; Ahn, K. S.; Suh, W. H.; Lee, M. J.
Alpha-fetoprotein (AFP) was first described in the human fetus in 1956 and became a marker protein of primary liver cancer in adults. Serum AFP levels were measured by radioimmunoassay in 212 patients with a variety of malignant and nonmalignant diseases to determine the incidence of leveis elevated above 40 ng/ml. The results obtained are as follows: In 44 cases of total 212 patients, abnormal AFP levels above 40 ng/ml in serum were measured; 24 of 31 patients with primary hepatocellular carcinoma and primary hepatocellular carcinoma with liver cirrhosis (77.4%), 7 of 51 patients with only liver cirrhosis (13.7%), 4 of 10 patients with metastatic liver cancer (40.0%), 4 of 15 patients with chronic hepatitis (26.7%), 2 of 23 patients with acute hepatitis (8.7%), and each one patient with 6 pancreatic carcinoma and 9 cholangiocarcinoma had elevated serum AFP levels. One pregnant woman with gestation 35 weeks had elevated level, but within normal limit during pregnancy
Kim, Ki-Jo; Kim, Ji-Young; Baek, In-Woon; Kim, Wan-Uk; Cho, Chul-Soo
Syndecan-1 (SDC-1) is a major constituent of the endothelial glycocalyx, which plays a role in maintaining vascular homeostasis and functions as a glomerular filtration barrier. SDC-1 is readily shed into the blood under various conditions, but the clinical implication of circulating SDC-1 in patients with systemic lupus erythematosus (SLE) remains unclear. We aimed to investigate the association of serum SDC-1 level with certain clinical manifestations of SLE. We measured serum SDC-1 levels by ELISA in 111 patients with SLE, 18 with rheumatoid arthritis (RA), and 20 healthy subjects, and investigated its association with clinical manifestations and laboratory variables. Serum SDC-1 levels were higher in patients with SLE than in those with RA and healthy controls (both p SDC-1 levels than patients with inactive nephritis and those without nephritis (both p SDC-1 levels were correlated with renal SLEDAI score (r = 0.540, p SDC-1 levels and activity index (r = 0.632, p = 0.015). Serum SDC-1 levels are increased in SLE patients with nephritis, indicating that SDC-1 might be a useful serum biomarker for active LN.
Zhang, Xing; Guo, Jing; Fan, Shufeng; Li, Yanyuan; Wei, Liliang; Yang, Xiuyun; Jiang, Tingting; Chen, Zhongliang; Wang, Chong; Liu, Jiyan; Ping, Zepeng; Xu, Dandan; Wang, Jiaxiong; Li, Zhongjie; Qiu, Yunqing; Li, Ji-Cheng
It is very difficult to prevent pulmonary tuberculosis (TB) due to the lack of specific and diagnostic markers, which could lead to a high incidence of pulmonary TB. We screened the differentially expressed serum microRNAs (miRNAs) as potential biomarkers for the diagnosis of pulmonary TB. In this study, serum miRNAs were screened using the Solexa sequencing method as the potential biomarkers for the diagnosis of pulmonary TB. The stem-loop quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assay was used to verify differentially expressed serum miRNAs. The receiver operating characteristic (ROC) curve and logistic regression model were used to analyze the sensitivity and specificity of the single miRNA and a combination of miRNAs for diagnosis, respectively. Using the predicted target genes, we constructed the regulatory networks of miRNAs and genes that were related to pulmonary TB. The Solexa sequencing data showed that 91 serum miRNAs were differentially expressed in pulmonary TB patients, compared to healthy controls. Following qRT-PCR confirmation, six serum miRNAs (hsa-miR-378, hsa-miR-483-5p, hsa-miR-22, hsa-miR-29c, hsa-miR-101 and hsa-miR-320b) showed significant difference among pulmonary TB patients, healthy controls (P<0.001) and differential diagnosis groups (including patients with pneumonia, lung cancer and chronic obstructive pulmonary disease) (P<0.05). The logistic regression analysis of a combination of six serum miRNAs revealed that the sensitivity and the specificity of TB diagnosis were 95.0% and 91.8% respectively. The miRNAs-gene regulatory networks revealed that several miRNAs may regulate some target genes involved in immune pathways and participate in the pathogenesis of pulmonary TB. Our study suggests that a combination of six serum miRNAs have great potential to serve as non-invasive biomarkers of pulmonary TB.
Freis, A; Schlegel, J; Kuon, R J; Doster, A; Jauckus, J; Strowitzki, T; Germeyer, A
Miscarriage is a common complication in pregnancy and there is still a lack of biomarkers usable in asymptomatic patients before the event occurs. Periostin (PER), whose levels rise particularly during injury or inflammation, has been shown to play an important local role in implantation and early embryonic development. As PER has been described as a biomarker in various medical conditions we intended to evaluate if changes in PER serum levels may help to identify women at risk for spontaneous abortion in the first trimester. Women between 18 and 42 years without confounding comorbidities who conceived by IVF/ICSI and ovarian hyperstimulation were analysed in the study after informed consent. Maternal serum samples from 41 patients were assessed at the time of pregnancy testing (PT) and the following first ultrasound checkup (US). Patients were subsequently divided in two groups: (1) patients with subsequent miscarriage in the first trimester (n = 18) and (2) patients with ongoing pregnancy (n = 23), allowing for statistical analysis and investigating the change of PER levels per individual. PER levels were measured using enzyme-linked immunosorbent assay. Statistical analysis was performed using the Fisher exact and Student's t test. p ≤ 0.05 was considered to be significant. There was no significant difference concerning possible confounders between the two groups. We did not find any significant difference in PER levels at the time point of PT or US. By investigating the interindividual changes of PER between the two time points however, we observed that patients with a following miscarriage showed increasing levels of PER at the time point of PT compared to US in contrast to patients with an ongoing pregnancy who demonstrated a decrease in PER levels. These alterations were significant in the absolute as well as in the relative comparison. The relative expression of PER between PT and US is significantly altered in asymptomatic women with subsequent
Rodier, Marion; Quirié, Aurore; Prigent-Tessier, Anne; Béjot, Yannick; Jacquin, Agnès; Mossiat, Claude; Marie, Christine; Garnier, Philippe
The recombinant form of tissue plasminogen activator (rt-PA) is the only curative treatment for ischemic stroke. Recently, t-PA has been linked to the metabolism of brain-derived neurotrophic factor (BDNF), a major neurotrophin involved in post-stroke neuroplasticity. Thus, the objective of our study was to investigate the impact of rt-PA treatment on post-stroke circulating BDNF levels in humans and in animals. Serum BDNF levels and t-PA/plasmin activity were measured at hospital admission and at up to 90 days in stroke patients receiving (n = 24) or not (n = 14) rt-PA perfusion. We investigated the relationships between serum BDNF with concurrent t-PA/plasmin activity, neurological outcomes and cardiovascular scores at admission. In parallel, serum BDNF levels and t-PA/plasmin activity were assessed before and after (1, 4 and 24h) the induction of ischemic stroke in rats. Our study revealed higher serum BDNF levels and better neurological outcome in rt-PA-treated than non-treated patients. However, serum BDNF levels did not predict stroke outcome when the whole cohort of stroke patients was analyzed. By contrast, serum BDNF levels when measured at admission and at day 90 correlated with cardiovascular scores, and those at day 1 correlated with serum t-PA/plasmin activity in the whole cohort of patients whereas no association could be found in the rt-PA-treated group. In rats devoid of cardiovascular risk, no difference in post-stroke serum BDNF levels was detected between rt-PA- and vehicle-treated animals and no correlation was found between serum BDNF levels and t-PA/plasmin activity. Overall, the data suggest that serum BDNF levels may not be useful as a prognostic biomarker of stroke outcome and that endothelial dysfunction could be a confounding factor when serum BDNF levels after stroke are used to reflect of brain BDNF levels.
Ozuna, J; Friel, P
The primary purpose of the present study was to determine if altering the timing of phenytoin administration in relation to delivery of tube feedings increased serum phenytoin levels. Stopping tube feedings for two hours before and two hours after administration is a procedure that nurses could employ independently for better patient care. However, this adds an extra procedure to the nurse's already busy routine. It also requires the nurse to adjust either the tube feeding flow rate or bolus amount in order to deliver the same amount of calories per day. Based on this study, it appears that this intervention procedure is not effective for the patient and is time-consuming for the nurse. Instead, the focus for increasing phenytoin serum levels in patients receiving tube feedings should probably be on increasing the dosage.
Full Text Available Fluorosis induced by exposure to high level fluoride is quite widespread in the world. The manifestations of fluorosis include dental mottling, bone damage, and impaired malfunction of soft tissues. However, the molecular mechanism of fluorosis has not been clarified until now. To explore the underlying mechanisms of fluorosis and screen out serum biomarkers, we carried out a quantitative proteomics study to identify differentially expressed serum proteins in Wistar rats treated with sodium fluoride (NaF by using a proteomics approach of isobaric tagging for relative and absolute quantitation (iTRAQ. We fed Wistar rats drinking water that had 50, 150, and 250 mg/L of dissolved NaF for 24 weeks. For the experimental duration, each rat was given an examination of the lower incisors to check for the condition of dental fluorosis (DF. By the end of the treatment, fluoride ion concentration in serum and lower incisors were detected. The results showed that NaF treatment can induce rat fluorosis. By iTRAQ analysis, a total of 37 differentially expressed serum proteins were identified between NaF-treated and control rats. These proteins were further analyzed by bioinformatics, out of which two proteins were validated by enzyme-linked immunoadsorbent assays (ELISA. The major proteins were involved in complement and coagulation cascade, inflammatory response, complement activation, defense response, and wound response, suggesting that inflammation and immune reactions may play a key role in fluorosis pathogenesis. These proteins may contribute to the understanding of the mechanism of fluoride toxicity, and may serve as potential biomarkers for fluorosis.
Agrawal, Amit; Karan, Shailesh Chandra
Serum prostate-specific antigen (PSA) is an important tumour, marker which is widely used to trigger trans-rectal ultrasound (TRUS)-guided prostate biopsy. However, the PSA levels vary with race and ethnicity. Therefore, there is a need to have an Indian reference range. All adult male patients meeting the inclusion and exclusion criteria were enrolled in this study. They were subjected to assessment of serum total PSA, digital rectal examination and trans-abdominal ultrasound. If any one or more of these were found abnormal, then a TRUS-guided 12-core prostate biopsy was done. Patients who were detected to have prostatic cancer were excluded from the final analysis. The data so obtained was grouped among the following three age groups: 40-49, 50-59 and 60-70 years, and the age-specific PSA values, prostatic volume and PSA density were found. A total of 1772 patients were analysed. The mean serum total PSA was 1.76 ng/ml with a standard deviation of 2.566 ng/ml. Group-wise age distribution of the mean serum total PSA was 1.22, 1.97 and 2.08 ng/ml in 40-49, 50-59 and 60-70 years age groups. The mean total PSA and the age-specific PSA range tend to be lower in the Indians than the Western population.
Full Text Available The effects of Cortisol upon the serum immunoglobulin concentration areexamined. The experiment involved male guinea pigs of the body weight from 300 to400 g that were nonnally fed and lived under the common laboratory conditions. Theguinea pigs were divided into an experimental and a control group. The experimentalgroup's guinea pigs were given every day (in a 6 days' period a subcutaneous dose of80 g of corti sol/kg/per day, while the control group ones were given only one ml ofthe physiological solution. Two weeks after the last received dose of Cortisol orphysiological solution the cordial puncture was applied to take a blood sample inwhich the level of the serum IgA, IgG and IgM was determined. In the experimentalgroup animals the serum IgG value was 11,2 mg/ml at the beginning and 8,7 mg/ml at the end of the experiment (reduction for 22,1%, while the TgA concentration at theend of the experiment was reduced for 5,8%, while the IgM concentration for 12,9%.The serum immunoglobulin concentration in the control group guinea pigs does notreveal any significant differences at the beginning and the end of the experiment.
Ozmen, Mustafa; Oktay, Esin; Tarhan, Emine F; Aslan, Ozgur; Oflazoglu, Utku; Koseoglu, Mehmet H
Procalcitonin is a marker of bacterial and fungal infection and sepsis. The present study evaluated the relationship between serum procalcitonin levels and disease activity in patients with ankylosing spondylitis (AS). A total of 61 patients who met the 1984 New York criteria for AS were studied. Twenty-four age- and sex-matched healthy volunteers were recruited to this study as a control group. Disease activity was assessed by the Bath AS Disease Activity Index (BASDAI). The functional status of patients was evaluated by the Bath AS Functional Index (BASFI). Spinal mobility was measured by the Bath AS Metrology Index (BASMI). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and serum procalcitonin levels were measured. Thirty patients were on anti-tumor necrosis factor-alpha treatment and 31 patients were on conventional treatment. Seventeen (28%) of the AS patients were active (BASDAI > 4) and 44 (72%) of the AS patients were in remission. The median ESR was 14 (34-6) mm/h and 4 (7-2) mm/h (P < 0.001) for the patient and control groups, respectively. The median CRP level was 0.91 (2.72-0.37) mg/dL and 0.15 (0.25-0.07) mg/dL in the patient and control groups, respectively (P < 0.001). Median BASDAI, BASFI and BASMI scores for all AS patients were 3.6 (5.25-2.29), 2.5 (4.22-0.91) and 3 (5-1), respectively. Serum procalcitonin levels were normal (< 0.05 ng/mL) for all patients and controls. Serum procalcitonin levels were not high in AS patients and controls, and the levels were independent of disease activity and medications. If bacterial or fungal infection is suspected in an AS patient, serum procalcitonin level may be useful for diagnosis. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.
Cotter, T P
A case of a 32-year-old XY genotype female is described, presenting with mediastinal and abdominal lymphadenopathy and associated with an elevated serum angiotensin I converting enzyme (SACE) level. Lymph node histology showed a malignant dysgerminoma of ovarian origin. Combined chemotherapy led to a radiological regression of the lymphadenopathy and coincided with a decrease in SACE concentration. The authors suggest that SACE may be a marker for disseminated germinoma tumours and may be useful for monitoring treatment.
Group 1 served as control while groups 2, 3 and 4 were respectively gavaged with 200mg/kg body weight, 400mg/kg body weight and 600mg/kg body weight of the extract daily for 21 days. At the end of treatments, animals were sacrificed, serum and liver tissues obtained for assay of total protein concentration and levels of ...
Full Text Available Background Myocardial infarction results as a consequence of atherosclerotic plaque rupture, with plaque stability largely depending on the lesion forming extracellular matrix components. Lipid enriched non-calcified lesions are considered more instable and rupture prone than calcified lesions. Matrix metalloproteinases (MMPs are extracellular matrix degrading enzymes with plaque destabilisating characteristics which have been implicated in atherogenesis. We therefore hypothesised MMP-1 and MMP-9 serum levels to be associated with non-calcified lesions as determined by CT-angiography in patients with coronary artery disease. Methods 260 patients with typical or atypical chest pain underwent dual-source multi-slice CT-angiography (0.6-mm collimation, 330-ms gantry rotation time to exclude coronary artery stenosis. Atherosclerotic plaques were classified as calcified, mixed or non-calcified. Results In multivariable regession analysis, MMP-1 serum levels were associated with total plaque burden (OR: 1.37 (CI: 1.02-1.85; p Conclusion MMP-1 serum levels are associated with total plaque burden but do not allow a specification of plaque morphology.
Niccoli, Giampaolo; Menozzi, Alberto; Capodanno, Davide; Trani, Carlo; Sirbu, Vasile; Fineschi, Massimo; Zara, Chiara; Crea, Filippo; Trabattoni, Daniela; Saia, Francesco; Ladich, Elena; Biondi Zoccai, Giuseppe; Attizzani, Guilherme; Guagliumi, Giulio
To compare angiographic and optical coherence tomography (OCT) data pertinent to thrombi, along with the histologic characteristics of aspirated thrombi in patients presenting with ST elevation myocardial infarction (STEMI) with or without inflammation, as assessed by C-reactive protein (CRP) and myeloperoxidase (MPO). In the OCTAVIA (Optical Coherence Tomography Assessment of Gender Diversity in Primary Angioplasty) study, 140 patients with STEMI referred for primary percutaneous intervention were enrolled. The patients underwent OCT assessment of the culprit vessel, along with blood sampling of CRP and MPO, and histologic analysis of the thrombus. Biomarkers were available for 129 patients, and histology and immunohistochemistry of the thrombi were available for 78 patients. Comparisons were made using the median thresholds of CRP and MPO (2.08 mg/L and 604.124 ng/mL, respectively). There was no correlation between CRP and MPO levels in the whole population (p = 0.685). Patients with high CRP levels had higher thrombus grades and more frequent TIMI flow 0/1 compared with those with low CRP levels (5 [1st quartile 3; 3rd quartile 5] vs. 3.5 mg/L [1; 5], p = 0.007, and 69.3 vs. 48.5%, p = 0.04, respectively). Patients with high MPO levels more commonly had early thrombi than had those with low MPO levels (42.5 vs. 20.0%, p = 0.04). CRP and MPO were not correlated in STEMI patients, possibly reflecting different pathogenic mechanisms, with CRP more related to thrombus burden and MPO to thrombus age. © 2016 S. Karger AG, Basel.
Full Text Available To evaluate the role of Cystatin C (Cys-C in tumorigenesis and progression of prostate cancer (PCa, we retrospectively collected the clinical information from the records of 492 benign prostatic hyperplasia (BPH, 48 prostatic intraepithelial neoplasia (PIN, and 173 PCa patients, whose disease was newly diagnosed and histologically confirmed. Pretreatment serum Cys-C levels were compared across the various groups and then analyzed to identify relationships, if any, with clinical and pathological characteristics of the PCa patient group. There were no significant differences in serum Cys-C levels among the three groups (P > 0.05. In PCa patients with normal SCr levels, patient age was correlated with serum Cys-C level (P ≤ 0.001 but did not correlate with alkaline phosphatase (AKP, lactate dehydrogenase (LDH, prostate specific antigen (PSA, Gleason score, or bone metastasis status (P > 0.05. Age and SCr contributed in part to the variations in serum Cys-C levels of PCa patients (r = 0.356, P ≤ 0.001; r = 0.520, P ≤ 0.001. In conclusion, serum Cys-C levels predict renal function in patients with prostate neoplasia, but were not a biomarker for the development of prostate neoplasia, and were not correlated with the clinicopathological characteristics of PCa.
Zhang, Jie; Hisada, Aya [Department of Environmental Studies, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8563 (Japan); Yoshinaga, Jun, E-mail: firstname.lastname@example.org [Department of Environmental Studies, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8563 (Japan); Shiraishi, Hiroaki [National Institute for Environmental Studies, Onogawa 16-2, Tsukuba, Ibaraki 305-8563 (Japan); Shimodaira, Kazuhisa; Okai, Takashi [Department of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555 (Japan); Noda, Yumiko; Shirakawa, Miyako; Kato, Nobumasa [Department of Psychiatry and Neurology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555 (Japan)
Possible association between environmental exposure to pyrethroid insecticides and serum thyroid-related measures was explored in 231 pregnant women of 10–12 gestational weeks recruited at a university hospital in Tokyo during 2009–2011. Serum levels of free thyroxine (fT4), thyroid stimulating hormone (TSH) and thyroid biding globulin (TBG) and urinary pyrethroid insecticide metabolite (3-phenoxybenzoic acid, 3-PBA) were measured. Obstetrical information was obtained from medical records and dietary and lifestyle information was collected by self-administered questionnaire. Geometric mean concentration of creatinine-adjusted urinary 3-PBA was 0.363 (geometric standard deviation: 3.06) μg/g cre, which was consistent with the previously reported levels for non-exposed Japanese adult females. The range of serum fT4, TSH and TBG level was 0.83–3.41 ng/dL, 0.01–27.4 μIU/mL and 16.4–54.4 μg/mL, respectively. Multiple regression analysis was carried out by using either one of serum levels of thyroid-related measures as a dependent variable and urinary 3-PBA as well as other potential covariates (age, pre-pregnancy BMI, parity, urinary iodine, smoking and drinking status) as independent variables: 3-PBA was not found as a significant predictor of serum level of thyroid-related measures. Lack of association may be due to lower pyrethroid insecticide exposure level of the present subjects. Taking the ability of pyrethroid insecticides and their metabolite to bind to nuclear thyroid hormone (TH) receptor, as well as their ability of placental transfer, into consideration, it is warranted to investigate if pyrethroid pesticides do not have any effect on TH actions in fetus brain even though maternal circulating TH level is not affected. -- Highlights: • Pyrethroid exposure and thyroid hormone status was examined in pregnant women. • Urinary 3-phenoxybenzoic acid was used as a biomarker of exposure. • Iodine nutrition, age and other covariates were included
Kolberg, Janice A; Jørgensen, Torben; Gerwien, Robert W
of approximately 6,600 Danes in a nested case-control design with the primary outcome of 5-year conversion to type 2 diabetes. Nondiabetic subjects, aged >or=39 years, with BMI >or=25 kg/m(2) at baseline were selected. Baseline fasting serum samples from 160 individuals who developed type 2 diabetes and from 472......OBJECTIVE: The purpose of this study was to develop a model for assessing the 5-year risk of developing type 2 diabetes from a panel of 64 circulating candidate biomarkers. RESEARCH DESIGN AND METHODS: Subjects were selected from the Inter99 cohort, a longitudinal population-based study...... model performance was estimated using a validated bootstrap bias-correction procedure. RESULTS: A model using six biomarkers (adiponectin, C-reactive protein, ferritin, interleukin-2 receptor A, glucose, and insulin) was developed for assessing an individual's 5-year risk of developing type 2 diabetes...
Full Text Available The incidence of abomasal mucosal diseases in dairy cows suffering from gastrointestinal disorders is becoming more frequent in modern intensive production. Clinical signs are often non-specific. In this study, 67 dairy cows with gastrointestinal disorders and 9 healthy dairy cows as the control group were used. In order to make a tentative diagnosis, a complete physical examination was performed, and the fecal samples were taken from each cow for the fecal occult blood (FOB and the fecal egg count (FEC. Blood samples were taken from the coccygeal vein for WBC, Hematocrit (PCV evaluations, and serum biochemical analysis. Serum pepsinogen activity and total protein; albumin and globulin were measured using validated standard methods. The statistical analysis was performed using SPSS software. The level of significance was set at P<0.05. A significant increase in serum pepsinogen activity was seen in all the cases of abomasal displacements compared to the control group. Among the abomasal displacement groups a significant increase in serum pepsinogen activity was seen in abomasal displacements with suspected abomasal ulcer in comparison with those without any signs of abomasal ulcer (positive FOB and melena. No considerable differences were observed between WBC, PCV, and total protein and globulin in different gastrointestinal disorders and the control group. In this study, the serum pepsinogen activity in all dairy cows with signs of abomasal ulcer (melena and positive fecal occult blood test was higher than the control group, since all of the cases had negative abomasal parasites; these increases in the signs of abomasal ulcer could predict abomasal ulcer complication in the cases of displacements.
Nejatinamini, Sara; Ataie-Jafari, Asal; Qorbani, Mostafa; Nikoohemat, Shideh; Kelishadi, Roya; Asayesh, Hamid; Hosseini, Saeed
Serum uric acid levels is reported to be associated with a variety of cardiometabolic risk factors; however, its direct association with metabolic syndrome (MetS) remains controversial. Thus, we examined the association of serum uric acid concentrations with the MetS components. MetS was defined according to the National Cholesterol Education Program (NCEP) criteria. This case-control study comprised 101 non-smoking individuals (41 in the MetS group and 60 in the non-MetS group). Blood pressure, fasting plasma glucose, insulin, HOMA-IR, lipid profiles, uric acid, and anthropometric measures were determined, and body composition was assessed by using bioelectrical impedance analysis (BIA). After adjustment for confounding factors, serum uric acid was significantly higher in MetS group than non-MetS group (5.70 ± 1.62 vs 4.97 ± 1.30 mg/dL, respectively, P = 0.001). After controlling for age, sex and body mass index in partial correlation analysis, uric acid was positively correlated with triglycerides, and negatively with HDL-C. In multiple logistic regression analysis, every 1 mg/dl elevation in the serum uric acid level increased the risk of MetS approximately by 2-folds (OR: 2.11, 95 % CI: 1.30-3.41). This study showed that those individuals with MetS have higher uric acid levels; the association of uric acid and MetS components supports that it might be an additional components of MetS.
Alana Ausciutti Victorino
Full Text Available Background / objectives. Hyaluronic acid (HA is rarely described in dermatomyositis (DM. Thus, we determined any clinical association of serum levels of hyaluronic acid (HA in patients with dermatomyositis (DM. Materials and Methods. This cross-sectional single-center analysis 75 DM and 75 healthy individuals, during the period from January 2012 to July 2013. An anti-HA antibody assay was performed using specific ELISA/EIA kits, according to the manufacturer’s protocol. Results. The patients with DM and control subjects had comparable demographic distributions (p>0.05. The median time duration between disease diagnosis and initial symptoms was 6.0 [3.0-12.0] months, with a median DM disease duration of 4.0 [1.0-7.0] years. The median level of serum HA was significantly increased in patients with DM compared to the control group [329.0 (80.0-958.0 vs. 133.0 (30.0-262.0 ng/mL, respectively; p0.05. Serum HA also did not correlate with gender, ethnicity, auto-antibodies or drug use (p>0.05, but did correlate with cutaneous features, such as photosensitivity (p=0.001, “shawl” sign (p=0.018, “V-neck” sign (p=0.005 and cuticular hypertrophy (p=0.014. Conclusions. A high level of serum AH was observed in DM compared to healthy individuals. In DM, HA did not correlate to demographic, auto-antibodies and therapy parameters. However, HA correlated specifically with some cutaneous features, suggesting that this glycosaminoglycan could be involved in modulating cutaneous inflammation in this population. More studies are necessary to understand the correlation between AH and patients with DM.
Teupser, Daniel; Baber, Ronny; Ceglarek, Uta; Scholz, Markus; Illig, Thomas; Gieger, Christian; Holdt, Lesca M; Leichtle, Alexander; Greiser, Karin H; Huster, Dominik; Linsel-Nitschke, Patrick; Schäfer, Arne; Braund, Peter S; Tiret, Laurence; Stark, Klaus; Raaz-Schrauder, Dorette; Fiedler, Georg M; Wilfert, Wolfgang; Beutner, Frank; Gielen, Stephan; Grosshennig, Anika; König, Inke R; Lichtner, Peter; Heid, Iris M; Kluttig, Alexander; El Mokhtari, Nour E; Rubin, Diana; Ekici, Arif B; Reis, André; Garlichs, Christoph D; Hall, Alistair S; Matthes, Gert; Wittekind, Christian; Hengstenberg, Christian; Cambien, Francois; Schreiber, Stefan; Werdan, Karl; Meitinger, Thomas; Loeffler, Markus; Samani, Nilesh J; Erdmann, Jeanette; Wichmann, H-Erich; Schunkert, Heribert; Thiery, Joachim
Phytosterols are plant-derived sterols that are taken up from food and can serve as biomarkers of cholesterol uptake. Serum levels are under tight genetic control. We used a genomic approach to study the molecular regulation of serum phytosterol levels and potential links to coronary artery disease (CAD). A genome-wide association study for serum phytosterols (campesterol, sitosterol, brassicasterol) was conducted in a population-based sample from KORA (Cooperative Research in the Region of Augsburg) (n=1495) with subsequent replication in 2 additional samples (n=1157 and n=1760). Replicated single-nucleotide polymorphisms (SNPs) were tested for association with premature CAD in a metaanalysis of 11 different samples comprising 13 764 CAD cases and 13 630 healthy controls. Genetic variants in the ATP-binding hemitransporter ABCG8 and at the blood group ABO locus were significantly associated with serum phytosterols. Effects in ABCG8 were independently related to SNPs rs4245791 and rs41360247 (combined P=1.6 x 10(-50) and 6.2 x 10(-25), respectively; n=4412). Serum campesterol was elevated 12% for each rs4245791 T-allele. The same allele was associated with 40% decreased hepatic ABCG8 mRNA expression (P=0.009). Effects at the ABO locus were related to SNP rs657152 (combined P=9.4x10(-13)). Alleles of ABCG8 and ABO associated with elevated phytosterol levels displayed significant associations with increased CAD risk (rs4245791 odds ratio, 1.10; 95% CI, 1.06 to 1.14; P=2.2 x 10(-6); rs657152 odds ratio, 1.13; 95% CI, 1.07 to 1.19; P=9.4 x 10(-6)), whereas alleles at ABCG8 associated with reduced phytosterol levels were associated with reduced CAD risk (rs41360247 odds ratio, 0.84; 95% CI, 0.78 to 0.91; P=1.3 x 10(-5)). Common variants in ABCG8 and ABO are strongly associated with serum phytosterol levels and show concordant and previously unknown associations with CAD.
Wang, Dejiang; Di, Xiangjun; Fu, Lu; Li, Yingnan; Han, Xiao; Wu, Hui; Cai, Linjun; Meng, Xiangyu; Jiang, Chunlai; Kong, Wei; Su, Weiheng
As a progressive age-related neurodegenerative disorder, Alzheimer's disease (AD) is a global health concern. Despite the availability of psychological testing, neuroimaging, genetic testing, and biochemical assays of cerebrospinal fluid, convenient and accurate blood biomarkers for the prediction, diagnosis, and preclinical studies of AD are still lacking. The present study aims to longitudinally evaluate the feasibility of β-amyloid proteins, α2-macroglobulin (α-2M), complement factor H (CFH), and clusterin as blood biomarkers of AD. Using APP/PS1 transgenic and wild-type mice, cognitive impairment and amyloid plaque counts in the brain were evaluated over a range of ages using the Morris water maze test and immunohistochemistry methods, respectively. Serum Aβ40, Aβ42, α-2M, CFH, and clusterin levels were measured by enzyme-linked immunosorbent assay and correlated with progression of AD. APP/PS1 transgenic mice presented progressive AD characteristics at the ages of 3, 6, 9, and 12 months. Serum Aβ42 levels and Aβ42/Aβ40 ratios increased significantly in transgenic 3- and 6-month-old mice compared with controls. Serum CFH levels decreased significantly in 3- and 6-month-old transgenic mice compared with controls. Meanwhile, serum clusterin levels increased significantly in 12-month-old transgenic mice compared with controls. The α-2M level was not significantly different between transgenic and wild-type mice. The APP/PS1 transgenic mouse is a model of familial AD. The present study indicated that the serum Aβ42 level, Aβ42/Aβ40 ratio, and CFH level are potential biomarkers in preclinical and early stages of AD, whereas serum clusterin level is a potential biomarker in the late stage of AD.
Full Text Available Background. Chronic infection with hepatitis B virus (HBV is a leading cause of cirrhosis and hepatocellular carcinoma. By traditional Chinese medicine (TCM pattern classification, damp heat stasis in the middle-jiao (DHSM and liver Qi stagnation and spleen deficiency (LSSD are two most common subtypes of CHB. Results. In this study, we employed iTRAQ proteomics technology to identify potential serum protein biomarkers in 30 LSSD-CHB and 30 DHSM-CHB patients. Of the total 842 detected proteins, 273 and 345 were differentially expressed in LSSD-CHB and DHSM-CHB patients compared to healthy controls, respectively. LSSD-CHB and DHSM-CHB shared 142 upregulated and 84 downregulated proteins, of which several proteins have been reported to be candidate biomarkers, including immunoglobulin (Ig related proteins, complement components, apolipoproteins, heat shock proteins, insulin-like growth factor binding protein, and alpha-2-macroglobulin. In addition, we identified that proteins might be potential biomarkers to distinguish LSSD-CHB from DHSM-CHB, such as A0A0A0MS51_HUMAN (gelsolin, PON3_HUMAN, Q96K68_HUMAN, and TRPM8_HUMAN that were differentially expressed exclusively in LSSD-CHB patients and A0A087WT59_HUMAN (transthyretin, ITIH1_HUMAN, TSP1_HUMAN, CO5_HUMAN, and ALBU_HUMAN that were differentially expressed specifically in DHSM-CHB patients. Conclusion. This is the first time to report serum proteins in CHB subtype patients. Our findings provide potential biomarkers can be used for LSSD-CHB and DHSM-CHB.
Karaman, Erbil; Karaman, Yasemin; Alkış, İsmet; Han, Agahan; Yıldırım, Gökhan; Ark, Hasan Cemal
The aim of this study was to determine the relationship between serum concentrations of cancer antigen-125 (CA-125) and pre-eclampsia severity. We evaluated 91 females with a singleton pregnancy. Serum CA-125 levels were measured in subjects with severe pre-eclampsia (n=34) and those with mild pre-eclampsia (n=24). Females with healthy pregnancies (n=31) served as the control group. The three study groups were statistically similar in terms of maternal age, gestational age, and body mass index. The CA-125 level was significantly higher in the severe pre-eclampsia group than that in the mild pre-eclampsia and control groups (pCA-125 levels between the mild pre-eclampsia and control groups was observed. CA-125 level was positively correlated with proteinuria (r=0.489, p=0.000), systolic blood pressure (r=0.503, p=0.018), and diastolic blood pressure (r=0.532, p=0.000). In contrast, CA-125 was negatively correlated with birth weight (r=0.266, p=0.012) and gestational age at birth (r=0.250, p=0.018). CA-125 level increased in severe pre-eclampsia, which reflected abnormal trophoblastic invasion and chronic inflammation. Elevated levels of CA-125 in pre-eclamptic patients may be a marker of the disease severity. Copyright © 2013 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.
Hepatitis C virus and alcoholic steatohepatitis (Petta et al., 2008). Since the kidney is involved in the catabolism of RBP4, renal injury such as chronic... hepatic injury (Beckett et al., 1987). Alpha GST also has been shown to be indicative of proximal tubular damage caused by proteinuria, a major cause...nephrotoxic acute kidney injury,” Toxicology., 245, 3, Mar 2008 pp. 182-93. Fernholm A, “FDA soon may support Biomarker Tests,” San Francisco Chronicle
Full Text Available BACKGROUND: In bone the Wnt signaling pathway has diverse roles in bone modeling and remodeling. Dickkopf related protein 1(DKK-1,as an end ogenous inhibitors of the canonical Wnt/–catenin path ways pecific to bone and Osteoprotegerin(OPG,have been demonstrated to be key molecules involved in bone erosion and bone remodeling.The present study aimedto evaluate DKK-1 and OPG in women with osteoporosis to predict activity and severity of this common disease. METHODS: The study population included 44 women with osteoporosis and 44 controls with normal bone mineral density (BMD. Serum levels of DKK-1 and OPG were measured by standard methods. RESULTS: The serum Dkk1 concentration in the osteoporosis group (2.91 ± 1.27 was significantly increased compared to the control group (2.07 ± 0.87 (P < 0.010. The serum concentration of OPG was significantly higher incontrol group than patients (4.70 ± 2.16 vs. 4.56 ± 1.21; P = 0.005. CONCLUSIONS: Although the results of this study indicate that DKK-1 and OPG may play different roles in the pathogenesis of osteoporosis, the increase of DKK-1 level and its correlation with FN-BMD might be related to disease activity and bone remodeling in osteoporosis.
Full Text Available Background: Delayed-onset muscle soreness (DOMS causes muscle damage and edema that can hinder performance and increase risks for secondary injuries. Kinesiology Tape (KT may be an effective modality for aiding in recovery, however, no study has investigated the effects of KT on the physiological biomarkers such as serum creatine kinase (CK level, concurrently with measures of performance and function, during recovery from DOMS. Objective: Investigate the effects of KT on serum CK level, electromyographic (EMG activity of the quadriceps muscles, and performances of countermovement jump (CMJ and triple single-leg hop for distance (HopD during recovery from DOMS. Method: Fifty-eight healthy college-age participants were randomly assigned to KT (n=15, placebo (n=19, and control (n=24 groups. Serum CK level and quadriceps EMG activity and performance during CMJ and HopD were collected at baseline, immediately after repetitive eccentric quadriceps exercise, 48 hours, and 72 hours post-exercise. The EMG recording of rectus femoris, vastus medialis, and vastus lateralis during the CMJ and HopD were normalized to the baseline maximum voluntary isometric contraction. Results: A significant main effect of time on the serum CK level, EMG activity, and performance (p0.05. Conclusion: Taping interventions did not improve the serum CK level or muscle activity and performance during recovery from DOMS. Kinesiology tape may not be the first choice of method for enhancing recovery from DOMS in otherwise healthy individuals.
Kehlet, Stephanie Nina; Bager, C. L.; Willumsen, N.
disorders.Methods: A fragment of decorin cleaved in vitro using human articular cartilage was identified by mass-spectrometry (MS/MS). Monoclonal antibodies were raised against the neo-epitope of the cleaved decorin fragment and a competitive ELISA assay (DCN-CS) was developed. The assay was evaluated...... homeostasis contributing to extracellular matrix remodeling diseases. Here, we present the development and validation of a competitive enzyme-linked immunosorbent assay (ELISA) quantifying a specific fragment of degraded decorin, which has potential as a novel non-invasive serum biomarker for fibrotic lung...
Full Text Available Aneta Cymbaluk-Płoska,1 Anita Chudecka-Głaz,1 Ewa Pius-Sadowska,2 Agnieszka Sompolska-Rzechuła,3 Bogusław Machaliński,2 Anna Surowiec,1 Janusz Menkiszak1 1Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, 2Department of General Pathology, Pomeranian Medical University, 3Department of Statistics, West Pomeranian University of Technology, Szczecin, Poland Introduction: Endometrial cancer is the one of the most common cancers of the genital organ. HE4 and MMP2 are both proteins whose serum levels increase in endometrial cancer.Aim: To explore the diagnostic potential of the serum levels of HE4 and MMP2 in patients with endometrial cancer and benign endometrial diseases. To assess the relationship between the serum levels of HE4 and MMP2 and the typical prognostic factors in patients with endometrial cancer.Materials and methods: Included in the study was a group of 112 patients presenting with bleeding abnormalities at the Pomeranian Medical University in years 2012–2016. Serum HE4 concentrations were measured using the Elecsys Electrochemiluminescence Immunoassay (ECLIA. MMP2 concentrations were quantified in the serum using multiplex immunoassays.Results: We observed statistically significant differences in mean serum levels of HE4 and MMP2 between the group of endometrial cancer patients and the group of patients with no changes in the endometrium (P=0.002/0.003. The diagnostic potential of HE4 and MMP2 in differentiation of high (International Federation of Gynecology and Obstetrics [FIGO] III and IV vs low (FIGO I and II clinical stage of tumor and prediction of cellular differentiation grade (G1 vs G3 on the basis of the analysis of the area under the curve is, respectively, 0.86 and 0.82 for HE4 and 0.82 and 0.74 for MMP2. The HE4 marker was significantly more specific than MMP2 in every study group and amounted to 93% vs 86% in all patients included in the analysis, 94% vs 84% in pre
Akdemir, Nermin; Akhin, Okan
We sought to investigate the serum levels of asymmetric dimethylarginine in pregnant women with hyperemesis gravidarum. Thirty-seven patients with hyperemesis gravidarum and 33 healthy controls were included in the study. Participants in the control group had no symptoms, or suffered only mild nausea without vomiting. The groups did not differ in age, weight, gestational week, or levels of hemoglobin, glucose or creatinine. The group with hyperemesis gravidarum had higher levels of blood urea nitrogen and liver transaminase than the controls (p = 0.005, 0.01, and 0.04, respectively). They also had lower levels of sodium and thyroid-stimulating hormone (p = 0.004 and 0.03, respectively). Serum levels of asymmetric dimethylarginine were 0.79 ± 0.39 μM in the group with hyperemesis gravidarum and 0.68 ± 0.21 μM in the control group (p = 0.001). The results of this study showed the role of endothelial dysfunction in the pathogenesis of hyperemesis gravidarum.
Bellia, Alfonso; Garcovich, Caterina; D'Adamo, Monica; Lombardo, Mauro; Tesauro, Manfredi; Donadel, Giulia; Gentileschi, Paolo; Lauro, Davide; Federici, Massimo; Lauro, Renato; Sbraccia, Paolo
Obesity is frequently characterized by a reduced vitamin D bioavailability, as well as insulin-resistance and a chronic inflammatory response. We tested the hypothesis of an independent relationship between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and several circulating inflammatory markers in a cohort of severely obese individuals. Cross-sectional study was carried out among obese patients undergoing a clinical evaluation before bariatric surgery in our University Hospital. Serum 25(OH)D, fasting and post load glucose and insulin, high-sensitive C-reactive protein (hs CRP), fibrinogen, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leptin, adiponectin and lipid profile were collected. Insulin-resistance was assessed by insulin sensitivity index (ISI). Total body fat (FAT kg), total percent body fat (FAT%) and truncal fat mass (TrFAT) were assessed with dual-energy X-ray absorptiometry. A total of 147 obese subjects (89 women, 37.8 ± 7.1 years) with mean body mass index (BMI) of 43.6 ± 4.3 kg/m(2) were enrolled. Patients in the lowest tertile of 25(OH)D were significantly more obese with a higher amount of TrFAT, more insulin-resistant, and had higher levels of fasting and post-challenge glucose (p < 0.05 for all). In a multivariate regression analysis, serum 25(OH)D was inversely related to significant levels of hs CRP, IL-6 and TNF-α after accounting for age, gender, season of recruitment, BMI, FAT kg and TrFAT (p < 0.01 for all). In extremely obese subjects, 25(OH)D serum concentrations are inversely associated with several biomarkers of systemic inflammation, regardless of the total quantity of fat mass.
Full Text Available Although levels of iron are known to be increased in the brains of patients with Parkinson disease (PD, epidemiological evidence on a possible effect of iron blood levels on PD risk is inconclusive, with effects reported in opposite directions. Epidemiological studies suffer from problems of confounding and reverse causation, and mendelian randomization (MR represents an alternative approach to provide unconfounded estimates of the effects of biomarkers on disease. We performed a MR study where genes known to modify iron levels were used as instruments to estimate the effect of iron on PD risk, based on estimates of the genetic effects on both iron and PD obtained from the largest sample meta-analyzed to date.We used as instrumental variables three genetic variants influencing iron levels, HFE rs1800562, HFE rs1799945, and TMPRSS6 rs855791. Estimates of their effect on serum iron were based on a recent genome-wide meta-analysis of 21,567 individuals, while estimates of their effect on PD risk were obtained through meta-analysis of genome-wide and candidate gene studies with 20,809 PD cases and 88,892 controls. Separate MR estimates of the effect of iron on PD were obtained for each variant and pooled by meta-analysis. We investigated heterogeneity across the three estimates as an indication of possible pleiotropy and found no evidence of it. The combined MR estimate showed a statistically significant protective effect of iron, with a relative risk reduction for PD of 3% (95% CI 1%-6%; p = 0.001 per 10 µg/dl increase in serum iron.Our study suggests that increased iron levels are causally associated with a decreased risk of developing PD. Further studies are needed to understand the pathophysiological mechanism of action of serum iron on PD risk before recommendations can be made.
Awata, Hiroshi; Linder, Stephen; Mitchell, Laura E; Delclos, George L
The Centers for Disease Control and Prevention (CDC) recently found that Asians have considerably higher biomarker levels of cadmium, lead, mercury, and arsenic than whites, blacks, Mexican Americans, and other Hispanics in the United States. Our goal was to further evaluate the higher metal biomarker levels among Asians. Biomarker data (blood cadmium, blood lead, blood mercury, urinary total arsenic, and urinary dimethylarsinic acic) from individuals ≥ 6 years of age were obtained from the 2011-2012 National Health and Nutrition Examination Survey (NHANES). We compared geometric mean levels of these five metal biomarkers in Asians with those of four other NHANES race/ethnic groups (white, black, Mexican American, and other Hispanic), and across three Asian subgroups (Chinese, Asian Indian, and other Asian). We also evaluated associations between biomarker levels and sociodemographic, physical, dietary, and behavioral covariates across the Asian subgroups. Asians had significantly higher levels of all five metal biomarkers than other race/ethnic groups ( p LE, Delclos GL. 2017. Biomarker levels of toxic metals among Asian populations in the United States: NHANES 2011-2012. Environ Health Perspect 125:306-313; http://dx.doi.org/10.1289/EHP27.
Shehata, Elaine; Qayyum, Rehan
Several studies have examined the relationship between vitamin D (VD) and liver disease but none have explored this relationship in adults with normal liver enzymes. Our aim was to explore an independent association of VD with alanine aminotransferase (ALT) in a large sample of the US adults with liver enzymes in normal range (≤39 U/L). We used the continuous National Health and Nutrition Examination Survey from 2001 to 2006. We excluded individuals with